Vinh Vu

Reduction of chronic hepatitis B-related hepatocellular carcinoma with anti-viral therapy, including low risk patients

Anti‐viral therapy in chronic hepatitis B (CHB) is associated with a reduced risk of hepatocellular carcinoma (HCC) primary described in patients with cirrhosis.

Poor adherence and low persistency rates for hepatocellular carcinoma surveillance in patients with chronic hepatitis B.

AbstractOur goal was to examine rates and predictors for hepatocellular carcinoma (HCC) surveillance adherence and persistency, since studies of such adherence and persistency in patients with chronic hepatitis (CHB) are currently limited.Consecutive CHB patients (N = 1329) monitored for ≥1 year at 4 US clinics from January 1996 to July 2013 were retrospectively studied. Surveillance adherence was evaluated based on the American Association for the Study of Liver Diseases guidelines. Kaplan–Meier method was used to analyze surveillance persistency of 510 patients who had initially fair adherence (having at least annual surveillance imaging with further follow-up).Mean age was 48, with the majority being male (58%), Asian (92%), foreign-born (95%), and medically insured (97%). Patients with cirrhosis and those seen at university liver clinics were more likely to have optimal HCC surveillance than those without cirrhosis and those seen at community clinics (38.4% vs 21.6%, P <0.001 and 33.5% vs 14.4%, P < 0.001, respectively). HCC diagnosed in optimally adherent patients trended toward smaller tumor size (P < 0.08). On multivariate analysis also inclusive of age, sex, clinical visits, cirrhosis, clinic setting and antiviral therapy use, strong independent predictors for having at least annual imaging were a history of more frequent clinical visits (odds ratio [OR] = 2.5, P < 0.001) and university-based care (OR = 5.2, P < 0.001). Even for those with initially fair adherence, persistency dropped to 70% at 5 years.Adherence and persistency to HCC surveillance in CHB patients is generally poor. More frequent clinic visits and university-based settings were significant and strong predictors of at least annual HCC surveillance adherence.

Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients with normal to minimally elevated ALT and no cirrhosis

Abstract For chronic hepatitis B (CHB), alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) is often used as a major criteria to initiate treatment in absence of cirrhosis, though patients with lower ALT may not be free from future risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of antiviral therapy on HCC incidence based on ALT levels. We performed a retrospective study on 3665 patients consisting of United States and Taiwanese REVEAL-HBV cohort who were consecutive, treatment-naïve, noncirrhotic CHB patients aged ≥40 years. Patients were categorized by ALT cutoffs (≥2 × ULN vs <2 × ULN) and subgrouped by treatment status. Kaplan–Meier and Cox proportional hazards models were used to calculate cumulative incidence and hazard ratio (HR) of HCC adjusting for REACH-B scores. A total of 202 patients developed HCC. Antiviral treatment significantly reduced HCC risk: HR 0.24, 95% confidence interval 0.10–0.58; P = 0.001. HCC incidence per 100,000 person-years was significantly higher in untreated versus treated patients, even for those with ALT < 2 × ULN: 314.46 versus 0 per 100,000 person-years, P = 0.0042. For patients with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) ≥ 2000 IU/mL, the number-needed-to-treat (NNT) were 15 and 14 to prevent 1 incident HCC at year 10 for patients with ALT < 2 × ULN and ≥2 × ULN, respectively. After adjustment by REACH-B score, antiviral treatment significantly decreased HCC incidence even in patients with ALT < 2 × ULN. NNT to prevent 1 incident HCC after 10 years of therapy was low (14–15) in patients with mildly elevated HBV DNA ≥ 2000 IU/mL regardless of ALT levels.

Long-term follow-up and suboptimal treatment rates of treatment-eligible chronic hepatitis B patients in diverse practice settings: a gap in linkage to care

Background and aims Despite available effective therapies, only a minority of patients with chronic hepatitis B (CHB) receive treatment. Our goal is to study treatment rates and time to treatment initiation in patients who meet treatment criteria on long-term follow-up. Methods We performed a retrospective cohort study of 608 consecutive treatment-eligible patients with CHB (by 2008 US Panel or 2009 American Association for the Study of Liver Disease (AASLD) criteria) at a US community gastroenterology clinic and a university liver clinic between 2007 and 2011. Patients were observed until they started treatment or last follow-up if untreated. Results Mean age was 44 and most were Asian (96%) with community patients being younger and having lower alanine aminotransferase (ALT) levels. A total of 62% started treatment, and 38% remained untreated after median follow-up of 17 months (IQR=1–40 months). Overall, treatment rate was significantly higher at university liver clinic than in the community (66.7% vs 59.9%, p=0.01). In multivariate analysis, older age (HR 1.02, p=0.002), male gender (HR 1.37, p=0.02), and baseline ALT >45 U/L for males and >29 U/L for females (HR 2.24, p<0.0001) were significant predictors of treatment initiation, but not practice setting. Conclusions Approximately 40% of treatment-eligible patients still have not started treatment on longer follow-up. Treatment rates were higher at university clinics, but practice setting was not a predictor for treatment, but older age, male gender, and higher ALT levels were. Further studies are needed to determine the barriers for treatment initiation and to improve treatment rates in treatment-eligible patients.

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.

Ethnic differences in incidence of hepatitis B surface antigen seroclearance in a real‐life multicenter clinical cohort of 4737 patients with chronic hepatitis B infection

Hepatitis B surface antigen (HBsAg) positivity is associated with increased risk for cirrhosis and hepatocellular carcinoma (HCC). HBsAg seroclearance is thought to be rare in general, but cohort data from US patients are limited.

Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy.

Objectives It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV. Our goal was to examine virologic outcomes in such patients. Methods This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy, who were switched back to monotherapy with either ETV (n=16) or TDF (n=18), or continued on combination therapy (n=23). The majority of patients were Asian (91%) and male (65%), with a mean age of 41±12 years. Results The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs. 39%, P=0.004). Patients who remained on ETV+TDF also had virologic breakthrough, due to either confirmed or suspected nonadherence. On multivariate analysis inclusive of age, sex, and hepatitis B virus DNA levels at initiation of combination therapy, ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 112.7, P=0.03), as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 60.2, P=0.03). Conclusion TDF monotherapy, especially in those who have had CVS for at least 12 months on combination therapy, may be considered for some ETV partial responders who have achieved CVS with combination therapy, given the financial advantage and convenience of monotherapy.

Tu1010 Poor Adherence to Screening for Hepatocellular Carcinoma (HCC) in Chronic Hepatitis B (CHB) Patients in Community Gastroenterology and University Liver Clinics

asked to complete general demographics information, RAND 36-Item (SF-36) Health Survey Health Survey, and the Zarit Burden Scale. The quality of life of caregivers based on the SF-36 was compared using t-tests, using the scores of the national reference population as controls. Results: Of the 50 caregivers who consented to participate in the study, 48 (96.0%) participants returned their completed survey. Among the respondents, the mean age was 56.9 ±11.4 years, 40 (83.3%) were female, and 34 (70.8%) were spouses/significant other to the patient. Compared to the adjusted national normative data, caregivers scored substantially lower in categories of role limitations due to emotional problems (61.8 vs 81.8, p= 0.001); mental health (65.8 vs. 75.2, p= 0.005); social functioning (69.5 vs 83.5, p= 0.002), and general health (66.3 vs. 70.1, p<0.001). While the adjusted Physical Component Score (PCS) of the caregivers was at the national mean, the Mental Component Score (MCS) was lower than the national average of 43.0 ±13.9 vs the national mean of 50.0 ±10.0 (p= 0.001). Though only 8 of 48 (16.7%) subjects reported a formal clinical diagnosis for depression or anxiety, 23 subjects (47.9%) had a MCS less than 42, a strong predictor based on previous studies of clinical depression. Conclusions: Primary caregivers of patients with advanced liver disease have a significantly lower mental health compared to the general population. In our cohort, less than 20% of caregivers are formally diagnosed with clinical depression or anxiety, suggesting that there may be under recognition of mental health dysfunction in this population. Enhanced recognition of mental health dysfunction among caregivers of liver patients may result in improved quality of life of both caregivers and patients.