Sickling Process as the Major Cause of Sickle Cell Hepatopathy: A Clinicopathologic Study of 70 Living Patients.
Authors: Traina Fabiola , Jorge Stefano G. , Yamanaka Ademar , Costa Fernando F. , Saad Sara T.O. 
Published: October 2019

Abstract
Sickle cell hepatopathy encompasses a range of hepatic pathologies arising from a wide variety of insults to the liver in patients with sickle cell disease (SCD). Much of the literature on sickle cell hepatopathy lacks depth, since few sizeable or controlled studies are available, and most studies provide incomplete information regarding coexisting chronic infection with hepatitis B or C and hepatic iron deposition. Previous reports in living patients are rare and concern a limited number of cases. The present study aimed to evaluate the contributing effects of these various insults to the final pathologic and clinical picture in these patients. Clinical, biochemical, serological and abdominal ultrasound findings were analyzed prospectively in 70 patients diagnosed with SCD (36 females and 34 males, mean age of 27, range 9–56 years) from the Hematology and Hemotherapy Center of the State University of Campinas. The SCD types were distributed as follows: 57 HbSS, 6 HbSC, 2 HbSB0, 5 HbSB+. The study was approved by the National Ethical Committee Board and informed-written consent was obtained from all patients. The inclusion criteria for this study were a precise clinical and laboratory diagnosis of SCD and regular follow-up in the clinic. All patients were submitted to laboratory tests and to abdominal ultrasound. Abdominal ultrasound and image analyses were simultaneously performed by two gastroenterologists (SGJ and AY). Liver biopsies were obtained in those patients with diagnosis of hepatopathy and who were in agreement with the procedure. Hepatopathy was defined as abnormal plasma alanine transaminase (ALT) and/or cirrhosis or chronic hepatopathy detected by abdominal ultrasound. Hepatitis C was defined as a positive serum for anti-HCV antibody. Hepatitis B was defined as seropositivity for hepatitis B surface antigen (HbsAg) with a negative serum for hepatitis B surface antibody. Hemosiderosis was defined as ferritin level above 500 ng/ml and history of chronic transfusion. According to this definition, 36 of the 70 (51%) patients had hepatopathy. The cause for hepatopathy was hepatitis C or B in 4 patients, hemosiderosis in 8 patients and both in 3 patients. The reason for hepatopathy in the remaining 21 (58%) patients was justified only by the sickling process. Excluding all patients with hepatitis B or C and/or hemosiderosis, in a Wilcoxon rank-sum test, the diagnosis of hepatopathy was not associated with age, hemoglobin, leukocytes, platelets and fetal hemoglobin level; in a Fisher’s exact test the diagnosis of hepatopathy was not associated with sex, race, presence of alpha thalassemia, cholelithiasis, alcohol use, hepatotoxic drugs and diabetes. A liver biopsy was obtained in 12 of 36 patients with diagnosis of hepatopathy. In the group of patients without hepatitis and/or hemosiderosis, the pathological findings consisted of sinusoidal dilatation, intrasinusoidal congestion, portal fibrosis, pericellular fibrosis and focal necrosis. In the group with hepatitis, the pathological findings were the same. In the group with hemosiderosis, the pathological findings included those previously described in addition to hemosiderosis. These results showed that, in patients with SCD, hepatopathy is frequent and in most cases explained only by the sickling process.