Relation of IL28B Gene Polymorphism with Biochemical and Histological Features in Hepatitis C Virus-Induced Liver Disease

Abstract

Background/AimsPolymorphism at the IL28B gene may modify the course of hepatitis C virus (HCV) chronic infection. Our aim was to study the influence of IL28B rs12979860 gene polymorphism on the biochemistry and pathology of HCV-induced disease in the clinical course from mild chronic hepatitis C to hepatocellular carcinoma.MethodsWe have determined the rs12979860 single nucleotide polymorphism (SNP) upstream IL28B gene in two groups of patients with HCV-induced chronic liver disease: 1) 268 patients (159 men) with biopsy-proven chronic hepatitis C, to analyse its relation with biochemical, virological and histological features; and 2) 134 patients (97 men) with HCV-related hepatocellular carcinoma. The distribution of the analysed SNP in hepatocellular carcinoma patients was compared with that found in untreated chronic hepatitis C patients. All patients were white and most were Spaniards.ResultsIn multivariate analysis ALT values were higher (P = 0.001) and GGT values were lower (P<0.001) in chronic hepatitis C patients homozygotes for the major rs12979860C allele as compared with carriers of the mutated rs12979860T allele. Steatosis was more frequent (Odds ratio = 1.764, 95% C.I. 1.053–2.955) and severe (P = 0.026) in carriers of the rs12979860T allele. No relation was found between the analysed SNP and METAVIR scores for necroinflammation and fibrosis, and there were no differences in the distribution of the analysed SNP between hepatocellular carcinoma and untreated chronic hepatitis C patients.ConclusionThe IL28B rs12979860 polymorphism correlates with the biochemical activity and the presence and severity of liver steatosis in chronic hepatitis C.

Association Between IL-28B Polymorphism and Clinical Laboratory Features in Patients with Chronic Hepatitis D

“…This finding corresponds with the result of a Genome Wide Association study that demonstrated that the rs12979860CC was significantly associated with ALT levels which is regarded as a necro inflammatory marker of the liver cells. Another study showed that the carriers of the rs12979860CC genotype had higher values for ALT comparing with carriers of the rs12979860CT/TT genotypes among Spanish individuals, which is a similar result to our study [17]. As several previous studies have reported, IL-28B CC genotype is connected to a strong immune response against hepatitis viruses, which on a positive side leads to higher viral clearance, yet negatively, to a more advanced cell injury which explains the result of higher levels of ALT and AST in CC genotype group, and supporting an idea that the IL-28B genotypes are directly linked to the pathogenesis of liver damage in delta hepatitis [17][18][19].…”

“…Another drawback was the absence of histopathological examination, which is regarded as the gold standard for evaluating necro inflammation, liver fibrosis and cirrhosis. However, a recent study has not detected a parallel between IL-28B polymorphism and the necro inflammatory grade and the stage of fibrosis through liver biopsy in CHC patients [17]. Moreover, liver biopsy for chronic Hepatitis B infection before antiviral therapy in chronic hepatitis B (CHB) patients is not routinely part of contemporary practice, especially for those with obviously active CHB (ALT above 2 times ULN and HBV DNA>2000 IU/mL) [29,30].…”

Association of the interleukin-28B gene polymorphism with development of hepatitis virus-related hepatocellular carcinoma and liver cirrhosis: a meta-analysis

“…After our selection, 7 casecontrol studies including 1152 HCC and/or LC cases and 1326 controls fulfilled the inclusion criteria (Barreiro et al, 2011;Fabris et al, 2011;Falleti et al, 2011;Agundez et al, 2012;El-Awady et al, 2012;Eurich et al, 2012;Ren et al, 2012). The quality of the studies was considered acceptable for our meta-analysis.…”

“…There were 5 case-control studies Agundez et al, 2012;El-Awady et al, 2012;Eurich et al, 2012;Ren et al, 2012), which had been performed to study the rs12979860 poly morphism and HCC risk. The results of the meta-analysis are shown in Table 3.…”

IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase

“…Associations between IL-28B variants and HCC development [22] and recurrence [23] have recently been reported. Moreover, an association between the IL-28B rs12979860 CC genotype and higher ALT levels has also been described [24] . It is possible that the IL-28B genotype is associated with inflammatory activity in the liver and the progression of hepatic fibrosis.…”