Publications

Abstract

While both tenofovir alafenamide (TAF) and entecavir (ETV) are recommended first-line treatments for chronic hepatitis B (CHB), comparative data on their effectiveness remain limited. We aim to compare their virologic (VR), biochemical (BR), and complete (CR) response rates.This retrospective study enrolled treatment-naïve CHB patients who initiated either TAF or ETV in 2016 or after across 22 international centers and evaluated their treatment response after balancing their characteristics using inverse probability treatment weighting (IPTW) and via Fine-Gray competing-risks analysis of the balanced cohort.The study included 1,605 patients (784 TAF and 821 ETV patients with significant background differences), of whom 1,553 (96.8%) were from Asia. IPTW analysis yielded a total weighted cohort of 1,660 (822 TAF and 838 ETV patients with balanced characteristics). The 5-year cumulative VRs were high in both groups with a slightly higher rate in TAF patients (98.0% vs. 93.9%, P<0.001), and similar findings in a subgroup analysis by median HBV DNA (5.5 log IU/mL). However, there was no significant difference in the 5-year BR rates overall (93.7 vs. 92.8%, P=0.484) or by ALT cutoff of 2× upper limit of normal (ULN). TAF patients had a slightly higher 5-year cumulative CR overall (94.9% vs. 89.4%, P=0.001) and in high HBV DNA (96.9% vs. 87.9%, P<0.001) or ALT ≥2× ULN patients (97.3% vs. 90.6%, P<0.001), but not in those with lower HBV DNA or ALT.BR rates were similar with ETV and TAF, while VR and CR were higher with TAF though the difference was modest (<5% overall, 7-9% in high HBV DNA or ALT groups). Antiviral selection between TAF vs. ETV should be based mainly on cost, side effect profile, and patient preference.

View details for DOI 10.14309/ajg.0000000000003881

View details for PubMedID 41384853

Abstract

With rapid changes in the management landscape of chronic hepatitis B (CHB), this technical systematic review addresses four critical Population, Intervention, Comparator, Outcome (PICO) questions to provide guidance to the formulation of recommendations to the 2025 AASLD practice guidelines for management of CHB.The review was reported in accordance with PRISMA guidelines. Outcomes were evaluated across four key PICOs: (1) antiviral therapy for prevention of horizontal HBV transmission in high-risk groups, (2) antiviral therapy versus observation for persons in the immune-tolerant phase, (3) discontinuation versus continuation of nucleos(t)ide analogue therapy in HBeAg-negative individuals with undetectable HBV DNA, and (4) hepatocellular carcinoma (HCC) surveillance in non-cirrhotic individuals with HBsAg clearance or co-infections with HCV, HDV, or HIV.For PICO 1, limited evidence suggests antiviral therapy may reduce horizontal transmission risk, though with low certainty. PICO 2 analyses reveal uncertain benefits of treating persons in the immune-tolerant phase, with very low certainty due to heterogeneity and bias. PICO 3 analyses demonstrate that discontinuing antiviral therapy in persons who are HBeAg negative with undetectable HBV DNA increases HBsAg loss rates (OR 12.65, 95% CI 1.58-101.51) but carries moderate risks of virologic relapse (OR 47.17, 95% CI 2.79-797.35), and clinical flares. PICO 4 analyses on several cohort studies showed that in patients co-infected with HCV, HBV, or HIV, annual incidence of HCC was higher than the level where screening becomes cost-effective, suggesting that regular liver cancer screening could be beneficial for these patients.Despite low certainty, the findings support shared decision-making in high-risk horizontal transmission scenarios or in treating individuals in the immune tolerance phase, caution in discontinuing antiviral therapy in virologically suppressed individuals without HBsAg loss, and tailored HCC surveillance for those with co-infection or cirrhosis.

View details for DOI 10.1097/HEP.0000000000001584

View details for PubMedID 41186417

Abstract

Accumulating data related to prevention, surveillance and treatment of chronic hepatitis B (CHB) provided the impetus for this updated guideline, using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach.The guideline was developed in compliance with the National Academy of Medicine standards. The guideline panel developed structured questions following the Population, Intervention Comparison, Outcomes (PICO) framework. The panel addressed 6 PICO questions covering prevention (maternal to infant transmission and horizontal transmission), surveillance for liver cancer (among hepatitis B surface antigen positive (HBsAg) persons co-infected with hepatitis C virus, hepatitis D virus and/or human immunodeficiency viruses and after HBsAg loss) and treatment (HBsAg positive persons in immune-tolerant or indeterminate phases as well as withdrawal of antiviral therapy), providing evidence-based recommendations on these topics. Four systematic reviews of the literature were conducted, and two existing systematic reviews were utilized to support the recommendations in this practice guideline.This evidence-based guideline provides updated recommendations to optimize the care of persons with CHB.

View details for DOI 10.1097/HEP.0000000000001549

View details for PubMedID 41186418

Abstract

Evidence regarding the effect of glucagon-like peptidase 1 receptor agonist (GLP-1a), when compared with other glucose-lowering drugs (oGLD), on obesity-related cancer (ORC) in overweight or obese patients with type 2 diabetes (T2D) is limited.Using Merative™ Marketscan® Research Databases, we identified all overweight or obese patients with T2D aged 20-79 years who received GLP-1a or oGLD in the U.S. between January 2016 and June 2021. The primary outcome was ORC, defined as a component of 13 cancer types.Among 919,609 overweight or obese individuals with T2D (mean [SD] age, 52.3 [10.9] years; female, 53.5%), 16,653 newly diagnosed ORC were recorded during the 2,086,526 person-years of follow-up. GLP-1a users (vs oGLD users) were associated with lower incidence (7.5 vs 8.1 per 1000 person-years) and risk of ORC (adjusted hazard ratio [aHR] 0.87, 95%CI 0.83-0.91). This significant association was consistent when comparing GLP-1a with metformin (aHR 0.90, 95%CI 0.86-0.95), dipeptidyl peptidase-4 inhibitor (aHR 0.88, 95%CI 0.84-0.93), thiazolidinediones (aHR 0.84, 95%CI 0.71-0.99), sulfonylureas (aHR 0.81, 95%CI 0.74-0.88), sodium-glucose transport protein 2 inhibitor (aHR 0.73, 95%CI 0.66-0.80), insulin (aHR 0.70, 95%CI 0.65-0.76), all P <.05, and was strengthened with increasing weight (overweight, mild-to-moderate, and severe obesityHR 0.95, 95%CI 0.81-1.10 vs 0.90, 95%CI 0.84-0.97 vs 0.82, 95%CI 0.77-0.88; Pinteraction = .032).In a nationwide U.S. cohort of overweight or obese patients with T2D, GLP-1a, when compared with oGLD, was associated with a lower risk of ORC, with more pronounced risk reduction with increasing body weight.

View details for DOI 10.1093/jnci/djaf163

View details for PubMedID 40632592

View details for DOI 10.1016/j.metabol.2025.156350

View details for PubMedID 40617377

Abstract

Patients with cirrhosis are at high risk of developing adverse liver events. However, data on sex differences are limited.To compare risk of adverse liver events between male and female patients with cirrhosis.This population-based retrospective cohort study included adult patients with cirrhosis who were identified from a US private health insurance claims database (Merative MarketScan Research Databases) from January 1, 2007, to December 31, 2022.Males compared with females.The main outcome was the incidence of adverse liver events (decompensated cirrhosis [DC], hepatocellular carcinoma [HCC], and liver transplant [LT]). Propensity score matching on age, liver disease etiologies, geographic region, insurance type, specialty type, alcohol use disorder, obesity, baseline status of decompensation, and Charlson Comorbidity Index score was used to balance baseline characteristics of the male and female groups.The study included 438 706 patients with cirrhosis (mean [SD] age, 56.8 [15.4] years; 50.8% males), with a higher mean (SD) age in males than in females (57.6 [14.3] vs 55.9 [16.4] years). Propensity score matching yielded 169 711 pairs of female and male patients with similar baseline characteristics for subsequent analyses. Males compared with females had a higher incidence (per 1000 person-years) of DC (65.77 [95% CI, 64.74-66.81] vs 55.35 [95% CI, 54.46-56.25]; P < .001), HCC (6.98 [95% CI, 6.71-7.27] vs 3.35 [95% CI, 3.17-3.54]; P < .001), and LT (10.23 [95% CI, 9.89-10.58] vs 6.27 [95% CI, 6.01-6.52]; P < .001). In the Cox proportional hazards regression model, male sex was associated with 16% higher risk of DC (hazard ratio [HR], 1.16 [95% CI, 1.14-1.19]; P < .001), 63% of LT (HR, 1.63 [95% CI, 1.54-1.71]; P < .001), and 110% of HCC (HR, 2.10 [95% CI, 1.96-2.25]; P < .001). Among the major liver disease etiologies, male sex (compared with female sex) was associated with the highest risk of adverse liver events in patients with alcohol-related liver disease including DC (HR, 1.13 [95% CI, 1.08-1.19]; P < .001), HCC (HR, 2.40 [95% CI, 2.01-2.88]; P < .001), and LT (HR, 1.36 [95% CI, 1.21-1.53]; P < .001), followed by metabolic dysfunction-associated steatotic liver disease and hepatitis C virus (HCV) infection, but not in patients with HBV except for those with HCC (HR, 1.60 [95% CI, 1.08-2.36]; P = .02).The findings of this cohort study of adult patients with cirrhosis suggest that significant sex differences in liver complication risk exist, which was more pronounced in nonviral (alcohol-related liver disease and metabolic dysfunction-associated steatotic liver disease) compared with viral (HBV and HCV) cirrhosis. Sex disparities should be taken into consideration in future guidelines and programs for disease monitoring, prevention, and treatment of patients with cirrhosis.

View details for DOI 10.1001/jamanetworkopen.2025.23674

View details for PubMedID 40720121

Abstract

Type 2 Diabetes mellitus (T2DM), hepatitis steatosis (HS), and chronic hepatitis B (CHB) frequently co-exist, but the association of T2DM with liver histology was not been well characterized. The study investigated the impact of T2DM on the presence and severity of liver fibrosis and inflammation in CHB patients with biopsy-proven HS (CHB-HS).We enrolled CHB-HS patients who underwent liver biopsy from 19 medical centers (5 countries/regions) from 1990 to 2024. Propensity score matching (PSM) on age, sex, HBeAg and HBV DNA levels was performed to balance background risks between CHB-HS patients with and without T2DM in 1:3 ratio. The study included 1,019 CHB-HS patients (mean age 40.3±10.4 years, 75.4% male, 10.5% T2DM). In the PSM cohort (106 T2DM, 320 non-T2DM), T2DM patients (vs. non-T2DM) had higher proportions with significant (stage≥2) fibrosis (62.3% vs. 42.2%, p<0.01) but not with significant hepatic inflammation or moderate-to-severe steatosis (grade≥2 for both). On multivariable logistic regression analyses, T2DM was an independent factor associated with significant fibrosis (aOR 1.86, 95% CI: 1.15-3.01, p=0.01), but not other components of metabolic syndrome. Meanwhile, HBeAg+ and body mass index (BMI) rather than T2DM were associated with significant hepatic inflammation and moderate-to-severe steatosis, respectively, with similar findings in the total pre-PSM cohort.In CHB patients with concurrent HS, T2DM was an independent factor associated with significant fibrosis, HBeAg+ with hepatic inflammation, and BMI with moderate-to-severe steatosis, suggesting that both viral and metabolic control are crucial in the management of CHB patients with HS.

View details for DOI 10.1097/HEP.0000000000001442

View details for PubMedID 40560677

Abstract

Patients with chronic hepatitis B (CHB) with indeterminate phase make up a diverse cohort with likely different outcomes.We compared the hepatocellular carcinoma (HCC) risk in indeterminate CHB with different baseline types and by phase transition.This was a retrospective cohort study of 1986 (94.2% Asian) patients with indeterminate CHB from nine countries/regions. Patients were classified according to baseline hepatitis B e-antigen (HBeAg), alanine aminotransferase (ALT) and HBV DNA. The cumulative HCC incidence was compared.Based on the 2018 American Association for the Study of Liver Disease guidance, most indeterminate patients were HBeAg negative (84.9%). The 20-year HCC incidence was highest in type 1 (HBeAg positive, ALT<1×upper limit of normal (ULN), HBV DNA 20 000-106 IU/mL, 36.2%) and lowest in type 8 (HBeAg negative, ALT 1-2×ULN, HBV DNA<2000 IU/mL, 1.9%). The 20-year HCC incidence of those who remained indeterminate was 4.7%. Cumulative HCC incidence rates were high in patients with indeterminate CHB who transitioned to immune tolerant (15 years: 16.5%) or immune active (20 years: 13.7%) phase but low for those who transitioned to immune inactive phase (20 years: 2.5%). In multivariable analysis, compared with type 8, higher HCC risk was seen with HBeAg-positive type 1 (adjusted HR (aHR)=40.1, p<0.001), type 2 (ALT 1-2×ULN, HBV DNA≥20 000 IU/mL, aHR=25.1, p<0.001), HBeAg-negative type 9 (ALT>2×ULN, HBV DNA<2000 IU/mL, aHR=4.6, p=0.032) and type 10 (ALT<1×ULN, HBV DNA<2000 IU/mL but with moderate to severe inflammation/fibrosis, aHR=7.3, p=0.033). Similar directions in HCC risks were found in analyses based on the 2017 European Association for the Study of the Liver guideline.Several types of indeterminate CHB had high HCC risk. These data support the potential expansion of treatment criteria for higher risk types of indeterminate CHB.

View details for DOI 10.1136/gutjnl-2025-335033

View details for PubMedID 40467102

Abstract

Population-based data for metabolic dysfunction-associated steatotic liver disease (MASLD)-related mortality trends and forecasts in the United States are limited.To examine MASLD-related mortality trends in the United States from 2006 to 2023 and forecast mortality rates up to 2040 overall and in subgroups by age, sex, race and ethnicity, and urbanization.This cross-sectional study used data from the National Vital Statistics System dataset. Data on deaths attributed to MASLD were obtained for adults aged 25 years and older from January 1, 2006, to December 31, 2023.Trends were evaluated by average annual percentage change (AAPC) in age-standardized mortality rates (ASMRs) per 100 000 persons, and mortality rates were forecasted to 2040 using projection models.A total of 27 961 decedents aged 25 years and older with MASLD (15 251 [54.5%] aged ≥65 years; 15 450 [55.3%] female; 3373 [12.1%] Hispanic, 1480 [5.3%] non-Hispanic Black, and 21 936 [78.5%] non-Hispanic White) were documented from 2006 to 2023. ASMRs rose from 0.25 to 1.27 per 100 000 persons, with AAPCs increasing from 9.27% in 2006 to 2018 to 22.66% in 2018 to 2021, then decreasing to -1.23% from 2021 to 2023, leading to projected ASMRs of 2.24 per 100 000 persons in 2040. There were significant differences in the increases of ASMRs by age, with those aged 65 years or older having the steepest rise (AAPC, 15.34%; 95% CI, 14.40%-16.32%; P < .001; 45-64 years: 8.76%; 95% CI, 7.29%-10.22%; P < .001; 25-44 years: 2.65%; 95% CI, 0.49%-4.86%; P = .02) and a projected increase from 3.69 per 100 000 persons in 2024 to 7.12 per 100 000 persons in 2040. However, there was no significant difference in ASMRs by sex (AAPC among women: 11.24%; 95% CI, 10.09%-12.40%; P < .001; AAPC among men: 11.04%; 95% CI, 9.56%-12.63%; P < .001). ASMRs rose for all major racial ethnic groups, with the highest ASMR increase observed for non-Hispanic White individuals (AAPC, 11.12%; 95% CI, 9.48%-12.83%; P < .001), followed by Hispanic (AAPC, 10.67%; 95% CI, 9.11%-12.26%; P < .001), non-Hispanic Black (AAPC, 9.20%; 95% CI, 7.32%-11.11%; P < .001), and non-Hispanic Asian (AAPC, 7.97%; 95% CI, 4.66%-11.75%; P < .001) individuals, while the projected values for these 4 groups showed similar increasing trends to 2040. There were also significant differences in ASMRs by metropolitan categories overall, with the highest rise in nonmetropolitan areas (AAPC, 13.50%; 95% CI, 10.70%-16.32%; P < .001).In this cross-sectional study, MASLD-related mortality increased rapidly between 2006 and 2023 and was projected to rise over the next 20 years, with the largest disparities among those aged 65 years and older, among non-Hispanic White and Hispanic individuals, and among nonmetropolitan populations.

View details for DOI 10.1001/jamanetworkopen.2025.16367

View details for PubMedID 40526381

Abstract

Globally, the aetiology and epidemiology of chronic liver disease (CLD) are undergoing significant changes. We aimed to investigate the updated global burden of CLD, evaluate the cross-country inequalities, and provide 2050 predictions.Using the Global Burden of Disease Study (GBD) 2021 data resources, we analysed and forecasted CLD prevalence, incidence, and related death from 1990-2021 to 2050, respectively. We calculated average annual percent change (AAPC) by joinpoint regression model and quantified inequalities according to World Health Organisation-recommended health equity standards.In 2021, the number of prevalent, incident CLD and related deaths globally were 1.7 billion (95% uncertainty interval (UI): 1.6-1.8), 58.4 million (95% UI: 54.2-62.8) and 1.4 million (95% UI: 1.3-1.5), respectively. During 1990-2021, the age-standardised incidence rate (ASIR) increased, especially in those aged 15-49 (AAPC: 0.49%; 95% confidence interval [CI]: 0.45%-0.53%), in Europe (AAPC: 0.41%; 95% CI: 0.41%-0.42%) and the Americas (AAPC: 0.41%; 95% CI: 0.39%-0.42%), whereas the age-standardised death rate (ASDR) decreased globally (AAPC: -1.26%; 95% CI: -1.35% [-1.17%]) and across subgroups. During 1990-2021, the ASIR of metabolic dysfunction-associated steatotic liver disease (MASLD) increased the most in those aged 15-49 (AAPC: 0.72%; 95% CI: 0.67%-0.77%) and in the Western Pacific region (AAPC: 0.73%; 95% CI: 0.59%-0.86%). Socio-demographic index (SDI)-related inequalities decreased for the age-standardised prevalence rate (ASPR) and ASIR of CLD but increased for ASDR, placing a disproportionately heavier burden on low-SDI countries. From 2022 to 2050, the ASIR of CLD is projected to increase (AAPC: 0.20%; 95% CI: 0.19%-0.20%), but the ASDR is projected to decline (AAPC: -1.91%; 95% CI: -1.96% [-1.85%]).This study's findings highlight targeted interventions for CLD disparities, focusing on MASLD management, the younger population (15-49 years), and socio-demographic inequalities.

View details for DOI 10.1111/liv.70155

View details for PubMedID 40421876

Abstract

Significant liver fibrosis is an indication for antiviral therapy in chronic hepatitis B (CHB). Using liver histology assessed by Scheuer system, we evaluated the diagnostic performance of PRO-C3, GP73, and their combination for the presence of liver fibrosis, and compared them with FIB-4, APRI, Agile 3+, FAST, and LSM in treatment-naïve CHB patients from two centers. The study included 324 patients, of whom 167 had S2-4 (significant fibrosis) and 83 had S3-4 (advanced fibrosis). PRO-C3 levels were higher in those with S2-4 and S3-4 compared with S0-1 and S0-2 (both p < 0.001), with similar findings for GP73. PRO-C3 and GP73 were independently associated with S2-4 and S3-4 in multivariable analyses. The area under the curves (AUCs) of PRO-C3 for S2-4 and S3-4 were 0.81 and 0.80, respectively, and exceeded those of GP73 (0.75 and 0.73). The combination of PRO-C3 and GP73 also had significantly higher AUCs for both S2-4 (0.84 vs. 0.64) and S3-4 (0.80 vs. 0.65) as compared with FIB-4, with similar findings for APRI, GP73, LSM, FAST, and Agile 3+ for S2-4. In conclusion, PRO-C3 alone or in combination with GP73 is highly predictive for detecting significant liver fibrosis among CHB patients.

View details for DOI 10.1002/mco2.70236

View details for PubMedID 40502814

View details for PubMedCentralID PMC12152426

Abstract

Chronic hepatitis B (CHB) with indeterminate phase comprises a heterogeneous group of patients. We determined the prevalence of indeterminate CHB overall and characterised novel types and phase transition probabilities of novel types of indeterminate CHB.CHB patients were enrolled retrospectively from 24 centres (9 countries/regions). Indeterminate phase was defined based on the AASLD 2018 guidance.The cohort included 8375 patients with a mean age of 45.0 ± 13.7 years, 22.5% HBeAg-positive, and median ALT and HBV DNA of 30 U/L and 4.3 ± 2.2 log10IU/mL, respectively. Of the total cohort, half (47.2%) were in the indeterminate phase; and of these, the most prevalent group among HBeAg-positive patients was Type 2 (ALT 1-2 × ULN, HBV DNA≥ 20,000 IU/mL; 12.6%), while in HBeAg-negative patients it was Type 6 (ALT

View details for DOI 10.1111/apt.70194

View details for PubMedID 40395146

Abstract

Information about the association of glucagon-like peptidase 1 receptor agonist (GLP-1RA) with liver and non-liver complications is insufficient in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD). We conducted a target trial emulation study to evaluate whether GLP-1RA decreases the risk of liver and non-liver outcomes.Patients with T2D and MASLD initiating GLP-1RA or dipeptidyl peptidase-4 inhibitor (DPP-4i) were included from 2013 to 2022 in Merative™ Marketscan® Research Databases. Primary outcomes included (1) hepatocellular carcinoma (HCC) and cirrhosis, and (2) cardiovascular disease (CVD), chronic kidney disease (CKD), and non-liver cancer. Inverse probability of treatment weighting was applied to balance baseline characteristics and Cox regression models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI).In the intention-to-treat design, GLP-1RA, compared with DPP-4i, had a significantly lower incidence (per 1000 person-years) of HCC (0.8 vs 1.7; HR 0.53, 95%CI 0.39-0.71), of cirrhosis (29.3 vs 32.9; HR 0.91, 95%CI 0.86-0.96), of CVD (57.2 vs 73.9; HR 0.90, 95%CI 0.86-0.95), of CKD (4.5 vs 6.8; HR 0.73, 95%CI 0.64-0.84), and of non-liver cancer (16.9 vs 22.9; HR 0.82, 95%CI 0.77-0.89). In the per-protocol design, significant inverse associations for these study outcomes still were observed, with HR 0.60-0.77.In this emulated target trial of nationwide patients with T2D and MASLD, GLP-1RA use, when compared with DPP-4i, was associated with a significantly lower risk of liver and non-liver complications.

View details for DOI 10.3350/cmh.2024.1096

View details for PubMedID 40268291

View details for DOI 10.21037/hbsn-24-529

View details for Web of Science ID 001457240500001

Abstract

Given the rise of metabolic diseases, we investigated their long-term impact in chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogue (NA).We analyzed data from CHB patients who initiated NAs from 30 centers (7 countries/regions). We balanced patient characteristics with and without metabolic disease (diabetes, obesity, dyslipidemia, and hypertension) via propensity-score matching (PSM) to evaluate adverse liver events and motality.The study included 4,500 CHB patients (54.6% with ≥1 metabolic disease). PSM yielded 909 pairs of patients with balanced characteristics. When stratified by the number of metabolic disease, only patients with ≥2 metabolic diseases had increased cumulative incidence of cirrhosis and overall death (but not HCC or cause-specific death). However, when stratified by the presence of diabetes (regardless of the presence or number of other metabolic diseases), patients with diabetes (vs. those without) had significantly higher cumulative incidence of all outcomes: cirrhosis (P=0.009), HCC (P=0.023), overall, liver-related and non-liver-related death (P<0.001, P=0.026 and P<0.001, respectively). On Cox regression analysis, having ≥2 metabolic diseases was associated with cirrhosis, overall death and non-liver-related death but not HCC and liver-related death, while diabetes was significantly associated with higher risk of all outcomes: cirrhosis (HR=3.75, P=0.004), HCC (HR=2.02, P=0.020), overall, liver-related and non-liver-related death (HR=2.53, P<0.001; HR=2.65, P=0.016; HR=2.38, P<0.001).Having ≥2 metabolic diseases was associated with significantly higher risk of cirrhosis, overall death and non-liver-related death, but having diabetes as a single metabolic disease was significantly associated with all adverse outcomes including cirrhosis, HCC, overall, liver-related and non-liver-related death.

View details for DOI 10.3350/cmh.2024.1070

View details for PubMedID 40091278

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a global public health and economic burden worldwide in the past few decades. Epidemiological studies have shown that MASLD is a multisystem disease that is associated not only with liver-related complications but also with an increased risk of developing extrahepatic cancers. MASLD is a sexually dimorphic disease with sex hormones playing an important role in the development and progression of MASLD, especially by the levels and ratios of circulating estrogens and androgens. MASLD is associated with hormone-sensitive cancers including breast and gynecological cancer. The risk of breast and gynecological cancer is elevated in individuals with MASLD driven by shared metabolic risk factors including obesity and insulin resistance. Multiple potential mechanisms underline these associations including metabolic dysfunction, gut dysbiosis, chronic inflammation and dysregulated release of hepatokines. However, the effect of hormone therapy including hormone replacement therapy and anti-estrogen treatment on MASLD and female-specific cancers remains debatable at this time. This synopsis will review the associations between MASLD and breast and gynecological cancer, their underlying mechanisms, implications of hormonal therapies, and their future directions.

View details for DOI 10.1016/j.metabol.2025.156190

View details for PubMedID 40081614

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

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

View details for DOI 10.1001/jamanetworkopen.2024.48946

View details for PubMedID 39630453

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

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

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

View details for Web of Science ID 001351123500125

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

View details for DOI 10.3350/cmh.2022.0442

View details for PubMedID 36603574

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

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

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

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