Distribution of HCV genotype and single nucleotide polymorphisms (SNPs) of IL-28B gene in HIV/HCV-coinfected Thai populations

Introduction: Hepatitis C virus (HCV) infection remains a major silent killer, worldwide, particularly in resource poor settings where treatment of hepatitis C is mainly impossible. Pegylated interferon-α (PEG-IFN) plus ribavirin (RBV) are the recommended treatment for patients with chronic hepatitis C genotype 2/3. Recent study revealed that treatment responses against HCV infection by PEG-IFN and RBV are significantly associated with the single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) gene. There is limited data about the HCV genotype and SNPs of IL-28B in HIV-infected Thai population. Therefore, we aimed to investigate HCV genotype and the SNP patterns of the IL-28B gene in our HIV/HCV coinfection. Methods: Quantification of HCV RNA was done by a real-time polymerase chain reaction assay (Abbott with lower limit of detection of <12 copies/ml). HCV RNA-positive samples based on reverse transcriptase-polymerase chain reaction (RT-PCR) of the 5'UTR were amplified with primer specific for the core and NS5B regions. Nucleotide sequences of both regions were analyzed for the genotype by phylogenetic analysis. DNA sample was extracted from PBMCs or sera. Then SNPs within IL-28B gene were detected by TaqMan real-time PCR (rs8099917 and rs12979860). The data were analyzed by allelic discrimination (AD) software on the ABI-7900HT. Results: Totally 60 HIV/HCV-coinfected patients were studied. Median HCV RNA were 5.8 log10 copies/mL, 70% of them had HCV RNA >100,000 copies/mL. After sequencing, the phylogenetic analyses in this study showed that genotype 3 was the most prevalent in this population (56%); following by genotype 1 (30%) and 6 (13%). Approximately 4% of them had infected for both genotypes 1 and 3. For IL-28B at rs8099917 and rs12979860 position, 95% of them were major allele (T/T or C/C) and 5% were heterozygous (T/G or C/T). Conclusions: HCV genotype 3 is the most prevalent in our HIV/HCV coinfection. 95% of our patients have favorable IL-28B gene. This data is useful for further chronic hepatitis C treatment in Thailand

Supplementary Material for: Molecular Epidemiology and Genetic History of Hepatitis C Virus Subtype 3a Infection in Thailand

<b><i>Objective:</i></b> Among all hepatitis C virus (HCV) infections, subtype 3a is the most common genotype in Thailand. This study investigates the molecular epidemiology and epidemic history of HCV subtype 3a in Thailand. <b><i>Methods:</i></b> Three hundred and fifty-six serum samples were collected from HCV-infected Thai patients. The virus was isolated, after which the core and NS5B regions were sequenced. Subsequently, the HCV genotype was classified by phylogenetic analysis based on the core and NS5B regions. Molecular evolution analysis of HCV subtype 3a was estimated using BEAST (Bayesian Evolutionary Analysis by Sampling Trees) v.1.5.4. <b><i>Results:</i></b> Based on our phylogenetic analyses, subtype 3a (38.5%) was the most prevalent, followed by 1a (21%), 1b (13.8%), genotype 6 (19.9%) [comprised of subtypes 6e (0.3%), 6f (11%), 6i (1.9%), 6j (1.9%) and 6n (4.8%)] and 3b (5.6%). Our phylogenetic tree indicates the existence of a specific group of HCV subtype 3a strains in the Thai population. Molecular evolutionary analysis dated the most recent common ancestor of the Thai HCV subtype 3a strains as existing approximately 200 ago, and a Bayesian skyline plot showed that this particular strain spread to Thailand during the mid-1970s and early 1980s. This period overlaps with the Vietnam War (1955-1975) and the widespread use of injection stimulants introduced by the US Army during this time. <b><i>Conclusion:</i></b> The estimated history of HCV subtype 3a infection in Thailand may help to predict the future burden of HCV-related diseases and facilitate better public health control and surveillance

Interleukin-28B Polymorphisms and Response of Chronic Hepatitis C Patients from Indonesia to Pegylated Interferon/Ribavirin Treatment

This study demonstrated that Indonesian patients with chronic hepatitis C (mostly ethnic Java people) mostly were infected with hepatitis C virus (HCV) genotype 1; however, they carried mainly the major genotypes of interleukin 28B (IL-28B) single nucleotide polymorphisms (SNPs) (rs12979860 CC, rs11881222 TT, rs8103142 AA, and rs8099917 TT), and they mostly achieved sustained virological responses to pegylated interferon/ribavirin treatment

Estimating the Impact of Expanding Treatment Coverage and Allocation Strategies for Chronic Hepatitis C in a Direct Antiviral Agent Era

Hepatitis C virus (HCV) infection is an important worldwide public health problem, and most of the global HCV burden is in low- to middle-income countries. This study aimed to estimate the future burden of chronic hepatitis C (CHC) and the impact of public health policies using novel antiviral agents in Thailand. A mathematical model of CHC transmission dynamics was constructed to examine the disease burden over the next 20 years using different treatment strategies. We compared and evaluated the current treatment (PEGylated interferon and ribavirin) with new treatments using novel direct-acting antiviral agents among various treatment policies. Thailand’s CHC prevalence was estimated to decrease 1.09%–0.19% in 2015–2035. Expanding treatment coverage (i.e., a five-fold increment in treatment accessibility) was estimated to decrease cumulative deaths (33,007 deaths avoided, 25.5% reduction) from CHC-related decompensated cirrhosis and hepatocellular carcinoma (HCC). The yearly incidence of HCC-associated HCV was estimated to decrease from 2,305 to 1,877 cases yearly with expanding treatment coverage. A generalized treatment scenario (i.e., an equal proportional distribution of available treatment to individuals at all disease stages according to the number of cases at each stage) was predicted to further reduce death from HCC (9,170 deaths avoided, 11.3% reduction) and the annual incidence of HCC (i.e., a further decrease from 1,877 to 1,168 cases yearly, 37.7% reduction), but cumulative deaths were predicted to increase (by 3,626 deaths, 3.7% increase). Based on the extensive coverage scenario and the generalized treatment scenario, we estimated near-zero death from decompensated cirrhosis in 2031. In conclusion, CHC-related morbidity and mortality in Thailand are estimated to decrease dramatically over the next 20 years. Treatment coverage and allocation strategies are important factors that affect the future burden of CHC in resource-limited countries like Thailand

A cross-sectional study of hepatitis C among people living with HIV in Cambodia: Prevalence, risk factors, and potential for targeted screening

The epidemiology of hepatitis C in Cambodia is not well-known. We evaluated the prevalence of hepatitis C virus (HCV) and risk factors in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh to strengthen the evidence for suitable HCV testing strategies among people living with HIV (PLWH) in Cambodia. All consenting adult PLWH without a history of HCV treatment were tested for HCV between November 2014 and May 2016 according to the CDC algorithm (HCV antibody II electro-chemiluminescence immunoassay, followed by COBAS® AmpliPrep/COBAS® TaqMan® HCV PCR and INNO-LIA® HCV Score immunoblot end-testing). Genotyping was performed using the line probe assay Versant HCV genotype 2.0®. The study enrolled a total of 3045 patients (43% males, median age: 42.5 years, 55 years (11.2%). Genotype 1b (45%) and 6 (41%) were predominant. Coinfected patients had a higher aspartate-to-platelet ratio index, lower platelets, a lower HBsAg positivity rate and more frequent diabetes. Based on logistic regression, blood transfusion antecedents (adjusted odds ratio 2.9; 95% CI 1.7-4.9), unsafe medical injections (2.0; 1.3-3.2), and partner (3.4; 1.5-7.6) or household member (2.4; 1.3-3.2) with liver disease were independently associated with HCV in women. However, having a tattoo/scarification (1.9; 1.1-3.4) and household member (3.1; 1.3-7.3) with liver disease were associated with HCV in men. Thus, our study found intermediate endemicity of active hepatitis C in a large Cambodian HIV cohort and provides initial arguments for targeted HCV screening (>50 years, partner/household member with liver disease, diabetes, increased aspartate-to-platelet ratio index) as efficient way forward