Cytokine polymorphisms and genotypic susceptibility of HCV infection in ribavirin response to peg interferon

@#Immune responses are largely regulated by cytokines. Genetic polymorphisms of the regulatory coding regions are recognized to impact the expression of cytokines. The abnormal cytokine levels in hepatitis C virus (HCV) infection seems to be involved in disease progression, viral survival, and therapeutic response. The current study assesses the polymorphisms associated with IL-6, IL-10, IL28B, IFN-γ, TGF-β, and TNF-α on the genotypic susceptibility to HCV infection and Ribavirin response to Peg interferon. Droplet digital polymerase chain reaction (PCR) was used to assess the gene polymorphisms associated with IL-6 A/G (rs2069837), IL-10-1082 G/A (rs1800896)], IL28B C/T (rs12979860), IFN-γ +874 A/T (rs2430561), TGF-β 1-509 C/T (rs1800469) and TNF-α-308 G/A promoter (rs1800629) from stored samples of 200 healthy individuals and 300 HCV infected patients. There was a significant association of AG and AA genotypes of IL28B, IFN-γ, TGF-β1, and TNF-α over HCV susceptibility and treatment outcome. However, no association between IL-6 and IL-10 gene polymorphism to HCV susceptibility response to the treatment. The observations indicate IL28B CT, TGF-β1 CT, TT and TNF- AG with AA genotypes influence the cytokine expression, which is related to susceptibility and resistance to HCV infection and combined antiviral therapy.

Biodynamics of Hepatitis C Virus in Haemodialysis Patients in Pahang

Introduction: HCV infection is frequent in patients undergoing maintenance haemodialysis, with prevalence between 8 and 10%. Hepatitis C has an adverse effect on both patient and graft survival in those who get renal transplants. There are relatively scarce reports on the natural fluctuation in viral load level in patients on chronic haemodialysis. Materials and Methods: This is a longitudinal short-term three months study, where 27 chronic haemodialysis patients infected with known HCV genotypes were recruited from seven haemodialysis centres in Pahang. Serum samples were collected monthly, both pre- and post-haemodialysis sessions, over a period of three months. Viral RNA was extracted from serum using QIAamp Viral RNA Extraction kit (Qiagen). The HCV viral load was measured using one-step reverse transcriptase qPCR (Applied Biosystems) targeting the 5`HCV non-coding region (5’UTR). The serum α-IFN level was measured using commercial ELISA kit (Amersham, UK). Six biochemical liver function tests (AST, ALP, TP, albumin, ALT and TB) were also done for all pre-haemodialysis samples. Results: All patients showed persistent low level viral load that varied significantly over the study period (p = 0.001). HCV genotype 1 viral load was significantly higher than that of genotype 3. Conclusion: No apparent correlation could be recognized between the viral loads and the corresponding interferon-alpha levels which were detectable in only a few patients during the period of study.

Prevalence of hepatitis C virus genotypes and impact of T helper cytokines in achieving sustained virological response during combination therapy: A study from Central India.

Characterisation of host immune response to hepatitis C virus (HCV) genotypes may have an important prognostic and therapeutic implication. Genotype-3 was more prevalent in the examined cohort and demonstrated a significantly higher response to combination therapy than genotype-1. Sustained virological response (SVR) was 94.74% in genotype-3 and 45.45% in genotype-1. The patients who achieved SVR reported higher levels of circulating T helper 1 cytokines in comparison to subjects with no SVR in both the studied groups. Besides providing local prevalence, our study might also assist in understanding the host immune mechanisms involved to achieve SVR during combination therapy in chronic HCV patients.

Prevalence and genotypes of hepatitis C virus among injecting drug users from Salvador-BA, Brazil

Hepatitis C virus (HCV) is the major infectious disease agent among injecting drug users (IDUs), with seroprevalence ranging from 50-90 percent. In this paper, serological and virological parameters were investigated among 194 IDUs, 94 ex-IDUs and 95 non-IDUs that were sampled by the "snowball" technique in three localities renowned for both intense drug use and trafficking activities in Salvador, Brazil. The majority of the participants were male, but sex and mean age differed significantly between IDUs/ex-IDUs and non-IDUs (p < 0.05). Anti-HCV screening revealed that 35.6 percent, 29.8 percent and 5.3 percent of samples from IDUs, ex-IDUs and non-IDUs, respectively, were seropositive. HCV-RNA detection confirmed that the prevalence of infection was 29.4 percent, 21.3 percent and 5.3 percent for IDUs, ex-IDUs and non-IDUs, respectively. Genotyping analysis among IDUs/ex-IDUs determined that 76.9 percent were infected with genotype 1, 18.5 percent with genotype 3 and 4.6 percent with a mixed genotype; this result differed significantly from non-IDUs, where genotype 3 was the most frequent (60 percent), followed by genotype 1 (20 percent) and a mixed genotype (20 percent). We report a significantly higher prevalence of HCV infection in IDUs/ex-IDUs compared to the control group (p < 0.001). Although the sample size of our study was small, the differences in HCV genotype distribution reported herein for IDUs/ex-IDUs and non-IDUs warrant further investigation.

Seroprevalence of HBV, HCV and HIV co-infection in selected individuals from state of São Paulo, Brazil

Few studies are available on hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection in populations living in small and medium-sized Brazilian cities. We evaluated the seroprevalence of these viruses in selected individuals from a clinic of infectology, who were referred to the University Regional Hospital of the West Region of state of São Paulo, Brazil. Among a total of 7,021 individuals seen in the clinic following receipt of preliminary ELISA results or having the suggested clinical signs of viral hepatitis or HIV, 1,228 were systematically screened. Isolated or associated HBsAg, HCV and HIV antibodies were found in 44.9 percent of the subjects. Anti-HIV antibodies were found in 24.7 percent of the patients, 20.3 percent of whom had an HIV monoinfection and 4.4 percent of whom were co-infected with hepatitis viruses (HCV: 4 percent; HBV: 0.4 percent). Anti-HCV antibodies were found in 14 percent of the patients and 5.9 percent had anti-HBsAg antibodies. HCV infection affected males more than females (p < 0.05) and individuals > 50-years old had an increased prevalence of anti-HCV compared to HIV (p = 0.0001) or HBV (p = 0.0063). HCV-RNA was detected in 73.5 percent of the samples with a predominance of genotype 1 (72.5 percent). A significant percentage (44.9 percent) of the selected individuals was positive for antibodies against HBV, HCV and/or HIV; these patients would otherwise have remained undiagnosed.

Low occurrence of occult hepatitis B virus infection and high frequency of hepatitis C virus genotype 3 in hepatocellular carcinoma in Brazil

Occult hepatitis B virus (HBV) infection has been reported among patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). Our aim was to evaluate the presence of occult HBV infection in patients with HCV-related liver cirrhosis (LC) with or without HCC in São Paulo, Brazil. Serum and liver tissue samples from 50 hepatitis B surface antigen-negative patients with HCV-related LC who underwent liver transplantation at the University of São Paulo School of Medicine Hospital from 1993 to 2004 were divided into groups with LC only (N = 33) and with LC plus HCC (N = 17). HBV DNA was assayed for serum and paraffin-embedded liver tissue (tumoral and non-tumoral) using real time PCR and only 1 case with HCC had HBV DNA-positive serum. All liver samples were negative. HCV genotype 3 was detected in 17/39 (43.7 percent) cases. In conclusion, using a sensitive real time PCR directed to detect HBV variants circulating in Brazil, occult hepatitis B infection was not found among HCV-positive cirrhotic patients and was rarely found among HCV-positive HCC patients. These results are probably related to the low prevalence of HBV infection in our population. Furthermore, we have also shown that HCV genotype 3 is frequently found in Brazilian cirrhotic patients, particularly when they also have HCC. More studies involving a large number of cases should be carried out to confirm these data and to further characterize Brazilian HCV genotype isolates to elucidate genetic features that might be related to its carcinogenic potential.