Clinical Review Science, medicine, and the future

Cirrhosis: new research provides a basis for rational and targeted treatments

BMJ 2003; 327 doi: http://dx.doi.org/10.1136/bmj.327.7407.143 (Published 17 July 2003) Cite this as: BMJ 2003;327:143
  1. John P Iredale, professor (jpi@soton.ac.uk)1
  1. Division of Infection, Inflammation and Repair, University of Southampton, Southampton General Hospital, Southampton SO16 6YD
  • Accepted 18 June 2003

Liver transplantation and antiviral treatments for hepatitis have improved the outlook for many patients with liver disease. For patients with cirrhosis, new developments herald targeted treatments

Introduction

It is an exciting time to be working in hepatology. The success of liver transplantation and the advances in the radiological and endoscopic management of portal hypertension have improved the longevity and quality of life of patients with liver cirrhosis. Additionally, the development of effective antiviral treatments means that disease can be cured in many patients infected with hepatitis B and hepatitis C. However, these interventions also serve to highlight our current impotence in altering the underlying fibrotic process in many patients with liver disease. This rather depressing perspective may soon change: data from clinical and laboratory based research are showing that cirrhosis may be reversible. By highlighting the attributes required of an effective antifibrotic, a new dynamic model is likely to lead to the development of targeted treatment for liver cirrhosis.

Methods

This article is based on knowledge accrued over 13 years of work investigating the mechanisms of fibrosis and aspects of hepatic stellate cell biology and on regular Medline searches of the peer reviewed scientific literature during that time. The field has benefited from the recognition that certain mechanisms are common to hepatic, renal, and pulmonary fibrosis, and I have reviewed models of these processes while preparing this article. My examples highlight how laboratory based studies of the biology of hepatic fibrosis may inform the design of future treatments.

Clinical impact of cirrhosis

Liver fibrosis and its end stage, cirrhosis, represent enormous worldwide healthcare problems. In the United Kingdom, more than two thirds of the 4000 people who died of cirrhosis in 1999 were under 65, and the incidence of cirrhosis related death is increasing.1 Worldwide, the common causes of liver fibrosis and cirrhosis include hepatitis …

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