Histopathology and clinical correlates of end-stage hepatitis B cirrhosis: A possible mechanism to explain the response to antiviral therapy

Abstract

In chronic liver disease associated with histological necroinflammation, clinical severity is frequently greater in those with higher grades of activity. Conventional wisdom assumes that necroinflammation is mild or absent in patients with end-stage hepatitis B virus (HBV) cirrhosis due to the frequent presence of mildly elevated aminotransferase levels, the absence of hepatitis B e antigen (HBeAg), and low or undetectable HBV deoxyribonucleic acid (DNA) levels. However, a histopathologic analysis of such patients has not been undertaken. The aims of this study were 1) to assess severity and histological features of inflammation, 2) to correlate the severity of inflammation with biochemical and virologic parameters, and 3) to define the relationship between inflammation and clinical severity in explanted livers from patients undergoing liver transplantation for HBV cirrhosis. Characteristics of 34 consecutive patients undergoing liver transplantation for HBV cirrhosis were correlated with inflammation and immunohistological findings in the explanted livers. High-grade inflammation (grades 3 and 4) was found in many cases (47.1% interface hepatitis; 14.8% lobular inflammation; and 20.6% portal inflammation). The presence of positive cytoplasmic staining for hepatitis B core antigen (HBcAg) was associated with grade 3 or 4 interface hepatitis (P ‫؍‬ .046) and lobular hepatitis (P ‫؍‬ .005). There was no correlation between inflammatory activity and age, Asian ethnicity, aminotransferase levels, total bilirubin levels, HBeAg seropositivity, and detect-

Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells during Chronic HBV Infection

“…Although the count of CD68 + CD86 + cells was higher in the lobular areas in comparison to the portal areas in both HBV-infected and control donors, this does not indicate an activation of CD68 + cells in the lobular areas in the control group as the total CD68 + cell count is also higher in the lobular areas in these individuals compared to the portal areas, and the percentage of CD68 + CD86 + cells was similar between the two areas in the control group. These results indicate a higher activation of CD68 + cells in the lobular areas compared to the portal areas of the liver during chronic HBV infection, which corroborates with the results showing that detectable serum HBV DNA is associated with lobular inflammation [ 33 ].…”

Hepatitis B virus DNA in patients with hepatitis B‐related liver cirrhosis with or without hepatocellular carcinomas: a matched case‐control study

“…Chen et al 20 reported that the risk peaked at 7 log 10 copies/mL, while in a study on compensated HBV‐related cirrhosis, patients with HBV DNA >6 log 10 copies/mL had significantly increased risks of decompensation and death. HBV DNA > 6 log 10 copies/mL was also significantly correlated with histological liver damage and degree of fibrosis, which are crucial to the development of decompensation 29,30 . These findings suggest that cirrhotic patients with HBV DNA levels ≥6 log 10 copies/mL might die of liver failure or other complications before developing HCC.…”

Liver biopsy findings in chronic hepatitis B

“…However, in a retrospective analysis, Tong et al found that current treatment guidelines for chronic hepatitis B would identify only 20%‐60% of the patients who ultimately developed HCC, and only 27%‐70% of patients who died of non‐HCC liver‐related deaths for antiviral therapy 74. Sigal et al also found no correlation of inflammatory activity with clinical, biochemical, or virological parameters 75. Although patients with persistently elevated ALT levels (>70 U/L) may have progression of fibrosis by one stage within 4‐5 years of follow‐up,76 others have shown that up to 30% of patients with persistently normal ALT levels may also have significant fibrosis (stage 2‐4), can be at increased risk of mortality and may be candidates for therapy 42, 77–81.…”