Increased Expression of Cyclooxygenase-2 is Associated with the Progression to Cirrhosis

BACKGROUND/AIMS: To investigate the degree of cyclooxygenase-2 (COX-2) protein expression in chronic hepatitis and cirrhosis. METHODS: COX-2 protein expression was evaluated in 43 cases of chronic hepatitis and 24 cases of cirrhosis using immunohistochemical techniques. The COX-2 immunohistochemical staining score was assessed using the scoring systems of Pazirandeh et al and Qiu et al. and each scoring system was based on a sum of the parameters of staining intensity and distribution. RESULTS: The mean COX-2 expression scores in chronic hepatitis and cirrhosis were 2.5 +/- 1.3 vs. 3.3 +/- 1.1 (p = 0.008), and 3.2 +/- 2.0 vs. 4.5 +/- 1.7 (p = 0.006), respectively, based on the Pazirandeh et al. and Qiu et al. scoring systems. The percentage samples of high COX-2 expression score (4 to 5) in chronic hepatitis and cirrhosis were 16.3% vs. 45.8% (p = 0.022), and 23.3% vs. 50% (p = 0.021), respectively, based on the two scoring systems. The mean COX-2 expression scores based on the severity of hepatic fibrosis scored using Ishak's modified staging system (fibrosis score 0 to 3 vs. 4 to 6) were 2.4 +/- 1.3 vs. 3.2 +/- 1.1 (p = 0.009), and 3.1 +/- 2.0 vs. 4.3 +/- 1.8 (p = 0.009), respectively, based on the two scoring systems. CONCLUSIONS: COX-2 expression was significantly higher in liver cirrhosis group than in chronic hepatitis. COX-2 expression scores according to Ishak's staging was significantly higher in the advanced fibrosis group. COX-2 may play a role in the progression of hepatic fibrosis.

Correlative analysis of histological profile of the adjoining liver parenchyma with liver enzyme levels in hepatocellular carcinoma and their comparison with chronic liver disease in autopsy cases.

The exact mechanism and aetiological factor for hepatocarcinogenesis is not yet well defined. Besides genomic integration of hepatitis B viral particles, persistent chronic inflammation is postulated to be important initiating factor in viral related hepatocellular carcinoma (HCC). The objectives of the present study were--to correlate histological profiles of chronic liver disease in the adjoining non-tumor liver tissue in HCC with liver enzymes, to compare with those of non-carcinomatous chronic liver disease cases using the liver tissue and data collected at autopsy, and to correlate with hepatitis B and C positive status. Post mortem liver and data available at autopsy were used for the study. Changes of chronic liver disease was graded and staged according to Peter Scheur's (1991). In HCC, the non-malignant liver tissue was used for the study. Hepatitis B surface and core antibodies were demonstration by immunohistochemistry. HCV was documented by RT-PCR using the tissue extract of paraffin embedded liver tissue. HCC group had higher inflammatory grading and transaminases levels than non-HCC group. HBcAg alone and dual HBcAg and HCV positive cases were more in HCC group. Incidence of biliary epithelial cell injury was higher in HCV positive subgroup. Conclusion: higher incidence of inflammatory grading and enzyme level in alone HBcAg and dual HBcAg and HCV positivity in HCC group would suggest significant role of ongoing persistent chronic inflammation and actively replicating HBV and HCV infections in carcinogenesis.

Telomerase is strongly activated in hepatocellular carcinoma but not in chronic hepatitis and cirrhosis

Telomerase is highly activated in human immortal cell lines and tumor tissues, whereas it is not activated in primary cell strains and many tumor-adjacent tissues. It is suggested that telomerase activation is one of the critical steps in malignant transformation. In the present study, the telomerase activity was investigated in hepatocellular carcinoma tissues and non-tumor liver tissues from Korean patients with chronic hepatitis and cirrhosis. Eighty two liver tissues (24 chronic hepatitis specimens, 34 cirrhosis specimens, and 24 hepatocellular carcinomas) were obtained from 23 chronic viral hepatitis patients, 19 cirrhosis patients (including 7 liver transplants), and 24 patients with hepatocellular carcinoma, of which the surrounding non-tumor liver tissues were available in 16 patients (1 chronic hepatitis and 15 cirrhosis). As negative controls, 3 normal liver tissues were included. Protein from liver specimens was purified by a detergent lysis method as described elsewhere, and telomerase activity was measured in 2 diluents of each sample (1:1 and 1:100) by a telomeric repeat amplification protocol (TRAP). Telomerase was strongly activated in 79% (19/24) of the hepatocellular carcinomas, while weakly in 8% (2/24) of the chronic hepatitis tissues and in 24% (8/34) of the cirrhosis tissues. All of 3 normal control livers showed no telomerase activation. No relationship could be observed between the enhancement of telomerase activity and tumor nature. None of the chronic heaptitis or cirrhosis patients with mild telomerase activation in the liver have developed hepatocellular carcinoma for at least 2 years of follow-up period. These results suggest that the strong enhancement of telomerase activity may be a critical part of hepatocarcinogenesis, although the exact mechanism of such high activation in hepatocellular carcinoma is not clear. In addition, further study will be necessary to clarify the reason why no telomerase activity detectable by a conventional TRAP can be seen in some hepatocellular carcinoma.

Interferon alfa recombinante no tratamento da hepatite C crônica / Recombinant alfa interferon in the treatment of chronic hepatitis C

Introduçao. A hepatite crônica pelo vírus C apresenta tendência evolutiva para cirrose hepática e hepatocarcinoma. Tratamento, com drogas antivirais, está indicado numa tentativa de modificar a evoluçao da doença. Objetivo. Avaliar a resposta de pacientes com hepatite crônica ou cirrose pós-hepatite C ao tratamento com interferon alfa recombinante e identificar os fatores associados com boa resposta terapêutica. Métodos. Foram estudados 38 pacientes com hepatite crônica ativa ou cirrose pelo vírus C, tratados com 2,5 a 3,0MU de interfon três vezes por semana, por períodos de 6 a 12 meses. Considerou-se resposta completa e duradoura quando a ALT e AST se mantinham normais por período de seis meses após o término do tratamento, e resposta completa com recidiva naqueles em que houve elevaçao das enzimas após a suspensao da droga. Resultados. Houve normalizaçao da ALT e AST em 17 dos 38 pacientes (44,7 por cento). Deste grupo, 9/17 tiveram resposta completa e duradoura, e em 8/17 houve aumento das enzimas após a interrupçao do tratamento. Houve uma tendência de melhor resposta ao interferon nos pacientes jovens e naqueles com hepatite crônica ativa (ao invéz da cirrose). Os efeitos colaterais mais frequentes foram febre (80 por cento), mialgia (60 por cento), astenia (50 por cento), cefaléia (40 por cento) e artralgia (36 por cento). Conclusoes. O tratamento com interfon alfa recombinante mostrou resposta satisfatória e duradoura em 23 por cento dos casos, com melhor resultado em pacientes jovens e sem cirrose associada.

Hepatite crônica ativa e possível relaçäo com terapia imunossupressora / Chronic active hepatitis and possible relationship with immunossupressive therapy

Homem de 54 anos de idade, portador de cardiomiopatia chagásica que, a partir do 5§ mês de pós-operatório de transplante cardíaco, evoluiu com níveis séricos elevados de aminotransferase, bilirrubinas e gamaglutamiltransferase. Nos 12§ e 15§ meses pós-operatórios, foi submetido a biópsias de fígado, comprovando-se hepatite crônica em evoluçäo. Durante a investigaçäo etiológica, näo se conseguiu demonstrar a participaçäo agressiva viral, porém, a suspensäo temporária de azatioprina e sua reintroduçäo em doses menores, bem como a reduçäo de ciclosporina-A acompanharam-se de progressiva involuçäo das alteraçöes laboratoriais e clínicas, embora ainda persistisse modificaçäo discreta a moderada de funçäo hepática