Hepatitis B core antigen expression pattern predicts response to lamivudine therapy in patients with chronic hepatitis B

Shi, Kyeh Dong; Hwang, Seong Gyu; Choi, Ju Hyun; Hwang, Il Joon; Yoon, Jai Ho; Kim, Kwang Il; Kwon, Chang-Il; Hong, Sung Pyo; Park, Pil Won; Rim, Kyu Sung

doi:10.3350/kjhep.2008.14.2.197

Cited by 3 publications

(3 citation statements)

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“…Similar to previous studies, we showed that clinical and histological features of patients at baseline differed according to the clinical course of CHB 8,13,14,21–23. Various patterns of HBcAg expression (nuclear, mixed, and cytoplasmic) in hepatocytes were dominant in HBeAg-positive patients, with eventual loss of HBcAg following HBeAg seroclearance.…”

Section: Discussionsupporting

confidence: 86%

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

et al. 2017

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Background/AimsWe 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).MethodsWe 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.ResultsIn 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 HB-sAg 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).ConclusionsHepatocyte HBcAg/HBsAg expression is a good marker for disease status and predicting treatment response.

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Section: Discussionsupporting

confidence: 86%

“…A few studies have shown the possible relationship between the expression of hepatocyte HBcAg and the response to antiviral treatment 12,13. However, no studies have been conducted to investigate the correlation between the intracytoplasmic hepatocyte HBsAg expression pattern and antiviral treatment response.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…Uzun et al7 investigated the role of HBcAg expression in response to antiviral treatment in patients with chronic hepatitis B, who were treated with lamivudine and interferon combined or with lamivudine alone, and supported the idea that the absence or a low level of HBcAg expression may predict good viral response, especially in the HBeAg-negative group. Other studies showed that viral response to lamivudine differed significantly between the cytoplasmic and mixed type 17. The nucleoside analogue, entecavir, is known to inhibit viral replication and to restore T lymphocyte subpopulations 18.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients

Lee

Hwang²,

Yoon³

et al. 2013

Gut Liver

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Background/AimsHepatitis B core antigen is known to be a major target for virus-specific T cells and also reflects the progression of liver dissease and viral replication. Hepatitis B core antigen expression in hepatocytes leads to altered histological activity, viral replication, and immune response. The purpose of this study is to evaluate whether the topographical distribution of hepatitis B core antigen expression can predict the viral response to entecavir in patients with chronic hepatitis B.MethodsWe enrolled 91 patients with treatment-naïve chronic hepatitis B. All the patients underwent liver biopsy, and the existence and pattern of hepatitis B core antigen evaluated by immunohistochemistry. All patients received 0.5 mg of entecavir daily following a liver biopsy. We checked the viral response at 3, 6, and 12 months during antiviral therapy.ResultsOf the 91 patients, 64 (70.3%) had hepatitis B core antigen expression. Of the subcellular patterns, the mixed type was dominant (n=48, 75%). The viral response was significantly higher in the hepatitis B core antigen-negative group than in the hepatitis B core antigen-positive group (88.9% and 54.7%, respectively; p=0.001) after 12 months of entecavir therapy.ConclusionsChronic hepatitis B patients who are hepatitis B core antigen-negative have a better response to entecavir therapy than do hepatitis B core antigen-positive patients.

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Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study

Alpsoy¹,

Adanir²,

Bayramoğlu³

et al. 2022

WJH

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BACKGROUND Chronic viral B hepatitis (CHB) is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis. Currently, although combinations of different laboratory methods are used in the follow-up and treatment of CHB, the failure of these procedures in some cases has led to the necessity of developing new approaches. In CHB, the intrahepatic expression pattern of viral antigens, including hepatitis B surface antigen (HBsAg), is related to different phases of inflammation. However, many studies have focused on the intracytoplasmic properties of HBsAg staining, and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods. AIM To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB. METHODS A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study. Following diagnosis, all patients were treated with entecavir (0.5 mg) and followed up at three-month intervals. The percentage of immunohistochemical HBsAg (p-HBsAg) expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis. The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications. RESULTS A positive correlation between p-HBsAg and serum levels of hepatitis B virus (HBV) DNA and HBsAg was observed ( P < 0.001). The p-HBsAg value was significantly higher in younger patients than in older patients. When the groups were categorized according to the hepatitis B e antigen (HBeAg) status in HBeAg-positive cases, p-HBsAg was correlated with HBV DNA, hepatitis activity index (HAI) and fibrosis scores ( P < 0.001). In this group, p-HBsAg and HBsAg expression patterns were also correlated with the viral response (VR) and the serological response (SR) ( P < 0.001). Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR ( P < 0.001). In HBeAg-negative patients, although HBsAg expression patterns were correlated with both HAI and fibrosis, no relationship was observed among p-HBsAg, clinicopathological factors and VR. CONCLUSION In pretreatment liver biopsies, the immunohistochemical determination of HBsAg expression by quantitative methods, beyond its distribution within the cell, may be a good predictor of the treatment response, especially in HBeAg-positive cases.

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Hepatitis B core antigen expression pattern predicts response to lamivudine therapy in patients with chronic hepatitis B

Abstract: The expression pattern of HBcAg (including its possible absence) before initial therapy appears to predict the response to antiviral treatment.

Cited by 3 publications

References 24 publications

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

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

Hepatitis B Core Antigen Expression in Hepatocytes Reflects Viral Response to Entecavir in Chronic Hepatitis B Patients

Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study

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