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).

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).

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.

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.

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.

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.

The impact of obesity on patient survival in liver transplant recipients: a meta-analysis.

BACKGROUND & AIMS: It is controversial if obesity has an impact on overall survival after liver transplantation (LT). The goal of this study was to determine if obesity impacts liver transplant recipient survival. Through subgroup analysis, we also evaluated different body mass index (BMI) thresholds and the confounding effect of ascites on survival. METHODS: A systematic literature search from 1990 until July 2013. The main outcome was to evaluate the impact of obesity on survival in adult LT recipients. Dochotomous outcomes were reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: Thirteen studies with a total 2275 obese and 72 212 non obese patients were included in the analysis. The combined analysis showed no difference in mortality between control and increased weight patients (RR = 0.97, 95% CI [0.82, 1.13], P = 0.66) at last follow-up. Moreover, no differences in mortality were noted in subgroup analysis comparing different BMI thresholds. There was also no differences in survival when BMI was adjusted for ascites or in studies where the liver disease severity was similar. Obese patients had worse survival than nonobese patients in pooled analysis of studies which had similar causes of liver disease (RR = 0.69, 95% CI [0.52, 0.92], P = 0.01). CONCLUSION: The results of our pools analysis suggest that BMI does not specifically impact patient survival. However, obese patients have worse survival when analysis was performed in studies whose cohorts of obese and nonobese patients had similar causes of liver disease.

Treating fibrosing cholestatic hepatitis C with sofosbuvir and ribavirin: a matched analysis.

BACKGROUND: Fibrosing cholestatic hepatitis (FCH) is an uncommon but potentially fatal complication of recurrent hepatitis C (HCV) in liver transplant recipients. METHODS: We matched the treatment outcomes of 10 liver transplant recipients who developed FCH with those of 10 recipients with recurrent HCV without FCH treated with sofosbuvir and ribavirin. RESULTS: Baseline mean alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 186 U/L, 197 U/L, 243 U/L, and 6.7 mg/dL, respectively, in the FCH recipients and 82 U/L, 60 U/L, 110 U/L, and 0.99 mg/dL, respectively, in non-FCH recipients. The sustained viral response in FCH and non-FCH recipients was 40% and 80%, respectively. One-yr patient and graft survival rates were 90% and 80%, respectively, in FCH recipients, and 100% in non-FCH recipients. Seven FCH and six non-FCH recipients were treated for anemia with blood transfusion and/or erythropoietin growth factors. CONCLUSION: Our results suggest that the use of sofosbuvir and ribavirin is effective and tolerable in liver transplant recipients treated for recurrent FCH. There is a trend of lower sustained viral response, patient survival, and graft survival in the FCH recipients.

Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir.

INTRODUCTION: Loss of HBeAg and development of anti-HBe (seroconversion) is seen as a milestone and endpoint in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB). Among patients treated with nucleos(t)ide analogs (NA), recurrent viremia is common after discontinuation of therapy. Entecavir (ETV) and tenofovir (TDF) are highly potent NA. The durability of virological response and HBeAg seroconversion in patients treated with these agents is not well studied. METHODS: We retrospectively studied the outcomes of 54 HBeAg-positive CHB patients who were treated with either ETV (n = 30) or TDF (23) or both (n = 1) that achieved virological response and underwent seroconversion and consolidation therapy before cessation of treatment. RESULTS: Only 4 (7%) patients had sustained virological, serological, and biochemical remission. Thirteen patients (24%) continued to have HBV DNA levels below 2000 IU/mL and normal alanine aminotransferase activity (ALT). Thirty-seven patients (69%) developed HBV DNA >2000 IU/mL, with 20 having elevated ALT. Among these 37 patients, 23 (62%) remained HBeAg negative/anti-HBe positive, 12 (32%) became HBeAg positive, and 2 (5%) were HBeAg and anti-HBe negative. Duration of consolidation therapy did not correlate with low versus high level of virological relapse. CONCLUSIONS: Durability of HBeAg seroconversion associated with ETV or TDF was not superior to that reported in patients treated with less potent NA. Our results, aggregated with others, suggest HBeAg seroconversion should not be considered as a treatment endpoint for most HBeAg-positive patients treated with NA. Future updates of treatment guidelines should reconsider HBeAg seroconversion as an endpoint to therapy.

Impact of coffee on liver diseases: a systematic review.

Coffee is one of the most commonly consumed beverages in the world. Its health benefits including improved overall survival have been demonstrated in a variety of disease states. To examine the association of coffee consumption with liver disease, a systematic review of studies on the effects of coffee on liver associated laboratory tests, viral hepatitis, nonalcoholic fatty liver disease (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed. Coffee consumption was associated with improved serum gamma glutamyltransferase, aspartate aminotransferase and alanine aminotransferase values in a dose dependent manner in individuals at risk for liver disease. In chronic liver disease patients who consume coffee, a decreased risk of progression to cirrhosis, a lowered mortality rate in cirrhosis patients, and a lowered rate of HCC development were observed. In chronic hepatitis C patients, coffee was associated with improved virologic responses to antiviral therapy. Moreover, coffee consumption was inversely related to the severity of steatohepatitis in patients with non-alcoholic fatty liver disease. Therefore, in patients with chronic liver disease, daily coffee consumption should be encouraged.

Evaluation of alpha-fetoprotein in detecting hepatocellular carcinoma recurrence after radiofrequency ablation.

BACKGROUND AND AIM: The performance of alpha-fetoprotein (AFP) in the detection of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation was analyzed. METHODS: One hundred and forty-six solitary HCC lesions treated by radiofrequency ablation were evaluated. Using the AFP cutoff level at ≥ 20 ng/mL, tumors were categorized into AFP or non-AFP-producing HCC. Factors associated with true and false interpretations for cancer recurrence including analysis of elevated alanine aminotransferase (ALT) were evaluated. The performance of AFP using different cutoff levels adjusted for abnormal ALT was compared. RESULTS: Of 146 HCCs, 103 demonstrated no HCC recurrence while 43 had local recurrence. In non-recurrence HCC cases, increased AFP levels (false positive) were associated with concomitant ALT elevations, while those with normal AFP (true negative) had correspondingly normal ALT values (P < 0.001). The AFP false positive rate in cases of elevated ALT was significantly higher than those with normal ALT levels (31.9% vs 5.4%, P = 0.001). Among all positive AFP tests, those with false positive values (non-recurrence) had a significantly lower AFP level than the true positive (recurrence) HCC cases (39.8 ng/mL vs 372 ng/mL, P < 0.001). At the 20 ng/mL cutoff level, the sensitivities of AFP for detecting recurrence in non-AFP-producing HCC and AFP-producing HCC were 12.0%, and 72.2%, respectively. Using a modified AFP criteria of ≥ 100 ng/mL for cases where ALT ≥ 40 U/L, the sensitivity and specificity in AFP-producing tumors increased from 72.2% and 56% to 100% and 85%, respectively. CONCLUSION: Serum AFP is a useful test in the detection of HCC recurrence in AFP-producing HCC. The performance in AFP-producing HCC was significantly improved after adjusting for elevation of serum ALT.

Complete tumor encapsulation on magnetic resonance imaging: a potentially useful imaging biomarker for better survival in solitary large hepatocellular carcinoma.

The aim of this study was to determine the prognostic value of complete tumor encapsulation as visualized on magnetic resonance imaging (MRI) in patients with a solitary large hepatocellular carcinoma (HCC) beyond the Milan criteria for liver transplantation (LT). Between December 2000 and March 2011, 57 patients who had a solitary HCC exceeding 5 cm in diameter at the time of initial MRI before any treatment were identified. MRI images of the patients were independently reviewed by 2 experienced readers for the presence of complete tumoral encapsulation. The medical records of the patients were reviewed for an outcome analysis. Thirty of the 57 patients had completely encapsulated HCC according to MRI. There was excellent interobserver agreement between the 2 readers for the assessment of complete encapsulation (κ=0.86). Overall survival was significantly longer for patients with completely encapsulated HCC versus patients with incompletely or nonencapsulated tumors (P<0.001), and this included a subanalysis of 33 patients who received locoregional treatment (LRT; P=0.04). The presence of complete encapsulation was a strong predictor for survival in these patients according to both univariate [hazard ratio (HR)=0.24, 95% confidence interval (CI)=0.12-0.52, P<0.001] and multivariate analyses (HR=0.25, 95% CI=0.07-0.85, P=0.03). The rates of down-staging (P<0.001) and eventual LT (P=0.02) after LRT were also significantly higher in the patients with completely encapsulated tumors. In conclusion, complete tumor encapsulation on MRI is a potentially useful predictor for favorable biology in patients with a solitary large HCC. This new imaging biomarker may have a role in treatment selection for patients whose tumors exceed the Milan criteria size limits.

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.

An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus.

BACKGROUND & AIMS: Despite immunoprophylaxis, mother to child transmission (MTCT) of hepatitis B virus (HBV) still occurs in infants born to hepatitis B surface antigen (HBsAg)-positive mothers. We analyzed methods of risk assessment and interventions for MTCT. METHODS: We reviewed 63 articles and abstracts published from 1975-2011 that were relevant to MTCT; articles were identified using the PubMed bibliographic database. RESULTS: Administration of HB immunoglobulin and HB vaccine to infants at birth (within 12 hours), followed by 2 additional doses of vaccines within 6-12 months, prevented approximately 95% of HBV transmission from HBsAg-positive mothers to their infants. However, HBV was still transmitted from 8%-30% of mothers with high levels of viremia. It is important to assess the risk for MTCT and identify mothers who are the best candidates for intervention. The most important risk factor is maternal level of HBV DNA >200,000 IU (10(6) copies)/mL; other factors include a positive test result for the HB e antigen, pregnancy complications such as threatened preterm labor or prolonged labor, and failure of immunoprophylaxis in prior children. Antiviral therapy during late stages of pregnancy is the most effective method to reduce transmission from mothers with high levels of viremia, but elective cesarean section might also be effective. Antepartum administration of HB immunoglobulin, giving infants a double dose of HB vaccine, or avoiding breastfeeding had no impact on MTCT. CONCLUSIONS: HBsAg-positive mothers should be assessed for risk of MTCT, and infants should receive immunoprophylaxis. Pregnant women with levels of HBV DNA >200,000 IU/mL should be considered for strategies to reduce the risk for MTCT. We propose an algorithm for risk assessment and patient management that is based on a review of the literature and the opinion of a panel of physicians with expertise in preventing MTCT.

MRI detection of intratumoral fat in hepatocellular carcinoma: potential biomarker for a more favorable prognosis.

OBJECTIVE: The purpose of this study was to determine whether the presence of intratumoral fat in hepatocellular carcinoma (HCC) could serve as an imaging biomarker to predict a favorable prognosis. MATERIALS AND METHODS: After a search of the radiology and pathology databases from January 2002 to December 2010, a cohort of patients with fat-containing HCC imaged by chemical-shift MRI techniques was matched with a cohort of patients with nonfat-containing HCC for TNM stage and type of subsequent treatment. The number and type of tumor progression, time to tumor progression (TTP), and overall survival (OS) were determined for each cohort. RESULTS: There were 46 patients included in each cohort. Tumor progression was more prevalent in the non-fat-containing HCC cohort (30 patients, 65.2%) compared with the fat-containing HCC cohort (16 patients, 34.7%; p = 0.001). Distant metastasis occurred more commonly in the non-fat-containing HCC cohort (10 patient, 21.7%) compared with the fat-containing HCC cohort (two patients, 4.3%; p = 0.039). The median TTP was significantly longer in the fat-containing HCC group (52 months) compared with the non-fat-containing HCC group (27 months; p = 0.037). The significantly longer TTP was primarily observed in the locoregional treatment subgroup (p = 0.028). No statistical significance in OS and subanalysis by treatment was observed (p = 0.63-0.81). CONCLUSION: Fat-containing HCC, imaged on an MRI unit, may predict a more favorable prognosis compared with nonfat-containing HCC.

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.

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.

CT and MRI improve detection of hepatocellular carcinoma, compared with ultrasound alone, in patients with cirrhosis.

BACKGROUND & AIMS: In patients with cirrhosis, hepatocellular carcinoma (HCC) is detected by ultrasound (US), computed tomography (CT), or magnetic resonance imaging (MRI); US is recommended for screening and surveillance. We performed a retrospective analysis of the abilities of these cross-sectional imaging modalities to detect HCC. METHODS: We analyzed data from 638 consecutive adult patients with cirrhosis who received liver transplants within 6 months of imaging at a tertiary care institution. Imaging reports and serum alpha-fetoprotein levels were compared with results from pathology analysis of explants as the reference standard. Sensitivities of US, CT, and MRI were calculated overall and in defined size categories. False-positive imaging results and patient-based specificities were evaluated. RESULTS: Of the 638 patients, 225 (35%) had HCC, confirmed by pathology analysis of liver explants. In 23 cases, the lesions were infiltrative or extensively multifocal. In the remaining 202 explants (337 numerable, discrete nodules), respective lesion-based sensitivities of US, CT, and MRI were 46%, 65%, and 72% overall and 21%, 40%, and 47% for small (<2 cm) HCC. The sensitivity of US increased with the availability of CT or MRI data (P = .049); sensitivity values were 62% and 85% for lesions 2-4 and ≥ 4 cm, respectively. Patient-based specificities of US, CT, and MRI were 96%, 96%, and 87%, respectively. CONCLUSIONS: US, CT, and MRI did not detect small HCC lesions with high levels of sensitivity, although CT and MRI provide substantial improvements over unenhanced US in patients with cirrhosis who received liver transplants.

A proposed, evidence-based approach to the treatment of chronic Hepatitis B.

Patients with chronic hepatitis B virus infection are at increased risk for the development of cirrhosis and hepatocellular carcinoma. Viral suppression with antiviral therapy has been shown to decrease the risk of these complications. Criteria for initiation of antiviral therapy have evolved over time to include serum alanine aminotransferase elevation, serum hepatitis B virus DNA elevations, and histologic assessment. Current societal guidelines and a treatment algorithm have been developed to guide decision-making as regards to antiviral therapy. More recent data has shown the importance of basal core/core promoter mutations, serum albumin, and platelet count in predicting complications of chronic hepatitis B. We present a new treatment strategy for determining the need for antiviral therapy in patients with chronic hepatitis B.