Exposure to Agent Orange and Hepatocellular Carcinoma Among US Military Personnel.

Importance: Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers. Objective: To assess the association of AO exposure and HCC in a national cohort of Vietnam veterans. Design, Setting, and Participants: This retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO exposure were identified in the disability data via validated clinical surveys. Relevant clinical risk factors for cirrhosis and HCC were collected. Patients were stratified based on cirrhosis status, as defined by consecutive diagnosis found by documented International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision scores or calculated Fibrosis-4 scores. Data were collected from January 1, 2019, to December 31, 2020, and analyzed from December 2020 to October 2023. Main Outcome and Measures: Incident HCC was the primary outcome. AO and HCC association was estimated using a multivariable Cox regression analysis, with death and liver transplant as competing events. Results: Of the 296 505 eligible veterans (222 545 [75.1%] White individuals and 44 342 [15.0%] Black individuals), 170 090 (57%) had AO exposure (mean [SD] age, 21.62 [3.49] years; 131 552 White individuals [83.2%] and 22 767 Black individuals [14.4%]) and 35 877 (12.1%) had cirrhosis. Veterans who were not exposed to AO were more likely to smoke (109 689 of 126 413 [86.8%] vs 146 061 of 170 090 [85.9%]); use alcohol (54 147 of 126 413 [42.8%] vs 71 951 of 170 090 [42.3%]) and have viral hepatitis (47 722 of 126 413 [37.8%] vs 58 942 of 170 090 [34.7%]). In a multivariable competing risk model, AO exposure was not associated with HCC. Among veterans with cirrhosis, self-identification as Hispanic individuals (aHR, 1.51; 95% CI, 1.30-1.75; P <.001) or Black individuals (aHR, 1.18; 95% CI, 1.05-1.32; P = .004), and having a diagnosis of viral hepatitis (aHR, 3.71; 95% CI, 3.26-4.24; P <.001), alcohol-associated liver disease (aHR, 1.32; 95% CI, 1.19-1.46; P <.001), and nonalcoholic fatty liver disease (NAFLD) (aHR, 1.92; 95% CI, 1.72-2.15; P <.001) were associated with HCC. Among veterans without cirrhosis, hypertension (aHR, 1.63; 95% CI, 1.23-2.15; P <.001) and diabetes (aHR, 1.52; 95% CI, 1.13-2.05; P = .005) were also associated with HCC. Early smoking and alcohol use were significant risk factors for HCC. Conclusions and Relevance: In this large nationwide cohort study of Vietnam veterans, AO exposure was not associated with HCC. Smoking, alcohol, viral hepatitis, and NAFLD were the most important clinical risk factors for HCC.

Efficacy and Safety of a Botanical Formula Fuzheng Huayu for Hepatic Fibrosis in Patients with CHC: Results of a Phase 2 Clinical Trial.

Background: Hepatitis C virus (HCV) is a common cause of progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma worldwide. Despite the availability of effective direct-acting antivirals, patients often have significant hepatic fibrosis at the time of diagnosis due to delay in diagnosis and comorbidities which promote fibrogenesis. Thus, antifibrotic agents represent an attractive adjunctive therapy. Fuzheng Huayu (FZHY), a traditional Chinese medicine botanical formulation, has been used as an antifibrotic agent in chronic HBV infection. Our aim was to assess FZHY in patients with HCV infection and active viremia. Method: We randomized 118 patients with active viremia from 8 liver centers in the U.S. to receive oral FZHY (n = 59) or placebo (n = 59) for 48 weeks. Efficacy was assessed by histopathologic changes at the end of therapy. A subset of biopsies was further analyzed using qFibrosis to detect subtle changes in fibrosis in different zones of the hepatic lobules. Results: FZHY was well tolerated and safe. Patients with baseline Ishak fibrosis stages F3 and F4 had better response rates to FZHY than patients with baseline F0-F2 (p=0.03). qFibrosis zonal analysis showed significant improvement in fibrosis in all zones in patients with regression of the fibrosis stage. Conclusions: FZHY produced antifibrotic effects in patients with baseline Ishak F3 and F4 fibrosis stages. Reduction in fibrosis severity was zonal and correlated with the severity of inflammation. Based on its tolerability, safety, and efficacy, FZHY should be further investigated as a therapy in chronic liver diseases because of its dual anti-inflammatory and antiibrotic properties. Lay Summary. This is the first US-based, multicenter and placebo-controlled clinical trial that shows statistically significant reduction in fibrosis in patients with active HCV using an antifibrotic botanical formula. This has important implications as there is an immediate need for effective antifibrotic agents in treating many chronic diseases including NASH that lead to scarring of the liver. With artificial intelligence-based methodology, qFibrosis, we may provide a more reliable way to assess the FZHY as a therapy in chronic liver diseases because of its dual anti-inflammatory and antifibrotic properties.

First-line therapies for hepatitis B in the United States: A 3-year prospective and multicenter real-world study after approval of tenofovir alefenamide.

Real-world data are limited on tenofovir alafenamide (TAF). We aimed to study TAF real-world outcomes with other first-line regimens for chronic hepatitis B (CHB). We enrolled patients with CHB from 10 centers retrospectively and followed them for 36 months prospectively. We analyzed switching patterns of antiviral therapy and treatment outcomes of TAF, tenofovir disoproxil fumarate (TDF), and entecavir therapy. For efficacy and safety, we analyzed a subset of patients with complete data at 24 months after switching to TAF or remaining on TDF or entecavir. Among 1037 enrollees, 889 patients were analyzed. The mean age was 52%, and 72% were hepatitis B e antigen-negative. After enrollment, shifts in therapies were mostly in reduced use of TDF from 63% to 30% due to switching to TAF. Clinical parameters were compared at enrollment or initiation to measures at 24 months for patients remaining on TAF (187), TDF (229), or entecavir (181). At 24 months, a significantly higher portion of patients on TAF achieved hepatitis B virus (HBV) DNA ≤ 20 IU/ml (93% vs. 86%; p = 0.012) and normalized alanine aminotransferase (ALT) (66% vs. 56%; p = 0.031) with stable estimated glomerular filtration rates (eGFRs). However, a higher percentage of the patient with eGFR < 60 ml/mi/1.7 m2 was observed in the TDF-treated group (9% vs. 4%; p = 0.010). In patients who remained on entecavir or TDF for 24 months, ALT and HBV-DNA results did not differ significantly from baseline. Treatment of CHB in the United States has significantly shifted from TDF to TAF. Our data suggest that switching from TDF or entecavir to TAF may result in increased frequency of ALT normalization and potential clearance of viremia at the 24-month time point.

Nonalcoholic fatty liver disease-related hepatocellular carcinoma growth rates and their clinical outcomes.

AIM: Nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is projected to become the leading indication for liver transplantation. Previous studies indicate that tumor growth rates (TGR) may predict survival and were helpful in determining HCC surveillance intervals. Therefore, we aimed to determine its usefulness in predicting clinical outcomes and treatments. METHODS: We conducted a retrospective study of hepatitis B, C and NAFLD-HCC cases. TGR was measured using 2-consecutive pre-treatment contrast-enhanced imaging studies ≥ 25 days apart. A multivariate regression model was used to determine predictors of TGR. In addition, the Cox regression model was used to evaluate the relationship between TGR and overall survival. RESULTS: From 2000-2019, the study cohort comprised 38, 60, and 47 HBV, HCV, and NAFLD patients, respectively, with TGRs. NAFLD-HCC tumor size was inversely correlated to the extent of liver disease as measured by Child-Pugh score (7.2 cm in non-cirrhosis; 3.7 cm, 2.6 cm, and 2.1 cm in Child A, B, and C, respectively; P < 0.001). After adjusting for baseline characteristics, the TGR per month was fastest in HBV (9.4%, 95%CI: 6.3%-12.5%) compared to HCV (4.9%, 95%CI: 2.8%-7%) and NAFLD patients (3.6%, 95%CI: 1.6%-6.7%). Predictors of TGR included elevated AFP, low albumin, and smaller tumor size. Fast TGR in viral etiologies had higher mortality [adj. hazard ratio (HR) = 2.6, 95%CI: 1.2-5.7, P = 0.02] than slow TGRs, independent of treatments. Fast TGR in NAFLD had a trend towards higher mortality (HR = 3.6, 95%CI: 0.95-13.3, P = 0.059). CONCLUSION: NAFLD-HCC patients have more indolent growths than viral-related HCC TGRs. The addition of TGR as a biomarker may assist in stratifying treatment options.

Improved survival after treatments of patients with nonalcoholic fatty liver disease associated hepatocellular carcinoma.

Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Despite the rise in these disease entities, detailed long-term outcomes of large NAFLD-associated HCC cohorts are lacking. In this report, we compared the overall and recurrence-free survival rates of NAFLD HCC cases to patients with HBV and HCV-associated HCC cases. Distinguishing features of NAFLD-associated HCC patients in the cirrhosis and non-cirrhosis setting were also identified. We conducted a retrospective study of 125 NAFLD, 170 HBV and 159 HCV HCC patients, utilizing clinical, pathological and radiographic data. Multivariate regression models were used to study the overall and recurrence-free survival. The overall survival rates were significantly higher in the NAFLD-HCC cases compared to HBV-HCC (HR = 0.35, 95% CI 0.15-0.80) and HCV-HCC (HR = 0.37, 95% CI 0.17-0.77) cases. The NAFLD-HCC patients had a trend for higher recurrence-free survival rates compared to HBV and HCV-HCC cases. Within the NAFLD group, 18% did not have cirrhosis or advanced fibrosis; Hispanic ethnicity (OR = 12.34, 95% CI 2.59-58.82) and high BMI (OR = 1.19, 95% CI 1.07-1.33) were significantly associated with having cirrhosis. NAFLD-HCC cases were less likely to exhibit elevated serum AFP (p < 0.0001). After treatments, NAFLD-related HCC patients had longer overall but not recurrence-free survival rates compared to patients with viral-associated HCC. Non-Hispanic ethnicity and normal BMI differentiated non-cirrhosis versus cirrhosis NAFLD HCC. Further studies are warranted to identify additional biomarkers to stratify NAFLD patients without cirrhosis who are at risk for HCC.

Reactivation of Hepatitis B Virus: A Review of Clinical Guidelines.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-4-reading-myint a video presentation of this article https://www.wileyhealthlearning.com/Activity/7088610/disclaimerspopup.aspx questions and earn CME.

Economic Comparison of Serologic and Molecular Screening Strategies for Hepatitis C Virus.

Background: Hepatitis C virus (HCV) screening is traditionally performed using an enzyme-linked immunosorbent assay (ELISA), and HCV infection is confirmed by measuring the viral load using polymerase chain reaction (PCR). An alternative screening approach is to use only PCR, without the ELISA pretest. Methods: We compared the cost ratio of screening for HCV using 2 approaches: (1) ELISA followed by PCR testing, and (2) PCR testing alone. The results were analyzed using a decision analysis model. A sensitivity analysis and a threshold analysis were performed by varying both the prevalence of HCV infection (to encompass populations in which viral infection is overrepresented) as well as the costs of PCR testing. Results: Under baseline assumptions, the costs of PCR testing alone were substantially greater than the combination of ELISA and PCR testing. The cost per patient screened using combination testing was $42.30, whereas testing with only PCR cost $200.00 per patient. The prevalence of HCV had a greater impact on the cost ratio than did the costs of laboratory tests. The use of PCR testing alone became less costly only when the prevalence of HCV infection was greater than 69.5%. Otherwise, the costs of the 2 approaches were similar when the cost of PCR was 1% of that of ELISA. Conclusion: From a pharmacoeconomic basis, the current approach of HCV screening (ie, using ELISA and PCR testing) was found to be the less expensive screening strategy in a general US population and for most cohorts in which HCV infection was noted to be overrepresented. Screening for HCV is less costly using solely PCR testing only when the prevalence of HCV infection is greater than 69.5%.

Use of hepatitis C-positive grafts in hepatitis C-negative liver transplant recipients is cost effective.

BACKGROUND: The number of patients needing liver transplantation (LT) exceeds the number of available allografts. The current opioid epidemic in this country has increased the number of potential donors infected with hepatitis C (HCV). METHODS: We assessed the incremental cost-effectiveness ratio (ICER) by comparing the costs and number of liver transplants performed using HCV-positive and HCV-negative grafts into patients without HCV infection in a decision analysis model with a 1-year time horizon. RESULTS: The use of HCV-positive grafts was found to have an ICER below $50 000 across all MELD scores. Using our baseline cohort with a model for end-stage liver disease (MELD) score of 15-22, the ICER was $21 233/additional LT performed. As the MELD scores increased, the ICER decreased. Above a MELD score of 23, the use of HCV-positive grafts became cost saving (-$115 419). Our model was robust to all variables tested in the sensitivity analyses, except drug costs. CONCLUSION: The results of our decision analysis model highlight the potential pharmacoeconomic benefit of utilizing HCV-positive grafts in LT candidates who are not infected with HCV. The use of HCV-positive grafts is at least cost effective and even cost saving in patients with MELD scores above 23.

Late development of hepatocellular carcinoma after viral clearance in patients with chronic hepatitis C: A need for continual surveillance.

OBJECTIVE: Eradication of chronic hepatitis C (CHC) infection decreases the incidence of hepatocellular carcinoma (HCC), but a risk remains. We aimed to investigate HCC development-associated factors in CHC patients with sustained virological response (SVR) after antiviral therapies. METHODS: We compared CHC patients achieving SVR from 1996-2016 who did and did not develop HCC. Their median follow-up period was 8.01 years. RESULTS: Compared with 164 non-HCC SVR patients, 22 who developed HCC were older at SVR (P = 0.032), had a higher incidence of diabetes (P = 0.013) and higher pre-antiviral treatment alpha-fetoprotein (AFP) levels (P = 0.016), more had fibrosis stage 3 and cirrhosis (P = 0.0009) and hepatitis B core antibody (anti-HBc) positivity (P = 0.006). Eight and seven of 22 patients, respectively, developed HCC at 4-10 years and 10 years after SVR. The longest duration from SVR to HCC was 18.7 years. Independent factors associated with HCC development were anti-HBc positivity (hazard ratio [HR] 5.57, P = 0.012), age at SVR (HR 1.08, P = 0.014), higher pre-antiviral treatment AFP levels (HR 1.01, P = 0.01) and Hispanic ethnicity (HR 12.9, P = 0.002). HCC risk was significantly less in genotype 2 patients (HR 0.2, P = 0.02) or in those with higher pre-antiviral treatment albumin levels (HR 0.33, P = 0.04). CONCLUSIONS: The risk for HCC exists in a subset of CHC patients after SVR and may occur up to 18 years after viral clearance. Indefinite HCC surveillance is necessary in SVR patients with other risk factors.

Risk of Cardiovascular Events in Patients with Primary Biliary Cholangitis - Systematic Review.

Background and Aims: Hypercholesterolemia is a common finding in patients with primary biliary cholangitis (PBC) and is a well-defined risk factor for cardiovascular disease. However, studies have been mixed on whether PBC patients do, in fact, have higher cardiovascular risk. The aim of this study is to review the current literature and provide an evidence-based assessment of cardiovascular risk in PBC patients. Methods: We performed a systematic literature search on PubMed regarding patients with PBC and cardiovascular events from the database inception to July 1, 2017. A total of 33 articles fulfilling our inclusion criteria were found. Results: The majority of the studies evaluated yielded no statistically significant difference in cardiovascular disease in the PBC population compared to the general public. However, some reports found a statistically significantly increase in coronary artery disease. Several studies have looked at the specific lipid profile of patients with PBC with hypocholesteremia. While these lipid abnormalities differ by stage of disease, there is evidence to suggest that the specific lipid profile in PBC may have lower atherogenicity than in patients with hypercholesterolemia without PBC. Studies looking at patients with PBC with other risk factors for cardiovascular disease, such as hypertension and metabolic syndrome, have consistently found a higher risk for cardiovascular disease in these patients. Statin treatment is effective in reducing lipid levels and possibly improving endothelial inflammation in patients with PBC with hypercholesterolemia. Conclusions: There is not enough evidence to suggest an increased risk of cardiovascular disease in patients with PBC with hypercholesterolemia, except for those individuals with concomitant features of metabolic syndrome. In patients with PBC with no additional cardiovascular risk factors, individual risk/benefit discussion on lipid-lowering treatment should be considered.

Toward the elimination of hepatitis C in the United States.

The emergence of effective direct-acting antiviral (DAA) agents has reignited discussion over the potential for hepatitis C elimination in the United States. Eliminating hepatitis C will require a critical examination of technical feasibility, economic considerations, and social/political attention. Tremendous advancement has been made with the availability of sensitive diagnostic tests and highly effective DAAs capable of achieving sustained viral response (SVR) in more than 95% of patients. Eliminating hepatitis C also requires escalating existing surveillance networks to monitor for new epidemics. All preventive interventions such as clean syringe and needle exchange programs, safe injection sites, opioid substitution therapies, and mental health services need to be expanded. Although costs of DAAs have raised budget concerns for hepatitis C elimination, studies have shown that eliminating hepatitis C will produce a savings of up to 6.5 billion USD annually along with other intangible benefits such as increased work productivity and quality of life. Economic models and meta-analyses strongly suggest universal hepatitis C screening for all adults rather than just for birth cohort and high-risk populations. Social and political factors are at least as important as technical feasibility and economic considerations. Due to lack of promotion and public awareness, HCV elimination efforts continue to receive inadequate funding. Social stigma continues to impede meaningful policy changes. Eliminating hepatitis C is an attainable public health goal that will require intense collaboration and sustained public support. (Hepatology 2018;67:2449-2459).

Eradicating hepatitis B virus: The critical role of preventing perinatal transmission.

Prevention of hepatitis B virus (HBV) transmission from infected mothers to their newborns is critical to HBV control and eventual eradication. Mother-to-child perinatal transmission causes the highest chronic carrier rate (>85%) with a high rate of subsequent chronic liver disease and hepatocellular carcinoma. This risk is reduced by 90% with HBV vaccine given along with hepatitis B immune globulin (HBIG) starting at birth. New analyses of our data from US trials of HBIG and HBV vaccine in high-risk infants revealed better efficacy with yeast-recombinant vaccine than plasma-derived vaccine, especially in preventing late onset infections, with evidence that vaccine prevented transmission of maternal HBV infection with the glycine to arginine mutation in surface antigen codon 145 (sG145R). Most late infections with sG145R were in vaccine non-responders, suggesting escape from HBIG rather than from vaccine-induced antibody. Our findings also help explain survey results from Taiwan following universal childhood immunization implemented in the mid-1980s. We conclude that current vaccines will remain effective against surface antigen mutants. Anti-viral drugs in high-risk pregnant women, in combination with newborn HBIG and vaccine, show promise for eliminating residual breakthrough neonatal infections, critical to meeting WHO 2030 goals and for eradicating HBV.

Comparison of Triple-Drug Transcatheter Arterial Chemoembolization (TACE) With Single-Drug TACE Using Doxorubicin-Eluting Beads: Long-Term Survival in 313 Patients.

OBJECTIVE: We compared survival outcomes in 313 patients with unresectable hepatocellular carcinoma (HCC) treated with two different transcatheter arterial chemoembolization (TACE) regimens: triple-drug TACE or single-drug TACE using drug-eluting beads. MATERIALS AND METHODS: In this retrospective study, patient selection criteria were uniform. The triple-drug group (n = 166) underwent TACE using ethiodized oil with doxorubicin, cisplatin, and mitomycin-C with a microsphere embolic. The single-drug group (n = 147) underwent TACE using doxorubicin-eluting beads. Group characteristics were classified and analyzed, and survival was calculated using standard statistical methods. All patients were followed until death. Those undergoing orthotopic liver transplant (OLT) were also followed. RESULTS: There were no significant differences between the two groups in terms of demographics, Child-Pugh class, or Okuda stage. With patients undergoing OLT censored (n = 73), the mean (± standard error) survival in the triple-drug group was 23.49 ± 2.38 months, and the median survival was 16.00 ± 1.51 months. Mean survival in the single-drug bead group was 28.16 ± 2.75 months, and the median survival was 15.00 ± 1.50 months (p = 0.168). With patients undergoing OLT censored, the mean and median survival for the total cohort were 26.25 ± 1.97 and 15.00 ± 1.08 months, respectively. In the entire cohort that did not undergo OLT, patients with Child-Pugh class A disease survived significantly longer than did patients with Child-Pugh class B disease. Elevated α-fetoprotein levels were associated with shorter survival, and patients undergoing TACE with drug-eluting beads had shorter hospital stays. Although a greater percentage annual survival was observed in patients undergoing drug-eluting bead TACE who had Child-Pugh class A, Okuda stage I, and Barcelona Clinic Liver Cancer classes A and B disease starting at 36 months, this suggested survival advantage did not reach statistical significance. CONCLUSION: We found no significant survival difference in patients with unresectable HCC treated with triple-drug TACE compared with single-drug TACE using doxorubicin-eluting beads.

Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis.

In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. CONCLUSION: RFA as a first-line stand-alone bridge therapy to LT achieves excellent long-term overall and tumor-specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post-LT follow-up of up to 10 years. (Hepatology 2017;65:1979-1990).

Long-term survival after surveillance and treatment in patients with chronic viral hepatitis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the main cause of mortality in patients with chronic viral hepatitis (CVH). We determined the impact of surveillance and treatments on long-term outcomes in patients with CVH who developed HCC. Between 1984 and 2014, 333 patients with HCC and with hepatitis B or hepatitis C virus infection were evaluated. An adjusted lead time bias interval was added to patients with HCC who presented with HCC (no surveillance), and their survival was compared to patients whose HCC was detected by surveillance. After HCC treatments, survival rates within and beyond 3 years of follow-up were compared. In 175 (53%) patients, HCC was detected through surveillance using alpha-fetoprotein and abdominal ultrasound examinations. Compared to 158 (47%) patients with HCC who had no surveillance, more patients with HCC detected by surveillance received surgical and locoregional treatments (P < 0.0001 to P < 0.001), and their 1-, 3-, and 5-year overall and disease-free survival rates were significantly higher (P < 0.001 for both). During the first 3 years of follow-up, patients with HCC receiving liver transplantation had similar survival rates as those with liver resection or radiofrequency ablation (RFA); however, due to HCC recurrence, survival in resection and RFA patients became significantly less when followed beyond 3 years (P = 0.001 to P = 0.04). Factors associated with mortality included tumors beyond University of California at San Francisco criteria (hazard ratio [HR] 2.02; P < 0.0001), Child-Pugh class B and C (HR, 1.58-2.26; P = 0.043 to P = 0.015, respectively), alpha-fetoprotein per log ng/mL increase (HR, 1.30; P < 0.0001), previous antiviral therapy in hepatitis B virus patients (HR, 0.62; P = 0.032), and treatments other than liver transplantation (HR, 2.38-6.45; P < 0.0001 to P < 0.003). Conclusion. Patients with HCC detected by surveillance had prolonged survival. Due to HCC recurrence, survival rates after liver resection and RFA were lower when followed beyond 3 years after treatments. (Hepatology Communications 2017;1:595-608).

The Management of Hepatitis B in Liver Transplant Recipients.

Liver transplant (LT) is now an established indication for patients with chronic hepatitis B, mainly because of the development and use of hepatitis B immunoglobulin (HBIG) and oral antivirals for prophylaxis. The combination of low-dose HBIG and antivirals has been considered the standard prophylaxis regimen to prevent post-LT recurrence of hepatitis B. The important remaining issues are related to the long-term cost of HBIG and the risk of escape hepatitis B virus (HBV) mutants. Strategies for prevention of HBV after LT are constantly improving. With the availability of new nucleoside/nucleotide analogues, new post-LT strategies also should emerge.

Timing of Hepatitis C Antiviral Therapy in Liver Transplant Recipients With Direct-acting Agents.

Chronic hepatitis C virus infection is a substantial health care burden worldwide and is the leading cause of liver transplant in adults. In patients with detectable hepatitis C virus RNA at the time of transplant, interferon-based therapies for hepatitis C virus were poorly tolerated with low virologic response rates. Although reinfection after transplant is inevitable, the recent advent of direct-acting antiviral agents has revolutionized treatment of hepatitis C virus in the pre- and posttransplant settings. These antiviral agents have been shown to have high-sustained virologic response rates, shorter courses of treatment, and decreased frequencies of adverse effects. Here, we review the current literature on the use of direct-acting agents for treatment of patients with hepatitis C virus before and after liver transplant.

Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials.

BACKGROUND: Hepatic encephalopathy (HE) is a major complication of cirrhosis and is associated with decreased survival and increased health care utilization. AIM: The aim of this study was to evaluate the efficacy of probiotics in the management minimal hepatic encephalopathy HE (MHE) and overt HE (OHE) in comparison to no treatment/placebo and lactulose. METHODS: The main outcomes measured were mortality, improvement in MHE, progression to OHE in patients with MHE and hospitalization. We calculated odds ratios (OR) with 95% confidence intervals (CI). Study heterogeneity was assessed using the I(2) statistic. RESULTS: Fourteen studies totalling 1152 patients were included in the analysis. The use of probiotics had no impact on the overall mortality when compared to either lactulose (OR: 1.07, 95% CI: 0.47-2.44, P = 0.88) or no treatment/placebo (OR: 0.69, 95% CI: 0.42-1.14, P = 0.15). When probiotics was compared to no treatment/placebo, it was associated with a significant improvement in MHE (OR: 3.91, 95% CI: 2.25-6.80, P < 0.00001), decreased hospitalization rates (OR: 0.53, 95% CI: 0.33-0.86, P = 0.01) and decreased progression to overt hepatic encephalopathy (OR: 0.40, 95% CI: 0.26-0.60, P < 0.0001). However when compared to lactulose, probiotics did not show a significant difference in improvement of MHE (OR: 0.81, 95% CI: 0.52-1.27, P = 0.35), hospitalization rates (OR: 1.02, 95% CI: 0.52-1.99, P = 0.96) or progression to overt hepatic encephalopathy (OR: 1.24, 95% CI 0.73-2.10, P = 0.42). CONCLUSIONS: Overall the use of probiotics was more effective in decreasing hospitalization rates, improving MHE and preventing progression to OHE in patients with underlying MHE than placebo, but similar to that seen with lactulose. The use of probiotics did not affect mortality rates.

Timing of Antiviral Therapy in Candidates for Liver Transplant for Hepatitis C and Hepatocellular Carcinoma.

OBJECTIVES: Hepatitis C virus infection is the most common underlying reason for hepatocellular carcinoma and indication for liver transplant. The increased availability of non-interferon-based therapy has expanded the number of treatment-eligible patients. MATERIALS AND METHODS: We used a decision analysis model to compare 2 strategies of treating hepatitis C virus. Included patients were followed for 1 year after liver transplant. The probabilities and costs were obtained from a literature review, an expert panel, and our institution's experience. Sensitivity analyses were performed on all variables. RESULTS: Our model demonstrated that it would be less costly to treat patients after liver transplant than to treat patients while they wait for transplant. When we compared baseline values, the cost difference between the 2 strategies was $25,011 per patient and $41,535 per sustained viral response. Overall survival was 60.1% for both strategies. Our model was robust across most of the variables tested in the sensitivity analysis. CONCLUSIONS: Our results indicated that there is no substantial pharmacoeconomic or survival advantage of treating hepatitis C virus in patients with compensated cirrhosis and hepatocellular carcinoma before liver transplant versus after transplant.