Aisha Elsharkawy

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.

Comparison of liver biopsy and noninvasive techniques for liver fibrosis assessment in patients infected with HCV-genotype 4 in Egypt

In Egypt, as elsewhere, liver biopsy (LB) remains the gold standard to assess liver fibrosis in chronic hepatitis C (CHC) and is required to decide whether a treatment should be proposed. Many of its disadvantages have led to develop noninvasive methods to replace LB. These new methods should be evaluated in Egypt, where circulating virus genotype 4 (G4), increased body mass index and co‐infection with schistosomiasis may interfere with liver fibrosis assessment. Egyptian CHC‐infected patients with G4 underwent a LB, an elastometry measurement (Fibroscan©), and serum markers (APRI, Fib4 and Fibrotest©). Patients had to have a LB ≥15 mm length or ≥10 portal tracts with two pathologists blinded readings to be included in the analysis. Patients with hepatitis B virus co‐infection were excluded. Three hundred and twelve patients are reported. The performance of each technique for distinguishing F0F1 vs F2F3F4 was compared. The area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75 for APRI, Fib‐4, Fibrotest© and Fibroscan©, respectively (no influence of schistosomiasis was noticed). An algorithm using the Fib4 for identifying patients with F2 stage or more reduced by nearly 90% the number of liver biopsies. Our results demonstrated that noninvasive techniques were feasible in Egypt, for CHC G4‐infected patients. Because of its validity and its easiness to perform, we believe that Fib4 may be used to assess the F2 threshold, which decides whether treatment should be proposed or delayed.

Sofosbuvir‐based treatment regimens: real life results of 14 409 chronic HCV genotype 4 patients in Egypt

Chronic hepatitis C virus infection is one of the most important health problems in Egypt. The Ministry of Healths National Treatment Programme introduced sofosbuvir‐based therapy in October 2014.

Hepatitis C infection in Egypt: prevalence, impact and management strategies

Hepatitis C virus (HCV) infection is a major public health burden in Egypt, where it bears the highest prevalence rate in the world. Estimates for prevalence are based upon data reported from the 2008 and 2015 Egypt Demographic Health Surveys. In this review, we demonstrate the prevalence results of both surveys and analyze the difference in the results. The overall HCV prevalence is estimated to be declining. However, the clinical impact of chronic HCV infection is expected to grow considerably. A mathematical model shows that by increasing the rate of treatment, the expected number of patients will decline significantly in 2030. The current and expected future burden of chronic HCV infection to the Egyptian economy, including direct and indirect costs due to disability and loss of lives, has been estimated and discussed in this review. The economic burden will continue to grow, but a model shows that the introduction of highly effective therapies will result in a significant reduction in the cumulative total economic burden of HCV by 2030. In recognition of the HCV tremendous health and economic burden, the Egyptian government established the National Committee for Control of Viral Hepatitis to implement an integrated nationwide strategy to provide patient care and ensure global treatment access. This review illustrates the epidemiological and disease burden aspects of HCV in Egypt in addition to introducing the national plan and program for managing HCV, which has been successful so far in treating a large number of patients, with the aim of achieving disease control and eventual elimination in Egypt.

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.

Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience

BACKGROUND AND AIMS The introduction of direct-acting antivirals for hepatitis C virus (HCV) in Egypt led to massive treatment uptake, with Egypts national HCV treatment program becoming the largest in the world. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for patients with HCV, highlighting the difficulties and limitations of the program, as a guide for other countries of similarly limited resources. METHODS Baseline data of 337,042 patients, treated between October 2014 to March 2016 in specialized viral hepatitis treatment centers, were grouped into three equal time intervals of six months each. Patients were treated with different combinations of direct-acting antivirals, with or without ribavirin and pegylated interferon. Baseline data, percentage of patients with known outcome, and sustained virological response at week 12 (SVR12) were analyzed for the three cohorts. The outcomes of 94,258 patients treated in the subsequent two months are also included. RESULTS For cohort-1, treatment was prioritized for patients with advanced fibrosis (F3-F4 fibrosis, liver stiffness ≥9.5 kPa, or Fibrosis-4 ≥3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The prioritization strategy in the initial phase caused delays in enrollment and massive backlogs. Cohort-1 patients were significantly older, and more had advanced fibrosis compared to subsequent cohorts. The percentage of patients with known SVR12 results were low initially, and increased with each cohort, as several methods to capture patient results were adopted. Sofosbuvir-ribavirin therapy for 24 weeks had the lowest SVR12 rate (82.7%); while other therapies were associated with SVR12 rates between 94% and 98%. CONCLUSION Prioritization based on fibrosis stage was not effective and enrollment increased greatly only after including all stages of fibrosis. The availability of generic drugs reduced costs, and helped massively increase uptake of the program. Post-treatment follow-up was initially very low, and although this has increased, further improvement is still needed. LAY SUMMARY We are presenting the largest national program for HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured efficiently in large scale real-life programs. This is a clear statement that global HCV eradication is foreseeable, providing a model for other countries with limited resources and prevalent HCV. Moreover, the availability of generic products has influenced the success of this program.

Fibroscan of chronic HCV patients coinfected with schistosomiasis.

BACKGROUND AND STUDY AIMS Both hepatitis C virus (HCV) and schistosomiasis are highly endemic in Egypt and coinfection is frequently encountered. Such coinfection is responsible for leading to a more severe liver disease. Hence, the aim of the study was to assess the fibroscan in chronic HCV patients coinfected with Schistosoma. PATIENTS AND METHODS This study included 231 chronic HCV patients. Routine pre-treatment work-up was done including anti-schistosomal antibodies. Liver stiffness measurements using fibroscan and reference needle-liver biopsy were done. Patients were categorised into two groups: HCV patients with positive schistosomal serology and HCV patients with negative schistosomal serology. RESULTS Anti-schistosomal antibody was positive in 29% of the studied population. Positive schistosomal serology status was significantly associated with the disagreement between the results of liver biopsy (Metavir) and the fibroscan results (p value=0.02), which was more obvious in F2 and F3 fibrosis stages. The sensitivity of fibroscan for the detection of the F2 stage decreased from 64% among negative schistosomal serology patients to 30.8% among positive schistosomal serology patients, and for the F3 stage it decreased from 43.8% to 21.4%, respectively. Multivariate logistic regression showed that fibrosis stages (F0-F1 and F4) were the most independent factors that were associated with the agreement between fibroscan and liver biopsy (odds ratio (OR) 3.4, 7.12 and p value <0.001, <0.001, respectively). CONCLUSION Although the sensitivity of fibroscan for the detection of fibrosis stages (F2 and F3) was impaired in patients with positive schistosomal serology, fibrosis stages (F0-F1 and F4) were the most independent factors associated with the agreement between fibroscan and liver biopsy.

Impact of different sofosbuvir based treatment regimens on the biochemical profile of chronic hepatitis C genotype 4 patients

ABSTRACT Background: Huge efforts have been made to control chronic HCV in Egypt with introduction of Direct-Acting Antivirals (DAAs). Current study aims at evaluating effect of various DAA regimens on liver biochemical profile and haematological indices during treatment. Methods: 272 patients with chronic HCV genotype 4 treated by different DAA regimens (SOF/RBV, SOF/DAC ± RBV, SOF/SIM) for a duration of 12 or 24 weeks in Kasr Alainy Viral Hepatitis Center, Cairo University were followed up for serum bilirubin (BIL), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), prothrombin concentration, international normalized ratio (INR), and CBC at baseline, week-4 and end of treatment. Results: Mean age was 54 years. Males comprised 64.7%, 72.4% were treatment-naïve, 39% were cirrhotic. Overall SVR12 rate was (93.4%). With all regimens, ALT and AST declined after treatment. In cirrhotics, there was a rise in BIL and INR; with no change in ALB and a decrease in White blood cells. Drop in Hemoglobin and platelets in cirrhotic patients were noted with SOF/RBV, while SOF/SIM showed rise in BIL. Conclusion: DAAs are safe and effective in genotype 4 chronic HCV patients. It improves liver necro-inflammatory markers in cirrhotics and non-cirrhotics. Cirrhotic patients require careful observation being more vulnerable for treatment related complications.

Improvement of glycemic state among responders to Sofosbuvir - based treatment regimens: Single center experience†

Chronic HCV infection has emerged as a complex multifaceted disease with manifestations extending beyond the liver. HCV plays a direct role in glucose metabolism leading to both insulin resistance and type 2 diabetes. To evaluate the changes in the glycemic state following Sofosbuvir‐based treatment regimens in diabetic HCV patients. Four hundred chronic hepatitis C patients who underwent Sofosbuvir‐based treatment regimens were retrospectively screened. Sixty‐five diabetic HCV patients only enrolled in our analysis. Baseline demographic and laboratory data were recorded. Pretreatment Transient elastography was performed. At 24‐week post EOT (SVR24), Fasting Plasma glucose, and Hemoglobin A1c were re‐evaluated and compared with baseline. All enrolled diabetic patients were responders. They showed statistically significant decline in Fasting Plasma glucose and Hemoglobin A1c values at SVR24. Whatever the degree of hepatic fibrosis, the level of Fasting Plasma glucose and Hemoglobin A1c decreased at SVR24 in comparison to baseline level. Fifty‐one patients showed improvement in their Hemoglobin A1c values at SVR24 and this improvement was more likely to occur among patients with low Body mass index. The reduction in Fasting Plasma glucose >20 mg/dL (>1.1 mmol/L) and Hemoglobin A1c ≥0.5% was not associated with age, gender or hepatic fibrosis stage. Sofosbuvir‐based regimens are a highly efficient antiviral therapy for diabetic chronic HCV patients resulted in improvement in Fasting Plasma glucose and Hemoglobin A1c.

FibroScan, APRI, FIB4, and GUCI: Role in prediction of fibrosis and response to therapy in Egyptian patients with HCV infection.

BACKGROUND AND STUDY AIMS Multiple noninvasive methods have been used successfully in the prediction of fibrosis. However, their role in the prediction of response to hepatitis C virus (HCV) antiviral therapy is debatable. The aim of this study was to validate and compare the diagnostic performance of FibroScan, APRI (aspartate aminotransferase (AST)-to-platelet ratio index), FIB4, and GUCI (Göteborg University Cirrhosis Index) for the prediction of hepatic fibrosis and treatment outcome in HCV-infected patients receiving pegylated interferon and ribavirin (PEG-IFN/ribavirin). PATIENTS AND METHODS This study included 182 Egyptian patients with chronic HCV infection. They were classified into two groups based on the stages of fibrosis: mild to significant fibrosis (F1-F2) and advanced fibrosis (F3-F4). The APRI, FIB4, and GUCI scores were calculated before the antiviral treatment. The FibroScan was performed for all patients before treatment. RESULTS Stiffness and FIB4 have greater sensitivity and specificity in detecting advanced fibrosis of 80%, 77% and 88%, 84%, respectively. Based on multivariate regression analysis, FIB4, body mass index (BMI), and alpha-fetoprotein (AFP) level were found to be statistically significant predictors of advanced fibrosis (p-value: 0.000, 0.011, and 0.001, respectively) with odds ratio (OR: 3.184, 1.170, and 1.241, respectively). With respect to virological response, the stiffness, APRI, FIB4, and GUCI were significantly lower in sustained virological responders. However, these are not good predictors of response to PEG-IFN/ribavirin therapy. AFP was the only statistically significant predictor of response (p=0.002) with OR of 1.141 in multivariate regression analysis. CONCLUSION FibroScan and noninvasive scores such as APRI, FIB4, and GUCI can be used as good predictors of liver fibrosis in chronic hepatitis C. However, they are not good predictors of response to PEG-IFN/ribavirin therapy.