Factors for Diagnosis

Hepatic function tests and their interpretations are as follows:

• Bilirubin (total) - To diagnose jaundice and assess severity

• Bilirubin (unconjugated) - To assess for hemolysis

• Alkaline phosphatase - To diagnose cholestasis and infiltrative disease

• AST/serum glutamic oxaloacetic transaminase (SGOT) - To diagnose hepatocellular disease and assess progression of disease

• ALT/serum glutamate pyruvate transaminase (SGPT) - ALT relatively lower than AST in persons with alcoholism

• Albumin - To assess severity of liver injury (HIV infection and malnutrition may confound this.)

• Gamma globulin - Large elevations suggestive of autoimmune hepatitis, other typical increase observed in persons with cirrhosis

• Prothrombin time after vitamin K - To assess severity of liver disease

• Antimitochondrial antibody - To diagnose primary biliary cirrhosis

• ASMA - To diagnose primary sclerosing cholangitis

 

Imaging studies

Imaging studies are used to exclude causes of liver pathology, after which a diagnosis can be made.

• Ultrasonography: Ultrasonography is inexpensive compared with CT scanning and MRI and is performed in only a few minutes. Ultrasonography is effective to evaluate the gall bladder, bile ducts, and hepatic tumors.

• CT scanning: CT scanning can help detect focal hepatic lesions 1 cm or larger and some diffuse conditions. It can also be used to visualize adjacent structures in the abdomen.

• MRI: MRI provides excellent contrast resolution. It can be used to detect cysts, hemangiomas, and primary and secondary tumors. The portal vein, hepatic veins, and biliary tract can be visualized without contrast injections.

 

Liver biopsy

Histopathologic evaluation remains an important tool in diagnosis. A liver biopsy is not essential in every case, but a morphologic pattern consistent with the expected pattern provides supportive evidence.

 

 

Liver Toxicity

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. 

The general recommendations for evaluating and monitoring potential drug-induced hepatotoxicity may not be suitable for all situations and should be modified for special populations, such as people with preexisting liver disease or malignancies, and in light of accumulating data.

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. 

 

Fatty Liver Disease

No specific medical treatment is needed for patients with alcoholic fatty liver. Abstinence and adequate diet are the mainstays of therapy. No drug therapy is indicated for patients with alcoholic fatty liver unless the patient has alcoholic hepatitis. Bed rest has no proven benefit. Anabolic steroids may be detrimental.

Weight loss and control of comorbidities appear to slow the progress of nonalcoholic fatty liver disease (NAFLD) and may reverse some of the steatosis and fibrosis. In a randomized trial, improvement on liver biopsy was seen after a 7% weight loss resulting from lifestyle changes (improved diet, exercise, and behavioral modification). No established treatment is available for nonalcoholic steatohepatitis (NASH).

Abstinence from alcohol

Abstinence from alcohol may reverse steatosis in patients with alcohol-related fatty liver. The steatosis usually resolves within 2 weeks of discontinuance of alcohol. Almost all authorities agree that abstinence from alcohol improves survival and is the cornerstone of long-term management in these patients. Management of patients with alcoholism and fatty liver often requires recognition and treatment of alcohol withdrawal.

Diet and weight loss

No specific dietary restrictions are needed in patients with simple alcoholic steatosis. Patients with alcoholic fatty liver may have deficiencies of vitamins, minerals, and trace elements. Adequate replacement of these deficiencies should be a part of management. Protein-calorie malnutrition is a common finding in patients with alcoholic liver disease (ALD) and is associated with the major complications observed with cirrhosis. Consequently, it is vital to recognize and understand the significance of malnutrition in these patients.

Treatment of underlying disease

Patients with celiac sprue who follow a gluten-free diet can experience reversal of fatty liver disease. Patients with growth hormone deficiency who receive growth hormone can experience reversal of NASH.

Exercise

Multiple human studies have shown that exercise added to diet appears to improve results and increase insulin sensitivity by increasing muscle mass. Exercise that includes both cardiovascular fitness and weight training should improve NASH. Cardiovascular fitness often results in weight loss. Weight training will increase muscle mass and improve insulin sensitivity. Combining these 2 activities helps relieve the underlying derangements of NASH.

Pharmacologic therapy

A number of studies have been initiated to evaluate the therapeutic roles of lipid-lowering agents and insulin sensitizers in the management of fatty liver. Specifically, thiazolidinediones (eg, pioglitazone and rosiglitazone), metformin, gemfibrozil, and atorvastatin have all been found to yield laboratory and histologic improvement in small uncontrolled trials.

Long-term monitoring

All patients with chronic liver disease should be tested for hepatitis A total antibodies and vaccinated if necessary. Physicians should also consider testing for hepatitis B surface antibody and vaccinating in the appropriate clinical situation (ie, life expectancy > 20 years).

All patients with chronic liver disease are at risk for liver disease progression.

Patients should be educated to avoid alcohol and other hepatotoxic substances. If patients have a liver insult from another liver problem, they may have longer recovery times than patients without fatty liver disease would.

Patients with fatty liver disease should be seen regularly by a primary care physician, who may be able to detect disease progression through physical examination findings (eg, spider telangiectasia, palmar erythema, or splenomegaly), laboratory findings (eg, decreasing platelets, elevated bilirubin, or decreasing albumin), patient complaints (eg, encephalopathy, ascites, or fatigue), or incidental imaging study findings (eg, cirrhotic liver, splenomegaly, varices, or ascites).

Provide follow-up care for patients in an outpatient facility. In patients with alcoholic steatosis, determination of blood alcohol at every outpatient visit often is helpful in determining patient’s compliance with abstinence.

 

Hepatitis:

Acute Hepatitis A

Treatment for acute hepatitis caused by hepatitis A virus (HAV) is necessarily supportive in nature, because no antiviral therapy is available. Hospitalization is warranted for patients whose nausea and vomiting places them at risk for dehydration. Patients with acute liver failure require close monitoring to ensure they do not develop fulminant hepatic failure (FHF), which is defined as acute liver failure that is complicated by hepatic encephalopath.

Acute Hepatitis B

As is the case for acute HAV infection, no well-established antiviral therapy is available for acute HBV infection. Supportive treatment recommendations are the same for acute hepatitis B as for acute hepatitis A. Lamivudine, adefovir dipivoxil, and other antiviral therapies appear to have a positive impact on the natural history of severe cases of acute HBV infection. A study by Schmilovitz-Weiss described a rapid clinical and biochemical response in 13 of 15 patients with severe acute hepatitis B who received lamivudine.

Chronic Hepatitis B

At present, the key goal of antiviral treatment of HBV is the inhibition of viral replication. This is marked by the loss of hepatitis B e antigen (HBeAg) in patients with HBeAg-positive chronic hepatitis B and by the suppression of HBV DNA levels. Secondary aims are to reduce symptoms, if any, and prevent or delay the progression of chronic hepatitis to cirrhosis or HCC.

Interferon therapy: IFNs have both antiviral and immunomodulatory effects. Treatment with IFN alfa is appropriate for some patients with chronic hepatitis B.

Acute Hepatitis C

Acute hepatitis C is detected infrequently. When it is identified, early Interferon therapy should be considered. 

Chronic Hepatitis C

Patients who are infected with HCV genotype 1 or 4 typically undergo treatment for 48 weeks. Those who are infected with HCV genotype 2 or 3 typically undergo treatment for 24 weeks. HCV RNA levels are usually rechecked 1 month and 3 months after treatment is started and every 3 months thereafter.