Rana Muzaffar

Genetic variability in the precore and core promoter regions of hepatitis B virus strains in Karachi

BackgroundHepatitis B virus (HBV) genotypes have distinct geographic distribution. Moreover, much genetic variability has been described in the precore (PC) and basal core promoter (BCP) regions of the HBV genome. The local prevalence of HBV genotypes and mutations has not been well studied. The aim of the present study is to determine the prevalence of HBV genotypes and mutations in the PC and BCP region in HBV strains in Karachi.MethodsA total of 109 chronic hepatitis B patients with detectable HBV DNA by a PCR assay were enrolled in the study. Sera were tested for HBeAg, anti-HBe antibody and liver profile. HBV genotypes and mutations in the PC and BCP regions were detected by INNO-LiPA line-probe assays.ResultsOf the 109 patients investigated, 38 (35%) were HBeAg positive while 71 (65%) were HBeAg negative. Genotype D was present in 100% of the patients. Two patients had co-infection with genotype A. There was no significant difference in the baseline characteristics, mean ALT levels, and presence of clinical cirrhosis in patients with HBeAg positive or negative strains with or without PC and BCP mutations. Of the 38 HBeAg positive patients, 9 (24%) had PC and BCP mutations. In the HBeAg negative patient group, mutations were detected in 44 (62%) of the strains investigated. More than one mutation was common, seen in 26 (37%) patients with HBeAg negative disease and 6 (16%) patients with HBeAg positive disease. Twelve (17%) HBeAg negative patients had dual T1762 and A1764 mutations. None of the HBeAg positive patients had T1762 mutation. Mutations were undetectable in 27 (38%) of patients with HBeAg negative disease.ConclusionOur study shows that type D is the main HBV genotype in Karachi, Pakistan. Significant numbers of patients infected with this genotype have PC and BCP variants. Mutations at more than one site are common. Patients harboring these mutants do not differ significantly in their clinical presentation from patients having wild type infection.

Commercial transplants in local Pakistanis from vended kidneys: a socio-economic and outcome study.

Donor shortage and absence of transplant law lead to unrelated commercial transplants in Pakistan. We report the socio‐economic and outcome parameters of 126 local recipients of unrelated kidney vendor transplants presenting to our institute between 1997 and 2007. Their outcome was compared with 180 recipients of living‐related donor transplants matched for age, gender and transplant duration as controls. Age of commercial recipients was 35.63 ± 11.57 years with an M:F ratio of 2.4:1. Majority (92%) were transplanted in northern Pakistan paying US

CLINICAL PROFILE AND HLA TYPING OF AUTOIMMUNE HEPATITIS FROM PAKISTAN

7271 ± 2198. All were educated with 50% being graduates or above and rich earning a monthly salary of US

Plasma cell‐rich acute rejections in living‐related kidney transplantation: a clinicopathological study of 50 cases

517 ± 518 with 44% earning >US

Curriculum guide for research ethics workshops for countries in the Middle East.

500. Comparison of commercial recipients with controls showed high comorbidities 35 (28%) vs. 14 (8%) (P = 0.0001) with diabetes, hepatitis‐C and cardiovascular diseases. Donor age was 29.97 ± 6.16 vs. 32.63 ± 9.3 years (P = 0.035). Biologic agents induction in 101 (80%) vs. 14 (8%) (P = 0.0001), acute rejections in 42 (33%) vs. 31 (17%) (P = 0.005), 1‐year creatinine 1.84 ± 1.28 vs. 1.27 ± 0.4 mg/dl (P = 0.0001), surgical complications 28 (22%) vs. 14 (8%) (P = 0.001), tuberculosis 14 (11%) vs. 6 (6%) (P = 0.007), acute hepatitis 20 (16%) vs. 3 (2%) (P = 0.0001), cytomegalovirus 33 (26%) vs. 21 (11%) (P = 0.001) and recurrent urinary tract infection 35 (28%) vs. 30 (16%) (P = 0.034). Overall 1‐ and 5‐year graft survival was 86% and 45% vs. 94% and 80%, respectively (P = 0.00001). Total deaths were 34 (27%) vs. 12 (6.0%) (P = 0.001). In conclusion, recipients of the vended kidneys are poor candidates, educated, rich and often self‐selecting. Their outcome is poor, which will leave them poorer still and back to dialysis if not death.

Outcome of living-related donor renal allografts in hepatitis C antibody-positive recipients.

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.

Vasculitis with renal involvement in essential mixed cryoglobulinemia: Case report and mini-review

Acute rejections (ARs) with plasma cell‐rich infiltrates (PCARs) are associated with poor outcomes.

Reducing Immunosuppression Preserves Graft Function in Patients with BKVN - A Single Centre Study

To help ensure the ethical conduct of research, many have recommended educational efforts in research ethics to investigators and members of research ethics committees (RECs). One type of education activity involves multi-day workshops in research ethics. To be effective, such workshops should contain the appropriate content and teaching techniques geared towards the learning styles of the targeted audiences. To ensure consistency in content and quality, we describe the development of a curriculum guide, core competencies and associated learning objectives and activities to help educators organize research ethics workshops in their respective institutions. The curriculum guide is divided into modular units to enable planners to develop workshops of different lengths and choose content materials that match the needs, abilities, and prior experiences of the target audiences. The content material in the curriculum guide is relevant for audiences in the Middle East, because individuals from the Middle East who participated in a Certificate Program in research ethics selected and developed the training materials (e.g., articles, PowerPoint slides, case studies, protocols). Also, many of the activities incorporate active-learning methods, consisting of group work activities analyzing case studies and reviewing protocols. The development of such a workshop training curriculum guide represents a sustainable educational resource to enhance research ethics capacity in the Middle East.

Clinical Significance of Anti-Ribosomal P Protein Antibodies in Patients with Lupus Nephritis

EPATITIS C virus (HCV) is now the leading cause of posttransfusion hepatitis worldwide. 1 HCV infection has a prevalence of up to 48% in hemodialysis patients. 2 In our unit, positivity is 40% and this correlates with the number of blood transfusions received and the duration of dialysis. 3 We developed a criterion whereby all patients on hemodialysis with liver histology showing chronic or benign changes with stable liver enzymes for 3 months were selected for renal transplantation. Our initial results of short-term follow-up showed comparable results compared to HCV-negative recipients who underwent transplantation in the same period. 3 We now report a cumulative 3-year follow-up of 96 anti-HCV-positive recipients in comparison with 191 anti-HCV-negative individuals who underwent transplantation in the same period.

T and B cells immunophenotypes in blood and urine of patients with focal segmental glomerulosclerosis in relation todisease severity

The discovery of a strong association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has led to an increasingly rare diagnosis of idiopathic essential MC (EMC). The incidence of EMC is high in regions where there is a comparatively low HCV infection burden and low in areas of high infection prevalence, including HCV. The diagnosis of EMC requires an extensive laboratory investigation to exclude all possible causes of cryoglobulin formation. In addition, although cryoglobulin testing is simple, improper testing conditions will result in false negative results. Here, we present a 46-year-old female patient with a case of EMC with dermatological and renal manifestations, highlighting the importance of extensive investigation to reach a proper diagnosis. We review the need for appropriate laboratory testing, which is often neglected in clinical practice and which can result in false negative results. This review also emphasizes the significance of an extended testing repertoire necessary for better patient management. Despite a strong association of MC with HCV infection and other causes that lead to cryoglobulin formation, EMC remains a separate entity. Correct diagnosis requires proper temperature regulation during sample handling, as well as characterization and quantification of the cryoprecipitate. Inclusion of rheumatoid factor activity and complement levels in the cryoglobulin test-panel promotes better patient management and monitoring. Consensus guidelines should be developed and implemented for cryoglobulin detection and the diagnosis of cryoglobulinemic syndrome, which will reduce variability in inter-laboratory reporting.