Interferons and liver disease

Interferons [INF] are naturally occurring peptides which have antiviral, antitumour and immunomodulatory properties. Interferons alpha, beta and Gamma constitute the main forms. INF alpha is administered by subcutaneous injection in doses ranging from 3 million units three times a week for 24 weeks in treatment of chronic hepatitis C to 5 million units daily for 16 weeks in treatment of chronic hepatitis B. However caution must be exercised before declaring IFN alpha a panacea for chronic viral hepatitis. For example, in chronic hepatitis C only 25% of cases demonstrate a biochemical improvement which is sustained through 6 months follow-up after completion of treatment. Some but not all biochemical responders will have an associated loss of hepatitis C virus. The presence of cirrhosis and/or high viral titres are poor prognostic indicators for biochemical response. It is unclear in HCV infection whether an absent or transient biochemical response would respond to higher doses or longer courses of INF or whether a sustained response is associated with reduced morbidity. Similary, in chronic HBV infection with evidence of active replication, INF may induce seroconversion [HBeAg converting to anti-HBe; loss of HBV DNA] in about 50% of cases and a sustained loss of HBsAg in 10-20% of cases during long-term follow-up. A large viral load, lack of inflammatory activity in the liver with near normal liver enzymes prior to treatment and positive anti-HIV are poor prognostic factors. It is unknown whether INF alpha alters mortality in chronic hepatitis B infection. The efficacy of INF alpha in chronic hepatitis due to mutant forms of HBV has not been studied adequately. INF alpha may be efficacious in some patients with HBV plus HDV infection. INF therapy may be limited by unwanted side effects including leucopenia, thrombocytopenia and malaise

Acute hepatic failure

Fulminant hepatic failure [FHF] is defined as hepatic encephalopathy developing within 8 weeks of the onset of symptoms in a patient with a previously healthy liver, whereas when hepatic encephalopathy develops between 8 and 24 weeks after the onset of the syndrome it is called submassive hepatic necrosis [SHN]. Hepatic encephalopathy is divided into clinical grades, Grade one - four, in order of severity. Progression to more severe grades of encephalopathy [Grade three or four] is a serious prognostic development and indicates that the patient has a high risk of dying. FHF and SHN are always associated with a severe coagulopathy. FHF or SHN may be caused by viral hepatitis [HAV, HBV, HDV, and HEV]; metabolic disease [Wilson's]; toxins and rare causes such as acute fatty liver of pregnancy, Reye's syndrome or lymphoma. Acetaminophen [either taken alone in large doses or in combination with ethanol], phenytoin and volatile anaesthetics are important causes of drug-induced FHF. SHN is less commonly drug-related. Extremes of age [< 10, > 40 years], drugs other than acetaminophen, delayed development of encephalopathy after the onset of jaundice and the absence of an identifiable cause of hepatic injury are poor prognostic factors for spontaneous recovery to FHF. SHN invariably carries a poor prognosis. Cerebral oedema leading to raised intracranial pressure is a common mode of death in both conditions. Clinical management is directed to: [1] correcting metabolic disturbances, e.g. hypoglycaemia, [2] avoiding renal failure, [3] monitoring and treating elevations in intracranial pressure, [4] treating infection, [5] giving an antidote [e.g. N-acetylcysteine] to the offending toxin [e.g. acetaminophen]. Up to recently, orthotopic liver transplantation [OLT] offered the only hope to patients with FHF or SHN who were deteriorating despite maximal medical treatment. Results indicate approximately 65% 1-year survival after OLT for FHF. Recently, alternatives to OLT have been developed including temporary heterotopic partial liver grafting or extracorporeal perfusion through columns containing hepatocytes. How these new modalities will impact on management of FHF and SHN remains to be determined