A 29-year-old man was seen in the walk-in clinic because of diarrhea of 1 year’s duration and weight loss. Initial laboratory values included elevated hepatic aminotransferase levels and a ferritin level of 1716 ng per milliliter. A diagnostic procedure was performed.

Common causes of cirrhosis include chronic alcohol use, viral hepatitis (either HBV or HCV), nonalcoholic steatohepatitis, and    hereditary hemochromatosis.

Clinical Pearls

•What are clinical features associated with autoimmune hepatitis?   

Patients with autoimmune hepatitis may present with fatigue, lethargy, anorexia, nausea, abdominal pain, itching, and arthralgia of small joints. Diarrhea is not a common symptom of this illness. The International Autoimmune Hepatitis Group proposed a scoring system intended to help estimate the probability of this illness. Elements that make autoimmune hepatitis more likely include: female sex, a low ratio of alkaline phosphatase to aspartate aminotransferase, an elevated IgG level, presence of antinuclear antibody, negative viral tests, no history of drug use, and no history of substantial alcohol use. The presence of eosinophilia has been associated with autoimmune hepatitis, and an elevated ferritin level may occur with autoimmune hepatitis. Autoimmune hepatitis often occurs in Italian and Chinese populations. Autoimmune disorders are common among first-degree relatives of children with autoimmune hepatitis.

Table 2. Scoring Systems to Differentiate Autoimmune Hepatitis from Wilson’s Disease.

•How does Wilson’s disease typically present, and what tests are useful in making a diagnosis?

Patients with Wilson’s disease present with a range of hepatic manifestations, including persistently elevated serum aminotransferase levels, chronic hepatitis, cirrhosis, or fulminant hepatic failure. Wilson’s disease is considered in the differential diagnosis when there is coexisting liver disease and a neuropsychiatric disorder. A 2008 guideline for the diagnosis and management of Wilson’s disease suggests that a diagnosis of Wilson’s disease can be established by the presence of Kayser-Fleischer rings, a ceruloplasmin level of less than 20 mg per deciliter, and a 24-hour urinary copper level of greater than 40 micrograms. A liver biopsy is the next study that should be performed in patients in whom the diagnosis is being considered.

Morning Report Questions

Q: What is the most reliable diagnostic test for Wilson’s disease?

A: The most reliable diagnostic test for Wilson’s disease is copper quantitation in tissue. Values greater than 250 micrograms per gram of dry weight have 83.3% sensitivity and 98.6% specificity for Wilson’s disease; this diagnostic threshold is incorporated into practice guidelines of the American Association for the Study of Liver Diseases. A value greater than 1000 micrograms per gram of dry weight is considered virtually diagnostic of Wilson’s disease. It is important to note that hepatocytic copper deposition in Wilson’s disease may be uneven, and needle biopsies are often associated with sampling error; therefore, histochemical staining may be unreliable and yield false negative results. In addition, the most commonly used stains (rhodanine and rubeanic acid) mainly detect copper concentrated in lysosomes, a finding that is seen in the late stages of the disease. In the early stages, excess copper is diffusely distributed in the cytoplasm and is not detected by these stains. Thus, a negative histochemical stain for copper does not rule out the diagnosis of Wilson’s disease.

Q: How is Wilson’s disease treated?

A: Management of Wilson’s disease is determined by the clinical presentation of the patient. Asymptomatic patients, without signs of  hepatic or neurologic disease, can be treated with zinc. Zinc acts in the enterocyte to induce metallothionein, an endogenous metal chelator. For patients with evidence of neurologic or hepatic involvement, chelation therapy with penicillamine or trientine is indicated. The choice of chelator is influenced by the presence of neurologic disease. Patients with neurologic manifestations who are initially treated with trientine have higher rates of neurologic deterioration than patients with neurologic manifestations who are initially treated with penicillamine; thus, penicillamine may be preferred in this group. However, penicillamine is associated with high rates of adverse events leading to discontinuation of therapy, as compared with trientine. Therefore, in patients without neurologic involvement, trientine is a reasonable initial therapy. For patients with decompensated liver disease that is unresponsive to chelation therapy or for patients with fulminant hepatic failure, referral for evaluation for liver transplantation is warranted.