Syed Mujahid Hassan

CLINICAL PROFILE AND HLA TYPING OF AUTOIMMUNE HEPATITIS FROM PAKISTAN

Background Human leukocyte antigen (HLA) typing in autoimmune hepatitis (AIH) has been investigated in different populations and ethnic groups, but no such data is available from Pakistan. Objectives The aim of this study was to evaluate the clinical profile of autoimmune hepatitis (AIH), and determine the associated antigens and alleles by performing HLA typing. Patients and Methods A total of 58 patients, diagnosed and treated as AIH in the last 10 years were reviewed. Diagnosis was based on International AIH Group criteria. Forty one patients underwent liver biopsy. HLA typing was performed in 44 patients and 912 controls by serological method for HLA A and B, and by PCR technique using sequence specific primers for DR alleles. Results Of 58 cases, 35 were females (60.3%). The median age was 14.5 (range 4-70 years), and AIH score was 14 (10-22). Thirty-six (62.0%) patients had type 1 AIH, 10 (17.2%) type 2, and the remaining 12 were seronegative with biopsy proven AIH. Forty-nine patients (84.4%) had cirrhosis. Twenty-four (41.4%) patients had ascites at the time of presentation. Among 41 patients who underwent liver biopsy, thirty-two had advance stages III and IV disease, and twenty had severe grade of inflammation. Fifteen patients had other associated autoimmune diseases and one developed hepatocellular carcinoma. HLA A2 (P = 0.036), HLA A9 (23) (P = 0.018), HLA A10 (25) (P = 0.000), HLA A19 (33) (P = 0.000), HLA B15 (63) (P = 0.007), HLA B40 (61) ( P = 0.002), HLA DR6 (P = 0.001) with its subtypes HLA-DRB1*13 (P = 0.032) and HLA-DRB1*14 (p = 0.017) were more prevalent in AIH with statistical significance than controls. Conclusions AIH in our region presents with advanced disease affecting predominantly children and adolescents. There is a genetic association of HLA DR6 along with other alleles and antigens in our patients with AIH.

Prevalence of cryptosporidiosis in renal transplant recipients presenting with acute diarrhea at a single center in Pakistan

Background: Cryptosporidium is an intracellular protozoan organism which causes diarrhea, both in immunocompetent and immunocompromised hosts. Renal transplant recipients are prone to develop a variety of infections including protozoal infections. Objectives: The aim of this study was to determine the prevalence of cryptosporidiosis in our renal transplant recipients presenting with acute diarrhea. Patients and Methods: During six months of the study, 644 renal transplant recipients presented with acute diarrhea. Single stool sample was obtained for detailed analysis including gross and microscopic examination for red blood cells, pus cells, ova, cysts, and protozoa. The modified Ziehl-Neelsen (ZN) staining was done to identify the oocysts of cryptosporidia. Results: Out of 644 renal transplant patients, oocysts of cryptosporidia were identified in 343 patients (53%). Detailed stool analysis of these patients showed the presence of numerous pus cells in 27 (7.9%) patients, co-infection with giardia intestinalis cysts in 15 (4.3%), and entamoeba histolytica cysts in 10 (2.9%). In all, out of 343 patients, 43 (12.5%) had dual infection with bacteria and protozoa in addition to cryptosporidiosis. Conclusions: Cryptosporidium is an important pathogen causing acute diarrhea in renal transplant recipients in our set up. Stool examination is usually negative for pus cells. It is recommended that in all transplant recipients presenting with acute diarrhea modified ZN staining should be done to rule out cryptosporidiosis in highly endemic areas like Pakistan.

Clinical presentation of hepatitis D in Pakistani children.

Background There are limited data on hepatitis D in children. The aim of this study was to assess the clinical presentation of hepatitis D virus (HDV) infection in Pakistani children. Materials and methods All pediatric patients (age⩽18 years) seen in the clinic with chronic HDV infection and detectable HDV RNA (n=48) were compared with consecutive hepatitis B virus (HBV) monoinfection patients (n=48). A total of 50 patients underwent liver biopsy: 28 in the HDV group and 22 in the HBV group. Results There was a male preponderance (85.4%). Significant differences were noted in age (P=0.012), presence of cirrhosis (P=0.004), splenomegaly (P<0.001), esophageal varices (P=0.006), splenic varices (P=0.022), alanine aminotransferase, aspartate aminotransferase and &ggr;-glutamyl transferase levels (P<0.001 each), platelet count (P=0.015), international normalized ratio (P<0.001), severity of inflammation on liver biopsy (P=0.007), and advanced fibrosis (P=0.016) in the two groups, indicating more severe disease in the HDV group. In the HDV group, six patients had normal ALT, of whom three were positive for hepatitis B e antigen (HBeAg) and HBV DNA. HBV DNA was detectable in 50% and HBeAg in 52% of the HDV patients. There were no differences in the severity of liver disease in HBeAg-reactive and HBeAg-nonreactive patients. Six patients with hepatitis D had decompensation at the time of presentation; five were HBV DNA positive and three had reactive HBeAg. Only one patient with HBV monoinfection had decompensation. Conclusion Children with HDV infection have more aggressive liver disease than HBV monoinfection irrespective of HBeAg status.

Experience of Fibrosing Cholestatic Hepatitis With Hepatitis C Virus in Kidney Transplant Recipients

BACKGROUNDnFibrosing cholestatic hepatitis C (FCH-C) is a rare entity that occurs among immune-compromised patients resulting from the direct hepatotoxicity of a high intracellular viral load along with an ineffective immune system ultimately leading to a fatal outcome. We have describes herein 4 renal transplant recipients who were diagnosed with FCH-C at our institution in the last 8 months.nnnMETHODSnFour renal transplant recipients presented with jaundice and deteriorating liver function tests. They were diagnosed to display FCH-C based on the presence of hepatitis C virus (HCV) RNA and characteristic liver biopsy findings; there was no evidence of any other cause of cholestasis or biliary obstruction.nnnRESULTSnThe patients were men of ages 40, 25, 20, and 27 years. The durations after transplantation were 1.5, 10, 1.5 and 2.0 years, respectively. In all cases pretransplantation screening was negative for HCV antibody, HCV RNA, and hepatitis B surface antigen (HBsAg). All 4 patients were infected with genotype 1, whereas case 2 had coinfection with type 3. Cases 1 and 2 who were treated with interferon and ribavirin, showed improvement in cholestasis but did not achieve a rapid virological response. Case 1 developed graft dysfunction secondary to acute cellular rejection at 4 months after initiation of interferon treatment, which was treated with pulse steroids. Interferon-based therapy was stopped prematurely in both cases due to pancytopenia. Case 3 developed florid pyelonephritis and died without receiving therapy for hepatitis C. Case 4 was managed conservatively by decreasing the immunosuppression with regular monitoring.nnnCONCLUSIONnFCH-C is difficult to treat and shows high morbidity and mortality rates. Treatment is associated with a risk of graft rejection.

Gastritis profunda cystica presenting as gastric outlet obstruction and mimicking cancer: A case report.

Abstract Gastritis cystica profunda (GCP) is a rare, benign lesion of the stomach characterized by polypoid hyperplasia and/or ulcerated mucosal lesion and cystic dilatation of the gastric glands extending into the submucosa or muscularis propria of the stomach. Its etiology and pathogenesis are still incompletely understood. The most important factor is assumed to be a history of prior gastric surgery. We herein present a case of a young adult female with upper gastrointestinal (GI) symptoms. She underwent upper GI endoscopy twice, which revealed pyloric narrowing and intramural mass. Gastric endoscopic mucosal biopsies were performed, but no tumor was identified and her symptoms persisted. Imaging studies also revealed a mass lesion. Open laparotomy and partial gastrectomy with histopathology of the resected specimen revealed the true nature of the lesion. Surgery also improved her symptoms. GCP should be kept in the differential diagnosis of gastric mural mass lesions.

Prevalence and Characteristics of Duodenal Villous Atrophy in Renal Transplant Patients Presenting With Persistent Diarrhea in a Developing Country.

OBJECTIVESnPersistent diarrhea is a common complication after solid-organ transplant, including kidney transplant. Data on duodenal villous atrophy as a cause of persistent diarrhea in renal transplant recipients are scarce.nnnMATERIALS AND METHODSnWe conducted a prospective analysis of 207 patients who received renal transplants from 2009 to 2012 with persistent diarrhea and who underwent upper gastrointestinal endoscopy and duodenal biopsies. Duodenal biopsies were examined for duodenal villous atrophy. Age, sex, transplant duration, and drugs were compared between patients with and without duodenal villous atrophy. After exclusion of known causes of duodenal villous atrophy, a 3-month course of antibiotics was given and outcomes were analyzed.nnnRESULTSnOf 207 renal transplant recipients, 104 patients (49.8%) displayed duodenal villous atrophy. Of these, 92 (88.5%) were male patients. The mean age of patients with duodenal villous atrophy was 34.9 ± 10.3 years. The mean onset of persistent diarrhea in DVA-positive patients posttransplant was 2.16 ± 0.8 years. Celiac disease serology was positive in 18 (17.3) patients. Giardiasis was demonstrated in 11 patients (10.7%), whereas immunoproliferative small intestinal disease was shown in 7 patients (6.8%). The remaining 68 patients (65.38%) received antibiotics, with 50 recipients (74.6%) showing complete response, although 13 of these patients (26%) relapsed. Among the remaining 18 patients (26.47%), 9 (50%) had other causes and 9 (50%) had no cause found. Isoniazid prophylaxis showed statistically significant negative association with duodenal villous atrophy.nnnCONCLUSIONSnDuodenal villous atrophy is highly prevalent in renal transplant recipients irrespective of age, sex, and posttransplant duration. We found tropical sprue, giardiasis, immunoproliferative small intestinal disease, and celiac disease to be important causes of duodenal villous atrophy. Therefore, duodenal biopsy is recommended in renal transplant recipients with persistent diarrhea.

Clinical presentation of extrahepatic portal vein obstruction: 10-year experience at a tertiary care hospital in Pakistan

Abstract Objective: To evaluate the clinical presentation, possible etiological factors, management and outcome of patients in our hospital with extrahepatic portal vein obstruction (EHPVO). Materials and Methods: This study included patients with EHPVO followed up in our department during last 10 years. Patients of cirrhosis with EHPVO were excluded. Patients’ clinical presentation, etiology of EHPVO, management and outcome results were analyzed. Results: Of 30 patients, 19 (67.9%) were males. Median age was 12 years. Of 14 patients who underwent liver biopsy 9 had histological activity index stage of 1/6. History of omphalitis and pulmonary tuberculosis was present in one case each. Of 22 patients with the available thrombophilia profile, nine patients had a deficiency of protein C, five patients had a deficiency of protein S, one each had reduced level S of anti-thrombin III and factor V mutation. The predominant presenting symptom was hematemesis (15 patients, 53.6%). Seven patients (25%) had splenomegaly. Three patients (10.7%) had no esophageal varices on endoscopy. Three patients underwent splenectomy due to severe pancytopenia. Endoscopic retrograde cholangipancreatography was performed in four patients (14.3%) due to portal biliopathy. Common bile duct stenting was performed in all four patients. Of them, one patient underwent splenorenal shunt operation for indication of hemobilia. One patient died at the age of 40 years, due to cholangitis and sepsis. Conclusions: Results from this study show that the anticoagulant deficiency is a common cause of EHPVO in our setup. Hematemesis is a common presenting symptom. Some of these patients have symptomatic portal biliopathy.

Acute esophageal necrosis in a patient with end-stage renal disease on hemodialysis

Abstract Spontaneous acute esophageal necrosis (AEN) has been reported to be extremely rare. The condition is defined as a dark pigmentation of the esophagus associated with histologic mucosal necrosis. The exact pathogenesis is still unknown, but several etiologies have been suggested including ischemia, gastric outlet obstruction, hypersensitivity to antibiotics, gastric volvulus and viral infection. We herein present a case of a middle-aged man with end-stage renal disease who presented with AEN following a hemodialysis session. Its diagnosis and management are discussed with reference to the pathogenesis of the condition.

Primary Localized Amyloidosis of Urinary Bladder: A Case Report and Review of Literature

Amyloidosis is a disorder of protein metabolism characterized by extracellular deposition of abnormal protein fibrils. It may either be localized to any organ or systematically distributed throughout the body. The biochemical nature of proteins varies but the physical and tinctorial properties are shared by all the amyloidogenic proteins. In the West, it is mainly composed of amyloid light (AL) type immunoglobulin (Ig) light chains. Amyloidosis of the genitourinary tract is rare except for the kidney and isolated primary amyloidosis of the urinary bladder is even rarer. It mainly presents as intermittent painless gross hematuria. It mimics transitional cell carcinoma on imaging and endoscopic examination. We herein present a case of fifty six-years-old male with history of painless hematuria for three months. Cystoscopy revealed a 1 cm hyperemic area on the posterior wall of urinary bladder. The biopsy showed features of amyloidosis and amyloid A (AA) immunostaining was negative. Extensive workup was done to exclude other sites of involvement and a final diagnosis of primary localized amyloidosis of the urinary bladder was made. The patient is on regular follow-up.

Progressive familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC) is an important cause of cholestatic liver disease and biliary cirrhosis in pediatric population. Three cases of PFIC are described that were diagnosed on the basis of family history, pruritus, cirrhosis and / or paucity of interlobular bile ducts on liver biopsy and presence of extrahepatic biliary tree on imaging. These patients were initially labeled as suffering from extra-hepatic biliary atresia and neonatal hepatitis. PFIC-1 and 2 could not be differentiated on histological grounds, since these patients presented late and process of fibrosis was advanced.