Primary surgical resection versus liver transplantation for transplant-eligible hepatocellular carcinoma patients.
Digestive diseases and sciences
Wong, R. J., Wantuck, J., Valenzuela, A., Ahmed, A., Bonham, C., Gallo, A., Melcher, M. L., Lutchman, G., Concepcion, W., Esquivel, C., Garcia, G., Daugherty, T., Nguyen, M. H.
2014; 59 (1): 183-191
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting.The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT.The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio.The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p < 0.001) compared to LT patients. In the as-treated model of the pre-model for end stage liver disease (MELD) era, LT patients had significantly better 5-year survival compared to resection patients (100 vs. 69.5 %, p = 0.04), but no difference was seen in the ITT model. In the multivariate Cox proportional hazards model, inclusive of age, sex, ethnicity, tumor stage, and MELD era (pre-MELD vs. post-MELD), treatment with resection was an independent predictor of poorer survival (HR 2.72; 95 % CI, 1.08-6.86).Transplant-eligible HCC patients who received LT had significantly better survival than those treated with resection, suggesting that patients who can successfully remain on LT listing and actually undergo LT have better outcomes.
View details for DOI 10.1007/s10620-013-2947-8
View details for PubMedID 24282054
Abstract
Hepatitis C virus (HCV) is an important cause of hepatocellular carcinoma (HCC) in Asians; however, it is often overlooked due to the high prevalence of hepatitis B virus in Asians. This study examines HCV-related HCC in Asians.We conducted a retrospective cohort study of 792 consecutive Asian (n = 220) and non-Asian (n = 572) patients with HCV-related HCC identified at Stanford University Medical Center using International Classification of Diseases-9 diagnosis between July 1996 and June 2012.Asian patients were much older [66 (38-88) vs. 56 (31-87) years, P < 0.0001] and more likely to be female (33 vs. 19 %, P < 0.0001). A larger proportion of Asians were diagnosed with HCC within 2 years of HCV diagnosis (35 vs. 20 %, P = 0.001). Asian patients were more likely to undergo palliative therapy (46 vs. 28 %) and less likely to be listed for liver transplantation (20 vs. 48 %, P < 0.001), despite similar rates of meeting Milan criteria (52 vs. 58 %, P = 0.16). Overall, there was a trend for higher median survival rates in Asians (30 vs. 21 months, P = 0.091). Asians had higher long-term survival with palliative therapy only (5-year survival: 28 vs. 10 %, P < 0.0001); however, survival was similar among patients listed for liver transplantation.There were distinct differences in clinical presentations of Asian and non-Asian patients with HCV-related HCC. Asians with HCV-related HCC are less likely to undergo liver transplantation and more likely to have delayed HCV diagnosis. Improved strategies in HCV screening in Asians are needed, as it may lead to earlier diagnosis and treatment of HCV infection and possible prevention of HCC development.
View details for DOI 10.1007/s10620-013-2948-7
View details for Web of Science ID 000330585500030
View details for PubMedID 24282055
Abstract
The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.
View details for DOI 10.1007/s10903-013-9871-z
View details for PubMedID 23864445
Abstract
Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates.We conducted a retrospective cohort study of 333 consecutive treatment-naïve HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion-loss of HBeAg and antibody to HBeAg (anti-HBe) development.The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26-52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA ?1.5?×?upper normal limit (HR?=?2.86 [1.05-7.81], P?=?0.040), but not the choice of nucleos(t)ides.The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.
View details for DOI 10.1111/jgh.12108
View details for PubMedID 23278507
Abstract
Data from registration trials with highly selective patients have shown that hepatitis B envelope antigen (HBeAg)-positive patients with chronic hepatitis B respond well to entecavir (ETV) 0.5 mg daily, with an HBeAg seroconversion rate of 21% at 12 months. However, there are varying data on the treatment outcomes of ETV 0.5 mg daily in routine clinical settings, with seroconversion rates at 12 months ranging from 8 to 48% in studies limited to 44-90 patients from centers in Asia, Europe, and South America.In the present study, we examined long-term treatment efficacy and tolerability in 136 consecutive treatment-naive HBeAg-positive chronic hepatitis B patients treated between January 2005 and January 2011 with ETV 0.5 mg daily at community clinics and tertiary centers in the USA. The primary study end point was HBeAg seroconversion.Sixty-one percent of HBeAg-positive patients were men, mean age 39 ± 12 years, median hepatitis B virus DNA 7.48 (3.7-9.8) log10 IU/ml, median alanine aminotransferase 67 (14-1077) U/l, and median treatment duration 18 (6-60) months. At months 12, 24, and 36, complete viral suppression rates were 41, 66, and 85% and HBeAg seroconversion rates were 4.8, 20, and 30%, respectively. No patients experienced adverse events or developed genotypic resistance to ETV.In clinical settings, ETV is highly tolerable and potent at suppressing hepatitis B viremia; however, the rates of HBeAg seroconversion appear to be much lower than those reported, highlighting the importance of appropriate counseling and planning for long-term therapy.
View details for DOI 10.1097/MEG.0b013e32835b3677
View details for Web of Science ID 000314633700011
View details for PubMedID 23169311
Abstract
Graft survival in HCV (hepatitis C virus) infected recipients is worse than those transplanted for other liver diseases. We studied whether several donor cardiovascular risk factors (including advanced age, smoking, hypertension, and diabetes mellitus) contribute to worse outcomes for HCV positive and HCV negative liver transplant recipients.We obtained data from the United Network for Organ Sharing on all adult liver transplants performed in the United States between January 1, 1998 and December 31, 2003. In total, 27,033 transplant cases were evaluated. Independent predictors of graft survival were determined using Cox proportional hazards regression analysis after controlling for factors previously found to be associated with differences in transplant outcomes.Donor diabetes was a strong independent risk factor for graft failure [hazard ratio (HR) = 1.20, p = 0.006] only in HCV positive recipients. Neither donor smoking status nor hypertension predicted graft loss in either cohort. Consistent with previous studies, advanced donor age, donation after cardiac death, height, and African American donor all predicted graft loss amongst both cohorts.Accounting for donor diabetes in relation to recipient HCV status in the selection of liver recipients may result in improved graft survival.
View details for DOI 10.1007/s10620-012-2345-7
View details for Web of Science ID 000315291100039
View details for PubMedID 22923335
Abstract
We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence.We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study end points were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed up, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of ?-fetoprotein, approximately every 6 months, for a median time of 34 months (range, 6-99 mo).The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% nonviral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with nonviral diseases in Kaplan-Meier analysis (P = .04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child-Pugh-Turcotte score, viral cirrhosis was associated significantly with HCC, compared with nonviral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3-10.1; P = .02) but Asian ethnicity was not.In a diverse cohort of patients in the United States with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.
View details for DOI 10.1016/j.cgh.2012.08.011
View details for Web of Science ID 000312265900021
View details for PubMedID 22902757
Abstract
Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients.We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ?12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir).All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir.Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.
View details for DOI 10.1007/s10620-012-2402-2
View details for Web of Science ID 000309867800051
View details for PubMedID 23010744
Abstract
The primary treatment endpoint for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is HBeAg seroconversion; however, data on the durability of response are inconsistent.Our goal was to investigate the rate of recurrent viremia after HBeAg seroconversion and subsequent discontinuation of therapy.We retrospectively studied 88 consecutive Asian American patients who achieved HBeAg seroconversion [loss of HBeAg and development of antibody to HBeAg (anti-HBe)] among 458 HBeAg-positive patients who received oral antiviral therapy at 3 US clinics between March 1998 and November 2010. Recurrent viremia was defined as reappearance of detectable serum hepatitis B virus DNA (>100 IU/mL) on 2 consecutive laboratory tests from previously undetectable levels.Antiviral medications used at the time of HBeAg seroconversion included: lamivudine (23%), adefovir (34%), entecavir (36%), tenofovir (4%), and combination therapy (3%). Antiviral therapy was continued after HBeAg seroconversion in 49 patients (group I) and discontinued in the other 39 patients after consolidation therapy [median=12 months (range, 1 to 55 mo)] (group II). No patients in group I experienced recurrent viremia, whereas 90% in group II did. Elevated alanine aminotransferase also occurred in 38% of group II patients [median peak alanine aminotransferase 249 IU/mL (range, 93 to 1070 IU/mL)].Despite consolidation therapy, almost all patients who discontinued therapy after achieving HBeAg seroconversion and complete viral suppression experienced recurrent viremia, and close to half also experienced biochemical flares. HBeAg seroconversion does not seem to be a durable treatment endpoint for many patients, and they should be monitored carefully for virologic relapse and biochemical flares if antiviral therapy is withdrawn.
View details for DOI 10.1097/MCG.0b013e31825ceed9
View details for Web of Science ID 000312953400018
View details for PubMedID 22941429
Abstract
The majority of data on risk factors (RFs) for hepatocellular carcinoma (HCC) comes from studies involving populations without underlying liver disease. It is important to evaluate RFs for HCC in patients with chronic liver disease since HCC rarely occurs in those without underlying liver disease. We conducted a hospital-based case-control study of 259 incident HCC cases and 781 controls by convenience sampling between 02/2001 and 12/2009 from the liver clinic at Stanford University Medical Center. The study population was 41% White, 14% Hispanic, 3% African American, 40% Asian American, and 2% other race/ethnicity. RFs were examined through medical records and an in-person questionnaire. Alcohol and tobacco use was calculated by cumulative grams of alcohol or cumulative pack(s) of cigarette consumed over one's lifetime. Diabetes mellitus (DM) was defined by random glucose level of ?200 mg/dL. RFs were evaluated using multivariate logistic regression. Independent predictors of HCC risk, after mutual adjustment and additional control for alcohol use, etiology of liver diseases, and DM, included age >40 (OR = 8.5 [2.6-28.3]), male gender (OR = 3.5 [2.2-5.8]), presence of cirrhosis (OR = 2.8 [1.6-4.9]), Asian ethnicity (OR = 2.8 [1.8-4.6]), AFP > 50 (OR = 4.2 [2.6-6.8]), and cumulative lifetime tobacco use of >11,000 packs (OR = 1.7 [1.0-2.9]). Heavy prolonged cigarette smoking, but not alcohol use, was a significant independent predictor for HCC in patients with underlying liver disease. Besides older age, male gender, presence of cirrhosis, and elevated AFP, Asian ethnicity and heavy cumulative tobacco use are strong independent predictors of HCC.
View details for DOI 10.1007/s10552-012-9895-z
View details for Web of Science ID 000300891100006
View details for PubMedID 22258434
Abstract
Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos. We hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics, and our aim was to conduct a survey of risk factors in HCV-infected patients in these ethnic groups. In this prospective study, 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008. Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics. The laboratory profiles were similar, and genotype 1 was the most common infection in all groups (74-75%). The great majority of Caucasians (94%) and Hispanics (86%) identified with commonly known risk factors, which was in contrast to 67% of Asians (P < 0.0001). The most common risk factors in Asians were blood transfusions (50%) and acupuncture (50%). Furthermore, 74% of Caucasians and 66% of Hispanics identified more than one major risk factor, while only 20% of Asians reported having more than one risk factor (P < 0.0001). Survey for established risk factors for acquisition of HCV may be more appropriate for risk assessment of Caucasians and Hispanics, but not for Asian Americans. These findings may guide the development of HCV screening in our increasingly diverse population.
View details for DOI 10.1111/j.1365-2893.2011.01513.x
View details for Web of Science ID 000299097400014
View details for PubMedID 22239506
Abstract
There are conflicting data as to the prevalence of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) being assessed for liver transplantation (LT). The aims of this study were to compare the prevalence of CAD in patients with alcohol-related versus non-alcohol-related ESLD and to assess the diagnostic utility of dobutamine stress echocardiography (DSE) in predicting angiographically important CAD. Consecutive patients with ESLD being assessed for LT (n = 420, mean age 56 ± 8 years) were identified and divided into groups of those with alcohol-related ESLD (n = 125) and non-alcohol-related ESLD (n = 295). Demographic characteristics, CAD risk factors, results of DSE, and coronary angiographic characteristics were recorded. There were no significant differences in age or CAD risk factors between groups. The incidence of severe CAD (>70% diameter stenosis) was 2% in the alcohol-related ESLD group and 13% in the non-alcohol-related ESLD group (p <0.005). In the 2 groups, the presence of ?1 CAD risk factor was associated with significant CAD (p <0.05 for all). Absence of cardiac risk factors was highly predictive in ruling out angiographically significant disease (negative predictive value 100% for alcohol-related ESLD and 97% for non-alcohol-related ESLD). DSE was performed in 205 patients. In the 2 groups, DSE had poor predictive value for diagnosing significant CAD but was useful in ruling out patients without significant disease (negative predictive value 89% for alcohol-related ESLD and 80% for non-alcohol-related ESLD). In conclusion, there was a significantly lower prevalence of severe CAD in patients with alcohol-related ESLD. These findings suggest that invasive coronary angiography may not be necessary in this subgroup, particularly in the absence of CAD risk factors and negative results on DSE.
View details for DOI 10.1016/j.amjcard.2011.07.013
View details for Web of Science ID 000297880000006
View details for PubMedID 21890080
Abstract
Combination therapy for chronic hepatitis B virus (HBV) infection is recommended for patients with antiviral resistance (AVR) or partial response (PR) to earlier antiviral therapy; however, data on outcomes are limited.To determine the rate of complete viral suppression (CVS) with combination therapy and to compare CVS among different indications and treatment regimens.A cohort of 109 consecutive patients with chronic hepatitis B from 3 liver clinics in Northern California was retrospectively studied. All patients started combination therapy between April 2004 and August 2009 for the following indications: AVR (n = 29), PR (n = 60), or others (n = 20). Combination treatments included lamivudine (LAM), adefovir (ADV), telbivudine (LdT), entecavir (ETV), tenofovir (TDF), and emtricitabine (FTC). CVS was defined as undetectable serum HBV DNA <100 IU/mL.Among the patients, who were nearly all Asian (99%), 73% had ? 2 prior treatments and 82% had treatment failure (AVR or PR). Median treatment duration of combination therapy was 21 months (range, 6 to 50 mo). The majority (77%) achieved CVS after 6 months of various combination regimens: 80% for ETV+TDF, 76% for TDF+LAM or FTC or LdT, 75% for ETV+ADV, and 69% for ADV+LAM or LdT (P = 0.86). After 6 months of therapy, CVS was observed in a similar proportion of patients treated for PR and AVR (72% and 74%, respectively).Although the majority of 109 treatment-experienced patients had prior treatment failure, high rates of CVS were rapidly achieved and did not significantly differ between indications of AVR and PR or between ETV-based and TDF-based regimens.
View details for DOI 10.1097/MCG.0b013e318224d64f
View details for Web of Science ID 000296144000014
View details for PubMedID 21778896
Abstract
Studies of hepatitis B virus (HBV)/hepatitis C virus (HCV) dual infection are limited. Most are small, conducted outside the United States, and compare dual infection with HCV monoinfection. The goal of this study was to characterize HBV/HCV dual infection in a large multiethnic, matched, case-control study of dual-infected and HBV-monoinfected patients at two United States centers. Using an International Classification of Disease Version 9 electronic query and chart review, we identified 115 HBV/HCV dual-infected patients with serial HBV DNA, HCV RNA, and alanine aminotransferase (ALT) levels. As a control, 115 HBV-monoinfected patients were chosen randomly and matched with cases by age ±10 years, sex, Asian versus non-Asian ethnicity, and study site. Both groups had similar sex, ethnic, and age distributions (68% male, 83% Asian, age 52 ± 14 years). The median follow-up times were 33 and 38 months for the dual-infected and monoinfected groups, respectively. More monoinfected patients received HBV antiviral therapy than dual-infected patients (43% versus 24%; P = 0.002). No significant difference was detected between the proportion of monoinfected versus dual-infected patients with ALT above 40 U/L at presentation or during follow-up. Dual infection patients exhibited very little HBV/HCV codominance at baseline and throughout follow-up: patients had either HBV viremia with low or absent HCV RNA or detectable HCV RNA with low or absent HBV DNA. Asian ethnicity was predictive of HBV dominance after adjusting for sex, age, and baseline ALT elevation (odds ratio 7.35; P = 0.01).HBV/HCV dual-infected and HBV-monoinfected patients had similar clinical characteristics. Asian ethnicity is a major independent predictor of HBV-dominant disease, and HCV dominance with undetectable HBV DNA is more common in non-Asian individuals. Larger studies are needed to further characterize the natural history of HBV/HCV dual infection in Asian and non-Asian individuals.
View details for DOI 10.1002/hep.24308
View details for Web of Science ID 000291307300009
View details for PubMedID 21425314
Abstract
Patients with diabetes mellitus overall experience worse health outcomes than non-diabetics, but whether this is true among recipients of liver transplantation still remains unclear. The aim of this study was to compare the mortality of diabetic and non-diabetic patients following liver transplantation.We conducted a retrospective analysis of 530 adult patients undergoing liver transplantation at Stanford University Medical Center from February 1995 to July 2006. Information on diabetes mellitus was available for 431 patients; 96 patients who had acute liver failure (n = 17), combined liver and kidney transplantation (n = 28), or died prior to discharge (n = 51) were excluded from analysis.Over a mean follow-up of 4.5 years, survival was 81% in the diabetic group and 94% among controls (p = <0.0001). After controlling for age (mean +/- SD: 54.4 +/- 7.6 in diabetics, 50.1 +/- 9.6 in controls), body mass index (28.6 +/- 6.6 in diabetics, 27.1 +/- 5.4 in controls), presence of hepatitis C, and MELD score (17 +/- 9.6 in diabetics, 19 +/- 10.2 in controls), diabetes mellitus remained a significant predictor of death (HR 3.11, p = 0.01).Diabetes mellitus is an independent risk factor for mortality following liver transplantation. Further investigation of this relationship should focus on the impact of more intensive pre- and post-liver transplantation glucose control, cardiovascular risk factor reduction, and the effects of accelerated atherosclerosis in the setting of immune suppression.
View details for DOI 10.1007/s10620-010-1267-5
View details for Web of Science ID 000278900200039
View details for PubMedID 20467898
Abstract
Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.
View details for DOI 10.1111/j.1600-6143.2009.02576.x
View details for Web of Science ID 000265222200023
View details for PubMedID 19344435
Abstract
The dynamics of emerging nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI) resistance in hepatitis B virus (HBV) are not well understood because standard dideoxynucleotide direct polymerase chain reaction (PCR) sequencing assays detect drug-resistance mutations only after they have become dominant. To obtain insight into NRTI resistance, we used a new sequencing technology to characterize the spectrum of low-prevalence NRTI-resistance mutations in HBV obtained from 20 plasma samples from 11 NRTI-treated patients and 17 plasma samples from 17 NRTI-naive patients, by using standard direct PCR sequencing and ultra-deep pyrosequencing (UDPS). UDPS detected drug-resistance mutations that were not detected by PCR in 10 samples from 5 NRTI-treated patients, including the lamivudine-resistance mutation V173L (in 5 samples), the entecavir-resistance mutations T184S (in 2 samples) and S202G (in 1 sample), the adefovir-resistance mutation N236T (in 1 sample), and the lamivudine and adefovir-resistance mutations V173L, L180M, A181T, and M204V (in 1 sample). G-to-A hypermutation mediated by the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like family of cytidine deaminases was estimated to be present in 0.6% of reverse-transcriptase genes. Genotype A coinfection was detected by UDPS in each of 3 patients in whom genotype G virus was detected by direct PCR sequencing. UDPS detected low-prevalence HBV variants with NRTI-resistance mutations, G-to-A hypermutation, and low-level dual genotype infection with a sensitivity not previously possible.
View details for DOI 10.1086/597808
View details for Web of Science ID 000265035500007
View details for PubMedID 19301976
Abstract
Traditionally, the constellation of biochemistry tests including liver enzymes, total bilirubin, and hepatic synthetic measures (prothrombin time (PT) and serum albumin level) are referred to as liver function tests (LFTs). Abnormal LFTs can be encountered during primary health care visits, routine blood donation, and insurance screening. A reported 1% to 4% of asymptomatic patients exhibit abnormal LFTs, leading to a sizeable number of annual consultations to a gastroenterology and/or hepatology practice. A cost-effective and systematic approach is essential to the interpretation of abnormal LFTs. A review of pattern of abnormal LFTs, detailed medical history, and a comprehensive physical examination help establish a foundation for further individualized testing. Further investigation often involves biochemical testing for disease-specific markers, radiographic imaging, and even consideration of a liver biopsy. In the following account, markers of hepatic injury are reviewed followed by a discussion on an approach to various patterns of abnormal LFTs in an asymptomatic patient.
View details for DOI 10.1016/j.cld.2009.02.001
View details for Web of Science ID 000267207200002
View details for PubMedID 19442912
Abstract
To determine the yield of colonoscopy in a predominantly Asian American gastroenterology practice in California from 8/2003 to 2/2005.A total 2,723 subjects were included: 87% were Asian and 13% were non-Asian. Advanced neoplasia prevalence was 12% in Asian men and 9% in non-Asian men (P = 0.21), and 8% and 7% in women (P = 0.62). Similar results were found in asymptomatic patients (13% and 13%, P = 0.99, for men; 8% and 6%, P = 0.46, for women). Factors associated with presence of advanced neoplasia were total number of polyps and presence of right-sided lesions. Asian men were more likely to have neoplasia overall compared with non-Asian men with odds ratio (OR) of 2.14 (1.23-3.72); however, there were no significant differences in the prevalences of advanced neoplasia in the two groups.Colorectal neoplasia is as prevalent in Asian Americans and preventive guidelines for colorectal cancer should also be advocated for this ethnic group.
View details for DOI 10.1007/s10620-008-0499-0
View details for Web of Science ID 000261653400026
View details for PubMedID 18975084
Abstract
Excessive shunting through transjugular intrahepatic portosystemic shunts (TIPS) can cause life-threatening hepatic encephalopathy and insufficiency. Intentional reduction of flow may be effective but difficult to control. The present report describes refinements of the parallel stent/stent-graft technique of flow reduction that is adjustable in either direction. Six patients underwent TIPS reduction with varying stent positioning and a variety of commercial products. Flow was adjusted by iterative balloon dilatation of the stent and stent-graft, resulting in a mean gradient increase of 8 mm Hg. All cases were technically successful, but 1-year survival was seen in only the patient who underwent liver transplantation.
View details for DOI 10.1016/j.jvir.2008.08.011
View details for Web of Science ID 000260694700018
View details for PubMedID 18823797
Abstract
Transcatheter arterial chemoembolization (TACE) has become one of the most common treatments for unresectable hepatocellular carcinoma. Published studies of TACE report a 5-16% risk of serious complications. Compared with TACE, transcatheter arterial chemoinfusion (TACI) may have similar efficacy and fewer side effects.To examine the clinical outcomes of TACI.We performed a retrospective cohort study of 345 consecutive TACI cases in 165 patients performed at a single United States medical center between 1998 and 2002. Primary outcomes were tumour response and survival rates.Only seven patients were hospitalized for more than 24 h after the procedure, and only three patients had worsening of liver function within 30 days of TACI. Survival was significantly poorer for patients with tumour-node-metastasis (TNM) IV compared to those with TNM I-III and also for patients with Child's class B/C vs. A. Following adjustment for age, gender, ethnicity and aetiology of liver diseases, independent predictors of poor survival were Child's class B/C [Hazard Ratio (HR) = 1.69, P = 0.024] and TNM IV staging (HR = 1.63, P = 0.014).TACI appears to be safe and effective for unresectable hepatocellular carcinoma with TNM stage I-III; randomized controlled trials are needed to compare TACI to TACE.
View details for DOI 10.1111/j.1365-2036.2007.03424.x
View details for Web of Science ID 000249130100008
View details for PubMedID 17767468
Abstract
Survival rates after liver transplantation have improved steadily because of earlier referral and timely evaluation, judicious patient selection, improved surgical techniques, superior immunosuppressive regimens, and effective prevention of perioperative opportunistic infections. Indications and contraindications for liver transplantation are undergoing constant modifications with the goal of improving survival and functional status of patients who have end-stage liver disease or acute liver failure. Potential candidates for liver transplantation should meet minimal listing criteria and not have contraindications to liver transplantation. Currently, the Model for End-stage Liver Disease score is used for organ allocation, but it may have future application in patient-selection criteria.
View details for PubMedID 17606204
Abstract
Chronic hepatitis C virus infection (HCV) is associated with extrahepatic manifestations, including such dermatologic conditions as mixed cryoglobulinemia, porphyria cutanea tarda, and lichen planus. Patients with chronic HCV and extrahepatic manifestations are often excluded from clinical trials evaluating interferon (IFN) therapy due to concerns about poor response, adverse events, and toxicity. Thus, data regarding the efficacy of IFN not only on the underlying chronic HCV, but also on extrahepatic manifestations, are limited in these patients. Case reports suggest that the response of dermatologic extrahepatic manifestations to IFN in patients with chronic HCV is highly variable. This review summarizes available data on dermatologic conditions associated with chronic HCV and their response to IFN therapy.
View details for DOI 10.1016/j.cgh.2006.06.010
View details for Web of Science ID 000244511700004
View details for PubMedID 16919505
Abstract
Interferon (IFN)-alpha-based therapy for chronic hepatitis C is effective in fewer than 50% of all treated patients, with a substantially lower response rate in black patients. The goal of this study was to investigate the underlying host transcriptional response associated with interferon treatment outcomes. We collected peripheral blood mononuclear cells from chronic hepatitis C patients before initiation of IFN-alpha therapy and incubated the cells with or without IFN-alpha for 6 hours, followed by microarray assay to identify IFN-induced gene transcription. The microarray datasets were analyzed statistically according to the patients' race and virological responses to subsequent IFN-alpha treatment. The global induction of IFN-stimulated genes (ISGs) was significantly greater in sustained virological responders compared with nonresponders and in white patients compared with black patients. In addition, a significantly greater global induction of ISGs was observed in sustained virological responders compared with nonresponders within the group of white patients. The level of IFN-induced signal transducer and activator of transcription (STAT) 1 activation, a key component of the Janus kinase (JAK)-STAT signaling pathway, correlated with the global induction of ISGs and was significantly higher in white patients than in black patients. In conclusion, both treatment outcome and race are associated with different transcriptional responses to IFN-alpha. Because this difference is evident in the global induction of ISGs rather than a selective effect on a subset of such genes, key factors affecting the outcome of IFN-alpha therapy are likely to act at the JAK-STAT pathway that controls transcription of downstream ISGs.
View details for DOI 10.1002/hep.21267
View details for Web of Science ID 000239523200009
View details for PubMedID 16871572
Abstract
Gastrointestinal endoscopy is the primary diagnostic and therapeutic modality in the management of gastrointestinal bleeding. Esophagogastroduodenoscopy, small bowel enteroscopy, and colonoscopy are well-established standards for initial evaluation of gastrointestinal bleeding, and have been used effectively for diagnosis, prognosis, and therapy. Although thermal, injection, and mechanical methods have been the mainstay of endoscopic therapy, promising new technologies such as endoscopic ultrasound and wireless capsule endoscopy will further advance our ability to improve morbidity and mortality from severe gastrointestinal hemorrhage. Herein we review current standards and recent advances in the endoscopic management of upper, lower, and obscure gastrointestinal bleeding.
View details for PubMedID 16015556
Abstract
Patients older than 60 are undergoing transplantation with increasing frequency. Reports from several transplant centers document that overall short-term patient survival rates in seniors undergoing liver transplantation are comparable to survival rates of younger adults. However, specific subgroups of older patients may not fare as well. Seniors with far-advanced end-stage liver disease are high-risk for liver transplantation and have poor survival rates. In addition, seniors older than 65 have worse outcomes than those who are 60 to 65, and studies have shown increased mortality with increasing age as a continuous variable. On the other hand, the majority of seniors who survive liver transplantation have full or only minimally limited functional status. Preoperative evaluation of older patients for transplantation requires careful screening to exclude cardiopulmonary disease, malignancy, and other diseases of the aged. Paradoxically, seniors may benefit from a senescent immune system, which results in decreased requirements for immunosuppressive drugs, and possibly a lower rate of acute allograft rejection. Despite good overall short-term survival in the elderly, long-term survival may be worse because of an increased rate of long-term complications, such as malignancy and heart disease. In conclusion, although advanced age is a negative risk factor, advanced age alone should not exclude a patient from liver transplantation; however, it mandates thorough pretransplant evaluation and careful long-term follow-up with attention to usual health maintenance issues in the elderly.
View details for DOI 10.1002/lt.20155
View details for Web of Science ID 000223274300002
View details for PubMedID 15390320
Abstract
The results of lamivudine therapy in 4 patients with chemotherapy-induced hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced reactivation is a known complication in patients with chronic HBV infection or history of HBV infection with recovery. Reactivation of HBV infection has a broad spectrum of manifestations ranging from mild elevation of aminotransferase levels to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent chemotherapy when they presented with HBV reactivation manifested by sudden onset of fatigue, jaundice, and HBV serology consistent with active HBV infection (detectable serum HBV DNA) in the absence of other known causes of acute hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient) was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All 4 patients showed rapid decrease in aminotransferase levels within 2 weeks after initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed to improve in 2 patients, who both died. The remaining 2 patients had suppression of HBV DNA to undetectable levels after 1 and 4 months of treatment and had biochemical and clinical improvement. The 2 patients who died received lamivudine therapy for 8 days and for 3 weeks. There have been no randomized clinical trials to study the role of lamivudine for prophylaxis or treatment of HBV reactivation associated with chemotherapy. However, based on our limited experience, lamivudine may be efficacious in suppressing potentially fatal HBV reactivation secondary to chemotherapy in patients with chronic HBV infection or prior infection with recovery. Patients who undergo chemotherapy should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection. We recommend that patients with chronic HBV infection (positive HBV DNA and/or positive HBsAg) or history of HBV infection with recovery (positive hepatitis B core antibody with or without HBsAb) be considered for prophylactic lamivudine use to prevent chemotherapy-induced HBV reactivation.
View details for Web of Science ID 000183597500016
View details for PubMedID 12811213
Abstract
The prevalence of hepatitis C virus (HCV) infection varies in different populations, ranging from as low as 0.6% in volunteer blood donors to as high as 80% in injection drug users. The prevalence of HCV in a population can be predicted by risk factors associated with the transmission of infection. These risk factors include injection drug use, blood product transfusion, organ transplantation, hemodialysis, occupational injury, sexual transmission, and vertical transmission. We review the literature regarding the incidence and prevalence of HCV infection and the evidence supporting various modes of HCV transmission.
View details for Web of Science ID 000180031600015
View details for PubMedID 12488709
Abstract
Strategies for the diagnosis and treatment of chronic hepatitis C continue to evolve. Liver biopsy is now used selectively rather than routinely, and the combination peginterferon plus ribavirin is the treatment of choice for the majority of patients.
View details for PubMedID 14989044
Abstract
Advances in immunosuppressive therapy, operative techniques, and perioperative management have resulted in long-term patient survival rates approaching 90% following liver transplantation for chronic viral hepatitis. The increasing number of referrals for liver transplantation reflects the impact of chronic HCV infection as a cause of end-stage liver disease. Unlike hepatitis B, there is still no effective treatment in preventing recurrent hepatitis C after liver transplantation. The spectrum of allograft injury related to universal HCV infection recurrence ranges from no evidence of histologic injury to mild inflammation to severe disease with allograft failure in small proportion of patients. Various factors may explain these differing outcomes, including degree of pretransplantation viremia, HLA compatibility, presence of more pathogenic HCV genotypes, integrity of cellular immune response, and type of immunosuppression. Fortunately, patient survival does not seem to be affected short-term; the long-term outcome of liver transplantation for chronic hepatitis C is unclear but is likely to be decreased. Combination therapy with interferon plus ribavirin seems to be a promising treatment strategy for posttransplantation recurrent hepatitis C, and the use of pegylated interferon plus ribavirin may improve these results. Patients with moderate to severe allograft hepatitis are appropriate candidates for combination antiviral therapy. Histopathologically documented recurrent hepatitis C in liver transplant recipients is associated with impaired quality of life, inferior physical condition, and a higher incidence of depression compared with patients who did not have HCV and in those without HCV recurrence. In conclusion, it is possible that the continued improvements in antiviral therapy against HCV infection may ultimately decrease the number of patients needing liver transplantation. Suitable candidates with chronic HCV infection thus warrant treatment with pegylated interferon plus ribavirin combination therapy in the hope of decreasing disease progression. Recent studies, which require confirmation, suggest that nonresponders to standard antiviral therapy may benefit from maintenance therapy. The donor pool for patients with chronic hepatitis C and decompensated cirrhosis can be improved by using HCV-positive donors and by increasing utilization of newer surgical techniques, including adult-to-adult living-donor liver transplantation and split-liver transplantation.
View details for PubMedID 11685796
Abstract
The widespread recognition of the success of liver transplantation as a treatment for most types of acute and chronic liver failure has led to increased referrals for transplantation in the setting of a relatively fixed supply of cadaver donor organs. These events have led to a marked lengthening of the waiting time for liver transplantation, resulting in increased deaths of those on the waiting list and sicker patients undergoing transplantation. Nearly 5000 liver transplantations were performed in the United States in 2000, while the waiting list grew to over 17,000 patients. The mounting disparity between the number of liver transplant candidates and the limited supply of donor organs has led to reassessment of the selection and listing criteria for liver transplantation, as well as revision of organ allocation and distribution policies for cadaver livers. The development of minimal listing criteria for patients with chronic liver disease based on a specific definition for decompensation of cirrhosis has facilitated the more uniform listing of patients at individual centres across the United States. The United Network for Organ Sharing, under pressure from transplant professionals, patient advocacy groups and the federal government, has continuously revised allocation and distribution policies based on the ethical principles of justice for the individual patient versus optimal utility of the limited organ supply available annually. Beginning in 2002, it is likely that the Model for End-stage Liver Disease (MELD) score will be implemented to determine disease severity and direct donor organs to the sickest patients rather than to those with the longest waiting times.
View details for Web of Science ID 000172393600003
View details for PubMedID 11727003
Abstract
Hemorrhage is the most common serious complication of percutaneous liver biopsy. Liver biopsy is usually done in an outpatient setting because most significant hemorrhage is evident within a few hours after biopsy. Delayed hemorrhage occurs much less frequently but carries a much higher mortality. We present a 41-yr-old man with chronic hepatitis C who underwent a percutaneous liver biopsy uneventfully but was found to have a pseudoaneurysm of the hepatic artery 5 days later. Shortly after admission, the patient experienced bleeding into the liver from the pseudoaneurysm, which was controlled initially by angiographic embolization. However, recurrent bleeding could not be controlled by repeat angiography and surgical intervention, and the patient expired. The diagnosis and management of pseudoaneurysm of the hepatic artery complicating liver biopsy is reviewed.
View details for Web of Science ID 000166435400039
View details for PubMedID 11197259
Abstract
Eosinophilic esophagitis is a morphologic finding that may result from a wide spectrum of clinical conditions. The distinctive histological features accompanying eosinophilic esophagitis may facilitate the diagnosis of the underlying disease entity. Unfortunately, there are no pathognomonic histologic characteristics associated with eosinophilic esophagitis. Clinical signs and symptoms, immunological markers, endoscopic findings, and response to therapy may help establish or confirm the diagnosis of a clinical condition that results in eosinophilic esophagitis. The following discussion outlines the causes of eosinophilia in an esophageal biopsy sample.
View details for Web of Science ID 000086336500006
View details for PubMedID 10777180
Abstract
The accurate differentiation of gallstone-induced biliary colic from other abdominal disease processes is the most crucial step in the successful management of gallstone disease. Despite the availability of many imaging techniques to demonstrate the presence of gallstones, clinical judgment ultimately determines the association of symptoms with cholelithiasis and its complications. Adult patients with silent or incidental gallstones should be observed and managed expectantly, with few exceptions. In symptomatic patients, the intervention varies with the type of gallstone-induced complication. In this article, we review the salient clinical features, diagnostic tests and therapeutic options employed in the management of gallstones and their complications.
View details for Web of Science ID 000086196400009
View details for PubMedID 10750875
Abstract
Early recognition and prompt intervention are the most crucial steps in the management of gallstone-induced biliary disease. Many conditions can mimic the presentation of gallstone-induced complications. Therefore, participation of a clinically astute physician is essential in evaluating symptoms and interpreting diagnostic data in patients with symptomatic gallstones.
View details for Web of Science ID 000085880200002
View details for PubMedID 10728510
Abstract
The future therapy for chronic hepatitis C will probably include measures to decrease hepatocellular injury along with multidrug combinations, including inhibitors of the hepatitis C viral protease, helicase, or polymerase to reduce serum levels or eradicate HCV RNA. The results of recently concluded trials of IFN-alpha 2b plus ribavirin combination therapy have shown a twofold improvement in the biochemical and virologic response rates and superiority by other measures of efficacy with an acceptable safety profile. In view of these results, new guidelines for the management of chronic HCV infection are appropriate (Fig. 1).
View details for PubMedID 11291249
Abstract
We describe a fatal case of tuberculous peritonitis and review the literature on the diagnostic modalities available to diagnose this entity. We suspect a delayed diagnosis resulted in the death of our patient. Today, the prompt diagnosis of an unknown ascitic process involves laparoscopy. A patient with unknown large volume ascites is the easiest and safest to laparoscope. Using a mini laparoscope, a bedside procedure with instantaneous return can be done. The newer noninvasive tests like determination of ascites fluid adenosine deaminase activity and polymerase chain reaction may be helpful in the prompt diagnosis of peritoneal tuberculosis. We recommend that patients with clinical presentation suggestive of peritoneal tuberculosis have either an aggressive diagnostic workup using high-yield tests or a trial of antituberculous therapy.
View details for Web of Science ID 000079711100010
View details for PubMedID 10219360
Abstract
A 54-yr-old man with lymphoma and serological evidence of prior hepatitis B virus (HBV) infection, with detectable anti-HBc and anti-HBs, was treated with intensive chemotherapy. He had reactivation of HBV infection with acute hepatitis B manifest by detectable HBsAg and elevated aminotransferase levels >1000 IU/L. He was treated with lamivudine 150 mg daily and had prompt resolution of acute hepatitis B with return of elevated aminotransferases to normal, and initial loss of HBeAg with later loss of HBsAg. Lamivudine was continued during the course of further chemotherapy as prophylaxis against repeat HBV reactivation. Lamivudine is a nucleoside analogue that is a potent inhibitor of HBV reverse transcriptase and HBV replication. Lamivudine therapy should be considered for the treatment of HBV reactivation and might play a future role as preemptive therapy of HBV reactivation in patients with prior hepatitis B or chronic hepatitis B with inactive viral replication.
View details for Web of Science ID 000082426600048
View details for PubMedID 9934765
Abstract
Splenic rupture is an uncommon complication of colonoscopy. A high index of suspicion is a crucial factor in the prompt diagnosis of this rare but potentially fatal complication. We report a case of splenic rupture diagnosed 3 days after a colonoscopy and requiring splenectomy. We also reviewed 17 reported cases of splenic rupture after colonoscopy, including our case. The presumed mechanisms of splenic rupture during colonoscopy are direct trauma to the spleen, excessive splenocolic ligament traction, and decrease in the relative mobility between the spleen and the colon. Of the 17 cases reviewed, 10 had polypectomy and/or biopsy performed during colonoscopy. Other probable risk factors are identified and tabulated. The hemodynamic status of the patient is the primary factor used to determine the therapeutic option. Computed tomographic (CT) scan of the abdomen reliably demonstrates well-contained splenic laceration and subcapsular hematoma, and differentiates these splenic complications from perisplenic clot and hemoperitoneum. Thus, CT scan may help decide which patients may be managed operatively or nonoperatively. Splenectomy is the operative procedure of choice for splenic rupture after colonoscopy. Conservative management includes broad spectrum antibiotics, intravenous fluids, blood transfusion, and close hemodynamic monitoring. The factors mandating further evaluation of persistent abdominal pain after colonoscopy are hemodynamic instability, clinical features of acute abdomen, leukocytosis, and/or acute anemia. The onset of abdominal pain associated with one or more of these critical factors is usually within 24 h after colonoscopy. An emergent CT scan of the abdomen is the modality of choice to further evaluate these clinical features, but intestinal perforation and external bleeding must first be excluded.
View details for Web of Science ID A1997XK10700029
View details for PubMedID 9219800
