Therefore, we believe that any potential bias caused by precipitating factors was minimal in the present study. Rifaximin was also fairly AZD2281 well tolerated; only one patient experienced abdominal pain attributed to the drug. Renal toxicity and other serious side effects were absent, and no ethnically distinct side effects were observed. All HE therapeutic trials can be criticized from the perspective of evidence-based medicine.33 Criticisms include the definitions of study endpoints, the treatment of control groups, the proper quantification of therapeutic effects. Sanaka et al. prudently described the difficulties of designing good HE treatment tirals.34 The mental status evaluation system using the portal systemic encephalopathy (PSE) index developed by Conn et al.21 is currently widely used.

However, the Food and Drug Administration (FDA) strongly objected to the use of this system and favoured the adoption of a detailed mental status evaluation system for HE.34 Although the present study has a limitation due to its being an open-label study, and may not overcome some of the challenges previously mentioned, it shows that rifaximin is as safe and as effective as lactulose in Korean patients with HE. Rifaximin offers a useful therapeutic option in Asian patients with HE who are unable to tolerate treatment with disaccharides or who have an impaired renal function. Further clinical trials using a new mental state evaluation system, which satisfies the FDA’s requirements is required to confirm the efficacy of rifaximin for the treatment of HE.

ACKNOWLEDGEMENTS The authors thank Ajou Pharmaceutical, Co. Ltd. (Kyunggi-do, Korea) for supplying the rifaximin tablets and lactulose. We also thank Suk Hwa Yoon, RN for technical assistance and data collection. Footnotes This research was supported by a grant from Ajou Pharmaceutical, Co. Ltd. (Kyunggi-do, Korea) who also provided the rifaximin and lactulose.
The hepatitis viruses B and C are important causes of morbidity and mortality and can lead to chronic viral hepatitis, cirrhosis and hepatocellular carcinoma (HCC). The exact mechanisms of hepatocyte damage remain to be elucidated, but both immune-mediated reactions and direct cytopathic effects are likely to be involved. Much evidence suggests that apoptosis plays a major role in the pathogenesis of chronic viral hepatitis.

In both hepatitis B and C, cytotoxic T lymphocytes are involved in the immune clearance of virally infected hepatocytes (Chisari 1997). The Fas/Fas ligand system plays a major role; Fas ligand expressed on cytotoxic T lymphocytes binds to Fas antigen expressed on hepatocytes, inducing apoptosis (Galle et al. 1995; Hayashi & Mita 1999). Apoptosis is a genetically programmed form of cell death that plays a major role in development and tissue homeostasis Cilengitide in addition to pathological processes (Wyllie et al. 1980).