Expression of Hepatocyte Hepatitis B Core Antigen and Hepatitis B Surface Antigen as a Marker in the Management of Chronic Hepatitis B Patients

BACKGROUND/AIMS: We aimed to clarify the association of hepatitis B surface antigen (HBsAg)/hepatitis B core antigen (HBcAg) with the disease status and treatment response in patients with chronic hepatitis B (CHB). METHODS: We investigated 171 biopsy-proven entecavir-treated CHB patients (109 hepatitis B e antigen [HBeAg]-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous. The histologic activity index (HAI) and fibrosis stage followed Ishak system. RESULTS: In HBeAg-positive patients, older age, increased HAI score, advanced fibrosis, and reduced viral load were observed when HBcAg expression shifted from nucleus to cytoplasm in HBcAg-positive patients, and HBsAg expression from non-submembranous to submembranous in HBcAg-negative patients (all, p<0.05). In HBeAg-negative patients, only intracytoplasmic HBsAg expression patterns had clinical relevance with decreased ALT levels and viremia. In HBeAg-positive patients without favorable predictors of virologic response, negative HBcAg and membranous HBsAg expression predicted greater virologic response (both, p<0.05). The probability of HBeAg seroclearance was higher in patients with increased HAI or lacking HBcAg expression (both, p<0.05). Higher serum HBsAg levels and hepatocyte HBcAg positivity were associated with reduced serum HBsAg during first and post-first year treatment, respectively (both, p<0.05). CONCLUSIONS: Hepatocyte HBcAg/HBsAg expression is a good marker for disease status and predicting treatment response.

Clinical Significance of Intrahepatic HCV RNA Level in Chronic HCV Infection / 대한간학회지

BACKGROUND/AIMS: This study was carried out to identify the correlation between the serum HCV RNA and the liver HCV RNA level in chronic hepatitis C patients and to evaluate the differences of biochemistry, histology, HCV genotype and their response to antiviral therapy according to intrahepatic HCV RNA levels. METHODS: For thirty-six chronic hepatitis C patients (M:F=22:14, CH:LC=27:9), percutaneous liver biopsy was performed, and serum and liver HCV RNA level were measured. Seventeen patients were treated with IFN-alpha and ribavirin. RESULTS: There was a significant correlation between intrahepatic and serum HCV RNA levels (intrahepatic HCV RNA: 1.9+/-3.1x10(7) copies/g vs. serum HCV RNA: 3.2+/-3.2x10(6) copies/mL)(r=0.538, P<0.01). Total histological activity score (r=0.346, P=0.04) and periportal inflammation (r=0.398, P=0.01) were correlated with intrahepatic HCV RNA level. However, serum HCV RNA level was not correlated with histological activity. Serum ALT was not correlated with intrahepatic HCV RNA level. Intrahepatic HCV RNA level was higher in genotype 1 than genotype 2 or 3 (P=0.07). Intrahepatic HCV RNA level was not correlated with response to anti-viral therapy. CONCLUSION: Intrahepatic HCV RNA level was correlated with serum HCV RNA level and periportal inflammation in patients with chronic hepatitis C. It seems that intrahepatic HCV RNA level is more closely related to histological features than serum HCV RNA level.

Relationship between Intrahepatic Expression of Hepatitis Be Antigen and Histology in Patients with Hepatitis B Virus Infection / 대한내과학회지

BACKGROUND: It has been known that the sero- logic markers of infectivity and viral replication in patients with hepatitis B virus(HBV) infection are hepatitis B e antigen(HBeAg), HRV DNA and HBV DNA polymerase. METHODS: In order to clarify the relationship between chronic liver diseases and HBV infection, and the mechanism of chronicity in HBV related liver diseases, the expression patterns of hepatic HBeAg by imrnunohistochemical stain and histologic activity index(HAI) were studied from 10% formalin fixed paraffin embedded tissues in 114 patients performed liver biopsy. RESULTS: The results were as follows: 1) Incidence of serum HReAg positivity in HBsAg positive patients was 74.6% and that of hepatic HBeAg expression was 77.6% among serum HBeAg positive cases. Hepatic HBeAg expression was 72.4% in serum HBeAg negative cases. 2) In serum HBeAg positive cases, almost all infected hepatocytes exhibited cytoplasmic HBeAg expression and half of patients showed nuclear HBeAg expression, but cytoplasmic HBeAg expression was solely predominant in serum HBeAg negative cases. Hepatic HBeAg expression showed a decreasing trend from AVH and CPH, through CAH, to cirrhosis with or without HCC, which was a consistent finding with serum HBeAg in decreasing manner. Hepatic HBeAg expreassion was highly sustained in about 60-90% of cases, regardless of duration of their illnesses. 3) HAI showed slighf3y higher tendency in patients with hepatic HBeAg negative expression than in positive cases. CONCLUSION: The above results suggest that HBeAg may play a role as a viral target antigen for immune-mediated liver injury and may be also related to the pathogenetic mechanism of chronicity in chronic hepatitis B.

Histopathologic Analysis of the Repeated Renal Biopsies in the Course of Lupus Nephropathy

Lupus nephropathy shows a variable clinical course including remission, relapse and progression to renal failure. To examine the clinical or morphological parameters which might be related to the progression of lupus nephropathy, we have analyzed renal biopsies of 19 patients (M : F=5 : 14), who underwent repeated renal biopsies by morphology and morphometry. The average age of the patients was 22.8+/-9.0 years. The mean interval between two biopsies was 34.5+/-13.3 months. The first renal biopsies of these patients were diagnosed with WHO class IV (74%), class II (11%), class I (5%), class III (5%), and class V (5%). According to the clinical data the patients were divided into 3 groups, static, relapsing and progressive. At the time of the first biopsies, the amount of proteinuria in both the static and relapsing groups was significantly higher than that in the progressive group (P<0.05). The volume density of the renal cortical interstitium of the first biopsies in the progressive group was significantly greater than that in the static and relapsing groups (0.14+/-0.07 micrometer3/micrometer3 vs. 0.05+/-0.02 micrometer3/micrometer3, P<0.05; 0.14+/-0.07 micrometer3/micrometer3 vs. 0.05+/-0.04 micrometer3/micrometer3, P<0.05). The activity index of the second biopsies in the relapsing group was significantly higher than that in the static group (2.7+/-0.6 vs 1.2+/-1.0, P<0.05). In the progressive group, the percentage of glomeruli with global sclerosis and the volume density of the renal cortical interstitium in the second biopsies was elevated over the first biopsies (P<0.05). Half of the patients in the static and relapsing groups underwent a morphologic transformation on the second biopsy. However, of the 7 patients in the progressive group, only one showed a transformation from WHO class IV to class III, suggesting that the transformation is not related to the progression of lupus nephropathy. These results suggest that interstitial expansion and heavy proteinuria at the time of the first renal biopsy may bode for poor prognosis in lupus nephropathy. Furthermore, they suggest that an increased histologic activity index could be related to the relapse of the disease.

The Expression Rate and Pattern of HBcAg and HBsAg in the Hepatocytes According to the Histologic Activity of Cirrhosis

Since the discovery of hepatitis B virus as one of the causes of hepatitis, liver and hepatocellular carcinoma, many hepatitis B viral markers that appear in infected individuals have been discovered and many efforts to understand the relationship between the emergence of viral markers and the progression of hepatitis have been performed. Gudat (1975) compared the expression of HBcAg and HBsAg in various conditions and stages of hepatitis but the pattern of expression of viral markers and its significance have not been understood. Recently it was found by mierocytotoxicity assay that HBcAg might be the target of T lymphocytes. This study attempted to identify any correlation of the tissue expression rate and pattern of HBcAg and HBsAg with the histologic activity of 46 cases of liver cirrhosis using immunohistochemical staining. The expression rate and pattern of HBcAg and HBsAg in relation to the nodular size and positivity of serum HBeAg were also compared. The results were as follows; 1) The expression rate of HBcAg in the liver was 41.3% (19/46). and that of HBsAg was 67.4% (31/46). 2) The histologic activity of liver cirrhosis appeared to be correlated with the expression of HBcAg, especially cytoplasmic HBcAg. 3) The positivity of serum HBeAg was significantly higher in active liver cirrhosis. 4) There was no relationship between the tissue expression of HBsAg and the histologic activity of liver cirrhosis. relationship existed between the nodular size and expression rate and pattern of HBcAg and HBsAg. This study suggests that the tissue HBcAg, especially the cytoplasmic HBcAg is the most likely factor determining the histologic activity of liver cirrhosis, and that the cytoplasmic HBcAg may be the ultimate cause and target of most host immune response.