Epstein-Barr virus and Interleukin-28B polymorphism in the prediction of response to interferon therapy in hepatitis C patients

Background and study aims: In chronic hepatitis C virus [HCV], viral and host factors are known to be predictors for anti-viral therapy. IL-28B genotype strongly influences treatment outcome, while Epstein-Barr virus [EBV] co-infection could accelerate the course of chronic HCV infection. This study was conducted to assess whether EBV co-infection adds to the predictive value of IL-28B

Patients and methods: A total of 105 patients with chronic HCV were classified according to their response to treatment into two groups: 38 sustained virological responders [SVRs] and 67 nonresponders [NRs]. Collected sera at baseline and follow-up [FUP] were used for assessing EBV antibodies by enzyme-linked immunosorbent assay [ELISA] and the expression of EBV genes [BNLF-1, BZLF-1, and EBER-2] by polymerase chain reaction [PCR]. Collected peripheral blood was used for detecting IL-28B rs.12979860 single-nucleotide polymorphism

Results: Regarding IL-28B genotype frequencies, a significant difference [p = 0.003] was observed between SVRs [C/C = 51.4%, C/T = 48.6%, T/T = 0%] and NRs [C/C = 25%, C/T = 55%, T/T = 20%]. On assessing EBV infection at baseline and FUP, it was found that 61% and 55% were positive, respectively, with no significant difference between SVRs and NRs. As for anti-viral capsid antigen [VCA] antibodies, the NRs had significantly higher baseline anti-VCA immunoglobulin M [IgM] levels than SVRs [p = 0.01]. While FUP anti-Epstein-Barr nuclear antigen-1 [EBNA-1] IgG reported a significant decline within SVR patients [p = 0.02], neither baseline nor FUP anti-VCA IgG levels showed a statistically significant viral response. Finally, on comparing EBV markers with CC versus CT and TT genotypes, it was found that FUP anti-VCA IgG levels were significantly increased in CC genotype [p = 0.003]

Conclusion: Interleukin-28B polymorphism could be a possible predictor of response to pegylated interferon/ribavirin therapy [PEG-IFN/RBV]. Furthermore, co-infection with EBV did not affect the response to IFN-based therapy in HCV-infected patients

Evaluation of the diagnostic value of serum and tissue apoptotoic cytokeratin- 18 in patients with chronic hepatitis C

Hepatitis C virus [HCV] is considered the most common aetiology of chronic liver disease [CLD] in Egypt. The disease severity ranges from mild illness to cirrhosis and hepatocellular carcinoma. A role for apoptosis in liver damage caused by HCV chronic infection has been suggested. Cytokeratin 18 [CK-18] is the major intermediate filament protein in the liver and is a known caspase substrate in hepatocyte apoptosis. Therefore, we analysed the serum and tissue levels of CK-18 in patients with chronic HCV infection to evaluate its role in hepatocyte apoptosis. We also correlated CK-18 expression with the severity of hepatic pathology. This study examined 80 Egyptian patients with liver disease. There were 69 patients with chronic hepatitis C and 11 patients with hepatitis C-induced cirrhotic changes. Fifteen healthy controls were also included in the study. The levels of CK-18 fragment were quantified in paired serum and liver biopsy samples. The serum and tissue CK-18 levels were reduced in chronic HCV patients compared to early cirrhosis patients. This result indicates that serum levels of CK-18 and the hepatic expression of CK-18 might play an important role in disease progression. The serum and tissue levels of CK-18 were significantly increased and directly correlated with inflammation severity, stage of fibrosis, and ALT levels in the chronic HCV group and the cirrhotic liver group. There was no significant difference in viral load between patient cohorts. The serum level and the hepatic expression of CK-18 are related to disease activity and are directly correlated with METAVIR scoring. This result suggests that serum CK-18 levels may be useful for monitoring disease activity in chronic HCV and liver cirrhosis patients

Alterations in colonic mucosal lesions in patients with portal hypertension

Portal hypertensive colopathy [PHC] is a clinical entity in liver cirrhosis. The frequency and profile of colonic mucosal lesions of this entity are not well studied. The aim of this study is to evaluate the prevalence of colonic mucosal changes in patients with liver cirrhosis and their clinical significance. Forty patients with post-viral liver cirrhosis and portal hypertension [PHT] underwent upper gastrointestinal endoscopy as well as a full length colonoscopy to detect changes in colonic mucosa. PHC was diagnosed endoscopically by the presence of vascular ectasia, diffuse hyperaemic mucosa and rectal varices. Biopsies were obtained from the recto-sigmoid area as well as from any abnormal mucosal lesions apart from angiodysplastic areas. Diffuse hyperaemia, angiodysplasia and rectal varices were found in 40%, 32.5% and 17.5% of patients while haemorrhoids in 42.5%, respectively. The prevalence of PHC increased with worsening Child-Pugh class, the mere presence of oesophageal varices while platelet count was significantly associated with angiodysplastic lesions only. None of other upper endoscopic features of PHT was significantly related to PHC. Moreover, history of lower gastrointestinal [GI] bleeding was significantly associated with the presence of rectal varices and haemorrhoids. Colonoscopic features of PHC were significantly associated with the histopathological diagnosis revealing 79% sensitivity and 66.6% specificity. Conclusion: PHC is a frequent finding in patients with PHT. Colonoscopic features suggestive of PHC were in concordance with the histopathological evidence. Although the presence of haemorrhoids is not a feature of colopathy, yet it should be considered together with anorectal varices as a cause of lower GI bleeding

Quality of life of Egyptian donors after living-related liver transplantation

Quality of life after liver donation must remain a primary outcome measure when we consider the utility of living donor liver transplants. In making clinical decisions on the use of transplantation for chronic liver diseases, consideration should be given to the key factors likely to affect subsequent health related quality of life. It would be beneficial for donors, if factors predicting good quality of life are identified. The aim of this study was to assess the health related quality of life changes experienced by donors following living related liver transplantation using the Short Form 36 [SF-36] questionnaire. Between August 2001 and December 2006, 125 adults received liver grafts from living donors at Dar Al-Fouad Hospital, Cairo, Egypt. The SF-36v2 questionnaire was applied to 30 donors after at least 6 months following donation and maximally 4 years after donation [mean +/- SD:3.28 +/- 1.56 years]. Furthermore, 30 healthy volunteers were taken as a control group. None of the donors required re-surgery and no deaths were reported. Only 4 [13.3%] donors experienced minor complications, which did not affect their quality of life and had no long term effects. No significant difference was found between donors and control group when means of the Physical and Mental Component Summary were compared. The physical functioning domain was the only domain of health which showed a statistically significant difference between both groups. Health related quality of life of donors was not compromised after full recovery. All donors had good recovery and returned to regular activities within 2-4 months post donation

Clinical role of serum squamous cell carcinoma antigen in egyptian patients with hepatocellular carcinoma

Since major advances in our ability to treat hepatocellular carcinoma [HCC] are less likely to come from treating late stage disease it is therefore important to find early stage disease. Serum Alpha-fetoprotein [alpha - FP] is currently the most widely performed screening test, but this sensitivity poor. It has been reported, recently, that squamous cell carcinoma antigen [SCCA] could represent a useful screening marker in patients at risk. The aim of this study to investigate the diagnostic utility of serum SCCA as a non invasive marker in HCC patients compared to alpha-FP. We recruited for the study forty patients with HCC, 25 patients with liver cirrhosis and 15 healthy subjects. Serum levels of SCCA and alpha-FP together with clinical, laboratory, and imaging evaluation were done for all cases. Hepatic focal lesions with atypical CT pattern for HCC were confirmed histopathologically with ultrasound-guided biopsy. Mean values of serum SCCA in HCC group was significantly higher when compared with both the control and cirrhotic groups [p<0.001]. It was significantly elevated in HCC patients showing atypical enhancement pattern versus those with typical one [p<0.05]. At the value of the kit cutoff value [2 ug/l], the specificity and sensitivity of SCCA were 62% and 84% respectively. While when using the receiver operator curve [ROC] curve, to improve the specificity and sensitivity of SCCA, the cutoff value of 2.55 ug/l yielded a sensitivity and specificity of 52.5% and 96% respectively [best cutoff]. The diagnostic sensitivity of alpha-FP at a cutoff 200 ng/dl was 26% and the specificity 100%. The cutoff level of alpha-FP for diagnosis of HCC according to ROC was 91.5 ng/dl yielded a sensitivity and specificity of 62.5% and 92%, respectively [best cutoff]. Simultaneous measurement of alpha-FP and SCCA led to improve the sensitivity of serologic diagnosis of HCC up to 87.5%. SCCA represents a useful diagnostic biomarker for HCC detection, when combined with alpha-FP, it significantly increases the reliability of serologic diagnosis for this cancer. SCCA could specially diagnose those with atypical enhancement pattern in CT scan