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Concurrent NASH drives a ‘second hit’ to the liver in patients with HBV

Recent study data showed that concomitant chronic hepatitis B and nonalcoholic steatohepatitis were significantly more likely to lead to advanced fibrosis and liver-related outcomes including mortality compared with chronic hepatitis B alone.

“The metabolic syndrome is known to significantly elevate the risk of liver fibrosis progression in patients with [chronic HBV],” Hannah S.J. Choi, from the Toronto Center for Liver Disease in Ontario, Canada, and colleagues wrote. “In these patients, the development of concurrent NASH provides a secondary ‘hit’ to further perpetuate pre-existing hepatic injury due to HBV infection, and likely provides a barrier to reversing the profibrogenic phenotype.”

Choi and colleagues followed 1,089 patients with chronic HBV for a median of 10 years, of whom 17% also had NASH. Seventy-nine patients experienced at least one clinical event during follow-up, which included 24 deaths. One death was liver-related and the cause of four was unknown.

Development of hepatocellular carcinoma was the predominant liver-related event in both the group with NASH (n = 16) and the group without NASH (n = 19).

Multivariate analysis adjusted for age, sex, HBV e-antigen status and diabetes revealed that the presence of NASH (HR = 1.71; 95% CI, 1.06-2.76) and advanced fibrosis (HR = 2.73; 95% CI, 1.68-4.42) correlated independently with clinical outcomes.

The presence of NASH and concomitant advanced fibrosis correlated with liver-related outcomes (HR = 4.81; 95% CI, 2.59-8.95) compared with the absence of NASH advanced fibrosis. Further analysis revealed that hepatic activity (HR = 1.72; 95% CI, 1.03-2.86) and ballooning (HR = 1.77; 95% CI, 1.08-2.89) individually correlated with clinical outcomes when they replaced NASH in the model.

Patients who had advanced fibrosis had lower rates of event-free survival over time and the probability of event-free survival was further reduced with concurrent NASH (P < .01). This effect was increased by ballooning degeneration (HR = 2.14; 95% CI, 1.17-3.93) and hepatic activity (HR = 2.13; 95% CI, 1.04-4.39).

“Despite differences in patient demographics, disease severity, increased HCC, and assessment of NASH as a comorbid disease state in [chronic HBV], our findings are otherwise consistent with [nonalcoholic fatty liver disease] studies which identified AF as being the strongest predictor of clinical outcomes,” Choi and colleagues wrote.

They concluded that patients with chronic HBV should be evaluated for metabolic risk factors. If clinically significant features are present, a biopsy should be considered to assess for NASH and advanced fibrosis. – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.