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Publications
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The Diagnosis and Staging of Hepatocellular Carcinoma: A Review of Current Practices.
Clinics in liver disease
2025; 29 (1): 33-48
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Abstract
Promoting the early detection and diagnosis of hepatocellular carcinoma (HCC) is a critical strategy to improve patient outcomes as this can lead to greater access to curative treatments. This review highlights the diagnostic tests for HCC, including the use of the Liver Imaging Reporting and Data System systems and histopathology. Staging is essential for informing prognosis and guiding treatment decisions; this review also covers a widely used and well-validated staging system called the Barcelona-Clinic Liver Cancer (BCLC) algorithm. The BCLC incorporates tumor status, liver function, and patient performance to stage patients with newly diagnosed HCC.
View details for DOI 10.1016/j.cld.2024.08.007
View details for PubMedID 39608956
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AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals.
Gastroenterology
2025; 168 (2): 267-284
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Abstract
Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr. This clinical practice guideline update aims to inform frontline health care practitioners by providing evidence-based practice recommendation for the management of HBVr in at-risk individuals.The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel conducted a systematic evidence review to identify new studies since publication of the first version of this clinical practice guideline in 2014. The Evidence to Decision framework was used to develop recommendations regarding the role of antiviral prophylaxis and monitoring without antiviral prophylaxis for management of HBVr. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations.The panel agreed on 4 recommendations. Based on evidence and baseline risk assessment, the panel made a strong recommendation in favor of antiviral prophylaxis for individuals at high risk of HBVr. For individuals at moderate risk of HBVr, a conditional recommendation was made in favor of antiviral prophylaxis. For individuals at low risk of HBVr, a conditional recommendation was made in favor of monitoring alone without antiviral prophylaxis. Monitoring should be performed at 1- to 3-month intervals, and must include assessment of hepatitis B viral load in addition to assessment of alanine aminotransferase. For individuals deemed to be at-risk of HBVr, the panel agreed on a strong recommendation in favor of testing for HBV; given universal Centers for Disease Control and Prevention screening guidance for hepatitis B for all adults 18 years and older by testing for HBV surface antigen, hepatitis B surface antibody, and total hepatitis B core antibody, stratifying screening practices by magnitude of HBVr risk is no longer needed.This document provides updated guidance for the management of HBVr in at-risk individuals. Limitations and gaps in the evidence are highlighted. This guideline is expected to require updating in 5 years from publication.
View details for DOI 10.1053/j.gastro.2024.11.008
View details for PubMedID 39863345
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Sex Differences in Adverse Liver and Nonliver Outcomes in Steatotic Liver Disease.
JAMA network open
2024; 7 (12): e2448946
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View details for DOI 10.1001/jamanetworkopen.2024.48946
View details for PubMedID 39630453
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Bariatric Surgery Reduced Long-Term Mortality in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Cirrhosis.
Clinical and molecular hepatology
2024
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Abstract
Objective: With the obesity pandemic, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and a leading cause of end-stage liver disease and liver-related deaths in the U.S.A. Therefore, we aimed to compare the long-term outcomes of patients with MASLD and cirrhosis with and without bariatric surgery.Design: Patients were retrospectively identified from the California Department of Healthcare Access and Information database, 2005 to 2019, for a population-based cohort study. Propensity score matching (PSM) was used to balance background risks between patients with cirrhosis who underwent bariatric surgery and those who did not. Overall, liver-related, and non-liver-related mortality were analyzed.Results: Of 91,708 eligible patients with MASLD and cirrhosis, PSM yielded 2,107 patients who underwent bariatric surgery and 8,428 non-bariatric controls. Compared to matched controls, patients who underwent bariatric surgery had lower 5-year overall (24.9% vs. 37.1%; P < 0.0001), liver-related (3.3% vs. 14%; P < 0.0001), and non-liver-related mortality (22.3% vs. 26.9%; P = 0.046). In multivariable analysis, bariatric surgery was associated with decreased overall mortality (adjusted hazard ratio [aHR] = 0.63; P < 0.0001), liver-related (aHR = 0.24; P < 0.0001), and non-liver-related (aHR = 0.81; P = 0.0026) mortality. However, only laparoscopic surgeries were associated with lower overall mortality (aHR = 0.39; P < 0.0001) whereas open surgeries were associated with higher overall mortality (aHR = 1.24; P = 0.022).Conclusion: Patients with MASLD and cirrhosis who underwent bariatric surgery, specifically laparoscopic approaches, had significantly lower mortality risk than non-surgical counterparts.
View details for DOI 10.3350/cmh.2024.0564
View details for PubMedID 39541951
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Trends in Hepatocellular Carcinoma Mortality Rates in the US and Projections Through 2040.
JAMA network open
2024; 7 (11): e2445525
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Abstract
Importance: The burden of liver cancer varies worldwide. An upward trend in both hepatocellular carcinoma (HCC) incidence and mortality in the past 2 decades has been observed.Objective: To assess observed HCC-related age-standardized mortality rates (ASMRs) in the US for 2006 to 2022 and provide ASMR projections through 2040.Design, Setting, and Participants: This cross-sectional study used data from the National Vital Statistics System, which is accessible through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research website. Data on deaths attributed to HCC (from January 1, 2006, to December 31, 2022) were obtained for adults 25 years or older and were stratified by liver disease etiology, age, sex, and race and ethnicity. Etiologies included alcohol-associated liver disease (ALD), hepatitis B virus (HBV), hepatitis C virus (HCV), and metabolic dysfunction-associated steatotic liver disease (MASLD).Main Outcomes and Measures: The main outcomes were (1) observed ASMRs of HCC per 100 000 persons using Joinpoint regression (National Cancer Institute) to assess trends during 2006 to 2022 and (2) ASMRs projected for 2023 to 2040 using Prophet and AutoARIMA modeling.Results: This study included 188 280 HCC-related deaths from 2006 to 2022. Most deaths occurred among males (77.4%). The annual percentage change was 4.1% (95% CI, 2.2% to 7.7%) for 2006 to 2009 and decreased to 1.8% (95% CI, 0.7% to 2.0%) for 2009 to 2022, with an overall observed ASMR of 5.03 per 100 000 persons in 2022 and a projected ASMR of 6.39 per 100 000 persons by 2040, with consistent trends for both sexes. By etiology, ASMRs decreased for HCV- and HBV-related mortality but increased for ALD- and MASLD-related mortality. In 2022, MASLD surpassed HBV as the third-leading cause of HCC-related death and was projected to overtake HCV in 2032 as the second-leading cause; ALD was projected to be the leading cause of HCC-related death in 2026. In 2022, the ASMR was higher among individuals aged 65 years or older compared with those aged 25 to 64 years (18.37 vs 1.79 per 100 000 persons). The American Indian or Alaska Native population had the largest increase in projected ASMR by 2040 (14.71 per 100 000 persons) compared with the Asian population (3.03 per 100 000 persons).Conclusions and Relevance: In this cross-sectional study, ASMRs for ALD- and MASLD-related HCC death increased rapidly from 2006 to 2022; ALD-related HCC was projected to be the leading cause by 2026, with MASLD as the second-leading cause by 2032. These findings may serve as a reference for public health decision-making and timely identification of groups at high risk of HCC death.
View details for DOI 10.1001/jamanetworkopen.2024.45525
View details for PubMedID 39556395
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A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis.
Gastroenterology
2024
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Abstract
Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score [Gender, Age, AFP-L3, AFP, and Des-carboxy-prothrombin] has been shown to have excellent sensitivity and specificity for HCC in phase two studies. We performed a phase three biomarker validation study to compare GALAD with AFP in detecting HCC.This is a prospective study of patients with cirrhosis enrolled at seven centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per AASLD guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and DCP (des-gamma carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months prior to the clinical diagnosis. All analyses were conducted by an unblinded statistician in the EDRN data management and coordinating center.A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage) with an annual incident rate of 2.4%. The AUC for AFP and GALAD within 12 months prior to HCC 0.66 and 0.78 (p<0.001), respectively. Using cutoff for GALAD of -1.36, the specificity was 82% and sensitivity at 12 months prior to HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months prior to HCC diagnosis (p=0.001).GALAD score, compared to AFP, improves the detection of HCC within 12 months prior to the actual diagnosis.
View details for DOI 10.1053/j.gastro.2024.09.008
View details for PubMedID 39293548
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Global epidemiology, natural history, maternal-to-child transmission, and treatment of pregnant women with hepatitis C: a systematic review and meta-analysis of 311,905,738 women
WILEY. 2024: 81
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View details for Web of Science ID 001351123500125
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Synergistic association of sodium-glucose cotransporter-2 inhibitor and metformin on liver and non-liver complications in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease.
Gut
2024
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Abstract
Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate the long-term effect of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on liver and non-liver outcomes among patients with diabetic MASLD.This population-based cohort study retrieved patients with diabetic MASLD from Merative Marketscan Research Databases (April 2013 and December 2021). The active comparator was other glucose-lowering drugs (oGLDs). Primary outcomes were liver complications including hepatocellular carcinoma (HCC) and liver cirrhosis, as well as non-liver complications including cardiovascular disease (CVD), chronic kidney disease (CKD) and non-liver cancer. Propensity score matching was applied and Cox regression models were conducted.Compared with oGLD, SGLT-2i users had significantly lower risk of HCC (HR 0.76, 95% CI 0.62 to 0.93), liver cirrhosis (HR 0.80, 95% CI 0.76 to 0.84), CVD (HR 0.82, 95% CI 0.79 to 0.85) and CKD (HR 0.66, 95% CI 0.62 to 0.70), non-liver cancer (HR 0.81, 95% CI 0.76 to 0.86). Compared with patients without metformin and SGLT-2i, a stepwise decreasing risk was observed in users of either metformin or SGLT-2i (HRs 0.76-0.97) and in users of both medications (HRs 0.58-0.79). The lower risk also was shown in liver decompensation, compensated cirrhosis, major CVD, end-stage renal disease and specific common cancers (HRs 0.61-0.84).In a nationwide cohort, SGLT-2i users were associated with a substantially lower risk of liver and non-liver complications than oGLD users among patients with diabetic MASLD. The risk was further reduced with concomitant metformin use.
View details for DOI 10.1136/gutjnl-2024-332481
View details for PubMedID 39122360
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Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.
Journal of hepatology
2024; 81 (1): 33-41
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Abstract
BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium.METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses.RESULTS: We analyzed 12,566 adult treatment-naive patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p=0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p<0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p<0.001).CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.
View details for DOI 10.1016/j.jhep.2024.02.033
View details for PubMedID 38906621
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MAFLD in adults: non-invasive tests for diagnosis and monitoring of MAFLD.
Hepatology international
2024
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Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the liver manifestation of a metabolic syndrome and is highly prevalent in the general population. There has been significant progress in non-invasive tests for MAFLD, from the diagnosis of fatty liver and monitoring of liver fat content in response to intervention, to evaluation of liver fibrosis and its change over time, and from risk stratification of patients within the context of clinical care pathways, to prognostication. Various non-invasive tests have also been developed to assess for fibrotic metabolic dysfunction-associated steatohepatitis, which has emerged as an important diagnostic goal, particularly in the context of clinical trials. Non-invasive tests can be used to diagnose clinically significant portal hypertension so that intervention can be administered to reduce the risk of decompensation. Furthermore, the use of risk stratification algorithms can identify at-risk patients for hepatocellular carcinoma surveillance. Beyond the liver, various tests that evaluate cardiovascular disease risk, assess sarcopenia and measure patient reported outcomes, can be utilized to improve the care of patients with MAFLD. This review provides an up-to-date overview of these non-invasive tests and the limitations of liver biopsy in the management of patients with MAFLD.
View details for DOI 10.1007/s12072-024-10661-x
View details for PubMedID 38913148
View details for PubMedCentralID 7154715
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Updates in characteristics and survival rates of cirrhosis in a nationwide cohort of real-world U.S. patients, 2003-2021.
Alimentary pharmacology & therapeutics
2024
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Abstract
BACKGROUND: Adverse outcomes of cirrhosis remain a top priority.AIMS: We examined the distribution of cirrhosis causes, HCC incidence and mortality and related changes over time in a nationwide U.S.COHORT:METHODS: A retrospective study of a national sample of commercially insured patients with cirrhosis from Optum's de-identified Clinformatics Data Mart Database (CDM).RESULTS: A total of 628,743 cirrhosis cases were identified with 45% having NAFLD, 19.5% HCV, and 16.3% ALD. African Americans had the highest rate of decompensation (60.6%), while Asians had the highest rate of HCC (2.4%), both p<0.001. African Americans more frequently had HCV (28.4%) while Hispanic/Latinos more frequently had NAFLD (49.2%, p<0.001). Patients in the 2014-2021 cohort were significantly older (63.0±12.8 vs. 57.0±14.3), less frequently decompensated (54.5% vs. 58.3%) but more frequently had HCC (1.7% vs. 0.6%) and NAFLD (46.5% vs. 44.2%), all p<0.001. The overall annual incidence of HCC was 0.76% (95% CI: 0.75-0.77) with a 5-year cumulative incidence of 4.03% (95% CI: 3.98-4.09), with significant variation by sex, race/ethnicity, and cirrhosis aetiology. The overall median years of survival were 11.4 (95% CI: 11.3-11.5) with a 5-year cumulative survival of 73.4% (95% CI: 73.3%-73.6%), also with significant disparities in similar subgroups (lowest in cryptogenic cirrhosis and worse in 2014-2021 vs. 2003-2013). The 2014-2021 period was independently associated with worse survival (aHR: 1.14, 95% CI: 1.08-1.20).CONCLUSIONS: HCC incidence and survival vary by aetiology among patients with cirrhosis, with cryptogenic cirrhosis having the lowest survival and lower survival in the more recent time period.
View details for DOI 10.1111/apt.18024
View details for PubMedID 38693757
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Genome-wide association study identifies high-impact susceptibility loci for hepatocellular carcinoma in North America.
Hepatology (Baltimore, Md.)
2024
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Abstract
Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have increased risk for hepatocellular carcinoma (HCC). However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European-descent populations (EDP).We conducted a two-stage genome-wide association study (GWAS) on HCC not affected by hepatitis B virus infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted meta-analysis. All analyses were conducted in the presence and absence of hepatitis C virus (HCV). The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for non-viral HCC: 3p22.1, MOBP, rs9842969, [0.51, (0.40-0.65)]; 5p15.33, TERT, rs2242652, [0.70, (0.62-0.79)]; 19q13.11, TM6SF2, rs58542926, [1.49, (1.29-1.72)]; 19p13.11 MAU2, rs58489806, [1.53, (1.33-1.75)]; and 22q13.31, PNPLA3, rs738409, [1.66, (1.51-1.83)]. One region was identified for HCV-induced HCC: 6p21.31, HLA-DQB1, rs9275224, [0.79, (0.74-0.84)]. A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for non-viral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC.Our GWAS highlights novel genetic susceptibility of non-viral HCC among EDP from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.
View details for DOI 10.1097/HEP.0000000000000800
View details for PubMedID 38381705
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Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.
Clinical and molecular hepatology
2024
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events.We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events.19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and BMI 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of liver-related mortality (p=0.054), HCC (p=0.043), and liver-related events (p=0.050) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (p<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (p<0.05).People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.
View details for DOI 10.3350/cmh.2023.0485
View details for PubMedID 38281814
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Antiviral Therapy Utilization and 10-Year Outcomes in Resected Hepatitis B Virus- and Hepatitis C Virus-Related Hepatocellular Carcinoma.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2024: JCO2300757
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Abstract
There are limited data on antiviral treatment utilization and its impact on long-term outcomes of hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after hepatic resection. We aimed to determine the utilization and impact of antivirals in HBV- and HCV-related HCC.This cohort study included 1,906 participants (1,054 HBV-related HCC and 852 HCV-related HCC) from 12 international sites. All participants had HBV- or HCV-related HCC and underwent curative surgical resection. The primary outcome was the utilization of antiviral therapy, and the secondary outcome was long-term overall survival (OS).The mean (±standard deviation [SD]) age was 62.1 (±11.3) years, 74% were male, and 84% were Asian. A total of 47% of the total cohort received antiviral therapy during a mean (±SD) follow-up of 5.0 (±4.3) years. The overall antiviral utilization for participants with HBV-related HCC was 57% and declined over time, from 65% before 2010, to 60% from 2010 to 2015, to 47% beyond 2015, P < .0001. The overall utilization of antivirals for HCV-related HCC was 35% and increased over time, from 24% before 2015 to 74% from 2015 and beyond, P < .0001. The 10-year OS was lower in untreated participants for both HBV (58% v 61%) and HCV participants (38% v 82%; both P < .0001). On multivariable Cox regression analysis adjusted for relevant confounders, antiviral therapy initiated before or within 6 months of HCC diagnosis was independently associated with lower mortality in both HBV- (adjusted hazard ratio [aHR], 0.60 [95% CI, 0.43 to 0.83]; P = .002) and HCV-related HCC (aHR, 0.18 [95% CI, 0.11 to 0.31]; P < .0001).Antiviral therapy is associated with long-term survival in people with HBV- or HCV-related HCC who undergo curative resection but is severely underutilized.
View details for DOI 10.1200/JCO.23.00757
View details for PubMedID 38175991
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Incidence and predictors of hepatocellular carcinoma in NAFLD without diagnosed cirrhosis: a nationwide real-world U.S. study.
Hepatology international
2023
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Abstract
A substantial proportion of patients with nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) do not have cirrhosis. Data regarding the incidence and predictors of HCC development in NAFLD without cirrhosis are limited. We conducted a large, national study of NAFLD patients without documented cirrhosis to examine the incidence and predictors for HCC development.This retrospective study included 751,603 NAFLD patients (54% female) without documented cirrhosis derived from the deidentified Optum Clinformatics® Data Mart Database. Patients with cirrhosis, platelets < 120,000/µL or FIB-4 values > 2.67 were excluded.The mean age was 53.7 ± 15.0 years, 45.9% were male, 39.5% had diabetes, 57.6% were White, 18.4% Hispanic, 8.2% Black and 4.9% were Asian. The mean platelet count was 264,000 ± 72,000/µL, and 96.3% of patients had a FIB-4 < 1.30. Over 1,686,607 person-years of follow-up, there were 76 incident cases of HCC, resulting in an HCC incidence rate of 0.05 per 1000 person-years. There was a higher HCC incidence rate among patients with platelets ≤ 150,000/µL, versus those with platelets > 150,000/µL (0.23 per 1000 person-years, vs. 0.04 per 1000 person-years, p = 0.02) but not in subgroup analyses for age, sex, race/ethnicity or diabetes. Using multivariable Cox proportional hazards model adjusted multiple confounders, platelet count ≤ 150,000/µL remained an independent predictor of HCC development (adjusted HR 5.80, 95% CI 1.67-20.1, p = 0.006).HCC incidence in NAFLD without documented cirrhosis was below the threshold for cost-effective HCC surveillance in overall and multiple subgroup analyses. Platelet count < 150,000/µL may be a useful predictor of HCC development in this population.
View details for DOI 10.1007/s12072-023-10616-8
View details for PubMedID 38079023
View details for PubMedCentralID 8215299
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Updates in Characteristics and Survival Rates of Hepatocellular Carcinoma in a Nationwide Cohort of Real-World US Patients, 2003-2021.
Journal of hepatocellular carcinoma
2023; 10: 2147-2158
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Abstract
Causes of hepatocellular carcinoma (HCC) may change as treatments become available for some liver diseases. We examined the distribution of HCC cause and survival of a nationwide cohort of insured patients.Optum's de-identified Clinformatics® Data Mart Database (CDM), 2003-2021.A total of 34707 patients with HCC were included: mean age: 68.3±11.6 years, 61% male, 62% Caucasian, 74% cirrhosis. Non-alcoholic fatty liver disease (NAFLD) was the most common etiology (38.9%), then hepatitis C virus (HCV) (25.3%), cryptogenic (18.0%), alcohol-associated liver disease (9.4%), other liver diseases (5.8%) and hepatitis B virus (HBV) at 2.6%. NAFLD patients were the oldest (mean age 71.1±11.2) and had the highest Charlson Comorbidity Index (CCI) (mean 10.5±3.9), while HCV were the youngest (mean age 64.2±9.2 years) and HBV had the lowest CCI (mean 7.2±4.4) (both P<0.0001). The overall 5-year survival was 18.8% (95% CI 18.2-19.3) but was lower in the recent 2014-2021 period vs 2003-2013 (18.1% vs 19.5%, P=0.003). The 2014-2021 cohort (inclusive of HCV treatment advances) was significantly older, with more females, fewer Caucasians, more African Americans, more Hispanics, fewer Asians, more cirrhosis, more NAFLD, and higher CCI (all P<0.001). On multivariable analysis, males (aHR: 1.13), Caucasians (aHR: 1.46), African Americans (aHR: 1.53) and Hispanics (aHR: 1.28) vs Asians, 2014-2021 (vs 2003-2013) cohort (aHR: 1.12), NAFLD (aHR: 1.14) or cryptogenic liver disease (aHR: 1.45) were associated with increased mortality (all P<0.001).HCC patients in more recent time 2014-2021 were more likely to be older, more likely to have nonviral etiology, and had worse survival compared to those from 2003 to 2013.
View details for DOI 10.2147/JHC.S420603
View details for PubMedID 38076642
View details for PubMedCentralID PMC10700040
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Treatment rates and factors associated with direct-acting antiviral therapy for insured patients with hepatitis C-related hepatocellular carcinoma - A real-world nationwide study.
Alimentary pharmacology & therapeutics
2023
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Abstract
Since the inception of the interferon-free direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection, guidelines as to who should receive this potentially curative treatment have evolved. Treatment with DAAs is now considered for all patients except for those considered moribund.To determine the DAA treatment rate for patients with HCV-related hepatocellular carcinoma (HCC).This was a retrospective study from January 2015 to March 2021 of a national sample of privately insured patients with HCV-related HCC using Optum's Clinformatics® Data Mart (CDM) Database - a large, de-identified, adjudicated claims database.We identified 3922 patients with HCV-related HCC: 922 (23.5%) received DAA. Compared to untreated patients, DAA-treated patients were younger (65.2 ± 7.5 vs. 66.4 ± 7.5 years, p < 0.001), more frequently saw a gastroenterology/infectious disease (GI/ID) physician (41.2% vs. 34.2%), and had decompensated cirrhosis (56% vs. 53%, p = 0.001). In multivariable analysis, younger age (HR: 0.98, 95% CI: 0.97-0.99, p < 0.001), GI/ID care (HR: 3.06, 95% CI: 2.13-4.51, p < 0.001), and having cirrhosis (compensated: HR: 1.60, 95% CI: 1.18-2.21, p = 0.003; decompensated: HR: 1.45, 95% CI: 1.07-1.98, p = 0.02) were associated with receiving DAA treatment, but not sex, race, or ethnicity. DAA-treated patients had significantly higher 5-year survival than untreated patients (47.2% vs. 35.2%, p < 0.001). Following adjustment for age, sex, race/ethnicity, Charlson Comorbidity Index, and HCC treatment, receiving DAA treatment was associated with lower mortality (aHR: 0.61, 95% CI: 0.53-0.69, p < 0.001).DAA treatment remains underutilised in insured patients with HCV-related HCC; fewer than one in four patients received treatment. Seeing a specialist and having decompensated cirrhosis were predictors for DAA treatment; additional efforts are needed to increase awareness of HCV treatment.
View details for DOI 10.1111/apt.17794
View details for PubMedID 37937485
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Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology.
Nature reviews. Gastroenterology & hepatology
2023
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Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.
View details for DOI 10.1038/s41575-023-00818-8
View details for PubMedID 37537332
View details for PubMedCentralID 9670241
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Diagnostic Performance of the Fibrosis-4 Index and Nonalcoholic Fatty Liver Disease Fibrosis Score in Lean Adults With Nonalcoholic Fatty Liver Disease.
JAMA network open
2023; 6 (8): e2329568
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Abstract
The diagnostic performance of the fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for advanced fibrosis in lean patients with NAFLD is limited.To evaluate the diagnostic performance of the FIB-4 and NFS in lean individuals with NAFLD.This diagnostic study included adults with biopsy-proven NAFLD from 6 referral centers in Asia from 1995 to 2019. Cohorts were matched by age and sex between the lean and nonlean groups. All statistical analyses were executed from October 2022 to March 2023.The diagnostic performance of the FIB-4 and NFS at the current cutoff for advanced hepatic fibrosis in lean (body mass index [BMI] below 23 [calculated as weight in kilograms divided by height in meters squared]) and nonlean (BMI above 23) patients were evaluated.A total of 1501 patients were included in analysis (mean [SD] age, 46.1 [16.4] years); 788 male (52.5%), 115 lean (7.7%), 472 (30.2%) Korean, 821 (48.7%) Japanese, and 341 (21.3%) Taiwanese. Among the age- and sex-matched cohort, the mean (SD) age was 52.3 (15.1) years and 41.2% (47 of 114) were male. The diagnostic performance and areas under the operating characteristic curve of the FIB-4 (lean, 0.807 vs nonlean, 0.743; P = .28) and NFS (lean, 0.790 vs nonlean, 0.755; P = .54) between the 2 groups were comparable in the age- and sex-matched cohort. The sensitivity and specificity of the NFS showed increasing and decreasing tendency according to the BMI quartiles (P for trend < .001), while those of the FIB-4 did not (P for trend = .05 and P = .20, respectively). Additionally, although the areas under the operating characteristic curve of the FIB-4 and NFS were not significantly different in the lean group (0.807 vs 0.790; P = .09), the sensitivity of the current NFS cutoff values was lower in the lean group than in that of FIB-4 (54.4% vs 81.8%; P = .03).In this cohort study, the performance of the FIB-4 and NFS in diagnosing advanced fibrosis did not differ significantly between the 2 groups overall. However, in lean NAFLD, while the sensitivity for diagnosing advanced hepatic fibrosis remained reasonable at the current cutoff level, the sensitivity of NFS at the current cutoff was too low to be an adequate screening tool.
View details for DOI 10.1001/jamanetworkopen.2023.29568
View details for PubMedID 37589973
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Antiviral therapy substantially reduces hepatocellular carcinoma risk in chronic Hepatitis B patients in the indeterminate phase.
Hepatology (Baltimore, Md.)
2023
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Abstract
BACKGROUND AIMS: Hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared to the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase.APPROACH RESULTS: We analyzed 855 adult (59% male), treatment-naive CHB patients without advanced fibrosis in the indeterminate phase at 14 centers (U.S., Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46 ± 13 years, the median ALT was 38 (IQR, 24 - 52) U/L, the mean HBV DNA was 4.5 ± 2.1 log10 IU/mL and 20% were HBeAg positive. The two groups were similar after IPTW. After IPTW (n = 819), the 5-, 10- and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients(n = 425), respectively (p = 0.02), with consistent findings in subgroup analyses for age > 35 years, males, HBeAg positive, HBV DNA > 1,000IU/mL, and ALT < upper limit of normal. In multivariable Cox proportional hazards analysis adjusted for age, sex, HBeAg, HBV DNA, ALT, diabetes, and platelets, antiviral therapy remained an independent predictor of reduced HCC risk (adjusted HR 0.3, 95%CI 0.1 - 0.6, p = 0.001).CONCLUSION: Antiviral therapy reduces HCC risk by 70% among indeterminate phase CHB patients. These data have important implications for the potential expansion of CHB treatment criteria.
View details for DOI 10.1097/HEP.0000000000000459
View details for PubMedID 37184202
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Utilization of Antiviral Therapy for Patients With Hepatitis B-Related Hepatocellular Carcinoma: A Nationwide Real-World US Study.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2023
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Abstract
Although oral antiviral therapy (OAV) is reported to improve outcomes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), it is underutilized. We determined the rate and factors associated with OAV utilization among patients with HBV-related HCC in a US population with health insurance.Patients with HBV-related HCC were identified from the de-identified administrative health claims database for patients with private insurance, Optum Clinformatics (2003-2021).We identified 2129 patients with HBV-related HCC: 71% male, mean age 62.7 ± 12.5 years, 40% Asian individuals, 72% with cirrhosis, and 37% received OAV. The treatment rate improved over time (40.5% after 2010 vs 26.3% earlier; P < .001). Significantly lower treatment rates were noted for females, non-Asian patients, noncirrhotic patients, and patients without gastroenterologist/hepatologist or infectious disease (GI/ID) specialist care (P < .0001). OAV treatment predictors included Asian race and ethnicity (adjusted odds ratio [aOR], 3.6; 95% CI, 2.8-4.5; P < .001), male sex (aOR, 1.6; 95% CI, 1.3-2.0; P < .001), seeing a GI/ID specialist (aOR, 1.5; 95% CI, 1.10-1.99; P = .0091), having compensated cirrhosis (aOR, 2.2; 95% CI, 1.7-2.8; P < .001), and being treated from 2011 to 2021 (aOR, 2.3; 95% CI, 1.8-3.0; P < .001); being younger (aOR, 0.98; 95% CI, 0.98-0.99; P < .001) was less likely for treatment. OAV initiated at or before HCC diagnosis was associated independently with improved survival (adjusted hazard ratio, 0.84; 95% CI, 0.72-0.99; P = .037).Among patients with HBV-related HCC, only 1 in 3 received OAV despite having insurance coverage. Efforts must continue to develop ways to improve HBV OAV treatment, especially among females, non-Asian patients, and patients without cirrhosis or not seen by specialists.
View details for DOI 10.1016/j.cgh.2023.04.020
View details for PubMedID 37805836
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Development and validation of a REcurrent Liver cAncer Prediction ScorE (RELAPSE) following liver transplantation in patients with hepatocellular carcinoma: analysis of the us multicenter hcc transplant consortium.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2023
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Abstract
Hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need.Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the United States Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (MLA; Random Survival Forest [RSF] and Classification and Regression Tree (CART) models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant (EurHeCaLT) study group.Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria (MC), 16.1% were initially beyond MC with 9.4% downstaged prior to LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1-, 3-, and 5-years was 89.7%, 78.6%, 69.8% and 86.8%, 74.9%, 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 mo) and non-HCC mortality of 20.8%. A multivariable model identified maximum AFP (HR = 1.35 per-log SD, 95%-CI:1.22-1.50,p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95%-CI:1.04-1.28,p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95%-CI 1.35-1.73,p < 0.001), microvascular (HR = 2.37, 95%-CI:1.87-2.99,p < 0.001) and macrovascular (HR = 3.38, 95%-CI:2.41-4.75,p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95%-CI:1.29-2.37,p < 0.001; poor HR = 2.62, 95%-CI:1.54-3.32,p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). MLAs incorporating additional covariates improved prediction of recurrence (RSF C-statistic = 0.81). Despite significant differences in EurHeCaLT recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2 and 5-year recurrence risk discrimination (AUC 0.77 and 0.75, respectively).We develop and externally validate a RELAPSE score which accurately discriminates post-LT HCC recurrence risk, and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.
View details for DOI 10.1097/LVT.0000000000000145
View details for PubMedID 37029083
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Global incidence of non-alcoholic fatty liver disease: a systematic review and meta-analysis of 63 studies and 1,201,807 persons.
Journal of hepatology
2023
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Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. We aimed to estimate the pooled global NAFLD incidence.We performed a systematic review and meta-analysis of cohort studies of adults without NAFLD at baseline to evaluate the global incidence of ultrasound-diagnosed NAFLD.A total of 63 eligible studies (1,201,807 persons) were analyzed. Studies were from Mainland China/Hong Kong (n=26), South Korea (n=22), Japan (n=14), other (n=2, Sri Lanka, Israel); 63.8% were clinical center studies; median study year 2000 to 2016; 87% were good quality. Among the 1,201,807 persons at risk, 242,568 persons developed NAFLD with incidence rate of 4,612.8 (95% CI 3,931.5-5,294.2) per 100,000 person-years; no statistically significant differences by study sample size (P=0.90) or study setting (P=0.055). Males had higher incidence versus females (5,943.8 vs. 3,671.7, P=0.0013). Both the obese (vs. nonobese) and the overweight/obese groups (vs. normal weight) were about 3 times more likely to develop NAFLD (8,669.6 vs. 2,963.9 and 8,416.6 vs. 3,358.2, respectively) (both P<0.0001). Smokers had higher incidence than nonsmokers (8,043.2 vs. 4,689.7, P=0.046). By meta-regression, adjusting for study year, study setting, and study location, study period of 2010 or after and study setting were associated with increased incidence (P=0.010 and P=0.055, respectively). By country, China had a higher NAFLD incidence compared to non-China regions (P=0.012) and Japan a lower incidence compared to non-Japan regions (P=0.005).NAFLD incidence is increasing with a current estimate of 4,613 new cases per 100,000 years. Males and overweight/obese had significantly higher incidence rates compared to females and those of normal weight. Public health interventions for prevention of NAFLD are needed with a special emphasis on males, overweight/obese persons, and higher risk region. Impact and Implications; Non-alcoholic fatty liver disease (NAFLD) affects approximately 30% of people worldwide and appears to be increasing but data to estimate the incidence rate are limited. In this meta-analytic study of over 1.2 million people, we estimated the incidence rate of NAFLD was 46.13 per 1000 person years with significant differences by sex, BMI, geography, and time-period. As treatment options for NAFLD remain limited, prevention of NAFLD should remain the focus of public health. Studies such as these can help policy makers in determining which and whether their prevention interventions are impactful.
View details for DOI 10.1016/j.jhep.2023.03.040
View details for PubMedID 37040843
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Global burden of hepatitis B virus: current status, missed opportunities and a call for action.
Nature reviews. Gastroenterology & hepatology
2023
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Abstract
Chronic hepatitis B virus (HBV) infection affects about 296 million people worldwide and is the leading aetiology of cirrhosis and liver cancer globally. Major medical complications also include acute flares and extrahepatic manifestations. In addition, people living with HBV infection also experience stigma. HBV-related cirrhosis resulted in an estimated 331,000 deaths in 2019, and it is estimated that the number of deaths from HBV-related liver cancer in 2019 was 192,000, an increase from 156,000 in 2010. Meanwhile, HBV remains severely underdiagnosed and effective measures that can prevent infection and disease progression are underutilized. Birth dose coverage for HBV vaccines remains low, particularly in low-income countries or regions where HBV burden is high. Patients with HBV infection are inadequately evaluated and linked to care and are undertreated worldwide, even in high-income countries or regions. Despite the goal of the World Health Organization to eliminate viral hepatitis as a public health problem by 2030, the annual global deaths from HBV are projected to increase by 39% from 2015 to 2030 if the status quo remains. In this Review, we discuss the current status and future projections of the global burden of HBV infection. We also discuss gaps in the current care cascade and propose future directions.
View details for DOI 10.1038/s41575-023-00760-9
View details for PubMedID 37024566
View details for PubMedCentralID 6096795
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Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes.
Journal of hepatocellular carcinoma
2023; 10: 413-428
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Abstract
Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk. Treatment with NAs is also associated with significant improvement in the long-term survival of patients with HBV infection who already have HCC. DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. Similarly, DAA therapy can reduce disease progression, liver and non-liver complications, and improve the long-term survival of patients with chronic HCV infection with or without HCC. Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. Since there is currently no specific pharmacotherapy effective for NAFLD, lifestyle modification and prevention of complications are important to improve prognosis. Additionally, ALD is the second fastest-growing cause of HCC-related deaths, especially with an accelerated trend since the COVID-19 pandemic. This review provides an overview of the epidemiologic trends in the etiologies of HCC, and the progress of treatments for each etiology and the impact on outcome in the patients with HCC.
View details for DOI 10.2147/JHC.S347959
View details for PubMedID 36926055
View details for PubMedCentralID PMC10013586
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Effectiveness and tolerability of camrelizumab combined with molecular targeted therapy for patients with unresectable or advanced HCC.
Cancer immunology, immunotherapy : CII
2023
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Abstract
There is a lack of effective programmed cell death protein 1 (PD-1)-targeted immunotherapy with good tolerability in patients with advanced hepatocellular carcinoma (HCC) and severely compromised liver function. We assessed patient outcomes after combined camrelizumab and molecular targeted therapy in a multicenter cohort study in China. The study included 99 patients with advanced HCC (58 Child-Pugh A and 41 Child-Pugh B), 84 of them received camrelizumab combined with molecular targeted therapy from January 10, 2019, to March 31, 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed. The median follow-up was 12.1 months. For patients with Child-Pugh B, the OS probability at 12-months, ORR and DCR were 49.7%, 31.7% and 65.9%, respectively, and the median PFS was 5.1 months [95% confidence interval (CI) 3.0-7.1], which were comparable with Child-Pugh A patients, although median OS was shorter in Child-Pugh B patients (20.5 vs.13.4 months, P = 0.12). In multivariate analysis, macrovascular infiltration (MVI), but not sex, age, hepatitis B virus etiology, extrahepatic metastasis, Child-Pugh B, or AFP > 400 ng/ml, was associated with 12-months OS [hazard ratio (HR) 2.970, 95% CI 1.276-6.917, P = 0.012] and ORR (HR 2.906, 95% CI 1.18-7.16, P = 0.020). Grade 3/4 immune-related AEs occurred in 26.8% of Child-Pugh B patients, including one potentially treatment-related death. In both groups, the most common AEs were immune thrombocytopenia and hepatotoxicity. Camrelizumab combined with targeted therapy showed favorable effectiveness and tolerability with manageable toxicities in Chinese HCC patients, regardless of Child-Pugh A/B liver function. MVI was associated with suboptimal immunotherapy response and poor prognosis.
View details for DOI 10.1007/s00262-023-03404-8
View details for PubMedID 36840762
View details for PubMedCentralID 6813818
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Meta-analysis: Chemoprevention of hepatocellular carcinoma with statins, aspirin and metformin.
Alimentary pharmacology & therapeutics
2023
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Abstract
BACKGROUND: Emerging data suggest that statins, aspirin and metformin may protect against hepatocellular carcinoma (HCC) development. However, prior meta-analyses were limited by heterogeneity and inclusion of studies without adequate adjustment for baseline risks.AIM: To examine by an updated meta-analysis the association between these medications and HCC risk.METHODS: Medline and Embase databases were searched from inception to March 2022 for studies that balanced baseline risks between study groups via propensity score matching or inverse probability of treatment weighting, that reported the impact of statins, aspirin or metformin on HCC risk. Multivariable-adjusted hazard ratios (HRs) for HCC were pooled using a random effects model.RESULTS: Statin use was associated with reduced HCC risk overall (HR: 0.52; 95% CI: 0.37-0.72) (10 studies, 1,774,476), and in subgroup analyses for cirrhosis, hepatitis B/C, non-alcoholic fatty liver disease, studies accounting for concurrent aspirin and metformin consumption and lipophilic statins. Aspirin use was associated with reduced HCC risk overall (HR: 0.48; 95% CI: 0.27-0.87) (11 studies, 2,190,285 patients) but not in studies accounting for concurrent statin and metformin use. Metformin use was not associated with reduced HCC risk overall (HR: 0.57; 95% CI: 0.31-1.06) (3 studies, 125,458 patients). Most analyses had moderate/substantial heterogeneity, except in follow-up <60months for aspirin (I2 =0%).CONCLUSION: Although statin and aspirin use were associated with reduced HCC risk, only statin use was significant in subgroup analyses accounting for concurrent medications. Metformin use was not associated with reduced HCC risk. These data have implications for future clinical trial design.
View details for DOI 10.1111/apt.17371
View details for PubMedID 36625733
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NAFLD and Non-Liver Comorbidities.
Clinical and molecular hepatology
2023
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View details for DOI 10.3350/cmh.2022.0442
View details for PubMedID 36603574
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Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
2023; 29 (1): 34-47
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Abstract
NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.
View details for DOI 10.1097/LVT.0000000000000007
View details for PubMedID 36630156
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Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients.
Hepatobiliary surgery and nutrition
2022; 11 (6): 848-860
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Abstract
Guidelines recommend that hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and/or hepatic vein tumor thrombosis (HVTT) should undergo systemic therapy. However, recent data suggest that surgical resection may be beneficial in selected cases, but outcomes are heterogenous. We aimed to estimate pooled overall survival (OS), recurrence free survival (RFS) and complication rates in HCC patients with macrovascular invasion (MVI) following surgical resection.In this systematic review and meta-analysis, two investigators independently searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020, without language restrictions, for studies reporting outcomes of adult HCC patients with MVI who underwent liver resection with curative intent.We screened 8,598 articles and included 40 studies involving 8,218 patients. Among all patients with MVI, the pooled median OS was 14.39 months [95% confidence interval (CI): 10.99-18.84], 1-year OS was 54.47% (95% CI: 46.12-62.58%) and 3-year OS was 23.20% (95% CI: 16.61-31.42%). Overall, 1- and 3-year RFS were 27.70% (95% CI: 21.00-35.57%) and 10.06% (95% CI: 6.62-15.01%), respectively. Among patients with PVTT, median OS was 20.41 months in those with segmental/2nd order involvement compared to 12.91 months if 1st order branch was involved and 6.41 months if the main trunk was involved. The pooled rate of major complications was 6.17% (95% CI: 3.53-10.56%).Overall median survival was 14.39 months for HCC patients with MVI following resection. Median survival was higher in PVTT with segmental/2nd order involvement at 20.41 versus 6.41 months if the main trunk was involved.
View details for DOI 10.21037/hbsn-21-419
View details for PubMedID 36523924
View details for PubMedCentralID PMC9745615
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Prevalence, characteristics, and mortality outcomes of obese and nonobese MAFLD in the United States.
Hepatology international
2022
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Abstract
BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) establishes new criteria for diagnosis of fatty liver disease independent of alcohol intake. We aimed to describe the prevalence and compare characteristics and mortality outcomes of persons with nonobese and obese MAFLD.METHODS: Using data from 13,640 participants from the third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, we identified participants with fatty liver on ultrasound who had MAFLD and analyzed them by the presence of obesity.RESULTS: Overall prevalence of MAFLD was 19%; amongst those, 54% were obese and 46% were nonobese. Nonobese MAFLD was more common in participants older than 65 than in younger participants (56.8% vs. 43.2%, p<0.0001). Nonobese MAFLD was more common in males (63.2% vs. 48.3%, p<0.0001). Obese MAFLD was more common in females (51.7% vs. 48.3%, p<0.0001). After adjusting for several demographic factors and alcohol use, older age [adjusted odds ratio (aOR) 1.02, 95% CI 1.00-1.02, p=0.003] and being male (aOR: 1.65, 95% CI 1.25-2.17, p=0.001) were independent risk factors for nonobese MAFLD. Nonobese MAFLD participants had a higher 20-year cumulative incidence for all-cause mortality compared to obese MAFLD participants (33.2% vs. 28.8%, p=0.0137). However, nonobese MAFLD was not independently associated with mortality after adjusting for relevant confounders, while FIB-4>1.3 and cardiovascular disease were the strongest risk factors associated with increased mortality [adjusted hazard ratio (aHR) >2.7 for both, p<0.0001 for both].CONCLUSIONS: Nonobese MAFLD constitutes about half of the MAFLD in the United States, especially among males and the elderly. Notably, nonobese MAFLD carries higher mortality than obese MAFLD. Screening and diagnosis of MAFLD should be considered in nonobese populations.
View details for DOI 10.1007/s12072-022-10436-2
View details for PubMedID 36309601
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Gaps in hepatocellular carcinoma surveillance among insured patients with hepatitis B infection without cirrhosis in the United States.
Hepatology communications
2022
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Abstract
Suboptimal adherence to guidelines for hepatocellular carcinoma (HCC) surveillance among high-risk patients is a persistent problem with substantial detriment to patient outcomes. While patients cite cost as a barrier to surveillance receipt, the financial burden they experience due to surveillance has not been examined. We conducted a retrospective administrative claims study to assess HCC surveillance use and associated costs in a US cohort of insured patients without cirrhosis but with hepatitis B virus (HBV) infection, monitored in routine clinical practice. Of 6831 patients (1122 on antiviral treatment, 5709 untreated), only 39.3% and 51.3% had received any abdominal imaging after 6 and 12 months, respectively, and patients were up to date with HCC surveillance guidelines for only 28% of the follow-up time. Completion of surveillance was substantially higher at 6 and 12 months among treated patients (51.7% and 69.6%, respectively) compared with untreated patients (36.9% and 47.6%, respectively) (p < 0.001). In adjusted models, treated patients were more likely than untreated patients to receive surveillance (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.53-2.01, p < 0.001), and the proportion of those up to date with surveillance was 9.7% higher (95% CI 6.26-13.07, p < 0.001). Mean total and patient-paid daily surveillance-related costs ranged from
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Forecasted 2040 Global Prevalence of NAFLD using Hierarchical Bayesian Approach.
Clinical and molecular hepatology
2022
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Abstract
Background: Due to increases in obesity and type 2 diabetes, nonalcoholic fatty liver disease (NAFLD) is increasing. Current forecast models may not include non-obese NAFLD. We used a Bayesian approach forecasting the prevalence of NAFLD through 2040.Methods: Prevalence data from 245 articles involving 2,699,627 persons were used with a hierarchical Bayesian approach to forecast the prevalence of NAFLD through 2040. Subgroup analyses were conducted for age, gender, presence of metabolic syndrome, region, and smoking. Sensitivity analysis was conducted for clinical setting and study quality.Results: Forecasted 2040 prevalence rate was 55.7%, a 3-times increase since 1990 and 43.2% increase from the 2020 prevalence of 38.9%. The estimated average yearly increase since 2020 was 2.16%. For those aged <50 years and ≥50 years old, the 2040 prevalence rates were not different (56.7% vs 61.5%, P=0.52). There was a significant difference in 2040 prevalence by sex (males- 60% vs.50%, P+) but trend is stepper for females (2.5% vs 1.5%, P=0.025). No difference in trends overtime by region (P=0.48). The rate of increase was significantly higher in those without metabolic syndrome (3.8% vs. 0.84%, P=0.003) and for smokers (1.4% vs. 1.1%, P=0.011). There was no difference by clinical/community setting (P=0.491) or the quality of the studies (P=0.85).Conclusion: By 2040, over half the adult population is forecasted to have NAFLD. The largest increases occur in women, smokers and those without metabolic syndrome. Intensification of efforts raising awareness and determining long term solutions addressing driving factors of NAFLD are needed.
View details for DOI 10.3350/cmh.2022.0239
View details for PubMedID 36117442
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Gaps in hepatocellular carcinoma surveillance in a United States cohort of insured patients with cirrhosis.
Current medical research and opinion
2022: 1-35
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Abstract
Objective Surveillance for hepatocellular carcinoma (HCC) is known to be underutilized; however, neither the variation of surveillance adherence by cirrhosis etiology nor the patient-side economic burden of surveillance are well understood. To identify potential barriers to HCC surveillance, we assessed utilization patterns and costs among US patients with cirrhosis monitored in routine clinical practice. Methods: We conducted a retrospective study of insured adult patients with cirrhosis using national administrative claims data from January 2013 - June 2019. Time up-to-date with recommended surveillance, correlates of surveillance receipt, and surveillance-associated costs were assessed during a ≥6-month follow-up. Results: Among 15,543 patients with cirrhosis (mean [SD] age 64.0 [11.1] years, 50.7% male), 45.8% and 58.7% had received any abdominal imaging at 6 and 12 months, respectively. Patients were up-to-date with recommended surveillance for only 31% of a median 1.3-year follow-up. Those with viral hepatitis were more likely to receive surveillance than those with other etiologies (hazard ratio [HR] 1.55, 95% CI 1.11-2.17, p=0.010 for patients without a baseline gastroenterologist [GI] visit and 2.69, 95% CI 1.77-4.09, p<0.001 for patients with a GI visit, relative to those with nonalcoholic fatty liver disease and no GI visit). For all etiologies except NAFLD, the HR (95% CI) for surveillance receipt was higher among patients with vs without a baseline GI visit (alcohol-related, 1.164 [1.002-1.351] vs 0.880 [0.796-0.972]; viral hepatitis, 2.688 [1.765-4.093] vs 1.553 [1.111-2.171]; Other, 0.612 [0.519-0.722] vs 0.549 [0.470-0.641]). Mean total and patient-paid daily surveillance-related costs ranged from
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Cabozantinib plus atezolizumab in advanced hepatocellular carcinoma and the role of adjuvant antiviral therapy.
The Lancet. Oncology
2022
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View details for DOI 10.1016/S1470-2045(22)00383-7
View details for PubMedID 35798015
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Meta-analysis: global prevalence, trend and forecasting of non-alcoholic fatty liver disease in children and adolescents, 2000-2021.
Alimentary pharmacology & therapeutics
2022
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Abstract
BACKGROUND: NAFLD is increasing in children.AIMS: To determine the recent trend and forecast the future global prevalence of paediatric NAFLD METHODS: We searched PubMed, Embase, Web of Science and Cochrane library databases from inception to 1 May 2021 for studies of children and adolescents (≤21years) with NAFLD. Obesity was defined with weight at ≥95th percentile and overweight as 85th to <95th percentile as per the Center for Disease Control BMI-for-age percentile cut-offs.RESULTS: From 3350 titles and abstracts, we included 74 studies (276,091 participants) from 20 countries/regions. We included 14 studies in the general NAFLD prevalence analysis, yielding an overall prevalence of 7.40% (95% CI: 4.17-12.81) regardless of the diagnostic method, and 8.77% (95% CI: 3.86-18.72) by ultrasound. Among continents with more than one study, the prevalence of NAFLD was 8.53% (95% CI: 5.71-12.55) for North America, 7.01% (95% CI: 3.51-13.53) for Asia, and 1.65% (95% CI: 0.97-2.80) for Europe. NAFLD prevalence regardless of the diagnostic method was 52.49% (95% CI: 46.23-58.68, 9159 participants) and 39.17% (95% CI: 30.65-48.42, 5371 participants) among obese and overweight/obese participants, respectively. For the general population, trend analysis from 2000 to 2017 indicates an increasing global prevalence of paediatric NAFLD from 4.62% to 9.02% at a yearly increase of 0.26%, whereas forecast analysis predicts a prevalence of 30.7% by 2040.CONCLUSION: The prevalence of paediatric NAFLD varies by region and is 52.49% overall among the obese population and 7.40% in the general population. It is predicted to reach 30.7% by 2040.
View details for DOI 10.1111/apt.17096
View details for PubMedID 35736008
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Poor diagnostic efficacy of noninvasive tests for advanced fibrosis in obese or younger than 60 diabetic NAFLD patients.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2022
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Abstract
Serum-based non-invasive tests (NITs) have been widely used to assess liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). However, the diagnostic efficacy of NITs across ranges of age, body mass index (BMI), and presence of type 2 diabetes (T2DM) may vary and have not been well characterized.background METHODS: We analyzed 1,489 patients with biopsy-proven NAFLD from 6 centers in Japan, Taiwan, and Korea. Using histology as the gold standard, we compared the AUROCs of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and the new Hepamet fibrosis score (HFS) with a focus on performance in subgroups as stratified by age, BMI, and the presence of T2DM.By histology, 44.0% (655/1489) of the overall cohort had F2-4 and 20.6% (307/1489) had F3-4 fibrosis. FIB-4 had the highest AUROCs for both F2-4 (0.701 vs. NFS 0.676 and HFS 0.682, P=0.001) and F3-4 (0.767 vs. NFS 0.736 and HFS 0.752, P=0.002). However, for F3-4 fibrosis, the AUROCs of all 3 NITs were generally higher in older (>60 years), nonobese (BMI<25 kg/m2), and non-diabetic patients, though overall the best performance was observed with FIB-4 among nonobese (BMI<25) diabetic patients (AUROC 0.92). The worst performance was observed in younger patients with T2DM for all NITs including FIB-4 (AUROC 0.63-0.66).results CONCLUSION: FIB-4 had higher diagnostic efficacy for F3-4 than NFS or HFS, but this varied greatly by age, BMI and T2DM, with better performance in older, nonobese, and nondiabetic patients. However, all NITs including FIB-4 had unacceptably poor performance in young or obese diabetic patients.
View details for DOI 10.1016/j.cgh.2022.05.015
View details for PubMedID 35654298
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NAFLD versus MAFLD: Prevalence, Outcomes and Implications of a Change in Name.
Clinical and molecular hepatology
2022
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Abstract
Non-alcoholic fatty liver disease (NAFLD) affects about a third of the world's adult population and is a major public health concern. NAFLD is defined by the presence of hepatic steatosis and the absence of other causes of liver disease. As NAFLD is closely associated with the presence of the metabolic syndrome, several experts have called for a change in nomenclature from NAFLD to metabolic-associated fatty liver disease (MAFLD) to better reflect the underlying pathophysiology of NAFLD as a metabolically driven disease and shift to a "positive" diagnostic criteria rather than one of exclusion. Recent studies have suggested that the global prevalence of MAFLD is higher than that of NAFLD, and patients with MAFLD have more metabolic comorbidities compared to those with NAFLD. Emerging data also suggest that all-cause and cardiovascular mortality may be higher in MAFLD compared with NAFLD. In this synopsis, we discuss differences in clinical features, prevalence and clinical outcomes between NAFLD and MAFLD. In addition, we highlight the advantages and disadvantages of a name change from NAFLD to MAFLD from the perspective of the scientific community, care providers and patients.
View details for DOI 10.3350/cmh.2022.0070
View details for PubMedID 35545437
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Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients
HEPATOBILIARY SURGERY AND NUTRITION
2022
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View details for DOI 10.21037/hbsn-21-419
View details for Web of Science ID 000834075100001
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Global and regional long-term survival following resection for HCC in the recent decade: A meta-analysis of 110 studies.
Hepatology communications
2022
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Abstract
Surgical resection for HCC remains a major curative treatment option, but it is unclear whether there are differences in outcomes by region and whether outcomes have improved over time. We aimed to estimate pooled overall survival (OS), recurrence-free survival (RFS), and complication rates in patients with hepatocellular carcinoma (HCC) following curative surgical resection and to compare outcomes by region and by time period. In this systematic review and meta-analysis, we searched Pubmed, Embase, and Cochrane databases from inception to May 15, 2020. We selected studies reporting OS, RFS, and complications in adult patients with HCC undergoing curative surgical resection. Two authors independently searched the literature and extracted the data. We screened 6983 articles and included 110 eligible studies with 82,392 patients, with study periods spanning from 1980-2017. The global pooled 1-year and 5-year survival rates were 88.9% (95% confidence interval [CI] 87.1-90.4) and 56.2% (95% CI 52.8-59.6) for OS and 71.1% (95% CI 67.6-74.3) and 35.2% (95% CI 32.5-38.0) for RFS, respectively. Five-year OS was higher in Asia (57.03%) than in other regions (Europe 48.3%; North America 48.0%; and South America 49.5%); p=0.002. Five-year RFS was higher in patients with hepatitis B virus versus patients with hepatitis C virus (34.8% vs. 24.1%; p=0.02). There was no significant improvement in 5-year OS and RFS over time. The pooled rate for complications was 27.6% (95% CI 23.4-32.3), with 9.7% (95% CI 6.3-14.7) classified as major. One-year OS after surgical resection for HCC is excellent (~90%). However, 5-year OS (~55%) and RFS (~35%) are still poor, suggesting that long-term care is suboptimal. Greater efforts are required to improve survival through enhanced surveillance and preventing recurrence through antiviral therapy.
View details for DOI 10.1002/hep4.1923
View details for PubMedID 35234371
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Inhibition of Viral Replication Reduces Transcriptionally Active Distinct Hepatitis B Virus Integrations with Implications on Host Gene Dysregulation.
Gastroenterology
2022
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Abstract
Hepatocellular carcinogenesis of hepatitis B virus (HBV) infection may arise from integration of viral DNA into the host genome. We aimed to gauge the effect of viral inhibition on transcriptionally active HBV-host integration events and explore the correlation of viral integrations with host gene dysregulation.We leveraged data and biospecimens from an interventional trial, in which patients with HBV viremia above 2,000 IU/mL and minimally raised serum liver enzyme were randomized to receive tenofovir disoproxil fumarate (TDF) or placebo for 3 years. Total RNA sequencing was performed on paired liver biopsies taken before and after the 3-year intervention in 119 patients. Virus-host chimeric reads were captured to quantify the number of distinct viral integrations. Dysregulation of a host gene disrupted by viral integration was defined by aberrant expression >2 standard deviations away from samples without viral integration.The TDF (n=64) and placebo groups (n=55) were comparable at baseline. Expressed viral integrations were detected in all pre- and post-treatment samples. The number of distinct viral integrations significantly correlated with circulatory biomarkers indicative of viral activities including HBV DNA, RNA, and viral antigens (p<0.0003 for all correlations). Moreover, TDF versus placebo achieved a significantly greater reduction in distinct viral integrations, with 3.28-fold and 1.81-fold decreases in the expressed integrations per million reads, respectively (ANCOVA, p=0.037). Besides, viral integrations significantly correlated with host gene dysregulation.Inhibition of viral replication reduces the number of transcriptionally active distinct HBV-host DNA integrations in patients with substantial viremia. Given the mutagenic potentials of viral integrations, such treatment effects should be considered in patient management.
View details for DOI 10.1053/j.gastro.2021.12.286
View details for PubMedID 34995536
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Global multi-stakeholder endorsement of the MAFLD definition.
The lancet. Gastroenterology & hepatology
2022
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View details for DOI 10.1016/S2468-1253(22)00062-0
View details for PubMedID 35248211
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Is it safe to treat chronic hepatitis C patients with decompensated cirrhosis with PI-based DAA?
Journal of hepatology
2022
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View details for DOI 10.1016/j.jhep.2021.12.037
View details for PubMedID 35074472
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Performance of noninvasive tests of fibrosis among Asians, Hispanic and non-Hispanic Whites in the STELLAR trials.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2022
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Abstract
The effect of race on routinely available noninvasive tests of fibrosis is incompletely understood. This study evaluated the performance of noninvasive tests among White and Asian patients in the STELLAR trials (NCT03053050 and NCT03053063), which evaluated selonsertib in patients with advanced (F3-F4) fibrosis due to nonalcoholic steatohepatitis (NASH).Baseline liver biopsies were centrally read using the NASH Clinical Research Network system, and four noninvasive tests (Nonalcoholic fatty liver disease fibrosis score [NFS], Fibrosis-4 index [FIB-4], Enhanced Liver Fibrosis test [ELF] and liver stiffness [LS] by vibration-controlled transient elastography) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using areas under the receiver operating characteristics curves (AUROCs) with 5-fold cross-validation repeated 100 times.Among 3207 patients screened with evaluable liver histology, 2281 were Whites and 762 were Asians. 72% of Whites and 67% of Asians had advanced fibrosis. The AUROCs of the noninvasive tests for advanced fibrosis were similar in Whites and Asians: 0.73 and 0.75 for NFS, 0.78 and 0.80 for FIB-4, 0.79 and 0.81 for ELF, and 0.80 and 0.83 for LS, respectively. At the published cutoffs, the tests had similar sensitivities and specificities in the two groups. However, the sensitivities of NFS, FIB-4 and ELF were low in both White and Asian patients younger than 40 years.In the global phase 3 STELLAR trials, the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between White and Asian patients.
View details for DOI 10.1016/j.cgh.2022.01.015
View details for PubMedID 35074532
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County-Level Variation in Cirrhosis-Related Mortality in the US, 1999-2019.
JAMA network open
2022; 5 (2): e2146427
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View details for DOI 10.1001/jamanetworkopen.2021.46427
View details for PubMedID 35107576
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Statin Use and Reduced Hepatocellular Carcinoma Risk in Patients with Non-alcoholic Fatty Liver Disease.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2022
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Abstract
Recent evidence suggests potential clinical benefits of statin in cancer chemoprevention and treatment. Non-alcoholic fatty liver disease (NAFLD) is expected to become the leading cause of hepatocellular carcinoma (HCC). We aimed to investigate the association between statin initiation and the risk of HCC among patients with NAFLD.In this study using the Optum de-identified Clinformatics® database, cox proportional-hazards regression model was performed to determine the risk of HCC in statin initiators versus nonusers. We incorporated inverse probability of treatment weighting (IPTW) to minimize potential confounding.Among 272,431 adults with NAFLD diagnosis, IPTW model shows that statin initiators had a 53% less risk of developing HCC compared to nonusers (HR: 0.47, 95% confidence interval: 0.36-0.60). In the sub-cohort with FIB-4 data available, statin initiation was associated with a 56% hazard reduction of developing HCC in NAFLD after adjusting for FIB-4 score (HR: 0.44; 0.30-0.65). The association between statin initiation and lower risk of HCC development was observed for both lipophilic statin (HR: 0.49; 0.37-0.65) and hydrophilic statin (HR: 0.40; 0.21-0.76). Moreover, we observed a greater hazards reduction as the dose and duration of statin use increased. NAFLD patients with more than 600 cDDDs of statin had a 70% reduction in hazards of developing HCC (HR: 0.30; 0.20-0.43).Our study provides strong evidence for the association between statin initiation and reduced risk of HCC development in NAFLD patients. These findings imply that statin can be used as a protective medication for NAFLD patients to reduce the risk of HCC.
View details for DOI 10.1016/j.cgh.2022.01.057
View details for PubMedID 35158055
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Clinical profiles of Asians with NAFLD: A systematic review and meta-analysis.
Digestive diseases (Basel, Switzerland)
2021
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Abstract
NAFLD is increasingly prevalent in Asia, where people suffer more metabolic comorbidities at a lower body mass index (BMI), suggesting potential differences in their clinical profile. Therefore, we attempted to characterize the clinical profile of Asians with NAFLD via a meta-analytic approach.We searched Pubmed, EMBASE, and Cochrane databases from January 1, 2000 to January 17, 2019. Two authors independently reviewed and selected 104 articles (2,247,754 persons) that identified NAFLD in Asians and reported relevant data, especially BMI and ALT, and excluded individuals with other liver disease and excessive alcohol consumption. Individual patient-level data were obtained from seven cohorts in Asia to complement meta-analyzed data.Overall, the mean age was 52.07 (95%CI:51.28-52.85) years with those from Southeast Asia (42.66, 95%CI: 32.23-53.11) being significantly younger. The mean BMI was 26.2 kg/m2, higher in moderate-severe vs. mild hepatic steatosis (28.3 vs. 25.7) patients and NFS ≥-1.455 vs. <-1.455 (27.09 vs. 26.02), with 34% having non-obese NAFLD. The mean ALT was 31.74 U/L, higher in NFS <-1.455 vs. ≥-1.455 (33.74 vs. 27.83), though no differences were found by obesity or steatosis severity. The majority of males (85.7%) and females (60.7%) had normal to minimally elevated ALT (1-1.5x 95% ULN). Individual patient-level data analysis (N=7,668) demonstrated similar results.About one-third of Asians with NAFLD were non-obese and the majority did not have markedly elevated ALT. Therefore, abnormal ALT or BMI are not recommended as a criterion for NAFLD screening in this population. Additionally, there were significant differences in the clinical profiles of NAFLD among the different regions of Asia.
View details for DOI 10.1159/000521662
View details for PubMedID 34942625
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2019 global NAFLD prevalence - A systematic review and meta-analysis.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
2021
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Abstract
BACKGROUND & AIMS: The increasing rates of obesity and type 2 diabetes mellitus may lead to increased prevalence of NAFLD. We aimed to determine the current and recent trends on the global and regional prevalence of NAFLD.METHODS: Systematic search from inception to March 26, 2020 was performed without language restrictions. Two authors independently performed screening and data extraction. We performed meta-regression to determine trends in NAFLD prevalence.RESULTS: We identified 17,244 articles from literature search and included 245 eligible studies involving 5,399,254 individuals. The pooled global prevalence of NAFLD was 29.8% (95% CI 28.6-31.1); of these, 82.5% of included articles used ultrasound to diagnose NAFLD with prevalence of 30.6% (95% CI 29.2-32.0). South America (3 studies, 5,716 individuals) and North America (4 studies, 18,236 individuals) had the highest NAFLD prevalence at 35.7% (95% CI 34.0-37.5) and 35.3% (95% CI 25.4-45.9), respectively. From 1991-2019, trend analysis showed NAFLD increased from 21.9% to 37.3% [yearly increase of 0.7% (P<0.0001)], with South America showing the most rapid change of 2.7% per year followed by Europe at 1.1%.CONCLUSIONS: Despite regional variation, the global prevalence of NAFLD is increasing overall. Policy makers must work towards reversing the current trends by increasing awareness of NAFLD and promoting healthy lifestyle environments.
View details for DOI 10.1016/j.cgh.2021.12.002
View details for PubMedID 34890795
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Risk of hepatocellular carcinoma with tenofovir versus entecavir in chronic hepatitis B Reply
LANCET GASTROENTEROLOGY & HEPATOLOGY
2021; 6 (2): 87–88
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View details for Web of Science ID 000608617700016
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Substantial gaps in evaluation and treatment of patients with hepatitis B in the US.
Journal of hepatology
2021
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Abstract
HBV associated liver complication is reduced by antiviral therapy. Prior studies using local institutional cohorts have suggested suboptimal evaluation and treatment. We aimed to determine the proportion of patients with chronic HBV infection who received adequate evaluation, were treatment eligible, and received antiviral treatment using a large, nationwide cohort.This retrospective analysis utlized claims data of approximately 73 million enrollees across the US from Optum's de-identified Clinformatics® Data Mart Database, 2003-2019. Adults with chronic HBV infection observed for ≥ 6 months before and after index chronic HBV infection diagnosis were identified via ICD-9/ICD-10 codes and confirmed by positive HBsAg, HBeAg or HBV DNA PCR.We included 12,608 eligible patients in the study analysis (mean age 45.7 years, 52.1% male, 54.6% Asian, 18.1% Caucasian, 10.5% African American). About half of the cohort (n=6,559, 52.3%) did not have a complete laboratory evaluation (defined as having HBeAg, HBV DNA, and ALT tests) and only 72.4% (n=9,129) had an "adequate" evaluation (at least HBV DNA and ALT) during the entire study period. Of those with an adequate evaluation, 11.2% were treatment eligible by AASLD criteria and 13.9% by EASL criteria; and of these, 60.4% of AASLD eligible patients and 54.3% of EASL eligible patients received treatment within 12 months from becoming eligible.Half of chronic HBV infection patients in the US with private insurance did not have a complete laboratory assessment. Over one third of treatment-eligible patients did not receive antiviral therapy. Patients who visited a GI/ID specialist had a higher chance of receiving adequate evaluation and treatment. Urgent intervention is needed to identify and address the barriers for these care gaps.In this study, we used a national database that includes laboratory data in addition to medical and pharmacy claims data to assess the current real-world situation of chronic HBV infection care in the US. Among the 12,608 patients with chronic HBV infection included in our study, 52.3% never had a complete laboratory and only 73% had adequate evaluation. Among those who were treatment eligible by AASLD or EASL guidelines, only 60.4% and 54.3% received treatment within 12 months, respectively.
View details for DOI 10.1016/j.jhep.2021.08.019
View details for PubMedID 34474097