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HCV Genotype 6 Increased the Risk for Hepatocellular Carcinoma Among Asian Patients With Liver Cirrhosis

Objectives:Hepatitis C virus (HCV) infection is a well-documented risk factor for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classified, and the genotypes show a great variety of geographic distribution. HCV genotype 6 is prevalent in Southeast Asia and has been less studied than the other genotypes.Methods:This follow-up study was designed to evaluate the natural history of HCV genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV genotype 6 and 629 with other genotypes. The incidence of HCC per 1,000 person-years of various HCV genotypes was estimated by dividing the new HCC cases to the person-years of follow-up. The adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) were estimated by Coxs proportional hazards models.Results:After 4072 person-years of follow-up, there were 96 newly-developed HCC cases, confirming an incidence of 23.6 per 1000 person-years. By stratifying cirrhosis at study entry, the cumulative risk of HCC among HCV genotype 6 vs. non-6 was 2.9 vs. 2.2% for those without cirrhosis (P=0.45) and 76.2% (95% CI: 55.6–96.8%) vs. 36.2% (95% CI: 28.7–39.1%) for those with cirrhosis (P<0.05), respectively. Among patients with cirrhosis, HCV genotype 6 was significantly associated with HCC compared to patients with non-6 genotypes, with the adjusted HR=2.12 (1.33–3.39), P<0.05. In a model treating patients with genotypes other than 1 or 6 as the reference, the adjusted HR for HCC for HCV genotypes 1 and 6 were 1.13 (0.56–2.27) and 2.34 (1.12–4.86), respectively.Conclusions:Among patients with cirrhosis, those with HCV genotype 6 infection should be given high priority for antiviral therapy to decrease HCC risk and for vigilant adherence to HCC surveillance.

Soluble intercellular adhesion molecule-1 is associated with hepatocellular carcinoma risk: multiplex analysis of serum markers

Individualized assessment of hepatocellular carcinoma (HCC) risk in chronic liver disease remains challenging. Serum biomarkers including cytokines may offer helpful adjuncts to standard parameters for risk prediction. Our aim was to identify markers associated with increased HCC incidence. This was a prospective cohort study of 282 patients with both viral or non-viral chronic liver disease. Baseline serum cytokines and other markers were measured in multiplex with a commercially-available Luminex-based system. Patients were followed until death or HCC diagnosis. We performed Lasso-based survival analysis to determine parameters associated with HCC development. Cytokine mean florescence intensity (MFI) was the primary predictor and HCC development the primary outcome. 25 patients developed HCC with total follow-up of 1,363 person-years. Parameters associated with increased HCC incidence were cirrhosis, hepatic decompensation, and soluble serum intercellular adhesion molecule 1 (sICAM-1) MFI. No other molecules increased predictive power for HCC incidence. On univariate analysis, the parameters associated with HCC incidence in patients with cirrhosis were age, antiviral treatment, and high sICAM-1 MFI; on multivariate analysis, sICAM-1 remained associated with HCC development (adjusted HR = 2.75). On unbiased screening of serum cytokines and other markers in a diverse cohort, baseline sICAM-1 MFI is associated with HCC incidence.

Poor Adherence to Guidelines for Treatment of Chronic HBV Infection at Primary Care and Referral Practices

BACKGROUND & AIMS: The American Association for the Study of Liver Diseases (AASLD) guidelines for treatment of chronic hepatitis B virus (HBV) infection have changed with time. We assessed rates of treatment evaluation and initiation in patients with chronic HBV infection from different practice settings in the past 14 years. METHODS: Treatment‐naive patients with chronic HBV infection were recruited from different practice settings in California from January 2002 through December 2016. The study population comprised 4130 consecutive, treatment‐naive patients with chronic HBV infection seen by community primary care physicians (n = 616), community gastroenterologists (n = 2251), or university hepatologists (n = 1263). Treatment eligibility was assessed using data from the first 6 months after initial presentation based on AASLD criteria adjusted for changes over time. RESULTS: Within the first 6 months of care, the proportions of patients evaluated by all 3 relevant tests (measurements of alanine aminotransferase, hepatitis B virus e antigen, and HBV DNA levels) were as follows: 36.69% in community primary care, 59.80% in gastroenterologist care, and 79.97% in hepatology care (P < .0001 among the 3 groups). Higher proportions of patients were eligible for treatment in specialty practices: 12.76% in community primary care, 24.96% in gastroenterologist care, and 29.43% in hepatology care (P < .0001). Among treatment‐eligible patients, there was no significant difference in the proportions of patients who began antiviral therapy between those receiving treatment from a gastroenterologist (55.65%) vs a hepatologist (57.90%; P = .56). Of 243 evaluable patients receiving community primary care, only 31 were eligible for treatment and only 12 of these (38.71%) received treatment. CONCLUSIONS: In an analysis of patients receiving care for chronic HBV infection, we found the proportions evaluated and receiving treatment to be suboptimal, according to AASLD criteria, in all practice settings. However, rates of evaluation and treatment were lowest for patients receiving community primary care.

Changes in Renal Function in Patients With Chronic HBV infection Treated with Tenofovir Disoproxil Fumarate vs Entecavir

BACKGROUND & AIMS: It is unclear whether drugs used to treat chronic hepatitis B virus (HBV) infection cause significant renal impairment. We compare adjusted mean estimated glomerular filtration rates (eGFR; mL/min/1.73 m2) of patients with chronic HBV infection treated with tenofovir disoproxil fumarate (TDF) vs patients treated with entecavir. METHODS: We performed a retrospective study of patients with chronic HBV infections treated with TDF (n = 239) or entecavir (n = 171), from 2000 through 2016, followed for a mean time of 43–46 months. Levels of serum creatinine were measured ≥12 months while patients received treatment. Patients did not have prior exposure to adefovir or HCV, HDV, or HIV co‐infection. We performed propensity score matching (PSM) for age, sex, presence of hypertension, diabetes mellitus, baseline eGFR, cirrhosis, and follow‐up duration. We performed multivariate generalized linear modeling, adjusting for cirrhosis, diabetes, and hypertension, to estimate adjusted mean eGFR for matched and unmatched cohorts. Cox regression was used to identify predictors of renal impairment. RESULTS: eGFRs were ≥60, after PSM, in 116 patients given entecavir and in 116 patients given TDF; eGFRs were <60 in 32 patients given entecavir and 26 patients given TDF. Multivariate generalized linear modeling of the unmatched overall and <60 eGFR cohorts revealed significantly lower adjusted mean eGFRs in patients given TDF (all P < .001). However, in the eGFR ≥60 PSM cohort, the adjusted mean eGFR was similar between patients receiving either treatment. In Cox regression analysis, TDF was not associated with mild or moderate renal impairment compared with entecavir. CONCLUSION: In a retrospective study of patients with chronic HBV infections treated with TDF vs entecavir, we found that TDF was not associated with higher risk of worsening renal function during short‐ or intermediate‐term follow‐up periods, among patients without significant renal impairment. Additional studies, with longer follow‐up periods, are needed because treatment for chronic HBV infection is generally long term or life‐long. For patients with baseline renal impairment, significant renal decline was among patients given TDF compared to patients given entecavir.

Autoantibodies in chronic hepatitis C virus infection: impact on clinical outcomes and extrahepatic manifestations

Goals To examine the role that autoantibodies (auto-abs) play in chronic hepatitis C virus (HCV) regarding demographics, presence of extrahepatic manifestations and long-term outcomes in a large US cohort. Background Auto-abs have been reported to be prevalent in patients with chronic HCV infection, but data on the natural history of these patients are limited. Study The study included 1556 consecutive patients with HCV without concurrent HIV and/or HBV who had testing for antinuclear antibody (ANA), antimitochondrial antibody (AMA), antismooth muscle antibody (ASMA) and/or antiliver kidney microsomal antibody (LKM). Primary outcomes included development of cirrhosis, hepatic decompensations, hepatocellular carcinoma (HCC), mortality and/or sustained virological response (SVR) to antiviral therapy. Results A total of 388 patients tested positive for any auto-ab (ANA 21.8%, ASMA 13.3%, AMA 2.2% and LKM 1.2%). Patients who tested positive versus negative were more likely to be women (29.3% vs 20.9%, p<0.001) and less likely to achieve SVR with most treated patients receiving interferon-based therapies (37.2% vs 47.1%, p=0.031). There was no difference between groups for baseline laboratory data, disease state or rate of extrahepatic manifestations (42.8% vs 45.0%, p=0.44). Kaplan-Meier analysis revealed no statistically significant difference between groups for the 10-year development of cirrhosis, hepatic decompensations, HCC nor survival. Furthermore, auto-ab positivity was only found to be a predictor for a lower rate of SVR on multivariate analysis (adjusted OR=1.61, 95 %  CI 1.00 to 2.58, p=0.048). Conclusions In our cohort, auto-ab positivity was common, especially in women, and predicted a lower rate of SVR but otherwise had no impact on the natural history of chronic HCV or presence of extrahepatic manifestations.

Tu1052 Compared to Non-Asian Patients, Asians With HCV Infection Were Older With Significantly Higher Rates of Co-Morbidities, Cirrhosis, and Liver Cancer but Lower HCV Treatment Rates: Results of a Large U.S. Cohort of 8,559 Patients

BACKGROUND: Infection with HCV is prevalent in many parts of Asia, and most patients acquire the virus through iatrogenic exposure and had no known traditional risk factors. Many would not have met the current CDC or USPTF guidelines for HCV screening and diagnosis. This study seeks to characterize HCV infection in Asian vs. Non-Asian patients. METHODS: We conducted a retrospective study of all patients with HCV diagnosis seen at a U.S. university medical center between 2/1999 and 3/2014. Patients were identified via ICD-9 query with additional clinical and laboratory data obtained from patient medical records. A total of 12,312 patients were identified. Of these, 8,559 had known ethnicity and were included in study analysis: 7,335 Non-Asians (86%) and 1,208 Asians (14%). RESULTS: Compared to non-Asians, Asians were significantly older (mean age=56.7±16.1 vs. 53.5±12.1, p 6M IU/mL). In analysis of available treatment data from 2008 to 2014 (N=5224), treatment rates were low in both groups but significantly lower in Asians compared to Non-Asians (6.9% vs. 7.4%, p<0.0001). CONCLUSION:More than half the Asian patients were found to be outside the birth cohort, being significantly younger or older than their Non-Asian counterparts. Asian patients with CHC had more comorbidities and were much more likely to have advanced disease with HCC, almost double the rates in non-Asians. Asians also had significantly lower HCV treatment rates. Further efforts should be made in screening, diagnoses, and treatment of American Asians for CHC to prevent progression to advanced liver disease and improve health outcomes in this population. HCC screening should be offered to Asians coming from endemic areas with HCV prevalence of 2% or higher.