Drug Induced Liver Disease (Hepatotoxicity)-Chapter 12-TREATMENT FOR DILD Part-1

Early recognition of drug-induced liver reactions is essential to minimizing injury. Monitoring hepatic enzyme levels is appropriate and necessary with a number of agents, especially with those that lead to overt injury. For drugs that produce liver injury unpredictably, biochemical monitoring is less useful. ALT values are more specific than AST values. ALT values that are within the reference range at baseline and rise 2- to 3-fold should lead to enhanced vigilance in terms of more frequent monitoring. ALT values 4-5 times higher than the reference range should lead to prompt discontinuation of the drug.

              The most important treatment for drug-induced liver disease is stopping the drug that is causing the liver disease. In most patients, signs and symptoms of liver disease will resolve and blood tests will become normal and there will be no long-term liver damage. There are exceptions, however. For example, Tylenol overdoses are treated with oral N-acetylcysteine to prevent severe liver necrosis and failure. Liver transplantation may be necessary for some patients with acute liver failure. Some drugs also can cause irreversible liver damage and cirrhosis.

           No specific treatment is indicated for drug-induced hepatic disease. Treatment is largely supportive and based on symptomatology. The first step is to discontinue the suspected drug. Specific therapy against drug-induced liver injury is limited to the use of N -acetylcysteine in the early phases of acetaminophen toxicity. L-carnitine is potentially valuable in cases of valproate toxicity. In general, corticosteroids have no definitive role in treatment. They may suppress the systemic features associated with hypersensitivity or allergic reactions. Management of protracted drug-induced cholestasis is similar to that for primary biliary cirrhosis. Cholestyramine may be used for alleviation of pruritus. Ursodeoxycholic acid may be used. Lastly, consulting a hepatologist is also helpful.

Referral to liver transplantation center/surgical care

          No specific antidote is available for the vast majority of hepatotoxic agents. Emergency liver transplantation has increasing utility in the setting of drug-induced fulminant hepatic injury. Considering early liver transplantation is important. The Model for End-Stage Liver Disease score can be used to evaluate short-term survival in an adult with end-stage liver disease. This can help stratify candidates for liver transplantation. The parameters used are serum creatinine, total bilirubin, international normalized ratio, and the cause of the cirrhosis. Another criterion commonly used for liver transplantation is the Kings College criteria.

• Kings College criteria for liver transplantation in cases of acetaminophen toxicity are as follows:
• pH less than 7.3 (irrespective of grade of encephalopathy)
• Prothrombin time (PT) greater than 100 seconds or international normalized ratio greater than 7.7
• Serum creatinine level greater than 3.4 mg/dL in patients with grade III or IV encephalopathy
• Measurement of lactate levels at 4 and 12 hours also helps in early identification of patients who require liver transplantation.
• Kings College criteria for liver transplantation in other cases of drug-induced liver failure are as follows:
• PT greater than 100 seconds (irrespective of grade of encephalopathy) or
• Any 3 of the following criteria:
• Age younger than 10 years or older than 40 years
• Etiology of non-A/non-B hepatitis, halothane hepatitis, or idiosyncratic drug reactions
• Duration of jaundice of more than 7 days before onset of encephalopathy
• PT greater than 50 seconds
• Serum bilirubin level greater than 17 mg/dL  

Prognosis

             The prognosis is highly variable depending on the patient's presentation and stage of liver damage. In a prospective study conducted in the United States from 1998-2001, the overall survival rate of patients (including those who received a liver transplant) was 72%. The outcome of acute liver failure is determined by etiology, the degree of hepatic encephalopathy present upon admission, and complications such as infections.