Infections and the liver

Centre for Liver Research, MRC Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, Birmingham, UK.
Digestive Diseases (Impact Factor: 2.18). 07/2011; 29(2):184-90. DOI: 10.1159/000323884
Source: PubMed


Hepatitis B (HBV) and hepatitis C virus (HCV) have infected nearly half a billion individuals worldwide and are major indications for liver transplantation. Key requirements to successful outcomes with modern antiviral drugs are favourable host factors.
Single nucleotide polymorphisms near the IL28B gene location which encode for interferon (IFN)-λ3 have a large effect in determining the likelihood of patients obtaining a cure from pegylated IFN-α and ribavirin combination therapy or spontaneous clearance of the HCV. 80% of patients who carry two copies of this advantageous variant cleared the virus during IFN therapy and remained virus-free with a sustained viral response. This mutation is more common in Caucasian and Asian populations, whereas it is only found in the 40-50% of sub-Saharan Africans who are known to be more resistant to combination therapy. Similarly, host factors control tolerance to chronic HBV infection and can fluctuate over time with increased risk of progression to cirrhosis and particularly liver cancer. Loss of viral tolerance with reactivation and hepatitis is increasingly seen with the widespread use of biological treatments for diseases such as inflammatory bowel disease or rheumatoid arthritis. Natural disasters and conflicts in some parts of the world have also seen an increase in cases of hepatitis A and E virus infection and highlighted the global public health burden from viral-induced hepatitis.
Increased appreciation of the interaction between host factors and the viral life cycles is likely to significantly alter the way we target these infections in the future.

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    ABSTRACT: We examined the association of the interleukin-28B (IL-28B) gene rs12979860 T/C polymorphism with development of hepatitis virus-related hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Two investigators independently searched the PubMed, Elsevier, EMBASE, Web of Science, Wiley Online Library, and Chinese National Knowledge Infrastructure data bases. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) for rs12979860 and HCC/LC were calculated in a fixed-effect model (the Mantel-Haenszel method) and a random-effect model (the DerSimonian and Laird method) when appropriate. This meta-analysis included 7 eligible studies, with 1152 HCC and/or LC cases and 1326 controls. Overall, the rs12979860 T/C polymorphism was significantly associated with risk of hepatitis virus-related HCC and LC development (TT vs CC+CT, pooled OR = 1.597, 95%CI = 1.254-2.036). When they were grouped by type of hepatitis virus, similar results were found for hepatitis C virus-related groups (TT vs CC+CT, pooled OR = 1.732, 95%CI = 1.343-2.235, P value < 0.0001). In the overall analysis, the IL-28B rs12979860 T/C polymorphism was identified as a genetic risk factor for hepatitis virus-related HCC and LC development. A significant increase in the frequency of the T/T genotype was detected from chronic hepatitis to HCC and LC.
    Genetics and molecular research: GMR 10/2013; 12(3):3708-3717. DOI:10.4238/2013.September.19.1 · 0.78 Impact Factor


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