Serum aminotransferase level and the risk of hepatocellular carcinoma: a population-based cohort study in Japan

Abstract

Aminotransferase level is presumed to be a marker of hepatic inflammation, but uncertainty remains whether elevated aminotransferase levels are associated with an increased risk of hepatocellular carcinoma (HCC). We evaluated the incidence of HCC by aminotransferase level in 19 812 middle-aged and older individuals with and without hepatitis virus infection from a large-scale population-based cohort study (JPHC Study cohort II) in Japan. Hepatitis virus infection was identified at baseline in 1236 participants, namely 737 (3.7%) with hepatitis C virus, 479 (2.4%) with hepatitis B virus, and 20 (0.1%) with both. By the end of follow-up, a total of 109 newly arising HCC cases were diagnosed (71 men, 38 women), of which 87 (79.8%) had evidence of viral etiology. Alanine aminotransferase (ALT) was concentration-dependently associated with an increased risk of HCC in both virus-positive and virus-negative participants. Compared with virus-negative participants with ALT levels of less than 30 IU/l, a significant increase in the risk of HCC was observed in virus-negative participants with an ALT level greater than 30 IU/l, and in virus-positive participants with an ALT less than 30 IU/l, 30-69 IU/l, and > or =70 IU/l [Hazard ratio (95% confidence interval): 9.4 (3.9-22.3), 15.2 (6.1-37.6), 180.5 (89.4-364.2), 454.2 (221.5-931.2), respectively; P for trend <0.001]. In conclusion, our findings suggest that elevated ALT levels are strongly associated with the incidence of HCC regardless of hepatitis virus positivity. This finding indicates that ALT level is a good independent determinant of the need for intervention. Clinical application of these findings may help decrease HCC-associated mortality in hepatitis virus-endemic regions.

Prevalence of hepatitis B in the southeast of China

“…Our study agreed with previous studies reporting that being male individuals are associated with a higher level of ALT; however, unlike previous studies, we found that age older than 40 years is not associated with a higher level of ALT [26,27]. A population-based cohort study from Japan found that even virus-negative participants with an ALT level of at least 30 IU/l and virus-positive participants with an ALT level less than 30 IU/l showed a statistically significant risk of HCC [28]. Such people comprise a large proportion of our study; however, most of them are asymptomatic, and a regular follow-up of this group is necessary.…”

Plasma Levels of Adiponectin and Primary Liver Cancer Risk in Middle-Aged Japanese Adults with Hepatitis Virus Infection: A Nested Case–Control Study

“…To investigate whether adiponectin was associated with liver cancer through the pathway for insulin resistance (24), the ORs were adjusted for BMI (<18.5, 18.5-21.9, 22.0-24.9, and !25.0 kg/m 2 ) and diabetes (yes or no). We also adjusted for the following variables previously associated with liver cancer risk (20,25,26): alcohol consumption (never, past, <150, 150 to <450, !450 g/week ethanol), coffee consumption (almost never, 1 time/week to <1 cup/day, !1 cup/day), and serum alanine aminotransferase (ALT) levels (<30, 30-69, !70 IU/L). Because adjustment for smoking status (a suspected risk factor for liver cancer) and vegetable and fish intake [factors previously associated with liver cancer risk (27,28)] produced ORs that were almost identical to those without adjustment, results for these variables are not presented in this article.…”

Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity

“…However HBV or HCV-positive participants were not excluded, Table 2 Frequencies, odds ratios (non-adjusted and adjusted) and 95% confidence intrvals (95% CIs) of COMT genotypes (rs4680: Vall58Met (G/A)) for elevated serum ALT levels in the Japanese population. because they are known to have a higher risk of HCC in populations with elevated serum ALT activity as well as HBV or HCV-negative populations (Ishiguro et al, 2009). As these results indicate, the populations aged 35-44 and 55-69 might not have significantly lower non-adjusted and adjusted odds ratios.…”

“…Because Ishiguro et al (2009) reported that individuals with elevated levels of ALT activity (30 IU/L≤) had higher risk for HCC than those with normal ALT activity (b30 IU/L), 30 IU/L ≤ is defined as elevated, and b30 IU/L as normal. Furthermore, because serum ALT activity has the highest specificity as an index of liver damage, to minimize the influences of other damaged tissues, we did not use other indexes of liver damage (e.g., aspartate aminotransferase (AST) and gammaglutamyl transpeptidase (γ-GT) activities in serum).…”

“…Ishiguro et al revealed an association between elevated ALT activity (30 IU/L≤) and the risk of HCC in a Japan Public Health Center-based prospective Study (Ishiguro et al, 2009). They described that hepatitis virus (B or C) -negative or -positive subjects with elevated ALT activity (30-69 IU/L) have a 6.5 or 12-fold higher risk for HCC, than populations with normal ALT activity (b30 IU/L), respectively.…”