Change in treatment paradigm in people who previously injected drugs with chronic hepatitis C in the era of direct-acting antiviral therapy.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is highly prevalent among people who inject drugs but is often undiagnosed. The treatment paradigm for HCV patients has been changing since the availability of direct-acting antiviral (DAA) treatment. We aimed to evaluate the change in treatment paradigm of people who previously injected drugs (ex-PWID) in Hong Kong before and after the availability of DAA. METHOD: Consecutive ex-PWID referred from various nongovernmental organizations attended education talks at rehabilitation centers and received point-of-care rapid test for HCV antibody (anti-HCV) at the same session. Subjects tested positive for anti-HCV were invited to undergo further assessment. Afterwards, the patients were referred to the regional hospitals for follow-up and/or treatment. RESULTS: Three hundred sixty-five ex-PWID received HCV rapid test; 268 (73.4%) were found to be anti-HCV positive. Among these 268 HCV-positive ex-PWID, 234 (87.3%) attended the assessment session (mean age 52 years, 90.2% male, 45.5% genotype 1b, 41.1% genotype 6a, and median liver stiffness 5.9 kPa); 187 (69.8%) attended follow-up visits at regional hospitals. Seventy-one patients received antiviral treatment for HCV; 69 first received peginterferon and ribavirin (PegIFN/RBV), whereas 10 patients (eight PegIFN/RBV-treated patients) received DAA treatment. Fifty-two patients achieved sustained virologic response at 12 or 24 weeks. Treatment uptake rates of PegIFN/RBV and DAA treatment in the pre-DAA versus post-DAA era were 22.3% versus 48.5% and 0% versus 15.6%, respectively. CONCLUSIONS: Targeted screening in ex-PWID is effective in identifying patients with HCV infection in the community. To improve treatment uptake, further improvements in the referral system and treatment regimens are needed.

Cost-effectiveness of the highly effective direct-acting antivirals in the treatment of chronic hepatitis C in Hong Kong.

BACKGROUND AND AIM: In Asia-Pacific where cost is a major concern, peginterferon plus ribavirin (PR) often remain as the standard of care in chronic hepatitis C (CHC) treatment, while the direct-acting antivirals (DAAs) are commonly recommended as retreatment. Newer DAAs can achieve a sustained virological response (SVR) of nearly 100% with pan-genotypic coverage, that is "Highly Effective DAAs." We aimed to investigate the most desirable cost range for the Highly Effective DAAs using Hong Kong as an example. METHODS: Markov modeling was performed using PR as the reference strategy. The cost-effectiveness of the Highly Effective DAAs was compared with sofosbuvir-PR (first-line and rescue) and boceprevir-PR therapies. A 50-year-old genotype 1b hepatitis C virus (HCV) infected treatment-naïve patient with METAVIR F3 was used as the base case scenario to reflect the commonest HCV genotype in Hong Kong. RESULTS: The use of PR would incur a lifetime cost of US$35,854 and effectiveness of 14.85 quality-adjusted life-year (QALY). Sofosbuvir-PR as first-line treatment was dominated by other regimes. If Sofosbuvir-PR rescue therapy was used, the drug cost of Highly Effective DAAs should be set below US$43,553, with a cost-effectiveness ratio (CER) of US$3035/QALY compared with PR. In regions where Boceprevir-PR was still used as first-line therapy, the desirable drug cost of Highly Effective DAAs would be below US$56,985 to achieve a CER of US$5427/QALY. CONCLUSIONS: The most desirable costs of the Highly Effective DAAs would be below US$43,553 if Sofosbuvir-PR rescue therapy is used and below US$56,985 if Boceprevir-PR therapy is used.

Virus and Host Testing to Manage Chronic Hepatitis B.

Chronic hepatitis B virus (HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma worldwide. The past 50 years have seen rapid developments in HBV testing. Beginning from traditional serologic tests, the availability of sensitive HBV DNA assays allows a thorough understanding of the virology and natural history of chronic HBV infection. Quantification of hepatitis B surface antigen levels reflects the amount and transcriptional activities of covalently closed circular DNA in the liver and may be used to evaluate the stage of disease and guide antiviral therapy. The natural history of chronic HBV infection is also a manifestation of the interaction between the host and the virus, and recent genomic works have shed light on the host-virus relationship and may provide novel tests in the future. This review highlights recent advances in the application of HBV tests in the management of chronic hepatitis B.

Durability of peginterferon alfa-2b treatment at 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B.

UNLABELLED: Approximately 30%-40% of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with peginterferon and/or lamivudine achieve HBeAg seroconversion 6 months after the end of treatment. The durability and long-term effect of treatment are unknown. In this study, 85 HBeAg-positive patients who received peginterferon alfa-2b 1.5 microg/kg/week for 32 weeks and lamivudine 100 mg/day for 52 or 104 weeks were prospectively followed for 6.1 +/- 1.7 years posttreatment. Twenty-five (29%) patients had virologic response (HBeAg seroconversion and HBV DNA <10,000 copies/mL) at 5 years. The rate of HBeAg seroconversion rose progressively from 37% at the end of treatment to 60% at 5 years. Twenty-seven (32%) and 11 (13%) patients had undetectable HBV DNA (<100 copies/mL) at the end of peginterferon treatment and at 5 years, respectively. Two (2.4%) patients achieved hepatitis B surface antigen (HBsAg) seroclearance at 2.6 and 84 months posttreatment. Among virologic responders at the end of treatment, 82% and 57% and sustained HBeAg seroconversion and virologic response at 5 years. End-of-treatment serum quantitative HBsAg was significantly lower in patients with sustained virologic response at 5 years (median 1,431 IU/mL versus 2,689 IU/mL [P = 0.041]). At the last follow-up, the liver stiffness measurement by transient elastography was 5.8 +/- 2.7 kPa. Only two patients had liver stiffness suggestive of advanced fibrosis. Week 16 HBV DNA, end-of-treatment HBeAg seroconversion, and undetectable HBV DNA were independent factors associated with virologic response at 5 years. The duration of concomitant lamivudine treatment had no impact on any long-term response. CONCLUSION: Peginterferon has high durability in HBeAg-positive chronic hepatitis B patients with end-of-treatment virologic response.

Early hepatitis B virus DNA suppression can predict virologic response to peginterferon and lamivudine treatment.

BACKGROUND & AIMS: We aimed to investigate the early on-treatment HBV DNA response to predict sustained virologic response for peginterferon and lamivudine combination therapy. METHODS: Patients recruited in previous clinical trials receiving 32-week peginterferon alfa-2b and 52- to 104-week lamivudine combination treatment were studied. The areas under the receiver operating characteristic curve (ROC) of HBV DNA at different time intervals were analyzed to predict sustained virologic response, which was defined as HBeAg seroconversion and HBV DNA <10,000 copies/mL at 1 year after treatment. RESULTS: Fifty-seven patients had peginterferon started 8 weeks before lamivudine, and 9 patients had the 2 drugs commenced simultaneously. Eighteen (27%) patients developed sustained virologic response. The area under ROC for log HBV DNA to predict sustained virologic response reached 0.80 (95% confidence interval, 0.69-0.91; P < .001) at week 8 and plateaued off at subsequent time intervals. Among the 57 patients started with peginterferon monotherapy during the first 8 weeks, the area under ROC was 0.83 (95% confidence interval, 0.73-0.94; P < .001). Compared with other time intervals, the likelihood ratio for sustained virologic response was highest for HBV DNA <10,000 copies/mL at week 8 (10.35), with a high sensitivity (0.89) and negative predictive value (0.92). Two of 33 (6%) patients who had HBV DNA >or=10,000 copies/mL at week 8 developed sustained virologic response. CONCLUSIONS: HBV DNA >or=10,000 copies/mL at week 8 of peginterferon treatment had a low chance of sustained virologic response.

Virological response to different combination regimes of peginterferon alpha-2b and lamivudine in hepatitis B e antigen positive chronic hepatitis B.

OBJECTIVE: To investigate whether simultaneous commencement of peginterferon alpha-2b and lamivudine treatment has more potent hepatitis B virus (HBV) DNA suppression than staggered regimes. METHODS: Thirty HBeAg-positive chronic hepatitis B patients were randomized in 1:1:1 ratio to 32-week peginterferon started simultaneously with lamivudine (group 1), eight weeks before lamivudine (group 2) or eight weeks after commencement of lamivudine (group 3). All patients received lamivudine until week 104. RESULTS: At week 52, the log HBV DNA reduction in group 1 (6.38) was more profound than that in group 2 (3.43, P = 0.022) and tended to be superior to that in group 3 (4.44, P = 0.060). HBeAg seroconversion developed in six (67%) patients in group 1, three (33%) patients in group 2 (P = 0.35 versus group 1) and one (10%) patient in group 3 (P = 0.037 versus group 1). At week 104, the log HBV DNA reduction in group 1 (6.13) versus that in group 2 (5.24) and group 3 (5.15) was insignificantly different. Lamivudine resistance was found in four (14%) patients at week 104. There was 1.22 and 2.52 median log reduction in covalently closed circular DNA and total intrahepatic HBV DNA, respectively, at week 104, but there was no difference among the three groups. At 24 weeks post-treatment, sustained HBeAg seroconversion was observed in five (56%), three (33%) and four (40%) of the patients in groups 1, 2 and 3, respectively (P > 0.05). CONCLUSIONS: Simultaneous commencement of peginterferon and lamivudine tend to provide more profound viral suppression than staggered regimes in the early phase of treatment.

Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response.

BACKGROUND & AIMS: We aimed to evaluate serum hepatitis B surface antigen (HBsAg) quantitation as a surrogate marker for covalently closed circular DNA (cccDNA) and intrahepatic hepatitis B virus (HBV) DNA, and as a predictor of sustained virologic response to peginterferon and lamivudine combination therapy. METHODS: Twenty-six hepatitis B e antigen-positive chronic hepatitis B patients receiving combination treatment of 32-week peginterferon alfa-2b and 2-year lamivudine were studied. All patients had liver biopsy before and after treatment for cccDNA and intrahepatic HBV DNA measurement. Sustained virologic response was defined as sustained hepatitis B e antigen seroconversion and HBV DNA less than 10,000 copies/mL at the end of treatment until 1 year posttreatment. RESULTS: Seven patients developed sustained virologic response. At baseline, HBsAg correlated well with both log (cccDNA) (r = 0.54, P = .004) and log [total intrahepatic HBV DNA] (r = 0.43, P = .028). The median reduction of HBsAg was 1287 IU/mL (range, 12,223-26,763 IU/mL). Reduction of HBsAg has good correlation with reduction in log [cccDNA] (r = 0.68, P < .0001) and reduction in log [total intrahepatic HBV DNA] (r = 0.65, P < .0001). Patients with lower baseline cccDNA, intrahepatic HBV DNA, and HBsAg level but not serum HBV DNA level tend to develop sustained virologic response. A baseline HBsAg level of less than 10,000 IU/mL had sensitivity, specificity, and positive and negative predictive values for sustained virologic response of 86%, 56%, 43%, and 92%, respectively. CONCLUSIONS: Serum HBsAg levels correlate well with the cccDNA and intrahepatic HBV DNA. Low pretreatment HBsAg is better than HBV DNA to predict good response to peginterferon and lamivudine treatment.