Diagnostic Challenge: Hepatic Granulomas Associated With Portal Hypertension

Abstract

A 53-year-old man was referred to our clinic due to markedly elevated serum alkaline phosphatase (Alk-Phos) and mildly elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for the past 3 years. He had no drug history. There was no pruritus, fever, fatigue, icterus, rash, weight loss, respiratory symptoms, arthropathy, diarrhea, or peripheral lymphadenopathy. Physical examination was normal. Laboratory tests showed WBC 8000/ mm3, PMN 70%, lymphocyte 25%, Hgb 13.8 g/dl, ESR in first hour 25, ALT 65 IU/Lit, AST 59 IU/Lit, Alk- Phos 780 IU/Lit, gamma glutamyltranspeptidase (GGT) 800 IU/Lit, HBsAg negative, anti HBC negative, anti HCV negative, serum Albumin 4.2, g/dl serum gamma globulin 2 g/dl, antinuclear antibody (ANA) negative, anti-smooth muscle (anti-sm) Ab negative, anti liver kidney microsomal (anti LKM) Ab negative, and anti mitochondrial (AMA) Ab negative. Abdominal sonography revealed only mild splenomegaly. Magnetic resonance cholangiopancreatography (MRCP) study was normal. The patient underwent liver biopsy. Examination of the specimens revealed moderate periportal interface hepatitis, moderate portal inflammation, focal necrosis, marked bridging fibrosis, lobular non-caseating granulomatous inflammation and bile ductule proliferation. Acid fast staining for TB bacilli was negative. Other laboratory results were as follows: modified histopathologic activity index (HAI) grading 9, modified HAI staging 4, and combined HAI 13. Computerized topography (CT) scan of thorax was performed and showed enlarged nodes of anterior and middle (pretracheal and subcarinal), mediastinal and bilateral hilar nodes. There were multiple small sized centrilobular micronodules with formation of large lobular macronodules in the upper lobes and peribronchovascular nodular thickening. Then, a high resolution CT (HRCT) of the lungs, a PPD test and angiotensine converting enzyme (ACE) test were performed. HRCT study showed peribronchovascular nodular thickening of interestitium and centrilobular micronodules and nodularity of the interlobular fissures. ACE level was 79 (higher than normal) and induration of PPD test was 5mm.