Ropeginterferon alfa-2b every 2 weeks as a novel pegylated interferon for patients with chronic hepatitis B.

BACKGROUND: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to 8-14 isomers of other on-market pegylated interferon, allowing injection every two or more weeks with higher tolerability. It received European Medicines Agency and Taiwan marketing authorization in 2019 and 2020, for treatment of polycythemia vera. This phase I/II study aimed to have preliminary evaluation of safety and efficacy in chronic hepatitis B. METHODS: Thirty-one HBeAg-positive and 31 HBeAg-negative were stratified by HBeAg status and randomized at 1:1:1 ratio to q2w ropeginterferon alfa-2b 350 µg (group 1), q2w 450 µg (group 2) or q1w PEG-IFN alfa-2a 180 µg (group 3). Each patient received 48-week treatment (TW48) and 24-week post-treatment follow-up (FW24). RESULTS: The baseline demographics were comparable among the three groups, except for mean HBeAg in HBeAg-positive patients (2.90, 2.23, 2.99 log10 S/CO, respectively). Cumulative HBeAg seroconversion rate at follow-up period was 27.3% (3/11), 36.4% (4/11), and 11.1% (1/9) with time to HBeAg seroconversion starting from TW24, TW16, and TW48 in group 1, 2, and 3, respectively. The rate of HBV DNA < 2000 IU/mL and HBsAg levels < 1500 IU/mL at FW24 were comparable in all groups. Ropeginterferon alfa-2b (group 1 & 2) had numerically lower incidence of rash (9.5% and 4.5%) as compared to PEG-IFN alfa-2a (36.8%). Ropeginterferon alfa-2b 350 µg (group 1) had more ALT elevation (38.1%), however the rate was comparable in group 2 (9.1%) and group 3 (10.5%). CONCLUSION: In this preliminary study, ropeginterferon alfa-2b, although in only half the number of injections, is as safe and effective as pegylated interferon alfa-2a for chronic hepatitis B.

Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17-0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.

Persistent transaminase elevations in chronic hepatitis C patients with virological response during peginterferon and ribavirin therapy.

BACKGROUND/AIMS: The aim of this study was to determine the incidence of persistently abnormal transaminase levels despite clearance of serum hepatitis C virus (HCV) RNA during antiviral therapy for chronic hepatitis C. METHODOLOGY: One hundred and fifty-one patients with chronic hepatitis C undergoing peginterferon alpha and ribavirin therapy and post-treatment follow-up for 24 weeks were included. The blood cell counts, liver biochemistry and serum HCV RNA levels were determined before, during and at 24 weeks after treatment. RESULTS: Overall, 104 patients (68.9%) achieved sustained virological response. Fifty-four of them (52%) had persistently abnormal transaminase levels during treatment despite clearance of serum HCV RNA. Among them, 27 patients (26%) had persistently abnormal serum AST and ALT levels and another 17 patients (16.3%) displayed isolated elevated AST levels. These 44 patients had normalized transaminase levels by two to three months after the end of treatment. The delayed biochemical response correlated with a higher baseline hepatic fibrosis stage (p=0.017) and liver cirrhosis (p=0.001). CONCLUSIONS: Approximately 42% of the patients eventually achieving sustained virological response following peginterferon alpha and ribavirin therapy showed delayed biochemical normalization. Delayed biochemical response was associated with the baseline hepatic fibrosis stage and liver cirrhosis.

Anti-Viral Therapy and Decreased Sexual Desire in Patients with Chronic Hepatitis C.

PURPOSE: Peg-interferon (PegIFN)α2a or PegIFNα2b plus ribavirin (RBV) is the standard therapy for chronic hepatitis C virus (HCV) infection in Taiwan and Asia. It is commonly associated with adverse effects, but the issue of sexual and mental health is not well reported. This study aimed to evaluate the impact of anti-viral therapy with PegIFNα plus RBV on sexual desire and depression. METHODS: This prospective cohort study from 2009 to 2014 enrolled 181 patients with HCV who received PegIFNα2a (180 mcg/week) or PegIFNα2b (1.5 mcg/Kg/week) plus RBV (800-1200 mg/day) according to response-guide therapy for 24 to 48 weeks in a tertiary medical center. Patients with decreased sexual desire (DSD) before PegIFNα plus RBV were excluded. Patients were evaluated at baseline (week 0) and after 2, 4, 8, 12, 16, 20, and 24 weeks of PegIFNα plus RBV treatment using the structured Mini-International Neuropsychiatric Interview, for the diagnosis of a major depressive episode, and the 21-item Beck Depression Inventory (BDI), for monitoring depressive symptoms. The 21st item of the BDI was used to evaluate DSD. RESULTS: During therapy, 124 (68.5%) patients had DSD. The BDI score peaked at 14.8 weeks. The severity of DSD was greatest at 16 weeks of treatment. The average score of the 21st item of the BDI correlated with DSD. Depression history and the prevalence of subsequent major depressive disorder after anti-viral therapy was correlated to DSD (p = 0.05 and 0.001). Male patients complained of DSD more significantly than females (p = 0.031). CONCLUSIONS: Decreased sexual desire is common but is usually neglected in patients with chronic hepatitis C undergoing anti-viral therapy, especially among male patients. Physicians must be monitoring the side effects of sexual health and depression.

Pegylated-interferon alpha therapy for treatment-experienced chronic hepatitis B patients.

BACKGROUND: Studies are limited on pegylated interferon (Peg-IFN) therapy for chronic hepatitis B (CHB) patients who failed or relapsed on previous antiviral therapy. OBJECTIVES: We aimed to investigate the effect of Peg-IFN therapy in treatment-experienced CHB patients. STUDY DESIGN: A total of 57 treatment-experienced CHB patients at two medical centers were enrolled. All of the patients were treated with Peg-IFN α-2a at 180 µg weekly for 24 or 48 weeks. The hepatitis B serological markers and viral loads were tested every 3 months until 1 year after stopping Peg-IFN therapy. The endpoints were HBV DNA <2000IU/mL, hepatitis B e antigen (HBeAg) seroconversion, and a hepatitis B surface antigen (HBsAg) loss at 12 months post-treatment. RESULTS: In HBeAg-positive patients, 25.0%, 29.2%, and 12.5% of the patients achieved HBeAg seroconversion, HBV DNA <2000 IU/mL and a combined response, respectively, at 12 months post-treatment. Prior IFN therapy, a high baseline ALT level, a low creatinine level, undetectable HBV DNA at 12 weeks and a decline in HBV DNA >2 log10 IU/mL at 12 weeks of therapy were factors associated with treatment response. In HBeAg-negative patients, 9.1%, 15.2%, and 6.1% of the patients achieved undetectable HBV DNA, HBV DNA <2000 IU/mL, and an HBsAg loss, respectively, at 12 months post-treatment. No factor was significantly associated with the treatment response in the HBeAg-negative patients. The median HBsAg level declined from 3.4 to 2.6 log10 IU/mL in all the patients, and the 5-year cumulative rate of the HBsAg loss was 9.8% in the HBeAg-negative patients. Overall, none of the patients prematurely discontinued the Peg-IFN therapy. CONCLUSIONS: Peg-IFN re-treatment is effective for a proportion of HBeAg-positive treatment-experienced patients; it has limited efficacy for HBeAg-negative treatment-experienced patients. Peg-IFN might facilitate HBsAg loss in HBeAg-negative treatment-experienced patients.

Rapid Prediction of Treatment Futility of Boceprevir with Peginterferon-Ribavirin for Taiwanese Treatment Experienced Hepatitis C Virus Genotype 1-Infected Patients.

The efficacy and safety of the boceprevir (BOC)-containing triple therapy in Taiwanese treatment-experienced patients remains elusive. After 4 weeks of peginterferon/ribavirin lead-in therapy, patients with cirrhosis or previous null-response received triple therapy for 44 weeks; whereas others received 32 weeks of triple therapy followed by 12 weeks of peginterferon/ribavirin therapy. Patients with HCV RNA > 100 IU/mL at week 12 or with detectable HCV RNA at week 24 of treatment were viewed as futile. A total of 123 patients received treatment. The rates of sustained virological response (SVR) and relapse were 66.7% and 8.9%, respectively by using intention-to-treat analysis. Multivariate analysis revealed that factors associated with SVR included HCV-1b (odds ratio [OR]/ 95% confidence intervals [CI]: 19.23/1.76-525.15, P = 0.01), BOC adherence (7.69/1.55-48.78, P = 0.01), serum albumin (OR/CI:6.25/1.14-40.07, P = 0.03) levels and HCV RNA levels (OR/CI:0.34/0.12-0.79, P = 0.01). Twenty-six (21.1%) patients experienced severe adverse events (SAEs). Multivariate analysis revealed that APRI > 1.5 was the single factor associated with occurring SAEs (OR/CI: 3.77/ 0.97-14.98, P = 0.05). Merging the cut-off values of HCV RNA > 7 log IU/mL at baseline and HCV RNA > 6 log IU/mL at week 4 provided the earliest and best combing viral kinetics in predicting week 12/24 futility with the PPV of 100% and accuracy of 93.5%. HCV-1 treatment experienced Taiwanese patients treated with boceprevir-containing triple therapy in real world had comparable efficacy and safety profiles with those reported in clinical trials. Early viral kinetics before week 4 of treatment highly predicted futility at week 12 or 24 of treatment.