Persistently elevated serum TBA ups risk of hepatocellular carcinoma development

Stephen Padilla
22 Feb 2017

Persistently elevated serum total bile acid (TBA) may increase the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with regular antiviral treatment, according to a study presented at the 26th Conference of Asian Pacific Association for the Study of the Liver (APASL) in Shanghai, China.

Furthermore, this finding may help enhance routine surveillance for HCC in current clinical practice.

“Our retrospective study identified persistently elevated serum TBA as a major independent risk factor for HCC development in CHB patients receiving regular antiviral treatment,” researchers said. “A total of 37 (59.7 percent) HCC cases in our cohort were contributed by the patient populations with medium or high persistence of elevated serum TBA.”

During the initial follow-up, the serum alanine aminotransferase (ALT), HBV DNA and TBA level decreased progressively with the most marked decline due to antiviral treatment. [Sci Rep 2016;6: 38180]

A dose-response relationship was seen between persistence of elevated serum TBA and cumulative incidence of HCC in the whole cohort, in the subcohort of 937 cirrhotic patients without ascites and in the subcohort of 145 cirrhotic patients with ascites.

At the end of follow-up, the cumulative probability of HCC for the whole cohort was 2.7, 10.9 and 22.3 percent for patients with none-low, medium and high persistence of elevated serum TBA (p<0.001), respectively.

In the subcohort of cirrhotic patients without ascites, the respective cumulative probability at the end of follow-up was 6.4, 11.1 and 15.1 percent for patients with none-low, medium and high persistence of elevated serum TBA (p<0.001). The respective cumulative probability in the subcohort of cirrhotic patients with ascites at the end of follow-up was 0, 28 and 48 percent for patients with none-low, medium and high persistence of elevated serum TBA (p=0.002).

Patients with medium or high persistence of elevated serum TBA were more likely to have shorter length of follow-up, to have older age at entry, to be diagnosed with cirrhosis and ascites during follow-up, to have higher aspartate aminotransferase to platelet ratio index (APRI) score at the end of follow-up, and to have medium or high persistence of elevated serum ALT (p<0.05) than those with none-low persistence of elevated serum TBA.

Compared with patients with none-low persistence of elevated serum TBA, those with medium and high persistence of elevated serum TBA had multivariate adjusted ratios of 2.37 (95 percent CI, 1.16 to 4.84) and 2.57 (1.28 to 5.16), respectively.

“Accumulative metabolomics data has found elevated serum bile acid as a core metabolomics phenotype in almost all the types of liver diseases,” researchers said. “It is worthy to apply our findings on those liver diseases.”

A total of 2,262 CHB patients receiving regular antiviral treatment were analysed in a retrospective cohort study using data from the Hepatitis Biobank at Southwest Hospital Program from 2004 to 2014. A follow-up of at least 4 years was conducted in all CHB patients in the cohort, which also had serum TBA records in most (more than 90 percent) of the calendar years of their follow-up.

Also, patients were categorized according to persistence of elevated serum TBA during follow-up: none-low (elevated serum TBA in <1/3 of their follow-up time), medium (elevated serum TBA in 1/3 to 2/3 of their follow-up time) and high (elevated serum TBA in ≥2/3 of their follow-up time) persistence of elevated serum TBA. Similarly stratified during follow-up were the persistence of elevated serum ALT and HBV DNA.

Cox proportional hazard models and Kaplan-Meier analysis were used to estimate the association between HCC and persistence of elevated serum TBA.

“Bile acid has been associated with HCC in human and mice with bile acid receptor deficiency, and in mice with altered bile acid metabolism,” researchers said. “Elevated serum bile acid has been observed in CHB patients, while there is currently no epidemiological study to evaluate the independent contribution of elevated serum bile to HCC in CHB patient population.”

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