entecavir and Necrosis

Ground glass hepatocytes (GGHs) have been shown to predict the development of hepatocellular carcinoma (HCC). Type I GGH and type II GGH harbor hepatitis B virus (HBV) pre-S1 and pre-S2 deletion mutants, respectively. Whether anti-HBV therapy can inhibit the expression of GGHs and potentially reduce HCC development is explored in this study. Two sets of liver specimens were included: the first contained 31 paired biopsy specimens obtained from chronic HBV patients receiving oral nucleos(t)ide analogue (NA) treatment; the second contained 186 resected liver tissues obtained from HBV-related HCC patients receiving surgery: 82 received NA before surgery and 104 did not. Compared with the baseline biopsy specimens, type I (P=0.527) and type II GGH (P=0.077) were not significantly decreased after 48 weeks of NA treatment in the first set of patients. In the second set, despite suppression of viral load (P<0.001) and periportal necrosis (P=0.006) in treated patients, GGH (P=0.594), cccDNA (P=0.172) and serum pre-S mutants (p=0.401) were not significantly suppressed. A significant decrease of type I (P=0.049) and type II GGH (P=0.029) could only be observed in patients after long duration of treatment (median duration: 4.3 years). In the treated patients, the persisted type II GGH remained an independent variable associated with decreased local recurrence-free survival of HCC (P=0.019) as in non-treated patients (P=0.001). In conclusion, the persistence of GGHs could explain the residual risk of HCC development under anti-HBV treatment. Therefore, intrahepatic GGHs and pre-S mutant are potential additional targets for HCC prevention in patients already receiving anti-HBV treatment.

Topics: Adenine; Administration, Oral; Adolescent; Adult; Amino Acid Sequence; Antiviral Agents; Biopsy; Carcinoma, Hepatocellular; DNA, Circular; Drug Resistance, Viral; Fatty Liver; Female; Guanine; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Humans; Lamivudine; Liver; Liver Neoplasms; Male; Middle Aged; Necrosis; Organophosphonates; Protein Precursors; Sequence Deletion; Viral Load; Young Adult

Lamivudine, adefovir, telbivudine, and entecavir are nucleoside analogues that can inhibit hepatitis B virus replication and are licensed in China by the Food and Drug Administration. This study presents the cases of 2 patients who were chronically infected with HBV and suffered hepatic failure resulting from withdrawal of telbivudine and adefovir, respectively.

Topics: Adenine; Adult; Antiviral Agents; Guanine; Hepatitis B, Chronic; Histocytochemistry; Humans; Lamivudine; Liver Failure, Acute; Liver Transplantation; Male; Medication Adherence; Necrosis; Organophosphonates; Telbivudine; Thymidine

A sensitive chemiluminescence enzyme immunoassay has been developed for hepatitis B virus (HBV) core-related antigen (HBcrAg) detection. We aimed to investigate the usefulness of HBcrAg measurement for monitoring chronic hepatitis B disease. HBcrAg levels were measured by a chemiluminescence enzyme immunoassay in 54 untreated patients and 39 patients treated with either entecavir or lamivudine. The HBcrAg concentration correlated positively with the levels of serum HBV DNA (r = 0.820), intrahepatic total HBV DNA (r = 0.700), and covalently closed circular DNA (cccDNA) (r = 0.664; for all, P values were <0.001). A higher HBcrAg concentration was associated with a greater proportion of hepatitis B core antigen immunostaining. Although the differences were not statistically significant, patients with higher Knodell necroinflammation and fibrosis scores tended to have higher serum HBcrAg concentration levels. In the treated patients, the logarithmic reduction in HBcrAg at week 48 correlated positively with the logarithmic reduction of serum HBV DNA, intrahepatic total HBV DNA, and cccDNA. Of the 31 patients with undetectable serum HBV DNA (<300 copies/ml) at the end of treatment, 20 (65%) still had detectable HBcrAg. A greater reduction in posttreatment HBcrAg concentration was associated with histological improvement and a decrease in hepatitis B core antigen immunostaining. HBcrAg concentrations of <40,000 kU/ml at baseline and <200 kU/ml at week 24 were associated with a higher chance of having undetectable HBV DNA at week 48. In conclusion, serum HBcrAg levels correlated with HBV virological markers and reflected the chronic hepatitis B disease activity in the liver.

Topics: Adult; DNA, Viral; Enzyme-Linked Immunosorbent Assay; Female; Guanine; Hepatitis B Core Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Liver; Liver Cirrhosis; Luminescent Measurements; Male; Middle Aged; Necrosis; Statistics as Topic