Abstract
ObjectivesAlanine aminotransferase (ALT) level is one of the crucial indexes to evaluate disease status for chronic hepatitis B (CHB) patients. However, whether the ALT level after nucleos(t)ide analog (NA) treatment is associated with hepatocellular carcinoma (HCC) development remains unclear.Materials and MethodsWe evaluated the association between ALT level and HCC occurrence in NA-treated patients and investigated the predictive value of ALT flare for HCC. The associations between ALT level and HCC were analyzed by logistic regression and Cox proportional hazards models.ResultsThere were 21,223 CHB patients at Ruijin Hospital of China and 16,737 CHB patients in the Optum electronic health records (EHR) in the United States (US) treated with NAs between 2010 and 2018. Among them, 8,152 and 4,893 patients who achieved a normal ALT value were included in the study cohorts, respectively. A significant positive dose-dependent correlation between the peak ALT level and HCC was identified in both cohorts. Within the China cohort, ALT flare was significantly associated with increased risks of HCC compared to normal ALT (HR 2.55, 95%CI 1.45–4.50). Stronger increased risks associated with ALT flare were observed in the US cohort (HR 7.62, 95%CI 4.85–11.98).ConclusionsALT flare is a strong predictor for HCC occurrence in the CHB patients treated with NAs. Elevation of ALT, especially ALT flare warrants close monitoring for early HCC detection.
Highlights
An estimated 240 million people are chronically infected with hepatitis B virus (HBV) worldwide, with the highest prevalence of infection in Asia [1]
While ALT elevation may be associated with seroclearance of HBV DNA and HBV antigens under nucleos(t)ide analogs (NAs) treatment as well as during the progression of the disease [5, 6], other evidence suggests that elevated ALT in Chronic hepatitis B (CHB) patients without antiviral treatment at baseline can be associated with a significantly increased risk for developing hepatocellular carcinoma (HCC)
The study conducted in the Ruijin database was approved by the Human Ethics Committee, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and the analysis on the Optum database was exempt from an institutional review board (IRB) approval by the New England IRB
Summary
An estimated 240 million people are chronically infected with hepatitis B virus (HBV) worldwide, with the highest prevalence of infection in Asia [1]. Chronic hepatitis B (CHB) progresses to cirrhosis, liver failure, or hepatocellular carcinoma (HCC) in 15–40% of infected people [2]. Evidence from a large HBV cohort study, the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer in HBV (REVEAL-HBV) in Taiwan yielded similar results that elevated ALT was associated with a >five-fold increased risk of HCC among patients with CHB and HBV carriers [8, 9]. Another study of 588 Korean American CHB patients did not observe a significant association between ALT and HCC risk [10]. It is not clear whether or how, ALT elevations are associated with HCC, especially among those with NA treatment
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