Liver diseases that accompany Systemic Lupus Erythematosus (SLE) disease activity generally have good prognosis and do not progress to cirrhosis [1, 4].
It is important to distinguish SLE-associated hepatitis (SLE hepatitis) from auto immune hepatitis (AIH) since complications and therapies are different in the 2 conditions . SLE may result in end stage renal disease while AIH may lead to end stage liver disease.
We report the case of AIH-SLE overlap syndrome in immune competent young male patient. The diagnostic and therapeutic dilemmas are discussed.
A 22-year-old patient was admitted for jaundice, arthralgia and general weakness. His family history included SLE (mother) and fatal fulminant autoimmune hepatitis (aunt). Physical examination showed jaundice, tender hepatomegaly, and left ankle arthritis. No stigmata of chronic liver disease were noted.
Abdominal imaging showed hepatomegaly, normal spleen and absence of lymphadenopathy.
Laboratory studies included hemoglobin 12 mg/dl, white blood cells 2500 count/µl, platelets 51000 count/µl, aminotransferases SGOT 1125 U/l, SGPT-1033 U/l, gamma GGT-1114 U/l, alk phos 220 U/l, LDH 834 U/l, total bilirubin 18.2 mg/dl, direct bilirubin 13.7 mg/dl, albumin 2.7 gr/dl, globulin-2.5 gr/dl, prothrombine time-INR1.7, PTT 65 seconds, cholesterol 142 mg/dl. ANA positive, dsDNA 1/164, and anti ribosomal P antibody positive: 1/38. CH50 25 (/ml), ceruloplasmin19.7, Coombs’ positive, and haptoglobin 0.
Serology for hepatitis viruses (HAV, HBV, HCV, HEV, CMV, and EBV) and serology for parvovirus, brucella and syphilis was negative. ANCA, anti-SM, anti-SSA, anti-RNP, anti-smooth muscle, anti-LKM1, anti-SCL 70, anti-mitochondrial, anti-thyroglobolin, anti-cardiolipin, and anti-microsomal antibodies were all negative.
A 24-hour urine collection showed 70 mg of protein and 266 mcg of cooper. A transjugular liver biopsy disclosed severe interface hepatitis, with bridging necrosis and early fibrosis (Fig 1). Rhodanin and Orcenin staining were negative. Hepatic cooper was 80.76 mcg Cu/gr dry liver weight (normal: 3.58 +/- 1.71 microg/g). Genetic test for Wilson’s mutation was negative.
Figure 1 A transjugular liver biopsy disclosed severe interface hepatitis, piecemeal necrosis with bridging necrosis and early fibrosis.
The patient was treated with prednisone 60 mg daily with good clinical and biochemical response, but the aminotransferases levels remained elevated after 4 weeks. The bilirubin and albumin levels improved. At this time azathioprine 100 mg per day was added.
At follow up, the patient had been in remission for 6 months since the diagnosis with normal aminotransferases (SGOT 21, SGPT-38 U/l).
After careful exclusion of Wilson’s and other etiology of liver disease, the question remains as to whether to classify the patient as having a primary liver disease with autoimmune features (AIH) or having liver disease as a manifestation of SLE ( SLE hepatitis). Whether AIH- and SLE-associated hepatitis are 2 distinct entities remains unclear.
Several clinical and histological features have been used to discriminate AIH from SLE, since complications and therapy are very different in the 2 conditions .
Our patient met the American College of Rheumatology criteria for SLE (ACR 4 of 11) as well as the criteria for AIH (definite score 17) [2,3].
Interface hepatitis and bridging necrosis and portal plasma cell infiltrate are the hallmark of AIH whereas lobular hepatitis, fatty infiltration and necrosis of the central hepatic cells are more compatible with SLE [4, 8].
Anti-ribosomal P antibody is useful marker to differentiate SLE-associated hepatitis from AIH. This antibody was found in 44% of patients with SLE but was absent in patients with AIH . The presence of anti-sm antibody in patients with AIH suggests complication by SLE. Features of leucopenia, proteinuria, nephritis, malar rash, Coomb's positive, and hypocomplementemia are clearly indicative of SLE.
The positive family history of SLE in his mother supports the diagnosis of SLE , whereas the positive family history of fatal fulminant autoimmune hepatitis supports the diagnosis of AIH.
We believe that our patient had the AIH-SLE overlap syndrome with dominant manifestation due to hepatitis. This syndrome has been reported to respond rapidly to steroids therapy and the prognosis is generally good . Oka reported that 3% of patients with AIH satisfy the ACR criteria for SLE . Runyon reported that only 1.7% of patients with SLE had AIH or liver cirrhosis . Patients with liver dysfunction and SLE should be investigated for AIH as these 2 entities can occur together .
This article was first published on GastroHep.com on 30 January 2009.
AuthorsNassar Fą, Vaisbein Eą, and Assy N˛’ł
1. Department of Internal Medicine E, Western Galilee Hospital, Nahariya, Israel
2. Liver Unit, Ziv Medical Centre, Safed, Israel
3. Rappaport Faculty of Medicine, Technion Institute, Haifa, Israel
Corresponding authorDr N Assy
Ziv Medical Centre
Phone +972 4 6828441/5
Fax +972 4 6828442
Email Assy.firstname.lastname@example.org or Assy.email@example.com
- Usta Y, Gurakan F, Akcoren Z, et al. An overlap syndrome involving autoimmune hepatitis and systemic lupus erythematosus in childhood. World J Gastroenterol 2007; 13(19): 2764-7.
- Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997: 40(9): 1725.
- Czaja AJ, Freese DK, American Association for the Study of Liver Disease. Diagnosis and treatment of autoimmune hepatitis. Hepatology 2002; 36(36): 479-97.
- Youssef WI, Tavill AS. Connective tissue disease and the liver. J Clin Gastroenterol 2002; 35(4):345-9.
- Atsumi T, Sagawa A, Jodo S, et al. Severe hepatic involvement without inflammatory changes in systemic lupus erythematosus: report of two cases and review of the literature. Lupus 1995; 4(3): 225-8.
- Tojo I, Ohira H, Abe K, et al. Autoimmune hepatitis accompanied by systemic lupus erythematosus. Intern Med 2004; 43(3): 258-62.
- Oka H. The survey of autoimmune hepatitis in Japan. Annual Report of the Study Group on Severe Hepatitis. Japanese Ministry of Health and Welfare 1988; 235-41.
- Runyon BA, LaBrecque DR, Anuras S. The spectrum of liver disease in systemic lupus erythematosus. Report of 33 histologically-proved cases and review of the literature. Am J Med 1980; 69(2):187-94.
- Lu MC, Li KJ, Hsieh SC, et al. Lupus-related advanced liver involvement as the initial presentation of systemic lupus erythematosus. J Microbiol Immunol Infect 2006; 39(6): 471-5.