Hepatitis B exposure associated with cirrhosis and possibly HCC
Approximately a third of all patients with biopsy-confirmed NAFLD (34.8 percent; 95 percent confidence interval [CI], 30.5 percent to 39.2 percent) tested positive for anti-hepatitis B core antibody (anti-HBc). The study’s subjects were mainly middle-aged patients (mean age, 52 years; 54.6 percent male) of predominantly Chinese ethnicity (77.9 percent). Most patients had diabetes and hypertension, and the mean BMI was 28.9 kg/m2. In total, 57.1 percent of patients had nonalcoholic steatohepatitis (NASH), 38.0 percent had F2–4 fibrosis, and 11.5 percent had cirrhosis. [Am J Gastroenterol 2020, doi: 10.14309/ajg.0000000000000588]
“A recent meta-analysis suggests that NAFLD affects around 30 percent of the Asian population, where chronic hepatitis B is another common liver disease [with] many patients having evidence of occult or previous HBV infection, characterized by the presence of anti-HBc,” wrote the researchers. “Although fatty liver is less common in patients with a chronic HBV infection, comorbid patients have a higher risk of HCC and mortality.” [Lancet Gastroenterol Hepatol 2018;3:383-403; Hepatology 2017;65:828-835; Hepatology 2019;71:539-548; J Hepatol 2020;72:578-566]
Compared with anti-HBc–negative patients, those who were positive were older, more likely to be Chinese (89.4 percent), and had higher prevalence of diabetes (p=0.016) and hypertension (p=0.016), but had lower body weight (p=0.029), BMI (p=0.040) and liver enzymes (p range, <0.001–0.050), and higher HDL-cholesterol (p=0.014). Chinese patients were more likely to be anti-HBc–positive than Malays and Indians.
At a mean follow-up of 6.2 years, 18 patients developed liver-related events, such as ascites, incident varices, variceal haemorrhage, hepatic encephalopathy, and HCC (n=4). Eleven of the 170 anti-HBc–positive patients (6.5 percent) had liver-related events vs seven of the 319 anti-HBc–negative patients (2.2 percent; p=0.039). All four patients who developed HCC tested positive for anti-HBc; one patient had F3 fibrosis and three had cirrhosis. All patients had HBV DNA–negative serum.
Several reasons may explain the association between anti-HBc positivity and HCC in the absence of circulating HBV DNA. “In all chronic liver diseases, the clinical outcome is determined by not only the current but also past disease activity. Patients with active hepatitis in the past could still accumulate more liver injury with increased risk of HCC,” wrote the researchers. “Even with HBV DNA–negative serum, patients positive for anti-HBc often have detectable HBV DNA and/or covalently closed circular DNA in the liver. Furthermore, HBV DNA integration into the host genome is a common event in patients with chronic HBV.” [Hepatology 2011;54:829-836; J Hepatol 2016;64:S84-S101]
Almost all (n=16) of the patients who developed liver-related events had F2–4 fibrosis at the time of liver biopsy. More anti-HBc–positive than anti-HBc–negative patients had F2–4 fibrosis (44.7 percent vs 34.5 percent; p=0.027) and cirrhosis (18.8 percent vs 7.5 percent; p<0.001). According to multivariable analysis, older age, diabetes, and increased BMI remained independent factors associated with F2–4 fibrosis, while anti-HBc positivity and older age were independent factors associated with cirrhosis.