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

Role of fibroscan and APRI in detection of liver fibrosis: a systematic review and meta-analysis

Fibroscan and APRI are promising noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. However, their overall test performance in various settings remains questionable. The aim of our study was to perform a systematic review and meta-analysis of diagnostic accuracy studies comparing fibroscan and APRI with liver biopsy for hepatic fibrosis. Electronic and manual bibliographic searches to identify potential studies were performed. Selection of studies was based on reported accuracy of fibroscan and APRI compared with liver biopsy. Data extraction was performed independently by two reviewers. Meta-analysis combined the sensitivities, specificities, and likelihood ratios of individual studies. Extent and reasons for heterogeneity were assessed. 23 studies for fibroscan and 20 studies for APRI in full publication were identified. For patients with stage IV fibrosis [cirrhosis], the pooled estimates for sensitivity of fibroscan were 83.4% [95% confidence interval [CI], 71.7-95.0%] and specificity 92.4% [95% CI, 85.6-99.2%]. For patients with stage IV fibrosis [cirrhosis], the pooled estimates for sensitivity of APRI at cutoff point of 1.5 were 66.5% [95% CI, 25.0-100%] and specificity 71.7% [95% CI, 35.0-100%]. Diagnostic threshold bias was identified as an important cause of heterogeneity for pooled results in both patient groups. Fibroscan and APRI appear to be clinically useful tests for detecting cirrhosis however not useful tools in early stages of fibrosis

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

Doppler changes in chronic hepatitis C virus Egyptian patients with sustained virological response [SVR]

Duplex-doppler ultrasound is a non-invasive method for the assessment of hepatic haemodynamics beyond conventional gray-scale imaging. The clinical values of the methods used for the grading and staging of chronic hepatitis C virus [HCY] infection and the prediction of hepatic steatosis still have to be determined. Was to study the predictive value of pulse wave Doppler ultrasonography in Egyptian patients treated with interferon and Ribavirin through comparing the heamodynamics before and after treatment as well as the detection of the differences in Doppler parameters in IFN-SYR and IFN-NR patients. This study included 50 Hey patients treated with PEG-IFN and Ribavirin. Thirty six patients showed SYR while the remaining 14 patients were non responders. Real time abdominal ultrasonography was done with special concern on abdominal Doppler. Doppler was done by a single ultrasonographer pre and post treatment with special emphasis on liver heamodynamics [Portal vein diameter, Portal vein flow and mean velocities [PVPV] and [PVMV], portal vein circumference and area, hepatic artery resistance and pulsatility indices [HARI] and [HAPI], as well as splenic vein diameter, splenic artery resistance and pulsatility indices [SARI] and [SAPI]]. Hepatic veins phasicity: [triphasic, biphasic, or monophasic], congestion index [in cm/s], modified hepatic vascular index [in cm/s] [MHI], hepatic vascular index and portal hypetiension index were also measured. All the patients were treated by Pegylated interferon 180 microg/week and Ribavirin 13-15 mg/kg/day for 48 weeks [IfPCR still was positive after 24 weeks of treatment, treatment was discontinued, but the patient remained on follow up]. All patients in the study gave an informed consent. Liver biopsies were done for all patients prior to interferon therapy and at 72 weeks [6 months after the end of treatment] with histopathological grading according to METAYIR score. The chronic Hey infected patients in whom IFN and Ribavirin treatment resulted in complete response [SYR] showed that the mean PVPV was [17.59 +/- 5.79 cm/s] while post treatment was [16.39 +/- 3.76 cm/ s]. HAPI pre treatment was [1.77 +/- 0.7 cm/s], and post treatment was [1.62 +/- 0.46 cm/s], and the HARI pre treatment was [0.61 +/- 0.16 cm/s], while post treatment was [0.61 +/- 0.18 cm/s], with no statistical significant difference in the responder group, while the SVMV showed statistical significant difference pre [18.8 +/- 7.37 cm/s], and post treatment [15.2 +/- 4 cm/s]. Also the SVMV pre treatment was [14.7 +/- 5.71 cm/s], while post treatment was[12 +/- 3.74 cm/s], and this was statistically significant [p<0.05]. Pulse wave Doppler ultrasonography is an easy and non-invasive procedure for evaluating the chronic HCY liver disease, but not effective nor valid to estimate the effect and response to anti-viral therapy

Value of serum lentil affinity of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma on top of liver cirrhosis

Hepatocellular carcinoma [HCC] is a common complication in patients with liver cirrhosis [LC]. Detection of HCC at an early stage is critical for a favorable clinical outcome. AFP-L3% is an isoform of AFP which is very specific for HCC. The AFP-L3% is the percentage of AFP-L3 over the total AFP level. The study aimed to evaluate the utility of AFPL-3% in detection of HCC developing on top of liver cirrhosis, to compare the levels of both alpha- fetoprotein [AFP] and AFP-L3% in HCC versus LC patients without HCC and to define the cut-off level of each tumor marker with the best sensitivity and specificity for HCC detection. The study was conducted on 25 cases of HCC that developed on top of LC and 25 LC cases with no evidence of HCC, as well as 25 apparently healthy controls. The levels of AFP and AFP-L3% were measured for all cases. Biochemical parameters and viral markers were also tested. Imaging and histopathological evidence of HCC were a prerequisite for inclusion in HCC group. Patients included in the HCC group had total AFP value < 200 ng/ml, which is not a diagnostic level for HCC. Levels of AFP and AFP L-3% were significantly higher in patients with HCC compared to those without HCC [P < 0.01]. Receiver-operating characteristic [ROC] curve analysis indicated that the best cut-off value was 15.4% for AFP-L3% to detect HCC as the sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV] and accuracy were 79.2%, 100%, 100%, 83.3% and 96.2% respectively. For AFP, the best cut-off in the non diagnostic range was 77.8 ng/ ml as the sensitivity, specificity, PPV, NPV, and accuracy were 75%, 68%, 69.2%, 73.9% and 70.4% respectively, The mean serum level of AFP showed no significant difference [P>0.05] regarding Child Pugh classification, numbers of tumor foci nor rumor size, however, it showed a significant difference [P<0.05] regarding lymph nodes invasion and TNM classification in HCC patients. Meanwhile, AFP-L3% showed no significant difference [P>0.05] regarding all these parameters. There was a positive significant correlation [P<0.05] between AFP and both AST and ALT, while AFP-L3% showed inverse significant correlation [P<0.05] with PC%. No significant correlation [P>0.05] was observed between serum AFP and serum AFP-L3% in HCC patients. In patients with total AFP values <200 ng/ml who present a diagnostic dilemma, AFP-L3% had higher sensitivity, specificity, PPV, NPV and accuracy for HCC detection, and was not elevated in any of the patients without HCC with specificity of 100%

Hepatitis C virus and peripheral neurological complications in Egyptian patients

Neurological complications in HCV-infected patients occur predominantly in the peripheral nervous system. Vasculitic neuropathy is the most firmly linked neurologic illness associated with HCV infection. This type of neuropathy occurs frequently in the presence of cryoglobulinemia. HCV-related cranial neuropathies have been also reported. This study was conducted to investigate the various peripheral neurological complications of chronic hepatitis C infection and their possible pathogenetic mechanisms. This study was conducted on 160 patients with chronic hepatitis C infection comprised two subgroups: group I, composed of 80 chronic hepatitis C patients with clinically apparent neurological complication[s], and group II, composed of 80 chronic hepatitis C patients neurologically asymptomatic. Patients were subjected to clinical evaluation, estimation of hepatitis markers, cryoglobulins, anticardiolipin antibodies, antinuclear antibodies and nerve conduction studies. Peripheral neuropathies represented the most commonly encountered neurological disorders, occurring in 25 patients [31.25%]. The sensory peripheral neuropathy was the most common type, representing 32% of neuropathic patients [8/25]. A statistically significant difference was found between groups I and II regarding the presence of cryoglobulin and anticardiolipin antibody, being more common in group I. Antinuclear antibody was more common in group I than in group II. Results of nerve conduction studies showed nerves were more affected in group I and in cryoglobulin and ANA positive patients. Peripheral neuropathies represent the most common HCV-related peripheral neurological disorders especially when associated with cryoglobulins and ANA antibodies

Study of oesophageal motility in Egyptian cirrhotic patients before and after prophylactic endoscopic variceal ligation

The aim of this work is to study oesophageal motility in non bleeding cirrhotic patients before and after endoscopic ligation of oesophageal varices. This study was conducted on 90 subjects as follows: Group [I]: 50 patients with liver cirrhosis and large oesophageal varices [i.e. grade III, IV]. Group [II]: 20 patients diagnosed with liver cirrhosis but without oesophageal varices. Group [III]: 20 healthy volunteers. Written informed consent was obtained from all subjects. Complete laboratory investigations were done as well as abdominal ultrasonography, upper endoscopy and oesophageal motility was done by stationary and rapid pull through manometery using a low compliance pneumohydraulic perfusion system. EVL was done in 50 patients [Group I]. Oesophageal motility before EVL revealed that there was a significant decrease in the amplitude of the contractive wave at the middle and the distal oesophagus and there was an increase in the wave velocity in the distal oesophagus with significant increase in the abnormal waves with no effect on wave duration. Ascites had no effect on the oesophageal motility and the LES pressure; also there was no significant difference in patients in terms of Child Pugh grading. Oesophageal motility after EVL revealed no significant decrease in the amplitude of the contractive wave at the middle oesophagus, and the decreased amplitude in the distal oesophagus before EVL was returned to the level of normal healthy control. Also, there was increase in the velocity of wave after EVL in the distal oesophagus with no effect on wave duration. Prophylactic EVL is an effective method for primary prophylaxis of oesophageal varices with no serious complications. EVL normalized oesophageal motility and if it induced abnormal oesophageal motility, it was of little clinical significance and reversible