By : Dr Bhavik Champaneri 3rd year residentGuided by : Dr Manoj Ghoda Dr Rekha Bhavsar Dr Rajal Prajapati Dr Archana ShahDepartment of Pediatrics & GastrologyV.S.G.H , Ahmedabad
•A9-year-old boy was referred from dental OPD foropinion with chief complains of recurrent gum bleeding 1 year recurrent epistaxis
No complaints of• fever• weight loss• abdominal pain• abdominal distension•vomiting• rash over body• bleeding from any other site• altered sensorium• convulsion.
Past history: no history of similar illness, tuberculosis, blood transfusion. Family history: his maternal aunt (maasi) had recurrent “skin rashes”. Details were not available. No h/o tuberculosis, tb contact , similar illness.
General Examination: Consious Anxious T – normal Pr – 98 / min Rr -18 / min Bp -104/60 mmhg Icterus + No active bleeding from gums Gums normal
Systemic Examination:P/A : soft, L +5 cm below RCM firm, smooth, sharp margin Liver Span: 10 cm Spleen: not palpable No signs of free fluid.R/SCVS were unremarkableCNS
Hb : 10.3 g/dL;TC : 9200 with normal differentialPlatelets : 312,000PS : normocytic normochromic rbcs
Total bilirubin : 1.4 Direct 0.2, I : 1.2 SGPT: 1295 IU SGOT : 836 IU GGT : 116 IU ALP : 184 IU PT: 16 seconds APTT: 34.9 sec INR: 1.27 S. Alb: 3.6 g/dL S. globulin : 6.3 g/dL Renal function tests were normal
Chronic hepatitis B or C Wilson’s disease Autoimmune hepatitis Hematological malignancy Alpha 1 antitrypsin def
USG Abd: enlarged liver with coarsened echotexture. GB was normal and no stones were seen. CBD and IHBR were normal. Portal vein was 11 mm. and spleen was mildly enlarged.
Serologies for hepatitis A, B, C, and E viruses negative. The 24-hour urinary copper excretion, serum ceruloplasmin normal. KF ring was absent alpha-1 antitrypsin level normal. Antiplatelet antibodies negative.
Antinuclear antibodies (ANA) negative; serum anti-smooth muscle antibody (SMA) positive 1:2560 anti F-actin 154 units. Anti-liver-kidney microsomal antibody was negative perinuclear antineutrophil cytoplasmic antibody (p-ANCA) was detected at titers of 1:80.
This is very much suggested autoimmune hepatitis type I.
This is perhaps debatable. The diagnosis is almost certainly AIH, and if there is a resistance from the patient or the guardians, we would start the treatment for AIH. However, with age so young and possibility of prolonged treatment, it is desirable that all possible evidences are collected. Thus it was decided to proceed with liver biopsy after necessary correction of coagulation profile. Liver biopsy showed nodule formation, with fibrous expansion and bridging of portal tracts. "Interface hepatitis," characterised by a mononuclear inflammatory infiltrate at the edge of a portal tract infiltrating into adjacent lobules was also present.
The patient was started on oral corticosteroids prednisolone 2 mg/kg/day and azathioprine 2 mg/kg/day. Liver enzyme levels decreased steadily over the following several months. Repeat liver biopsy revealed persistent mild inflammation. We tried to reduce his steroid and were successful to bring it down to prednisone 5 mg per day and azathioprine 50 mg per day.
AIH is a process of inflammation and progressive destruction of the liver parenchyma. Characterized on biopsy by interface hepatitis and plasma cell infiltrate in the portal areas. Laboratory markers include circulating autoantibodies and hypergammaglobulinemia. Etiology : multifactorial, involving environmental factors interacting with a genetically predisposed population. Exposure to triggers, results in an immunoregulatory response and the generation of autoantibodies.
female predominance peak incidence in prepubertal age but recent evidences suggest that it could occur at any age. The most common presentation is that of acute hepatitis with nonspecific symptoms. Anorexia, nausea and vomiting, intermittent fatigue, weight loss, pruritus, and arthralgia of the small joints are common symptoms. Advanced cases present with gastrointestinal bleeding from portal hypertension or ascites, which developed after progression to liver cirrhosis. In some cases it is detected during the work up for incidental finding of elevated aminotransferases.
Type 1: anti-SMA, ANA titer, and the presence of anti F-actin antibody. It can also be associated with positive p-ANCA, anti-DNA antibody, and serum anti-asialoglycoprotein receptor (ASGPR) antibodies. It is strongly associated with human leukocyte antigens HLA-A1 DR3 and DR4 Associated extrahepatic autoimmune diseases include ulcerative colitis (with or without primary sclerosing cholangitis), arthritis, vasculitis, and autoimmune thrombocytopenia.
Type 2 : anti liver-kidney microsomal (LKM-1) antibody and frequently associated with anti-LC-1 (liver cytosol-1), and anti-ASGPR antibody. It can be accompanied by polyendocrinopathy, vitiligo, diabetes, and thyroiditis. It is associated with HLA-B14 and DRB1*07.
Cell-mediated and antibody-dependent cell- mediated cytotoxicity is believed to be the main pathological phenomena. Through the activation of CD8 and CD4 T cells, there is release of proinflammatory cytokines that induce hepatocellular damage. B-cell dysregulation also occurs with generation of IgG, which binds to normal liver membrane components and results in the formation of antibody-antigen complexes. The complexes engage natural killer cells, further contributing to liver injury.
Treatment of autoimmune hepatitis centers largely on immunosuppression. Corticosteroids and azathioprine have been used as first-line therapies. Corticosteroid therapy is commonly initiated at 2 mg/kg/day, with or without concurrent azathioprine, to allow faster reduction of the corticosteroid dose. 75% to 90% of patients achieve normalized serum aminotransferases within 6-9 months. If successful, the corticosteroids may be tapered and discontinued with close monitoring.
Alternative treatment options, especially for patients who do not respond to first-line therapy, include cyclosporine, tacrolimus, and mycophenolate mofetil. Successful treatment is directly related to the liver histology. If there is complete disappearance of inflammation on liver biopsy there are excellent chances that the patient will not relapse.