ABSTRACT
Type III interferon (IFNs) encoded by IFN lambda (IFNL) genes induce antiviral activity. The IFNL clusters include IFNL1/IL29, IFNL2/IL28A, IFNL3/IL28B and IFNL4 genes. The single nucleotide polymorphisms (SNPs, rs12979860 and rs8099917) associated with virological responses against hepatitis C virus (HCV) infections are recently mapped to IFNL4 gene. The IFNL gene polymorphisms also plays role in immune clearance, inflammation and risk of developing hepatocellular carcinoma. There is significant genetic heterogeneity of IFNL4 polymorphisms among ethnic populations that need to be regionally studied for viral infection, treatment response and relapse. The IFNL4 risk allele, genotype and haplotype frequencies across north Indian cohort were determined among chronic hepatitis C (CHC) cases (n = 141) and healthy controls (n = 111) by allele specific real-time PCR. Odds ratio was calculated for HCV exposure and treatment response using dominant and minor allele/genotype as reference. Non-random associations of these two SNP loci were evaluated by linkage disequilibrium plot. The minor allele (T) frequency of rs12979860C/T is 0.241 and 0.229; and minor allele (G) frequency for SNP rs8099917T/G is 0.174 and 0.171 among CHC cases and healthy control respectively. Coefficient of linkage disequilibrium (D') of these two SNPs is very high (D' = 0.98, r2 > 0.6) in CHC group than in healthy control (D' = 0.76, r2 = 0.39) which indicate that both SNPs are strongly linked in CHC population than healthy control. Favorable association of IFNL4 haplotype (C-T), genotype (CC for rs12979860 and TT for rs8099917) with anti HCV therapy were found significant (p = 0.009, 0.021 and 0.001) for SVR. Favorable genotypes are also found to be predominant across the Indian study population.
ABSTRACT
BACKGROUND AND AIM: Detection of an asymptomatic rise in the hepatic aminotransferase (ARHA) value has become a distinct and frequent clinical problem. We evaluated a three-step diagnostic algorithm in such patients for maximum yield. METHODS: Consecutive patients with an ARHA value 1.5-fold the upper limit of normal for at least 4 weeks and who were apparently healthy were included in the study. Each patient underwent standard biochemical investigations and a stepwise investigative protocol. In the first step, serological markers for hepatitis viruses, serum ferritin, 24-h urinary copper, alpha-1-antitrypsin phenotyping, and autoimmune markers were carried out. In step two, patients who tested negative for all the above markers had polymerase chain reaction (PCR) analysis for hepatitis B virus (HBV)-DNA and hepatitis C virus (HCV)-RNA. Patients without a diagnosis despite the above investigations underwent a liver biopsy as part of step three. RESULTS: Of 105 patients with ARHA, 38 were excluded for various reasons and 67 were included for the final analysis. The mean age was 35.11 +/- 11.96 years and 56 patients were men. The mean body mass index was 24.17 +/- 3.2 kg/m(2). The stepwise diagnostic algorithm achieved a diagnosis in 65/67 (97%) patients. Non-alcoholic steatohepatitis (NASH) and chronic viral hepatitis were the most common diagnoses, in 24 (36%) patients each. Using the diagnostic algorithm a diagnosis was reached in 34% of patients with only serological and biochemical investigations, whereas PCR for HBV and HCV could further detect the presence of active HBV or HCV viremia in 21% (14/97) and a liver biopsy was necessary to establish the diagnosis in 28/67 (42%) patients. CONCLUSIONS: A stepwise diagnostic algorithm in patients with ARHA resulted in an optimal use of PCR and invasive tests such as liver biopsy. Cryptic HBV and HCV infection was frequent among these patients and PCR was necessary in such cases. NASH and chronic viral hepatitis were the most frequent causes of ARHA.
