Fatty Liver Disease in a Prospective North American Cohort of Adults With Human Immunodeficiency Virus and Hepatitis B Virus Coinfection

Abstract

Background: Hepatitis B virus (HBV) and fatty liver disease (FLD) are common in human immunodeficiency virus (HIV). Correlates of FLD and its relationship with alanine aminotransferase (ALT) were examined longitudinally in HIV-HBV coinfection.

Methods: From 28/4/2014-7/11/2018, 114 HIV-HBV adults had liver biopsy and were followed for a median of 3 years (ancillary study of Hepatitis B Research Network). Steatohepatitis was based on presence of steatosis, ballooning, and perisinusoidal fibrosis. FLD was defined as ≥5% steatosis and/or steatohepatitis.

Results: Median age was 49 years, 93% were male, 51% black, 93% had HIV RNA <400 copies/mL and 83% HBV DNA <1000 IU/mL. Thirty percent had FLD (20% steatosis, 10% steatohepatitis). Those with FLD had higher median triglyceride (171 vs 100 mg/dL, P < .01) and small, dense LDL (44 vs 29 mg/dL, P < .01) and lower HDL-2-C (9 vs 12 mg/dL, P = .001). After adjusting for age, sex, and alcohol use, white and other versus black race (ORs, 8.49 and 16.54, respectively), ALT (OR, 3.13/doubling), hypertension (OR, 10.93), hyperlipidemia (OR, 4.36), and diabetes family history (OR, 5.38) were associated with having FLD (all P < .05). Steatohepatitis or steatosis alone (vs none) was associated with higher ALT over time (1.93 and 1.34 times higher, respectively; P < .001), with adjustment for age, sex, and HBV DNA.

Conclusions: About 30% with HIV-HBV coinfection had FLD including 10% with steatohepatitis. FLD was associated with non-black race, metabolic risks, an atherogenic lipid profile, and elevated ALT over time. Thus, identification of FLD and management of adverse metabolic profiles are critically important in HIV-HBV coinfection. Clinical Trial Registration. NCT01924455.

Keywords: cardiovascular risk; adipose tissue insulin resistance; inflammation; nonalcoholic steatohepatitis.

Figure 1.

A representative liver biopsy (same field): histologic findings of (A) steatosis, inflammation, and hepatocyte ballooning and (B) perisinusoidal fibrosis.

Figure 2.

The distribution of (A) LDL-P, (B) sdLDL-C, (C) small LDL-P, (D) HDL-P, and (E) HDL-2-C by FLD. Each box represents the first (lower end) to third (upper end) quartiles of lipid values (IQR), and the horizontal line in each box represents the median lipid value. The vertical line at either end of the box extends to the most extreme values or is cut off at 1.5 times the IQR; observations beyond this cutoff are displayed as circles. Abbreviations: FLD, fatty liver disease; IQR, interquartile range; HDL-2-C, HDL subclass 2-C; HDL-P, HDL particle; LDL-P, LDL particle; sdLDL-C, small, dense LDL cholesterol.

Figure 3.

The associations between (A) sdLDL-C and (B) small LDL-P with triglycerides by FLD. Abbreviations: FLD, fatty liver disease; LDL-P, LDL particle; sdLDL-C, small, dense LDL cholesterol.

Figure 4.

The distribution of (A) ALT and (B) AST over time by FLD status at enrollment. Each box represents the first (lower end) to third (upper end) quartiles of ALT or AST values (IQR), and the horizontal line in each box represents the median value. The vertical line at either end of the box extends to the most extreme values or is cut off at 1.5 times the IQR; observations beyond this cutoff are displayed as circles. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; FLD, fatty liver disease; IQR, interquartile range.