1 Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada.
2 Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
3 Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
4 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
BACKGROUND AND AIMS:
Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease are increasingly observed together in clinical practice, and development of non-alcoholic steatohepatitis (NASH) represents another leading cause of liver-related morbidity and mortality. Our aims were to determine whether biopsy-proven NASH impacts clinical outcomes in CHB patients and assess prognostic risk factors.
CHB patients attending two tertiary centres in North America/Europe over 13 years with available clinical and biopsy data were included. Patients were categorized as no-NASH or probable/definite NASH based on standardized histologic assessment. Clinical events (death, decompensation, transplant, and hepatoma) were evaluated, and Kaplan-Meier survival estimates and Cox proportional hazards regression were used to analyze the incidence of events.
There were 1089 CHB patients, classified as no-NASH (n=904, 83%) or NASH (n=185, 17%) with 52(6%) versus 27(15%) experiencing outcome events during follow-up, respectively. In the multivariable analysis adjusting for age, sex, HBeAg serostatus, and diabetes, the presence of NASH and concomitant advanced fibrosis (AF) was significantly associated with clinical outcomes (HR (95% CI): 4.8(2.6-9.0), p<0.01) when compared to absence of NASH and AF (reference). NASH and AF were associated with a greater risk of outcomes compared to AF (p=0.01) or NASH alone (p<0.01). Of the three histological determinants of NASH, ballooning and inflammation, but not steatosis, were independently associated with clinical outcomes (p<0.05) in place of NASH. NASH was significantly associated with increased risk of HCC and death (p<0.01), but not decompensation (p=0.33).
In our large combined tertiary centre cohort, patients with concomitant NASH and CHB had more AF and shorter time to development of liver-related outcomes or death, compared to patients with CHB alone. Among patients with AF, superimposed NASH predicted poorer clinical outcomes.