Peginterferon alpha and ribavirin combination therapy in patients with hepatitis C virus-related liver cirrhosis

Background/Aims

Pegylated interferon (peginterferon) and ribavirin combination therapy is less effective and associated with a higher frequency of serious complications in chronic hepatitis C patients with cirrhosis than in noncirrhotic patients. This study evaluated the efficacy and tolerability of peginterferon and ribavirin treatment in patients with hepatitis C virus (HCV)-related cirrhosis.

Methods

Eighty-six patients with clinically diagnosed liver cirrhosis were treated with either peginterferon alpha-2a (n=51) or peginterferon alpha-2b (n=35) plus ribavirin. The sustained virologic response (SVR) and adverse effects were analyzed retrospectively.

Results

Of the 86 patients (55 males), 48 patients (55.8%) had HCV genotype 1 infection and 38 (44.2%) had genotype non-1 infection. The overall SVR rate was 34.9% (30/86), and the rates of SVR in the genotype 1 and non-1 patients were 20.8% (10/48) and 52.6% (20/38), respectively. The multivariate analysis revealed that having HCV genotype 1 (P=0.003) and high baseline viral load (>8.0×10⁵ IU/mL, P=0.012) were the independent predictive factors for SVR failure. In 20.9% (18/86) of the patients, treatment was not completed due to adverse events (27.8%), loss to follow-up (50.0%), and other reasons (22.2%).

Conclusions

Peginterferon and ribavirin combination therapy was relatively effective and feasible for clinically diagnosed HCV patients, especially in those with genotype non-1 infection and low baseline viral load.     

Hepatic and renal safety profile of tenofovir in HIV-infected patients with hepatitis C, including patients on interferon plus ribavirin

The liver safety of tenofovir (TDF) was investigated in 142 HIV+ patients exposed to the drug for longer than 12 months. No evidence of liver enzyme elevations were seen, even in 66 patients with chronic hepatitis C virus (HCV) co-infection. Given that TDF is an adenosine analogue, like didanosine, exposure to ribavirin might increase intracellular phosphorylated TDF metabolites, which could result in a higher risk of nephrotoxicity. Signs of tubular dysfunction in blood or urine were not recognized in 17 HCV-HIV co-infected patients exposed to TDF during interferon plus ribavirin therapy.     

Evaluation of cost-effectiveness of peginterferon plus ribavirin for chronic hepatitis C treatment and direct-acting antiviral agents among HIV-infected patients in the prison and community settings

BackgroundIn Taiwan, the majority of chronic hepatitis C carriers with HIV co-infection are intravenous drug users and inmates in correctional facilities. Peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (HCV) infection more than decades. We evaluated the estimated cost-effectiveness of PegIFN/RBV from the National Health Insurance Research Database, covering the population of Taiwan from 1998 to 2013.Materials and methodsThis is an observational study, and study during was 2010–2016 and a total of 239 patients were treated with PegIFN/RBV. Of them, 156 patients were treated in the correctional facilities of Taipei, Taoyuan, Taichung and Taitung prisons, and 83 patients were treated in communities. The cost-effectiveness was analyzed in regimens of PegIFN/RBV and direct-acting antiviral agents.ResultsBy multivariate analysis, the patients completed PegIFN/RBV in prison (adjusted odds ratio [aOR]: 4.56, 95% confidence interval [CI]: 1.58–13.12, p = 0.005), HCV RNA level <800,000 IU/mL (aOR: 4.0, 95% CI: 1.27–12.66, p = 0.02) at baseline, and the presence of early virologic response (EVR) (aOR: 7.67, 95% CI: 1.89–31.06, p = 0.004) were independent predictors for sustained virologic response (SVR). For the subgroups of prisoners, HIV-infected prisoners and HIV-infected patients in communities, the SVR rate was 73.8%, 72.0% and 36.8%, and the average medical-care cost was US$7,701, $7,893, and $15,443 per SVR achieved, respectively. Also, the estimated medical-care cost for genotype 6 was US$9211.ConclusionsChronic HCV/HIV co-infected patients with genotype 1 and 6 in the community setting could benefit from DAAs in Taiwan.     

Serum procalcitonin levels in chronic hepatitis C patients under pegylated interferon-alpha plus ribavirin treatment.

OBJECTIVES: To evaluate the alterations of serum procalcitonin (PCT) levels in patients with chronic hepatitis C during pegylated interferon-alpha (PEG-IFNa) plus ribavirin (RIB) treatment and to correlate them with clinical and virological outcomes. STUDY DESIGN: Fifty-two consecutive patients (29 males, age=41.2+/-14.7 years) with chronic HCV-related liver disease (six cirrhotics) were evaluated for PCT levels at baseline and during the treatment course (at week 12, 24, 48 and 72) with PEG-IFNa plus RIB. Sustained virological response (SVR) was confirmed by undetectable serum HCV-RNA at the end of treatment and again 6 months after completion of treatment. RESULTS: Two patients exhibited culture-proved bacterial infections during the treatment course. Thirty-six patients (69.2%) exhibit SVR and 16 (30.8%) were non-responders. Serum PCT levels remained within normal limits (0.1-0.5 ng/mL) in all treated patients throughout the follow-up period except those two who exhibited bacterial infections during the treatment course. Virological responders exhibited significant decline of serum PCT levels over time compared to non-responders (p<0.001), even when adjusted for multiple baseline parameters (p=0.037). CONCLUSION: Serum PCT levels decline in chronic hepatitis C patients during PEG-IFNa plus RIB treatment, especially in the sustained virological responder group, while they elevate only when bacterial infections complicate the treatment course.     

Peginterferon alfa-2a in patients with chronic hepatitis C

BACKGROUND: Covalent attachment of a 40-kd branched-chain polyethylene glycol moiety to interferon alfa-2a results in a compound (peginterferon alfa-2a) that has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified interferon alfa-2a. We compared the clinical effects of a regimen of peginterferon alfa-2a with those of a regimen of interferon alfa-2a in the initial treatment of patients with chronic hepatitis C. METHODS: We randomly assigned 531 patients with chronic hepatitis C to receive either 180 microg of peginterferon alfa-2a subcutaneously once per week for 48 weeks (267 patients) or 6 million units of interferon alfa-2a subcutaneously three times per week for 12 weeks, followed by 3 million units three times per week for 36 weeks (264 patients). All the patients were assessed at week 72 for a sustained virologic response, defined as an undetectable level of hepatitis C virus RNA (<100 copies per milliliter). RESULTS: In the peginterferon group, 223 of the 267 patients completed treatment and 206 completed follow-up. In the interferon group, 161 of the 264 patients completed treatment and 154 completed follow-up. In an intention-to-treat analysis in which patients who missed the examination at the end of treatment or follow-up were considered not to have had a response at that point, peginterferon alfa-2a was associated with a higher rate of virologic response than was interferon alfa-2a at week 48 (69 percent vs. 28 percent, P=0.001) and at week 72 (39 percent vs. 19 percent, P=0.001). Sustained normalization of serum alanine aminotransferase concentrations at week 72 was also more common in the peginterferon group than in the interferon group (45 percent vs. 25 percent, P=0.001). The two groups were similar with respect to the frequency and severity of adverse events, which were typical of those associated with interferon alfa. CONCLUSIONS: In patients with chronic hepatitis C, a regimen of peginterferon alfa-2a given once weekly is more effective than a regimen of interferon alfa-2a given three times weekly.     

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

Background/AimsReal-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited.MethodsWe included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR₁₂) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported.ResultsThe SVR₁₂ rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR₁₂ were attributed to virologic failures. The SVR₁₂ rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR₁₂, 84.4% and 64.6% had improved Child-Pugh and model for end-stage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m²/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m²/month; P<0.001).ConclusionsSOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.     

Clinical features and treatment efficacy of peginterferon alfa plus ribavirin in chronic hepatitis C patients coinfected with hepatitis B virus

Background/Aims

Cross-sectional studies have documented that 2-10% of patients who are chronically infected with hepatitis C virus (HCV) are also positive for hepatitis B virus (HBV) surface antigen (HBsAg). Data related to HCV-HBV coinfection are lacking in Korea. This study evaluated the clinical characteristics, the treatment efficacy of peginterferon alfa plus ribavirin, and the changes induced by such treatment in HBV status in chronic hepatitis C (CHC) patients coinfected with HBV.

Methods

Eighteen (2.37%) HBsAg-positive CHC patients were selected from among the 758 subjects from the K(G)yeonggi-Incheon Peginterferon alfa and ribavirin in chronic hepatitis C Treatment (KIPECT) study, which evaluated the treatment efficacy and safety of peginterferon alfa plus ribavirin in CHC patients. Data on changes in the status of HBV infections were obtained.

Results

HCV genotype 1b was the most common (44%). The overall sustained virologic response rate was 72% in all patients, and 60% and 87.5% in genotypes 1 and 2, respectively. Two of the 18 patients were positive for HBeAg, and 15 had baseline HBV DNA level of less than 2,000 IU/mL. Two of the three whose levels exceeded this threshold showed no detectable DNA after treatment. After the completion of treatment, serum HBV DNA levels were increased in the two patients whose baseline HBV DNA levels were less than 2,000 IU/mL.

Conclusions

The prevalence of HBV coinfection in CHC patients was 2.37% and most of the patients were inactive carriers. The treatment efficacy was similar to that of HCV mono-infection. Reactivation of HBV replication was observed in some patients after CHC treatment.     

Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis

BACKGROUND: Chronic hepatitis C virus (HCV) infection in patients with cirrhosis is difficult to treat. In patients with chronic hepatitis C but without cirrhosis, once-weekly administration of interferon modified by the attachment of a 40-kd branched-chain polyethylene glycol moiety (peginterferon alfa-2a) is more efficacious than a regimen of unmodified interferon. We examined the efficacy and safety of peginterferon alfa-2a in patients with HCV-related cirrhosis or bridging fibrosis. METHODS: We randomly assigned 271 patients with cirrhosis or bridging fibrosis to receive subcutaneous treatment with 3 million units of interferon alfa-2a three times weekly (88 patients), 90 microg of peginterferon alfa-2a once weekly (96), or 180 microg of peginterferon alfa-2a once weekly (87). Treatment lasted 48 weeks and was followed by a 24-week follow-up period. We assessed efficacy by measuring HCV RNA and alanine aminotransferase and by evaluating liver-biopsy specimens. A histologic response was defined as a decrease of at least 2 points on the 22-point Histological Activity Index. RESULTS: In an intention-to-treat analysis, HCV RNA was undetectable at week 72 in 8 percent, 15 percent, and 30 percent of the patients treated with interferon alfa-2a and with 90 microg and 180 microg of peginterferon alfa-2a, respectively (P=0.001 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a). At week 72, alanine aminotransferase concentrations had normalized in 15 percent, 20 percent, and 34 percent of patients, respectively (P=0.004 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a). In the subgroup of 184 patients with paired liver-biopsy specimens, the rates of histologic response at week 72 were 31 percent, 44 percent, and 54 percent, respectively (P=0.02 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a). All three treatments were similarly tolerated. CONCLUSIONS: In patients with chronic hepatitis C and cirrhosis or bridging fibrosis, 180 microg of peginterferon alfa-2a administered once weekly is significantly more effective than 3 million units of standard interferon alfa-2a administered three times weekly.