Liver biopsy findings in chronic hepatitis B #

Mani, Haresh; Kleiner, David E.

doi:10.1002/hep.22930

Cited by 118 publications

(110 citation statements)

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“…4A and Movies S1 and S2) and serially sectioned at times of autopsy. In virtually all cases, MRI detected liver tumors (hepatomas) that, at autopsy, displayed the classic histological features of welldifferentiated HCCs associated with chronic HBV infection (14), consistent with what has been previously described by Nakamoto et al (10) in this experimental system. The hepatomas detected in both Vehicle-and Asp/Clo-treated groups were characterized by trabecular cords composed of several layers of neoplastic hepatocytes (Fig.…”

Section: Resultssupporting

confidence: 88%

Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B

Sitia

Aiolfi

Lucia

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

281

283

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Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host factors. The latter include a functionally inefficient CD8 + T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may prevent HCC. Because platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8 + T cells, we evaluated the long-term consequences of antiplatelet therapy in an HBV transgenic mouse model of chronic immune-mediated necroinflammatory liver disease that progresses to HCC. Treatment with aspirin and clopidogrel during the chronic phase of the disease diminished the number of intrahepatic HBV-specific CD8 + T cells and HBV-nonspecific inflammatory cells, the severity of liver fibrosis, and the development of HCC. Antiplatelet therapy improved overall survival without causing significant side effects. In contrast, the same antiplatelet regimen had no antitumor effect when HCC was induced nonimmunologically by chronic exposure to a hepatotoxic chemical. The unprecedented observation that antiplatelet therapy inhibits or delays immune-mediated hepatocarcinogenesis suggests that platelets may be key players in the pathogenesis of HBV-associated liver cancer and supports the notion that immune-mediated necroinflammatory reactions are an important cause of hepatocellular transformation during chronic hepatitis.

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Section: Resultssupporting

confidence: 88%

Antiplatelet therapy prevents hepatocellular carcinoma and improves survival in a mouse model of chronic hepatitis B

Sitia

Aiolfi

Lucia

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

281

283

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“…We also did not observe any association between HBeAg positivity or HBV DNA level and the severity of necroinflammatory activity and fibrosis. Also, no consistent relationship between serological and virological factors and liver histology was highlighted by other authors [19,22,25].…”

Section: Discussionmentioning

confidence: 78%

“…Liver biopsy remains the gold standard for evaluating hepatic pathology and assessing the severity of the disease, which is important for prognosis and management of CHB [10,21,22]. However, as an invasive procedure, it is performed only in selected patients with CHB [2,23,24].…”

Section: Discussionmentioning

confidence: 99%

“…Serum ALT level is considered as the most useful marker of the liver damage that should be used to identify patients qualifying for the antiviral therapy [1]. However, recent studies suggest that there is no correlation of clinical and laboratory parameters with the severity of the liver histology [22,[25][26][27]. It is estimated that about 10% of patients with normal ALT levels have bridging fibrosis or cirrhosis and 30% of patients with persistently normal ALT may have significant fibrosis [25].…”

Section: Discussionmentioning

confidence: 99%

“…The suboptimal correlation of liver histology with ALT, HBeAg and HBV DNA level reinforces their role in the management of CHB and suggests that liver biopsy should be more widely used in assessing the indications for therapy [6,22]. There is also a need for further studies on non-invasive methods used for the assessment of the degree of hepatic fibrosis, which could replace the liver biopsy.…”

Section: Discussionmentioning

confidence: 99%

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Predictors of Liver Disease Severity in Children with Chronic Hepatitis B

et al. 2016

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Background. Evaluation of the liver histology is essential for the management of chronic hepatitis B (CHB) in children.Objectives. The aim of this study was to analyze the histopathological features in children with CHB and compare them with clinical and laboratory data. Material and Methods. The study comprised 30 treatment-naïve children (mean age: 12.8 ± 2.4; mean duration of infection: 11.7 ± 2.5 years; 16/30 HBeAg-positive and 14/30 HBeAg-negative), who underwent a liver biopsy due to CHB. Liver biopsies were evaluated according to the modified Knodell score. Results. A histopathological evaluation revealed mild to severe necroinflammatory activity (mean grading: 5.4 ± 3.2) and fibrosis (mean staging: 1.7 ± 0.9), irrespective of the HBeAg-status, viral load and duration of infection. One case of cirrhosis was observed. A multiple regression analysis revealed that alanine and aspartate aminotransferase (ALT and AST) levels were associated with the necroinflammatory activity (p = 0.001 for ALT, and p = 0.006 for AST). No such correlation for fibrosis was observed; however, children with elevated AST were prone to more advanced fibrosis compared to children with normal AST level (p = 0.01). Conclusions. Children with CHB presented a wide range of liver changes over a decade after the infection. The severity of liver lesions did not differ according to the HBeAg status, viral load and duration of the infection. ALT and AST levels correlated positively with the inflammatory activity. AST seems to be a better predictor of fibrosis compared to ALT. Liver biopsy is a useful tool in evaluating the severity of liver disease in children with chronic hepatitis B, whereas clinical and laboratory parameters are weak predictors of liver injury (Adv Clin Exp Med 2016, 25, 4, 681-688).

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