A 47-year-old woman is evaluated for a 6-month history of increasing fatigue, malaise, pruritus, and arthralgias. She has had no shortness of breath, chest pain, or fever. The patient was found to have abnormal liver chemistry tests on 2 occasions over the past 3 months. She takes no medications, drinks a glass of wine with dinner every day, and does not use tobacco or illicit drugs. The patient received a blood transfusion in childhood after surgery for a leg fracture. Temperature is 36.5 C (97.7 F), blood pressure is 110/60 mm Hg, pulse is 86/min, and respirations are 12/min. BMI is 25 kg/m². There is no scleral icterus, lymphadenopathy, or skin rash. Cardiac examination reveals a 2/6 holosystolic murmur at the apex radiating to the axilla. The liver is palpable 4 cm below the right costal margin with no splenomegaly. There is no peripheral edema. Several of the small joints of the hands are mildly tender without erythema or swelling. Laboratory results are as follows: Which of the following is the most appropriate pharmacotherapy for this patient?

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11ec193a_97f4_e880_853d_3d9f49f2de04_MD0002_00 This patient's clinical presentation is consistent with autoimmune hepatitis (AH), which is characterized by gradual hepatocyte damage and nonspecific symptoms. Patients have persistently abnormal liver function studies (predominantly transaminases); multiple circulating autoantibodies, including antinuclear antibody (ANA), antismooth muscle antibody (ASMA), anti-liver/kidney microsomal-1 antibody (LKM-1), and anti-liver cytosol-1 antibody (LC-1), may also be present. Current guidelines recommend treatment for patients with suspected AH and any of the following: Transaminases >10 times normalTransaminases >5 times normal with hyperglobulinemiaEvidence of necrosis on liver biopsyIncapacitating symptoms Transaminases >10 times normal Transaminases >5 times normal with hyperglobulinemia Evidence of necrosis on liver biopsy Incapacitating symptoms Prednisone is the preferred therapy, usually combined with azathioprine to allow for lower glucocorticoid doses and fewer adverse effects. Such treatment leads to clinical, laboratory, and histological improvement in up to 90% of patients with 10%-40% achieving sustained remission; however, patients who develop cirrhosis usually require liver transplant. (Choice A) Patients intolerant of or refractory to prednisone and azathioprine can be treated with a calcineurin inhibitor (eg, tacrolimus, cyclosporine) or with other immunosuppressive agents (eg, sirolimus, methotrexate, mycophenolate mofetil). (Choice B) This patient's positive hepatitis C virus (HCV) antibody with negative HCV RNA may indicate spontaneously cleared prior infection or may be a false-positive HCV antibody result, which can occur in the setting of hypergammaglobulinemia from AH. Nonetheless, the negative HCV RNA assay rules out active infection and the need for treatment. (Choice C) Ursodeoxycholic acid is a bile acid supplement used to treat primary biliary cholangitis (PBC), which is characterized by autoimmune destruction of intrahepatic biliary ducts with a predominant elevation in alkaline phosphatase. Antimitochondrial antibodies are nearly 100% sensitive for PBC but are not specific. These antibodies are also positive in up to 20% of patients with AH; this patient's transaminitis >500 U/L and positive ASMA, both of which would be unusual in PBC, strongly favor a diagnosis of AH. (Choice E) Nucleotide analogues targeting the hepatitis B virus (eg, tenofovir, entecavir) are commonly used to treat active hepatitis B; however, this patient's hepatitis B serology indicates prior infection with subsequent immunity, and treatment is not indicated. Educational objective: Autoimmune hepatitis is characterized by persistently abnormal liver function studies (eg, transaminitis) and circulating autoantibodies, including antinuclear antibody (ANA), antismooth muscle antibody (ASMA), anti-liver/kidney microsomal-1 antibody (LKM-1), and anti-liver cytosol-1 antibody (LC-1). Prednisone is the preferred therapy and is usually combined with azathioprine to allow for lower glucocorticoid doses and fewer side effects. __________ References: Auto immune hepatitis. (http://www.ncbi.nlm.nih.gov/pubmed/27217697) Update on autoimmune hepatitis. (http://www.ncbi.nlm.nih.gov/pubmed/26357634)

A 47-Year-Old Woman Is Evaluated for a 6-Month History of Increasing