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Information on genetic variants associated with elevated serum alanine aminotransferase (ALT) levels remains limited. A genome‐wide association study was performed to identify single‐nucleotide polymorphisms (SNPs) associated with ALT levels. The ALT‐associated SNP was further evaluated for hepatocellular carcinoma (HCC) risk. A cohort of 892 anti‐HCV seropositive patients was used for genome‐wide SNP array to examine the associations with baseline ALT levels. SNPs <10−5 were further tested for associations with serial ALT levels then validated in 486 anti‐HCV seropositives. Multinomial logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals of SNPs associated with ALT. The SNP was evaluated for HCC risk by using Cox's proportional hazards models. After quality control, 803 participants with 564,464 SNPs were included in the analysis. Of these, 12 SNPs were associated with ALT (p < 10−5). Among the participants, 158 (19.7%) had ALT persistently ≤15 U/L, 327 (40.7%) ever >15 U/L but never >45 U/L, and 318 (39.6%) ever >45 U/L during follow‐up. The rs568800 was associated with serial ALT levels, and this was replicated in the external population significantly (p <.05). The A allele (vs C) of rs568800 was associated with ALT >15 U/L but ≤45 U/L and ALT >45 U/L, with the adjusted ORs of 1.41 (1.11–1.78) and 1.86 (1.34–2.60), respectively. The adjusted HRs for HCC were 2.09 (0.90–4.89) for AC and 2.64 (1.13–6.17) for AA (CC as a reference). In conclusion, the rs568800 was associated with serum ALT levels and HCC risk. Clinical utility should be evaluated among patients who have received antivirals. [ABSTRACT FROM AUTHOR]

Background The association between hepatitis C virus ( HCV) infection and the occurrence of type II diabetes remains controversial. Prospective studies are needed to assess its causal temporality. Methods A cohort of 21 559 adults enrolled from seven townships in Taiwan during 1991-1992 and followed till the end of 2010. Incident diabetes over a study time period from 2000 to 2010 was ascertained through computerized linkage with the National Health Insurance database and the National Death Certification profiles. Cox's proportional hazards models were used to estimate hazard ratios ( HRs) with 95% confidence intervals ( CIs). Antibodies against HCV (anti- HCV) were tested for all participants, and serum HCV RNA levels were measured for anti- HCV seropositives. Results During 180 244 person-years of follow-up, there were 1917 incident diabetes cases recorded. The cumulative risk for diabetes was 10.9% for anti- HCV seronegatives and 16.7% for anti- HCV seropositives respectively. The HR for diabetes of anti- HCV seropositivity was 1.53 (95% CI: 1.29-1.81) compared with anti- HCV seronegatives after adjustment for risk predictors. The adjusted HRs were 1.63 (1.31-2.02) for anti- HCV seropositives with positive HCV RNA compared to anti- HCV seronegatives ( P<.001). Conclusion Chronic HCV infection was associated with an increased risk for diabetes after adjustment for other risk predictors. [ABSTRACT FROM AUTHOR]