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Fatty Liver Disease May Lower Risk of Cirrhosis, HCC in Patients With Comorbid Chronic Hepatitis B


Patients with concurrent fatty liver disease and chronic hepatitis B exhibited higher cumulative rates of hepatitis B surface antigen seroclearance and lower cumulative rates of cirrhosis and hepatocellular carcinoma (HCC) across a 10-year period.

Patients with concurrent fatty liver (FL) disease and chronic hepatitis B (CHB) may be at a decreased risk of cirrhosis and hepatocellular carcinoma (HCC) compared with their counterparts without FL, according to study findings published in The Journal of Infectious Diseases.

As 2 common conditions that are independently associated with chronic liver injury, FL prevalence has been shown to range from 14% to 70% in patients with CHB, which includes both alcoholic FL disease and nonalcoholic FL disease. Although research on concurrent FL and CHB is limited, prior data have indicated that FL may contribute to hepatitis B surface antigen (HBsAg) seroclearance, which is associated with reduced risk of HCC.

“Due to conflicting data, it is not clear if patients with CHB with concurrent FL may be at higher risk for serious outcomes such as cirrhosis or HCC as compared to CHB without FL, since CHB and FL individually can cause cirrhosis and HCC,” noted researchers.

Seeking to further investigate the impact of FL on cirrhosis, HCC, and HBsAG seroclearance incidence in patients with CHB, they conducted a retrospective cohort study of Asian patients with CHB from 5 centers in the United States and 2 centers from Taiwan (N = 6786; mean [SD] age, 46.24 [11.63]; 63.47% male).

In the study, propensity score matching (PSM) was leveraged to balance the FL-CHB (n = 1079) and non-FL CHB (n = 1079) groups, with Kaplan-Meier methods used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups. Mean (SD) patient follow-up was 131.88 (77.28) months.

At baseline, 1442 patients (21.91%) were positive for hepatitis B e antigen (HBeAG) and 2552 patients (37.61%) received antiviral therapy. During follow-up, 564 patients developed cirrhosis, 281 patients developed HCC, and 478 patients had HBsAG seroclearance.

In comparing the FL-CHB and non-FL CHB groups, those with concurrent disease were found in the overall (unmatched), pre-PSM cohort to be at a lower cumulative 10-year incidence risk for cirrhosis (9.10% vs 12.07%; P < .0001) and HCC (3.74% vs 6.18%; P = .0001), and a higher cumulative 10-year incidence of HBsAg seroclearance (13.42% vs 9.97%; P = .004).

Similar results were found in the matched, PSM cohorts, in which the FL-CHB group exhibited lower cumulative 10-year incidence of cirrhosis (10.52% vs 15.47%; P = .0001), HCC (4.51% vs 6.48%; P = .06), and a higher rate of HBsAg seroclearance (16.19% vs 5.92%; P = .05) than the non-FL CHB group.

Furthermore, when stratified by antiviral treatment status, antiviral-treated patients in the FL-CHB group were found to be significantly 81% less likely to develop cirrhosis (HR, 0.19; 95% CI, 0.12-0.33; P < .001) and 79% less likely to develop HCC (HR, 0.21; 95% CI, 0.09-0.51; P = .001) than the non-FL CHB group. This significant association was not found in untreated patients.

“Further studies are needed to further confirm our findings and to investigate this association for other race/ethnicities as well as to characterize the precise mechanisms for these observations,” concluded the study authors.


Li J, Yang HI, Yeh ML, et al. Association between fatty liver and cirrhosis, hepatocellular carcinoma, and hepatitis B surface antigen seroclearance in chronic hepatitis B. J Infect Dis. Published online November 29, 2021. doi:10.1093/infdis/jiaa739

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