Aim. Our aim is to survey the treatment effect of PEG-IFN plus ribavirin in patients infected with HCV genotype 6a in Guangdong and Guangxi province of China and investigate best course of antiviral treatment for patients with HCV-6a infection. Methods. 515 eligible patients received subcutaneous 180 μg PEG-IFNα-2a or 1.5 μg/kg PEG-IFNα-2b once weekly plus oral ribavirin. Primary outcome was SVR by intention-to-treat analysis. Secondary outcome was RVR, cEVR, ETR, and relapse rate. Results. SVR in patients with HCV-6a infection treated for 48 weeks was comparable to that in patients with HCV-2/3 infection (80.9% versus 82.5%, p = 0.812) and higher than that in patients with HCV-1b infection (80.9% versus 67.2%, p = 0.014). ETR (98.9% versus 90.6%, p = 0.016), virological response at month 3 of end-of- treatment (88.8% versus 76.6%, p = 0.044), SVR (80.9% versus 65.6%, p = 0.032), and virological response at month 12 of end-of-treatment (76.4% versus 60.9%, p = 0.04) in patients with HCV-6a infection treated for 48 weeks were higher than those in patients with HCV-6a infection treated for 24 weeks. Conclusion. SVR in patients with HCV-6a treated for 48 weeks was comparable to that in patients with HCV-2/3 infection and higher than that in patients with HCV-1b infection; patients with HCV-6a infection treated for 48 weeks had a superior treatment response than patients treated for 24 weeks.

The optimal treatment of hepatitis C virus (HCV) genotype 6 is unclear owing to its limited geographic distribution. Because of a high predictive value of rapid virological response (RVR) for sustained virological response (SVR), we conducted an open-label randomized controlled trial to compare 24- and 48-week peginterferon/ribavirin combination therapy for patients with HCV genotype 6 in Southern China who achieved an RVR.

Treatment-naive, non-cirrhotic patients with chronic hepatitis C genotype 6 were treated with pegylated interferon α-2a (180 μg/week) and ribavirin (800–1,200 mg, according to weight) for 4 weeks. Patients who achieved an RVR, which was defined as HCV RNA negativity at week 4 (<50 IU), were randomized to receive either an additional 20 or 44 weeks of treatment (24- and 48-week treatment groups, respectively). The primary outcome measure was SVR. From January 2011 to June 2014, 152(152/210, 72.4%) patients with HCV genotype 6a and RVR were randomized 1:1 to the 24- or 48-week treatment group. The SVR rates in the 24- and 48-week groups in the intention-to-treat analysis were 90.8% (69/76) and 88.2% (67/76), respectively; those in the per-protocol analysis were 95.7% (67/70) and 97.0% (64/66), respectively. More patients in the 48-week group had anemia (46.1% vs. 28.9%, P = 0.03), but other adverse events were comparable between the groups. The limitation of the present study was that only patients from Southern China were enrolled which may inhibit the extensive application of the findings.

Twenty-four weeks of peginterferon/ribavirin combination therapy was non-inferior to 48 weeks in patients with HCV genotype 6a in Southern China who achieved an RVR.

ClinicalTrials.gov NCT01263860

• Adolescent
• Adult
• Aged
• Antiviral Agents/therapeutic use
• China
• Female
• Genotype
• Hepacivirus/drug effects
• Hepacivirus/genetics
• Hepacivirus/pathogenicity
• Hepatitis C/drug therapy
• Humans
• Interferon-alpha
• Male
• Middle Aged
• Polyethylene Glycols
• RNA, Viral/genetics
• Recombinant Proteins
• Ribavirin/therapeutic use
• Treatment Outcome
• Young Adult

End-stage liver disease and hepatocellular carcinoma due to hepatitis C virus (HCV) co-infection are increasingly common causes of death among HIV-infected individuals. However, there are few clinical investigations of HIV/HCV co-infected individuals from low and middle-income nations. Here, we compare the epidemiology of HCV-infected and HIV/HCV co-infected individuals in Southern China and examine hepatic fibrosis scores in co-infected individuals.

We conducted a retrospective cross-sectional study of treatment-naïve HIV/HCV co-infected and HCV mono-infected subjects. Bivariate and multivariate models were used to examine the association between demographics and HCV genotype. Among co-infected individuals, we also studied the relationship between fibrosis scores derived from non-invasive studies and HCV genotype.

Data were collected from 175 HCV-infected individuals, including 89 (51 %) HIV/HCV co-infected individuals. HIV/HCV co-infection was correlated with intravenous drug use (AOR 46.25, p < 0.001) and not completing high school (AOR 17.39, p < 0.001) in a multivariate model. HIV/HCV co-infected individuals were more likely to be infected with HCV genotype 6a (p < 0.0001) or 3a (p < 0.023), whereas increased fibrosis (FIB-4 score) was associated with HCV genotype 3a infection (β 2.18, p < 0.001).

Our results suggest that intravenous drug use is driving HIV/HCV co-infection in Southern China. While additional studies are needed, HCV genotype 6a is more common and genotype 3a appears to be associated with more severe hepatic fibrosis in co-infected individuals.

Future HIV/HCV co-infection research in China should focus on at risk populations, HCV testing uptake, and genotype-specific treatment.

The online version of this article (doi:10.1186/s12879-015-1135-1) contains supplementary material, which is available to authorized users.

• Asian Pacific countries
• Direct-acting antivirals
• HCV
• IL28B

• Direct-acting antivirals
• Genotype 4
• Genotype 5
• Genotype 6
• Hepatitis C virus
• Pegylated interferon
• Ribavirin

• Core protein
• Genotype
• Hepatitis C virus
• Interferon
• Interferon sensitivity-determining region
• Interferon/ribavirin resistance-determining region
• Nonstructural proteins 5A

• Animals
• Antiviral Agents/therapeutic use
• Drug Resistance, Viral/genetics
• Genotype
• Hepacivirus/drug effects
• Hepacivirus/genetics
• Hepacivirus/pathogenicity
• Hepatitis C/diagnosis
• Hepatitis C/drug therapy
• Hepatitis C/virology
• Humans
• Interferons/therapeutic use
• Mutation
• Phenotype
• Treatment Outcome
• Viral Core Proteins/genetics
• Viral Envelope Proteins/genetics
• Viral Nonstructural Proteins/genetics
• Viral Proteins/genetics

Hepatitis C genotype 6 (HCV-6) is prevalent in Southeast Asia. Data on the efficacy of direct-acting antiviral agents in chronic HCV-6 patients is limited and pegylated interferon (Peg-IFN) plus ribavirin (RBV) combination therapy remains standard therapy for those patients.

Meta-analysis was performed to assess the efficacy and safety of Peg-IFN plus RBV combination therapy for chronic HCV-6 patients.

Relevant studies were found by database search through Medline, Embase, Web of Science and The Cochrane Library. All published clinical trials assessing the efficacy of Peg-IFN plus RBV combination therapy for chronic HCV-6 patients were included. Sustained virological response rate (SVR) was pooled. We performed additional meta-analyses to compare the SVR outcomes of 24 versus 48 weeks of treatment in four head-to-head trials. Another second meta-analysis was also conducted to compare the efficacy of combination Peg-IFN plus RBV therapy in HCV-6 versus HCV-1 patients.

Thirteen studies met the inclusion criteria. The pooled SVR of all single arms was 75% (95% CI: 0.68–0.81). The SVR of 24 weeks treatment was significantly lower than that at 48 weeks, with a risk difference of −14% (95% CI: −0.25 to −0.02, p = 0.02). However, when restricted to the patients with rapid virological response (RVR), there was no significant effect on SVR between these two treatment groups, with a risk difference of −1% (95% CI: −0.1 to 0.07, p = 0.67). The SVR in HCV-6 patients was significantly higher than that in HCV-1 patients, with a relative risk of 1.35 (95% CI: 1.16–1.57, p<0.001). Side effects were common, but rarely caused treatment discontinuation.

The results of this meta-analysis suggest that Peg-IFN plus RBV is effective and safe for HCV-6 patients. Shortening treatment seems to be feasible in HCV-6 patients with RVR when tolerance to treatment is poor. However, this decision should be made cautiously.

Asia is endemic for hepatitis C virus (HCV) infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α) in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR) rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1) infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B) genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients receiving PEG-IFN α plus ribavirin therapy are high, health care providers should judiciously determine the clinical usefulness of these novel agents on the basis of treatment duration, anticipated viral responses, patient tolerance, financial burdens, and drug accessibility.

• HCV
• IL28B
• PEG-IFN α
• RGT
• SVR

• Clinical
• Epidemiology
• Genotype 6
• Hepatitis C virus
• Treatment

• Antiviral Agents/administration & dosage
• Antiviral Agents/adverse effects
• Biological Evolution
• Genotype
• Genotyping Techniques
• Hepacivirus/genetics
• Hepatitis C/drug therapy
• Hepatitis C/epidemiology
• Hepatitis C/virology
• Humans
• Interferons
• Interleukins/genetics
• Treatment Outcome

Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma and infects about 3% world population. Response to interferon therapy depends upon the genotype of the virus and factors associated with the host. Despite a good response to interferon therapy, a considerable number of genotype 3a infected patients remains unalleviated.

In total forty-nine patients including twenty-five non-responders (non-SVR) and twenty-four responders (SVR) were recruited. Patients were tested for viral status at different intervals and the isolated RNA was sequenced for the NS5A region in both groups. The comparison of PKRBD of HCV between the SVR and non-SVR patients did not confirm any significant difference in the number of mutations. However, when the sequence downstream to the PKRBD of NS5A was compared, two important statistically significant mutations were observed; at positions 2309 (Ala to Ser) and 2326 (Gly to Ala). These mutations were then analysed for tertiary protein structure and important structural changes were observed. Statistically significant difference was also observed when age groups of patients were compared; younger patients showed better response than the older ones.

The region between PKRBD and IRRDR may be important for prediction of response to IFN therapy for genotype 3a. ISDR and PKRBD have not shown any involvement in treatment response. Further functional analyses of these findings can help in understanding the involvement of the NS5A region in interferon treatment of HCV-3a infected patients.

• HCV
• antiviral agent
• cost effectiveness
• direct-acting antiviral
• ethics
• interferon-free

• Animals
• Antiviral Agents/pharmacology
• Disease Eradication
• Hepacivirus/drug effects
• Hepacivirus/physiology
• Hepatitis C/drug therapy
• Hepatitis C/prevention & control
• Hepatitis C/virology
• Humans

• P30 AI050409 NIAID NIH HHS
• 2P30-AI-050409 NIAID NIH HHS

Hepatitis C genotype 6 is endemic in Southeast Asia [prevalence varies between 10%-60% among all hepatitis C virus (HCV) infection], as well as also sporadically reported outside the area among immigrations. The diagnosis of HCV genotype can be inaccurate with earlier methods of genotyping due to identical 5’-UTR between genotype 6 and 1b, hence the newer genotyping methods with core sequencing are preferred. Risk factors and clinical course of HCV genotype 6 do not differ considerably from other genotypes. Treatment outcome of HCV genotype 6 with a combination of pegylated interferon and ribavirin is superior to genotype 1, and nearly comparable to genotype 3, with expected sustained virological response (SVR) rates of 60%-90%. Emerging data suggests that a shorter course 24-wk treatment is equally effective as a standard 48-wk treatment, particularly for those patients who attained undetectable HCV RNA at week 4 (RVR). In addition, baseline and on-treatment predictors of response used for other HCV genotypes appear effective with genotype 6. Although some pan-genotypic direct-acting antivirals have completed phase II/III studies (sofosbuvir and simeprevir) with clinical benefit demonstrated in small number of patients with genotype 6, broad availability of these agents in Southeast Asia may not be expected in the near future. While awaiting the newer therapy, response-guided therapy seems appropriate for patients with HCV genotype 6. Patients with RVR (representing > 70% of patients) are suitable for 24-wk treatment with expected SVR rates > 80%. Patients without RVR and/or those with poor response predictors may benefit from 48 wk of therapy, and a detectable HCV RNA at week 12 (with no early virological response) serves as a stopping rule. This treatment scheme is likely to have a major economic impact on HCV therapy, particularly in Southeast Asia, wherein treatment can be truncated securely in the majority of patients with HCV genotype 6.

• Hepatitis C
• Genotype 6
• Epidemiology
• Southeast Asia
• Treatment
• Pegylated interferon
• Ribavirin
• Response-guided therapy

• Adolescent
• Adult
• Aged
• Antiviral Agents/therapeutic use
• Female
• Gene Frequency
• Genotype
• Hemoglobins/analysis
• Hepacivirus/classification
• Hepacivirus/drug effects
• Hepacivirus/genetics
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/virology
• Humans
• Interferons/therapeutic use
• Interleukins/genetics
• Male
• Middle Aged
• Platelet Count
• Polymorphism, Single Nucleotide
• Pyrophosphatases/genetics
• Ribavirin/therapeutic use
• Treatment Outcome
• Young Adult
• Inosine Triphosphatase

• prevention
• universal screening
• testing
• direct-acting antiviral
• cure
• linkage to care