Effect Of Histology-proven Nonalcoholic Fatty Liver Disease On Long-term Prognosis Of Chronic Hepatitis B Virus Infected Patients

Background& Objective: There is an increasing number of chronic hepatitis B virus(HBV)infected patients co-existing non-alcoholic fatty liver disease(NAFLD).Our aims were to investigate the impact of histology-proven NAFLD and pathological features on clinical outcomes in chronic HBV infected patients.Method: Chronic HBV infected patients in the hospital between January 2005 and December 2020 with available clinical and biopsy data were included.All liver specimens were reviewed and calculated for NAS in accordance to CRN(Nonalcoholic steatohepatitis clinical research network).Fatty liver is considered when the number of hepatocytes with steatosis is more than 5%.And according to METAVIR scoring system,fibrosis was assessed.Cirrhosis was diagnosed by abdominal ultrasound or FIB-4 score or APRI.HCC was diagnosed histologically or radiologically(detection of a positive lesion with at least two imaging techniques: ultrasonography,triphasic computed tomography,magnetic resonance imaging).Clinical events(cirrhosis,hepatoma and death)were evaluated with Kaplan-Meier survival estimates.Risk factors were assessed by Cox proportional hazards regression.Propensity score matching(PSM)was adapted to adjust for baseline characteristics.Results: Our study cohort included 456 chronic HBV infected patients with median follow-up of 70.5(29-133)months.NAFLD was histologically proven in 152 patients(33.3%).Compared to patients without NAFLD,the NAFLD group had more patients with diabetes mellitus and higher BMI,LDL,TG,PB and ALT level(P<0.05).Antiviral proportion,duration and type were not significantly different in NAFLD group and non-NAFLD group(P<0.05).During follow-up,there were 34 participants experienced cirrhosis diagnosed by ultrasound.respectively.27 and 7 patients were considered as cirrhosis according to APRI and FIB-4,respectively.NAFLD was not significantly associated with cirrhosis before and after match(P<0.05 by log-rank test).While fibrosis was associated with increased risk of cirrhosis after match(P<0.05 by log-rank test).The analysis of the subjects receiving antiviral treatment showed that the antiviral duration of more than 5 years could reduce the risk of cirrhosis judged by APRI and FIB-4(log rank,P<0.05).Before match,Age,balloon degeneration,fibrosis,PLT were independent risk factors for cirrhosis diagnosed by ultrasound(P<0.05).After match,multivariate analysis showed that diabetes mellitus and PLT were independent risk factors for the cirrhosis diagnosed by ultrasound(P<0.05).A total of10 patients(2.2%)developed HCC.The median interval between liver biopsy and HCC diagnosis was 100.5 months.K-M survival analysis showed that the cumulative risk of HCC increased significantly in groups with NASH,NAFLD,severe lobular inflammation,ballooning and severe liver fibrosis(F3-4)(log rank,P<0.05).There was no significant difference in the risk of HCC among patients with different degrees of portal inflammation(log rank,P=0.3).Multivariate analysis showed that NAS,liver fibrosis and diabetes were independent risk factors for HCC(P<0.05).After matching follow-up duration,there was no significant difference between NAFLD group and non-NAFLD group in the risk of HCC development(log rank,P = 0.064).But concurrent NASH,lobular inflammation,ballooning and severe liver fibrosis were still related to HCC(log rank,P<0.05).Multivariate analysis showed that NASH,liver cirrhosis,blood glucose and TC were independent risk factors for HCC(P<0.05).At the time of last follow-up,the proportion of obesity patients(33.99%)increased when compared with baseline(29.17%).K-M survival analysis showed that there was no significant difference in the risk of cirrhosis,HCC and total events between different BMI changes(log rank,P>0.05).Conclusion: Patients with chronic HBV infection complicated with NASH have an increased risk of HCC.Liver cirrhosis,blood glucose and TC are the risk factors of HCC.Age and diabetes mellitus were independent risk factors for cirrhosis diagnosed by ultrasound.NAFLD is associated with metabolic factors such as diabetes mellitus,dyslipidemia and BMI.Steatosis,as a component of NAS,is correlated with BMI.Clinically,patients concurrent chronic HBV infection with high BMI and significant metabolic abnormalities should consider biopsy to evaluate the presence of NASH and fibrosis degree,as these patients may need closer monitoring for liver related complications.