Muhammad Mubarak

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

BACKGROUND Fibrosing 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. METHODS Four 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. RESULTS The 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. CONCLUSION FCH-C is difficult to treat and shows high morbidity and mortality rates. Treatment is associated with a risk of graft rejection.

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Levels and Its Association with Renal Allograft Rejection

ABSTRACT Background: CCL2 is a chemoattractant for monocytes/macrophages, T cells, and natural killer cells. It is shown to be involved in the immunological responses against renal allograft. This study was conducted to access the role of urinary CCL2 expression in predicting the rejection episodes in renal transplant patients. Method: A total of 409 urine samples included in this study. The samples were consisted of (a) biopsy-proven graft rejection (n = 165); (b) non-rejection (n = 93); (c) non-biopsy stable-graft (n = 42), and (d) healthy renal donors (n = 109). The samples were quantified for the CCL2 using the MCP-1/CCL2 ELISA kit. The data were analyzed using the Statistical Package for Social Sciences (SPSS®) and MedCalc® statistical software. Results: Results showed that the CCL2 levels were significantly increased in rejection group when compared with the non-rejection, stable-graft, and control, P < 0.05. The receiver operating curve’s characteristics illustrated that the urinary CCL2 level is a good predictor for graft rejection, with an area under the curve of 0.81 ± 0.03 with optimum sensitivity and specificity of 87% and 62%, respectively, at a cut-off value of 198 pg/mL. Kaplan–Meier curve also showed better cumulative rejection-free graft survival time in group with less than 198 pg/mL of CCL2 as compared to those with expression levels of more than 198 pg/mL (30 weeks vs. 3 weeks; log-rank test, P < 0.001). Conclusion: In our study, noninvasive investigation of CCL2 levels in urine has showed potential to predict rejection episodes. It is suggested that the CCL2, with others markers, may help in early detection and monitoring of graft rejection episodes.

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.

Renal Allograft Biopsy Findings in HLA Identical Renal Transplant Recipients

Objectives HLA identical transplants are immunologically privileged and have the best graft survival in both deceased and living donor settings, yet the grafts do fail. This study describes the causes of graft failure in HLA identical transplants as detected on renal allograft biopsies. Patient and Methods: Between 1992 and 2012, 3749 live-related transplants were performed at our center. Of these, 756 (20%) were HLA identical. Immunosuppression comprised of triple drug regimen: CyA/AZA or Tacrolimus/MMF with steroids. Graft dysfunction episodes were confirmed by biopsy, when indicated. Graft biopsies were reported according to Banff classification. All recipients were followed-up lifelong, where all treatment is provided free including immunosuppression drugs. Results In the follow-up period of 4 to 20 years, 160/756 (21%) of the identical grafts were lost with 5, 10, 15 years survival rates of 85%, 68% and 60% respectively. A comparison of those who lost grafts (Group A, n=160) vs. those who maintained function (Group B, n=596) showed that in Group A, donors were older (35±9 vs. 32±9, p=0.001), GFR was lower (97±24 vs. 110±23 ml/min, p=0.001) and there were more females (46% vs. 33%, p=0.031). Among recipients in group A, there were more females (25% vs. 18%, p=0.03) and hypertensives (60% vs. 49%, p=0.04). Acute rejection rates in group A were higher (13% vs. 4.8% p=0.001), as was cyclosporine toxicity on biopsy (14% vs. 11%, p=0.20) and recurrence of original disease (9% vs. 4%, p=0.03) as compared to Group B. Of the 160 grafts lost, 24% were functioning but lost due to death of recipients, 7% were lost due to recurrence, 7% to infection in the graft, 6% to acute rejection and 50% to interstitial fibrosis/tubular atrophy (IFTA). Conclusion HLA identical grafts have superior survival due to immunological privilege, but are susceptible to non-immunological injury, including CyA toxicity.

Diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis 4 scores in predicting advanced liver fibrosis in patients with end-stage renal disease and chronic viral hepatitis: Experience from Pakistan

Abstract Objectives The aim was to assess the diagnostic accuracy of APRI and FIB-4 in assessing the stage of liver fibrosis in end stage renal disease (ESRD) patients with chronic viral hepatitis and to compare the two tests with standard tru-cut liver biopsy. Material and Methods The study was conducted at Sindh Institute of Urology and Transplantation Karachi (SIUT) from May 2010 to May 2014. All ESRD patients, being considered as candidates for renal transplantation and in whom liver biopsy was performed were included. Fibrosis stage was assessed on liver biopsy using Ishak scoring system. The serum transaminases and platelet counts were used to calculate APRI and FIB-4 scores. Results Out of 109 patients, hepatitis C and B virus infections were present in 104 (95.4%) and 3(2.8%), respectively, while 2 (1.8%) patients had both infections. The mean Ishak fibrosis score was 1.95 ± 2. Advanced fibrosis was noted in 37 (34%) patients. Univariate analysis showed that advanced liver fibrosis was associated with lower platelets counts (P=0.001) and higher aspartate aminotransferase (AST) (P=0.001), alanine aminotransferase (ALT) (P=0.022), APRI score (P=0.001) and FIB-4 score (P=0.001). On logistic regression analysis, only APRI score (P < 0.001) was found to be the independent variable associated with advanced liver fibrosis. APRI score cutoff ≥1 indicating advanced fibrosis showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 91.9%, 90.3%, 82.9%, 95.6%, respectively with area under the curve (AUC) of 0.97. Similarly, a FIB-4 score cutoff ≥1.1 had sensitivity, specificity, PPV and NPV of 70.27%, 66.67%, 52% and 81.36%, respectively with AUC of 0.74. Conclusion APRI is more accurate noninvasive test for assessing advanced liver fibrosis in ESRD patients as compared to FIB-4. It can be used to obviate the need for liver biopsy in this high risk population.

Noninvasive clinical predictors of portal hypertensive gastropathy in patients with liver cirrhosis

Abstract Background and Objectives Portal hypertensive gastropathy (PHG) is described endoscopically as “mosaic-like appearance” of gastric mucosa with or without the red spots. It can only be diagnosed by upper gastrointestinal (GI) endoscopy. The aim of this study was to determine the diagnostic accuracy of platelet count to spleen diameter ratio (PSR) and right liver lobe diameter to albumin ratio (RLAR) in the detection of PHG using upper GI endoscopy as a gold standard in patients with liver cirrhosis. Material and Methods This cross-sectional study was conducted in the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi. All consecutive patients with ages 18–65 years who were screened using esophagogastroduodenoscopy (EGD) to exclude esophageal varices were enrolled. At the same time, findings related to PHG were noted. After informed consent, all the patients had blood tests including platelet count and albumin and abdominal ultrasound determining spleen diameter and right liver lobe diameter. Results Out of 111 patients, 59 (53.15%) were males with a mean age of 44 ± 12.61 years. Rate of PHG was observed in 84.68% (94/111) cases confirmed by EGD. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PSR were 87.23%, 5.88%, 83.67%, 7.69%, and 74.7%, respectively, and those of RLAR were 28.72%, 70.59%, 84.38%, 15.19%, and 35.14%, respectively. Conclusion PSR is better predictor of PHG than RLAR but at the expense of relatively lower specificities and NPV likely because of underlying pathophysiology (portal hypertension) which is similar for esophageal varices, PHG, and ascites.

Celiac Crisis in Refractory Celiac Disease Type I with Neurological Manifestations: A Diagnostic Dilemma

Celiac crisis is a life-threatening condition in which patients have profuse diarrhea and severe metabolic disturbances. Refractory Celiac Disease (RCD) is a rare condition defined as persistence of symptoms despite being on Gluten Free Diet (GFD) for 6 months. Neurological involvement in Celiac Disease (CD) is seen in around 8 - 10% of adult patients; however, it is rare in children. Herein we present a case of an adolescent presenting with neurological symptoms and celiac crisis and diagnosed as RCD, type 1. He was treated with high dose steroids. This case underscores the need to consider RCD in patients presenting in celiac crisis and showing no improvement on GFD.