Impacts of the Egyptian national screening and treatment programme for viral hepatitis C: A cost-effectiveness model.

BACKGROUND & AIMS: Egypt used to have one of the highest prevalences of HCV infection worldwide. The Egyptian Ministry of Health launched a national campaign for the detection and management of HCV to reduce its burden. This study aims to carry out a cost-effectiveness analysis to evaluate the costs and benefits of the Egyptian national screening and treatment programme. METHODS: A disease burden and economic impact model was populated with the Egyptian national screening and treatment programme data to assess direct medical costs, health effects measured in disability-adjusted life years and the incremental cost-effectiveness ratio. The scenario was compared to a historical base case, which assumed that no programme had been conducted. RESULTS: Total number of viremic cases is expected to decrease in 2030 by 86% under the national screening and treatment programme, versus by 41% under the historical base case. Annual discounted direct medical costs are expected to decrease from $178 million in 2018 to $81 million by 2030 under the historical base case, while annual direct medical costs are estimated to have peaked in 2019 at $312 million before declining to $55 million by 2030 under the national screening and treatment programme. Under the programme, annual disability-adjusted life years are expected to decline to 127 647 by 2030, leading to 883 333 cumulative disability-adjusted life years averted over 2018-2030. CONCLUSIONS: The national screening and treatment programme is highly cost-effective by the year 2021, cost-saving by 2029 and expected to save about $35 million in direct costs and $4705 million in indirect costs by 2030.

Prevalence and clinical characteristics of patients with metabolic dysfunction-associated fatty liver disease with hepatitis C virus infection-a population-based study.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) was proposed in 2020 to identify fatty liver disease associated with metabolic risks. Metabolic abnormalities with hepatitis C virus (HCV) and MAFLD frequently co-exist. However, data on the co-existence are still lacking. AIM: To explore the prevalence and characteristics of metabolic profiles among a large cohort of patients with HCV infection between 2007 and 2020 based on new diagnostic criteria METHODS: We recruited 288,222 patients with chronic HCV infection with demographic data, laboratory parameters, and ultrasound from a web-based registry of the National Committee for Control of Viral Hepatitis in Egypt from 2007 to 2020. RESULTS: Among the participants, 41.9% (95% CI: 41.69-42.05) met diagnostic criteria for MAFLD, with a significant increase in the period 2014-2020 compared to 2007-2013 (43.3% vs. 19%, respectively). Participants with MAFLD had a high prevalence of obesity, diabetes mellitus and hypertension. The prevalences increased significantly over time (obesity: 66.7% vs. 76.9%, p < 0.01; diabetes mellitus: 14.6% vs. 31.5%, p < 0.01; hypertension: 0.9% vs. 7.6%, p < 0.01; prediabetes: 28.8% vs. 25.9%, p < 0.01) for the periods 2007-2013 and 2014-2020, respectively. The percentage of advanced fibrosis by fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) was significantly higher in participants with MAFLD during 2014-2020 than during 2007-2013 (FIB-4; 18.4% vs. 8% and NFS; 17.1% vs. 7%). CONCLUSION: MAFLD is highly prevalent in patients with HCV infection and has risen over time. This rising prevalence parallels the alarming rise in obesity, diabetes mellitus and hypertension. Early detection of metabolic dysfunction in patients with HCV infection is recommended to prevent MAFLD progression.

Efficacy of combined Sofosbuvir and Daclatasvir in the treatment of COVID-19 patients with pneumonia: a multicenter Egyptian study.

BACKGROUND: Limited experimental and clinical evidence suggests a potential role for sofosbuvir/daclatasvir in treating COVID19. We aim to evaluate the efficacy of generic sofosbuvir/daclatasvir in treating COVID-19 patients with pneumonia. RESEARCH DESIGN AND METHODS: This multicenter prospective study involved 174 patients with COVID-19. Patients were randomized into two groups. Group A (96 patients) received sofosbuvir (400 mg)/daclatasvir (60 mg) for 14 days in combination with conventional therapy. Group B (78 patients) received conventional therapy alone. Clinical, laboratory, and radiological data were collected at baseline, after 7, 14, and 28 days of therapy. Primary endpoint was rate of clinical/virological cure. RESULTS: A lower mortality rate was observed in group (A) (14% vs 21%, P = 0.07). After 1 month of therapy, no differences were found in rates of ICU admission, oxygen therapy, or ventilation. Additionally, a statistically significant shorter duration of hospital stay (9% vs 12%, P < 0.01) and a faster achievement of PCR negativity at day 14 (84% versus 47%, P < 0.01) were noticed in group (A). CONCLUSION: Adding sofosbuvir/daclatasvir to conventional therapy of COVID-19 is promising. Their use is associated with shorter hospital stay, faster PCR negativity and may be reduced mortality.

Impact of successful HCV treatment using direct acting antivirals on recurrence of well ablated hepatocellular carcinoma.

BACKGROUND: There are many contradictory studies that dealt with hepatocellular carcinoma (HCC) recurrence rate of well ablated hepatitis C virus (HCV) related HCC. We aim to assess the recurrence rate of previously ablated HCC in patients who received direct acting antiviral (DAA) for their HCV. RESEARCH DESIGN AND METHODS: This is a retrospective data analysis of 523 HCV patients who have a history of successfully ablated HCC and eligible for HCV treatment. Retrieval was done to demographic/clinical data, HCV pretreatment investigations, HCV treatment outcome. Follow up for survival and HCC recurrence was done every 3 months using abdominal ultrasound and alfa-fetoprotein. RESULTS: Mean age was 53.83 years. Sofosbuvir/daclatasvir/ribavirin was the most used regimen (35.4%) with 438 patients (83.7%) achieved sustained virologic response (SVR). The median duration for surveillance was 159 weeks. Hundred and five patients developed recurrent HCC, with a crude recurrence rate of 20.1%. There was no difference between HCV responders and non-responders in crude recurrence rate (p = 0.94) but HCC developed earlier in non-responders (p = <0.01). CONCLUSION: Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended.

Pregnancy outcome of anti-HCV direct-acting antivirals: Real-life data from an Egyptian cohort.

We aimed to assess the pregnancy outcome in women with chronic HCV who had negative pregnancy test prior to the anti-HCV course and had unintended pregnancy while on HCV treatment. Hundred patients with a mean age of 30 ± 6.7 y were included and advised to withhold antivirals and continue follow-up in viral hepatitis and obstetrics centres till delivery. All patients received a 12-weeks regimen of anti-HCV [sofosbuvir plus daclatasvir (SOF/DCV): n = 95, SOF/DCV plus ribavirin: n = 3, and paritaprevir/ritonavir/ombitasvir plus ribavirin: n = 2]. Only nine patients completed the full antiviral course against medical advice, and 91 stopped between on-treatment weeks 4 and 8. Eighty-eight patients delivered full-term babies, eight had preterm babies and two had abortions. Of the nine patients who completed the full course of DAAs, seven (77.8%) delivered normal babies, attended their post-treatment week 12 visit, and all (100%) achieved sustained virological response. No major antiviral-related adverse events were reported.

Evaluation of red cell distribution width to platelet ratio as a novel non-invasive index for predicting hepatic fibrosis in patients with chronic hepatitis C.

BACKGROUND AND STUDY AIMS: Assessing the extent of fibrosis is an essential part of therapeutic decisions in patients with chronic hepatitis C (CHC). Liver biopsies are the "gold standard" for evaluating liver fibrosis but have many limitations. Thus, noninvasive predictors of fibrosis have been developed. This study aimed to determine the effectiveness of red cell distribution width (RDW) to platelet ratio as a simple noninvasive method for predicting the hepatic fibrosis stage in patients with CHC. PATIENTS AND METHODS: This cross-sectional study included 197 Egyptian patients with CHC. A routine pretreatment reference needle liver biopsy was performed. Fib-4, transient elastography (TE) by Fibroscan, AST to Platelet Ratio Index (APRI), and RDW to platelet ratio (RPR) were measured. Predictors of significant fibrosis (Metavir score ≥ F2) and advanced fibrosis (Metavir score ≥ F3) were identified. RESULTS: Fib-4, TE, APRI, and RPR values differed significantly when comparing different stages of fibrosis (p < 0.01). Fib-4, TE, APRI, and RPR were reliable diagnostic tools at cutoff values of 1.17, 7.75, 0.18, and 0.07, respectively, for predicting significant fibrosis and cutoff values of 1.99, 8, 1.77, and 0.08, respectively, for predicting advanced fibrosis. Using logistic regression analysis, TE was identified as an independent predictor associated with significant and advanced fibrosis. Fib-4 was significantly associated with advanced fibrosis only. CONCLUSION: The use of Fib-4, TE, APRI, and RPR measurements may decrease the need for liver biopsies for predicting significant and advanced fibrosis. RPR showed fair sensitivity, specificity, positive and negative predictive values, and overall accuracy for predicting significant fibrosis in patients with CHC.

The interrelation between lipid profile in chronic HCV patients and their response to antiviral agents.

OBJECTIVES: This study aims to assess the changes of lipid profile in chronic HCV patients; before, during, and after treatment with DAAs and their association with treatment response. METHODS: 301 chronic HCV patients who received SOF-based therapy were included. Serum lipid profile was assessed at different check points; baseline, 6 weeks on treatment, end of treatment (EOT) and 12 weeks after EOT; and compared between SVR and non-SVR groups. RESULTS: SVR group had significantly higher baseline lipid parameters compared to non-SVR group with significant increase in lipid parameters at different time points apart from HDL-C. Non-SVR group showed non-significant change in lipid parameters apart from LDL-C. On week6 on treatment, cholesterol level > 125 mg/dl was 92.8% sensitive, 97.3% specific with 95.5% NPV, and AUC of 0.989 in prediction of SVR. Similarly, LDL > 57 mg/dl was 83.7% sensitive, 100% specific with 93.3%, NPV and AUC of 0.952. Baseline cholesterol and LDL were significantly associated with SVR. CONCLUSION: Higher baseline lipid parameters and their further elevation starting from week 6 on treatment are good predictors of SVR in HCV patients. Successful HCV therapy with DAAs is associated with a significant increase in lipid parameters.

Sustained virologic response and changes in liver fibrosis parameters following 12-wk administration of generic sofosbuvir and daclatasvir in HIV/HCV-coinfected patients with HCV genotype 4 infection.

BACKGROUND: Novel direct-acting antiviral agents have shown great efficacy and tolerability in HCV-monoinfected patients. However, data are lacking regarding their efficacy and safety in HIV/HCV-genotype (GT) 4-coinfected patients. METHODS: A single-centre, prospective study including HIV/HCV-GT 4-coinfected patients who were treated with sofosbuvir and daclatasvir (SOF/DCV) was conducted for 12 wk. Sustained virological response (SVR) at week 12 post-treatment (SVR12), adverse events (AEs) and changes in liver stiffness measurement (LSM) at SVR12 in comparison with baseline were evaluated. RESULTS: SVR12 was achieved in 46 of 50 patients (92%). No significant difference in SVR12 was noticed among patients who received antiretroviral therapy (ART) regimens compared with those who did not receive ART regimens or between those with insignificant fibrosis (

Liver stiffness measurements and FIB-4 are predictors of response to sofosbuvir-based treatment regimens in 7256 chronic HCV patients.

Objectives: To assess the role of baseline liver stiffness (LS) by Transient elastography (TE) and FIB-4 in the prediction of virological response to sofosbuvir - based regimens in chronic HCV patients.Methods: A retrospective, multicenter study including 7256 chronic HCV patients who received different sofosbuvir-based regimens. Baseline demographic and laboratory data were recorded. TE was performed with FIB-4 calculation at baseline.Results: Sustained virological response at week 12 post-treatment (SVR12) was 91.4%. Pretreatment TE values and FIB-4 were significantly lower among sustained responders (17.8 ± 11.5 kPa, 2.66 ± 1.98, respectively) versus relapsers (24.5 ± 13.9 kPa, 4.02 ± 3.3, respectively). Best cutoff levels for LS by TE and FIB-4 score for prediction of failure to treatment response were 16.7 kPa and 2.4, respectively. Among different treatment protocol, patients with FIB-4 > 2.4, TE values >16.7 kPa are more prone to treatment failure except when using SOF/SIM treatment regimens.Conclusion: Baseline LS by TE and FIB-4 score may be useful for predicting treatment outcome in the new era of DAAs and could be integrated into pretreatment assessment of chronic HCV patients for better optimization of patient management.

Evaluation of accuracy of elastography point quantification versus other noninvasive modalities in staging of fibrosis in chronic hepatitis C virus patients.

BACKGROUND: Elastography point quantification (ElastPQ) is a newly noninvasive method incorporated into a conventional ultrasound system for staging of liver fibrosis in patients with chronic liver diseases. AIM: The aim was to evaluate ElastPQ reproducibility and its accuracy in staging of liver fibrosis in hepatitis C virus (HCV) patients in comparison with transient elastography (TE) and fibrosis scores [FIB-4 and aspartate aminotransferase-to-platelet ratio index (APRI)] using liver biopsy as a reference standard and also to predict the sensitivity and specificity of ElastPQ as well as proposing a cut-off for advanced fibrosis. PATIENTS AND METHODS: A single-center, cross-sectional study enrolled 72 chronic HCV patients. Baseline demographic and laboratory data were recorded. ElastPQ and TE were performed. Fibrosis scores were calculated. The performance of ElastPQ was compared with that of TE and noninvasive methods (FIB-4, APRI) using liver biopsy as a reference standard using receiver operating characteristic curve analysis. RESULTS: ElastPQ is a valuable diagnostic tool for the diagnosis of F≥1, F≥2, and F≥3, with area under the receiver operating characteristic curve of 0.79, 0.74, and 0.83, respectively. The best cut-off values for ElastPQ were 4.9, 6.6, and 10.7 kPa for mild fibrosis, significant fibrosis, and advanced fibrosis, respectively. ElastPQ correlated positively with all other fibrosis indices (TE, APRI, and FIB-4) as well as liver biopsy. Area under the curve for the diagnosis of advanced fibrosis (F3/F4) using ElastPQ was 0.83 at a cut-off value of 10.7 kPa (P<0.01). CONCLUSION: ElastPQ is a promising noninvasive US-based method for assessing liver fibrosis in HCV-related chronic liver disease patients with good diagnostic performance comparable to that of liver biopsy and TE.

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 Egypt's 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.

Impact of old Schistosomiasis infection on the use of transient elastography (Fibroscan) for staging of fibrosis in chronic HCV patients.

BACKGROUND AND AIM: In tropical regions, Hepatitis C virus (HCV) - Schistosomiasis coinfection remains one of the health problems. With the new era of HCV treatment and the variety of methods of assessment of liver fibrosis so we aimed to evaluate the effectiveness of FibroScan for staging hepatic fibrosis in HCV-Schistosomiasis coinfected patients. METHODOLOGY: Three groups of patients were enrolled. Group 1: chronic HCV with out antischistosomal antibody (122 patients), Group 2: chronic HCV with positive antischistosomal antibodies and without periportal tract thickening (122 patients), Group 3: chronic HCV with positive antischistosomal antibodies and ultrasonographic picture of periportal tract thickening (108 patients). Routine laboratory workup, serum Antischistosomal antibody, and Schistosomal antigen in serum were performed. Ultrasound guided liver biopsy with histopathological examination; abdominal ultrasound and fibroscan examination were done for all patients. RESULTS: The agreement between results of liver biopsy and results of fibroscan in the staging of fibrosis was the best in group 1 (55.7%), Although the agreement was higher among those with no periportal tract thickening (70.7%) and the disagreement was higher among those with positive schistosomal serology (66.5%), yet this relation was not statistically significant. Multivariate logistic regression analysis showed that disagreement is significantly associated with older age, higher BMI (≥30), and increase in anti Schistosomal antibody titer. CONCLUSION: Fibroscan is a reliable, non-invasive tool for staging hepatic fibrosis among HCV-schistosomiasis co-infected patients with no effect of the induced periportal tract thickening on the readings. Only higher antischistosomal antibody titres may cause disagreement between liver biopsy and fibroscan.

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

BACKGROUND AND AIM: 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. METHODS: This is a retrospective study including 337 chronic HCV Egyptian patients with genotype 4 mainly. They were treated with Sofosbuvir-based treatment regimen. Transient elastography values were recorded as well as FIB-4 and APRI were calculated at baseline and SVR12. RESULTS: There was a significant improvement of platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores at SVR12. Liver stiffness measurements were significantly lower in SVR12 (14.8 ± 10.7 vs 11.8 ± 8.8 kPa, P = 0.000). About 77% of responders and 81.1% of cirrhotic patients showed improvement in liver stiffness measurements at SVR12.Univariate and multivariate regression analysis showed that failure to achieve improvement in liver stiffness measurements were significantly associated with relapsers and low baseline liver stiffness measurement. CONCLUSION: Sofosbuvir-based treatment resulted in a clinically significant improvement in parameters of liver fibrosis.

Relation of ALT and AST levels to the histopathological changes in liver biopsies of patients with chronic hepatitis C genotype 4.

BACKGROUND AND STUDY AIMS: Worldwide, Egypt has a high prevalence of adult hepatitis C virus (HCV) infection. Serum alanine aminotransferase (ALT) activity is most commonly measured to assess hepatic disease. The revision of the definition of the normal limits for the ALT level is advisable. The aim of this work was to compare the histopathological changes in the liver tissue biopsies of HCV-infected patients, clinically presenting with ALT levels below normal, based on the conventional, previously used upper limit of normal (ULN) of ALT (40U/L for men and 30U/L for women) with the proposed new ULN (30U/L for men, and 19U/L for women). PATIENTS AND METHODS: This is a retrospective cross-sectional study. A total of 668 cases of chronic hepatitis C genotype 4 were included. Patients were classified according to grades of histological activity and fibrosis stages (by the Metavir scoring system). They were also classified into normal and high groups according to the old and new cutoffs of both aspartate transaminase (AST) and ALT levels. RESULTS: The results of our study showed that the serum AST level in our study showed a better correlation with the histopathological changes in liver biopsy rather than ALT, especially when using the old cutoff of the ULN for AST. The serum ALT level in our study (both the old and the new cutoffs) did not show a significant correlation with the histopathological status in the liver biopsies of our patients. CONCLUSION: This study concluded that the old cutoff of the ULN AST is a better predictor of fibrosis.

IP-10 Serum Level in Chronic Hepatitis C Virus Patients: Relation to Fibrosis and Response to Combined Interferon/Ribavirin Therapy.

Despite the appearance of the direct acting antiviral drugs, pegylated interferon/ribavirin (PEG-IFN/RBV) still has a place in the standard of care (SOC) therapy for chronic HCV4. Studies were conducted to find an accurate prediction in response to SOC therapy. Pretreatment serum interferon-γ-inducible protein-10 (IP-10) is an independent predictive factor of sustained virological response (SVR) in HCV1-infected patients. To assess whether the pretreatment serum level of IP-10 influences hepatic fibrosis and PEG-IFN/RBV therapy response, a study was conducted on 88 chronic Hepatitis C virus (HCV) patients who received PEG-IFN/RBV. Patients were subjected to a pretreatment routine laboratory evaluation, liver biopsy, and serum IP-10 assessment. They were followed up for 6 months after cessation of therapy (week 72). Patients were classified into 3 groups according to their response; nonresponders, relapsers, or sustained virological responders. The relation of pretreatment IP-10 with fibrosis and response was assessed. The studied groups were matched regarding their demographic data. There was no statistically significant association between the pretreatment IP-10 level and fibrosis (P=0.86) and no relation to response was found at week 12, 24, 48, and 72 (P=0.58, 0.8, 0.47, and 0.43, respectively). Pretreatment IP-10 could not predict either fibrosis or response to PEG-IFN/RIB therapy in chronic HCV Egyptian patients.

Circulating microRNA, miR-122 and miR-221 signature in Egyptian patients with chronic hepatitis C related hepatocellular carcinoma.

AIM: To explore the potential usefulness of serum miR-122 and miR-221 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: This prospective study was conducted on 90 adult patients of both sex with HCV-related chronic liver disease and chronic hepatitis C related HCC. In addition to the 10 healthy control individuals, patients were stratified into; interferon-naïve chronic hepatitis C (CH) (n = 30), post-hepatitis C compensated cirrhosis (LC) (n = 30) and treatment-naïve HCC (n = 30). All patients and controls underwent full clinical assessment and laboratory investigations in addition to the evaluation of the level of serum miRNA expression by RT-PCR. RESULTS: There was a significant fold change in serum miRNA expression in the different patient groups when compared to normal controls; miR-122 showed significant fold increasing in both CH and HCC and significant fold decrease in LC. On the other hand, miR-221 showed significant fold elevation in both CH and LC groups and significant fold decrease in HCC group (P = 0.01). Comparing fold changes in miRNAs in HCC group vs non HCC group (CH and Cirrhosis), there was non-significant fold elevation in miR-122 (P = 0.21) and significant fold decreasing in miR-221 in HCC vs non-HCC (P = 0.03). ROC curve analysis for miR-221 yielded 87% sensitivity and 40% specificity for the differentiation of HCC patients from non-HCC at a cutoff 1.82. CONCLUSION: Serum miR-221 has a strong potential to serve as one of the novel non-invasive biomarkers of HCC.

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.

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.

The impact of interleukin 28b gene polymorphism on the virological response to combined pegylated interferon and ribavirin therapy in chronic HCV genotype 4 infected egyptian patients using data mining analysis.

BACKGROUND: Chronic HCV represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. Interleukin IL-28B gene polymorphism has been shown to relate to HCV treatment response, mainly in genotype1. OBJECTIVES: We aim to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in genotype 4 Egyptian patients by regression analysis and decision tree analysis. PATIENTS AND METHODS: The study included 263 chronic HCV Egyptian patients receiving peg-interferon and ribavirin therapy. Patients were classified into 3 groups; non responders (83patients), relapsers (76patients) and sustained virological responders (104 patients). Serum IL 28 B was performed, DNA was extracted and analyzed by direct sequencing of the SNP rs 12979860 of IL28B gene. RESULTS: CT, CC and TT represented 56 %, 25 % and 19% of the patients, respectively. Absence of C allele (TT genotype) was significantly correlated with the early failure of response while CC was associated with sustained virological response. The decision tree showed that baseline alpha fetoprotein (AFP ≤ 2.68 ng/ml) was the variable of initial split (the strongest predictor of response) confirmed by regression analysis. Patients with TT genotype had the highest probability of failure of response. CONCLUSIONS: Absence of the C allele was significantly associated with failure of response. The presence of C allele was associated with a favorable outcome. AFP is a strong baseline predictor of HCV treatment response. A decision tree model is useful for predicting the probability of response to 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.