Autoimmune Hepatitis Differential Diagnoses

Updated: Oct 20, 2021
  • Author: David C Wolf, MD, FACP, FACG, AGAF, FAASLD; Chief Editor: BS Anand, MD  more...
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DDx

Diagnostic Considerations

Because autoimmune hepatitis is a potentially treatable condition, a missed diagnosis can have serious consequences. The diagnosis should be considered in all patients with hepatitis, especially females. Untreated autoimmune hepatitis can result in death due to liver failure.

Similarly, a wrong diagnosis of autoimmune hepatitis can expose the patient to unnecessary complications of immunosuppressant therapy, which can be serious and life threatening.

Regardless of the mode of presentation (ie, acute vs chronic), autoimmune hepatitis usually becomes a chronic disease. It is unnecessary to wait 6 months to prove the chronic nature of the disease.

The differential diagnosis for autoimmune hepatitis should include many causes of chronic liver disease, including α1-antitrypsin deficiency, Wilson disease, viral hepatitis, hepatotoxic drugs, and excessive alcohol consumption.

Autoimmune hepatitis and hepatitis C

The prevalence rate of hepatitis C virus (HCV) infection in patients with autoimmune hepatitis is similar to that in the general population. This implies that HCV is not an important factor in the etiology of autoimmune hepatitis.

Positive tests for antibodies to liver-kidney microsome type 1 (anti-LKM1) have been described in patients with HCV infection; they have biopsy findings of chronic hepatitis C and no evidence for autoimmune hepatitis. [54]

False-positive results on anti-HCV enzyme-linked immunoassay (ELISA) tests are described in the setting of hypergammaglobulinemia, including that observed in patients with autoimmune hepatitis. In these patients, hepatitis C is rule out by the performance of HCV RNA testing using a polymerase chain reaction (PCR) assay.

In general, patients with definite autoimmune hepatitis have median serum titers of anti-smooth muscle antibody (ASMA) and antinuclear antibody (ANA) of 1:160 and 1:320, respectively. In contrast, ASMA and ANA titers may be in the range of 1:80 or less in patients with chronic viral hepatitis and in other liver diseases.

Histologically, both autoimmune hepatitis and chronic hepatitis C are marked by portal inflammation. However, moderate-to-severe plasma cell infiltration of the portal tracts and lobular inflammation are more common in patients with autoimmune hepatitis. Portal lymphoid aggregates, steatosis, and bile duct damage are more common in patients with chronic HCV.

Overlap syndromes

Patients with autoimmune hepatitis may present with features that overlap with those classically associated with patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).

About 7% of patients with autoimmune hepatitis have a disease that overlaps with PBC. They may have detectable anti-mitochondrial antibody (AMA) (usually in low titer), histologic findings of bile duct injury and/or destruction, and the presence of hepatic copper. The natural history of the disease tends to echo type 1 autoimmune hepatitis. Patients with the autoimmune hepatitis–PBC overlap syndrome may improve with steroid therapy. However, there should be a low threshold to institute treatment with ursodiol.

About 6% of patients with autoimmune hepatitis have a disease that overlaps with PSC. Patients with the autoimmune hepatitis–PSC overlap syndrome frequently have concurrent inflammatory bowel disease. Liver chemistries usually have a mixed hepatocellular and cholestatic pattern. Liver biopsy findings reveal bile duct injury. As in PSC, magnetic resonance cholangiopancreatography (MRCP) may reveal bile duct beading and structuring. Typically, cases of autoimmune hepatitis-PSC overlap syndrome are resistant to steroid therapy. Treatment with ursodiol should be considered.

Autoimmune cholangitis is characterized by mixed hepatic and cholestatic liver chemistries, positive ANA and/or ASMA, negative AMA, antibodies to carbonic anhydrase, and histology that resembles PBC. Some authors contend that this condition is AMA-negative PBC. Patients may have an unpredictable response to therapy with steroids or ursodiol.

Differential Diagnoses