Maissa El Raziky

Coinfection with hepatitis C virus and schistosomiasis: Fibrosis and treatment response

AIM To assess whether schistosomiasis coinfection with chronic hepatitis C virus (HCV) influences hepatic fibrosis and pegylated-interferon/ribavirin (PEG-IFN/RIB) therapy response. METHODS This study was designed as a retrospective analysis of 3596 chronic HCV patients enrolled in the Egyptian National Program for HCV treatment with PEG-IFN/RIB. All patients underwent liver biopsy and anti-schistosomal antibodies testing prior to HCV treatment. The serology results were used to categorize the patients into group A (positive schistosomal serology) or group B (negative schistosomal serology). Patients in group A were given oral antischistosomal treatment (praziquantel, single dose) at four weeks prior to PEG-IFN/RIB. All patients received a 48-wk course of PEG-IFN (PEG-IFNα2a or PEG-IFNα2b)/RIB therapy. Clinical and laboratory follow-up examinations were carried out for 24 wk after cessation of therapy (to week 72). Correlations of positive schistosomal serology with fibrosis and treatment response were assessed by multiple regression analysis. RESULTS Schistosomal antibody was positive in 27.3% of patients (15.9% females and 84.1% males). The patients in group A were older (P = 0.008) and had a higher proportion of males (P = 0.002) than the patients in group B. There was no significant association between fibrosis stage and positive schistosomal serology (P = 0.703). Early virological response was achieved in significantly more patients in group B than in group A (89.4% vs 86.5%, P = 0.015). However, significantly more patients in group A experienced breakthrough at week 24 than patients in group B (36.3% vs 32.3%, P = 0.024). End of treatment response was achieved in more patients in group B than in group A (62.0% vs 59.1%) but the difference did not reach statistical significance (P = 0.108). Sustained virological response occurred in significantly more patients in group B than in group A (37.6% vs 27.7%, P = 0.000). Multivariate logistic regression analysis of patient data at treatment weeks 48 and 72 showed that positive schistosomal serology was associated with failure of response to treatment at week 48 (OR = 1.3, P = 0.02) and at week 72 (OR = 1.7, P < 0.01). CONCLUSION Positive schistosomal serology has no effect on fibrosis staging but is significantly associated with failure of response to HCV treatment despite antischistosomal therapy.

The Effect of Peginterferon Alpha-2a vs. Peginterferon Alpha-2b in Treatment of Naive Chronic HCV Genotype-4 Patients: A Single Centre Egyptian Study

Background Egypt has one of the highest (16-8%) prevalence rates of HCV infection in the world. Approximately 90% of Egyptian HCV isolates belong to a single subtype (4a), which responds less successfully to interferon therapy than other subtypes. Studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naive HCV-infected patients have shown conflicting results. Objectives Assessing the effects of Peginterferon alpha-2a versus Peginterferon alpha-2b on the sustained virological response in naive chronic HCV genotype-4 Egyptian patients. Patients and Methods This retrospective study cohort consists of 3718 chronic HCV patients admitted to a large, Egyptian medical center. 1985 patients had been treated with PEG-IFN alfa-2a plus RBV and 1733 patients with PEG-IFN alfa-2b plus RBV between years 2007-2011. Efficacy outcomes were sustained virologic response (SVR) and treatment discontinuation rates due to serious adverse effects. Results The ETR & SVR in patients treated with PEGIFN alfa-2a was 64.1% and 59.6% as compared to treatment with PEGIFN alfa-2b where these parameters were 58.2% and 53.9% respectively (P < 0.05). Treatment discontinuation rates, were similar in the two types of PEGIFN [0.66 (0.37-1.16); P = 0.15]. Significant dose reduction was evident with peginterferon alfa-2b (35.3%) than peginterferon alpha-2a (27.3 %) (P < 0.01). Patients with lower base line AFP and ALT were most likely to achieve SVR using INF alpha 2-a. Conclusions Peginterferon alpha-2a has a higher efficacy regarding ETR and SVR as compared to Peginterferon alfa-2b in treatment of naive chronic HCV genotype-4 patients.

Single nucleotide polymorphism at exon 7 splice acceptor site of OAS1 gene determines response of hepatitis C virus patients to interferon therapy

Background and Aim:  Response to interferon therapy and disease progression in hepatitis C virus (HCV) infected patients differs among individuals, suggesting a possibility of a contribution of host genetic factors. 2′‐5′‐oligoadenylate synthetase 1 (OAS1), an important component of the innate immune system with a proven antiviral function, may therefore have a relationship with the response to interferon therapy and clinical course of HCV disease. Our aim was to determine the frequency of single nucleotide polymorphism (SNP) at exon 7 splice acceptor site (SAS) of the OAS1 gene in relation to the interferon response and status of HCV infection.

Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon

Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow‐up disease progression. Multiple non‐invasive methods have been used successfully in the prediction of fibrosis; however, early changes in non‐invasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB‐4 and AST to platelet ratio index (APRI) in patients treated with Sofosbuvir‐based treatment regimen.

Optimizing treatment for HCV genotype 4: PEG-IFN alfa 2a vs. PEG-IFN alfa 2b; the debate continues

Hepatitis C virus (HCV) remains one of the leading causes of morbidity and mortality worldwide. Combined therapy with pegylated interferon (PEG‐IFN) and ribavirin is the current standard of care treatment for HCV genotype 4. Two types of PEG‐IFN are commercially available. The limited number of trials that were conducted for HCV genotype 4 and the few head to head comparisons make it impossible to know which is the best option? In this article we review all available PEG‐IFN trials performed worldwide for HCV genotype 4 since 2004. Unless another molecule is developed as a standalone for the treatment of HCV, PEG‐IFN will continue to be a source of debate.

Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4.

This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon‐based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa‐2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real‐time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide −155, −443 and −1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at −443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide −443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment. Copyright

Human leukocyte antigen class II alleles (DQB1 and DRB1) as predictors for response to interferon therapy in HCV genotype 4.

Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66%) of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1∗0313 allele and DRB1∗04-DRB1∗11, DQB1∗0204-DQB1∗0313, DQB1∗0309-DQB1∗0313, and DQB1∗0313-DQB1∗0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1∗02, DQB1∗06, DRB1∗13, and DRB1∗15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1∗1301, DRB1∗1361, and DRB1∗1369 alleles and DRB1∗1301-DRB1∗1328, DRB1∗1301-DRB1∗1361, DRB1∗1301-DRB1∗1369, DRB1∗1328-DRB1∗1361, and DRB1∗1328-DRB1∗1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.

Hepatic fibrosis and serum alpha-fetoprotein (AFP) as predictors of response to HCV treatment and factors associated with serum AFP normalisation after treatment.

BACKGROUND AND STUDY AIM Elevated levels of alpha-fetoprotein (AFP) can be seen in patients with chronic hepatitis C (CHC) and liver cirrhosis without hepatocellular carcinoma and were negatively associated with treatment response. However, factors associated with its changes are not identified. We aimed in this study to verify a cut-off value for AFP as a predictor of response to standard of care (SOC) antiviral therapy in Egyptian chronic hepatitis C virus (HCV)-infected patients and identify factors associated with its changes post treatment. PATIENTS AND METHODS A total of 175 chronic non-cirrhotic HCV-infected patients were evaluated for baseline serum AFP and liver biopsy were classified according to Ishak scoring system of hepatic fibrosis. All patients were scheduled to receive SOC antiviral therapy for 48weeks and had been followed up to week 72. Reassessment of AFP and repeated liver biopsy at week 72 were feasible only in 79 patients. RESULTS High baseline AFP levels were observed in non-respondents (non-sustained virological respondents (non-SVRs)) (P<0.01); the AFP level decreased in all patients post treatment (P=0.01), especially in the SVRs (P<0.01). In multivariate analysis, hepatic fibrosis was a predictor of response to treatment (P=0.02), while body mass index (BMI) (25-30kgm(-2)), hepatic activity (A2), hepatic fibrosis stage (F2-F4) and fibrosis improvement were predictors of AFP difference (P=0.007, 0.01, 0.012, <0.001, 0.030, and 0.018), respectively. The diagnostic performance to predict the HCV treatment response was best by adding both AFP and hepatic fibrosis stage factors; the best cut-off value for AFP was 3.57ngdl(-1) with 50% sensitivity and 68% specificity with area under the curve (AUC) of 0.55 and for hepatic fibrosis stage was 3, with a sensitivity of 88%, a specificity of 30% with an AUC of 0.58. CONCLUSION In chronic HCV-infected patients, serum AFP below 3.57ngdl(-1) and hepatic fibrosis ⩽stage 3 are expected to have good response to treatment; BMI (25-30kgm(-1)), A2, fibrosis >2 and fibrosis improvement predict AFP change post treatment.

APRI test and hyaluronic acid as non-invasive diagnostic tools for post HCV liver fibrosis: Systematic review and meta-analysis

BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV) accounts for a sizable proportion of chronic liver disease cases and represents the most common indication for liver transplantation. Precise diagnosis of hepatic fibrosis stage is considered a funnel-neck in proper management and follow-up of HCV-infected patients. Given the possible complications of liver biopsy, a non-invasive method for assessing hepatic fibrosis is needed. This study aimed to evaluate the diagnostic accuracy of APRI and hyaluronic acid as non-invasive diagnostic assessment tools for post HCV liver fibrosis. PATIENTS AND METHODS Systematic literature searching identified studies performed on Egyptian territory to evaluate APRI and hyaluronic acid as non-invasive tests of fibrosis and using liver biopsy as the reference standard. Meta-analysis was performed for areas with an adequate number of publications. Validation of meta- analysis on APRI was done on a subset of 150 treatment-naïve post-hepatitis C patients. RESULTS Both APRI and hyaluronic acid have superior predictive power for hepatic cirrhosis (F4) than for significant fibrosis (F2-F3). The pooled estimate for sensitivities and specificities of APRI and hyaluronic acid to diagnose F4 were (84% and 82%) and (83% and 89%) respectively. In the subgroup of treatment naïve post-hepatitis C patients, APRI had higher diagnostic performance to diagnose liver cirrhosis with 93.8% sensitivity and 72.4% specificity (AUC; 0.908, 95%CI; 0.851-0.965, p-value; <0.001) compared to its accuracy to diagnose significant hepatic fibrosis with 65.1% sensitivity and 77.8% (AUC; 0.685, 95% CI; 0.59-0.78, p-value; 0.001). CONCLUSION APRI score and hyaluronic acid levels are simple and reliable non-invasive markers to detect advanced fibrosis among post-hepatitis C patients.

Antischistosomal therapy: Current status and recent developments.

Schistosomiasis remains one of the most prevalent parasitic infections in the world. Currently, Praziquantel (PZQ) is the drug being used to treat human schistosomiasis on a large scale. Millions of people are treated annually with praziquantel, and drug-resistant parasites thus are likely to evolve. This review focuses on current knowledge about the mechanisms of action of PZQ, possibility of PZQ resistance, potentially alternative drugs, and prospects for development of new schistosomicides .Vaccines production strategies represent an essential component for the future control of schistosomiasis as an adjunct to chemotherapy.