De novo malignancies after liver transplantation: a single-center experience

The recipients of liver transplantation [LT] are subjected to lifelong immunosuppression with its many drawbacks. De novo and recurrent malignancy in transplant recipients are attributed to attenuation of immunosurveillance. In the present study, we present our experience with de novo malignancies encountered after both deceased and living donor liver transplantations. Retrospective study of patients referred to LT center between April 2001 and January 2010. Various data were collected including type of malignancy and histopathologic features, immunosuppression regimen, and patient survival. Of 248 LT procedures performed in 238 patients [10 retransplants], 8 patients [3.4%] developed de novo post-LT malignancies. De novo malignancies included post-LT lymphoproliferative disorders [PTLD] in 5 patients who were all Epstein-Barr virus [EBV] positive, and who were treated successfully with anti-CD20 monoclonal antibody therapy, reduction of immunosuppression, and control of EBV activity; urinary bladder cancer in 1 patient who was treated with radical surgical resection and chemotherapy but died of bone and lung metastasis within 1 year of diagnosis; endometrial carcinoma in 1 patient who was treated with radical surgical resection; and Kaposi sarcoma in 1 patient who was successfully treated with surgical excision and reduction of immunosuppression. EBV-associated PTLD is the most frequently encountered de novo malignancy after LT and is easily treatable by chemotherapy and reduction of immunosuppression

Comparison and validation of laminin-based score and fibroscan for prediction of liver fibrosis in Egyptian patients with chronic hepatitis C

The constraints of liver biopsy and the limitations of single parameters in assessing liver fibrosis have boosted the development of scores combining markers to improve accuracy. Laminin-based score was devised by the study group in 2006. The present study was conducted to validate the diagnostic accuracy of this score and of transient elastography [T.E.] In another group of ninety Egyptian patients with chronic hepatitis C. Patients were biopsied and subjected to assessment of score parameters [serum albumin, AST, prothrombin concentration, laminin, portal vein diameter] and liver stifihess by T.E. Patients were classified using modified Knodell score into 7 groups [stage 0-stage 6]. A significant relation between the stage of fibrosis and the laminin-based score was found. The score demonstrated high accuracy for diagnosing significant fibrosis and cirrhosis. Liver stiffness correlated significantly with staging of fibrosis as well as with laminin-based score. T.E. demonstrated high accuracy for diagnosing significant fibrosis and cirrhosis. Both methods proved useful to discriminate stages F4 and F5. When both methods were combined, the diagnostic accuracy was increased to 93.7% for diagnosing significant fibrosis. Laminin-based score and T.E. Proved their clinical value and may reduce the need for repeated liver biopsies

Host genetic determinants in chronic hepatitis C virus infection in Egyptian patients

Mechanisms underlying viral persistence and liver damage in chronic HCV are not yet fully clarified, but a complex interplay of virological and immunological factors is implicated. An immunogenetic resistance or susceptibility to chronic hepatitis C virus [HCV] infection may contribute to the course of liver disease and may be linked to the human major histocompatibility complex [MHC]. This study was designed to study the distribution of the HLA class II alleles in patients with chronic hepatitis C and HCV-related cirrhosis to investigate whether these alleles might be associated with protection from or susceptibility to chronic HCV infection. We also aimed to address the correlation of the host HLA class II genotype with the lymphoproliferative response to phytohaemagglutinin [PHA] in vitro. The study included 60 unrelated patients with chronic hepatitis C [15 females, 45 males; mean age, 43 +/- 8.3 years]. A control group of 60 ethnically matched healthy blood donors was also studied [8 females, 52 males; mean age, 25 +/- 4.1 years]. HLA-DRB alleles were studied for patients and controls by a PCR-sequence-specific-primer low-resolution method. HLA-DRB1 03011 and HLA-DRB1 13011 were the most frequently distributed among HCV patients; their percentage of distribution were 26.8% and 28.3% respectively. Conversely, HLA-DRB1 07011 was found at significantly reduced frequency in HCV patients compared to that of the control group. The results also showed that the level of IFN-y was significantly increased in HCV patients [948.5 +/- 135.5] compared to that of the control group [193.6 +/- 21.26]. [t = 30.15, p

Plasma and ascitic fluid level of calprotectin in chronic liver disease: malignant and non malignant

Calprotectin was widely investigated in alcoholic liver disease and proved to be a new prognostic marker of survival independent of the severity of liver disease as well as marker of malignancy. However it was not widely investigated in other causes of liver cirrhosis. Of the present work was to study the level of calprotectin both in plasma and ascitic fluid in patients with hepatitis C [HCV] related chronic liver disease with and without malignancy, and to find out whether one or both of them correlate with the severity of liver damage and presence of malignancy. This study was conducted at the Faculty of Medicine, Alexandria University and the National Liver Institute, Menoufiya University. Thirty patients with Hepatitis C related liver cirrhosis were recruited. Fifteen of these patients suffered from concomitant hepatocellular carcinoma [HCC] diagnosed by elevated alpha foeto-protein [AFP] and one imaging technique OR by two imaging techniques in the case of normal AFP. Calprotectin was significantly elevated in patients with cirrhosis and cirrhosis/HCC than in controls [p=<0.01]. However there was no significant difference in the levels of plasma or ascitic calprotectin between the cirrhotic group and the group with HCC. There was no correlation between plasma and ascitic calprotectin levels. Ascitic calprotectin correlated significantly with bilirubin, and markers of synthetic liver function [p=<0.05], but plasma calprotectin correlated only with prothombin activity [p=<0.05]. In patients with spontaneous bacterial peritonitis, ascitic calprotectin was significantly higher in patients having this complication [879.8 +/- 67.5] than patients without SBP [534.2 +/- 59.3 [p<0.01] and a highly significant correlation was found between ascitic calprotectin and total leucocytic count in ascitic fluid [p=<0.01]. Calprotectin is elevated in HCV-related cirrhosis but not further elevation with the occurrence of hepatocellular carcinoma. Ascitic calprotectin correlated with the degree of hepatocellular injury and was significantly higher in patients with SBP. Further studies are warranted to establish a role of plasma calprotectin for the risk assessment of infectious complications secondary to bacterial translocation in patients with HCV- related liver cirrhosis

Spontaneous bacterial empyema in cirrhotic patients: complements 3 and 4, opsonic power and C-reactive protein as pathogenic mechanisms and diagnostic tools

Hepatic hydrothorax occurs in approximately 5-12% of patients with cirrhosis and portal hypertension and may be complicated by spontaneous bacterial empyema [SBE]. Pathogenic mechanisms of SBE still need to be investigated. The present work assesses the role of complement components [C3, C4], opsonizing power and C-reactive protein in the pathogenesis of SBE in cirrhotic patients. Twenty five cirrhotic patients with hepatic hydrothorax were randomly selected and 10 patients with hydrothorax secondary to heart failure were included as controls in the study. Pleural fluid [PF] and serum samples were analyzed for: total protein [TP], albumin, lactic dehydrogenase [LDH], glucose, polymorph nuclear leukocytic count [PMNL], complement components [C3, C4], opsonic activity [on the basis of log-kill] and high sensitive C-reactive protein [CRP]. SBE was diagnosed when pleural fluid PMNL was > 250 cells/mm[3] with a positive culture or >500 cells/ mm[3] with a negative culture after exclusion of pulmonary infections. Thirteen patients [52%] [Group I] were diagnosed as SBE and 12 patients [48%] had no SBE [Group II]. There was no significant difference between patients and controls [GIII] as regards age, gender, serum proteins, serum C3, serum WBC and effusion CRP. Levels of serum albumin, total pleural effusion proteins, PT% and opsonic activity of groups I and II were significantly lower than in GIII with no significant difference between groups I and II. Levels of serum bilirubin and C4 of groups I and II were significantly higher than group III with no significant difference between groups I and II. Level of pleural effusion C3 in group I was significantly lower than in groups II and III and level of C3 in group II was significantly lower than in group III. Level of pleural effusion C4 in group I was significantly lower than group III, but there was no significant difference between groups I and II. In hepatic patients, 7 patients [28%] belonged to Child's class B and 18 [72%] to class C. Spontaneous bacterial empyema was detected in 56% of hepatic patients with Child's class C and in 43% of Child's class B. There was no significant difference between hepatic patients with and without SBE with regard to Child-Pugh's score. In patients with SBE, levels of C3 and C4 were significantly less in pleural fluid than in serum but there was no significant difference with regard to opsonic activity. Local complement defects [especially C3] and opsonic activity in cirrhotic patients predispose to SBE. Serum CRP increases, but effusion CRP level should be reassessed as a cheap diagnostic tool