Seroprevalence of HBV/HCV coinfection among patients with HCV screened during the national campaign for HCV eradication in Egypt.

BACKGROUND AND STUDY AIMS: Little is known about the true prevalence of hepatitis B virus (HBV) coinfection in patients with hepatitis C virus (HCV). This multicenter nationwide study aimed to assess the seroprevalence of HBV among Egyptian patients with HCV and its possible risk factors. PATIENTS AND METHODS: This is a cross-sectional, multicenter, nationwide study. Data were extracted from the National Network of Viral Hepatitis Treatment Centers database. Baseline data of patients proved to be viremic during the national campaign for HCV eradication (October 2018-April 2019) were retrieved. Data included demographics, laboratory tests (HBsAg, CBC, liver biochemical profile, creatinine, AFP, HbA1c, and viral load), FIB-4 score calculation, and abdominal ultrasound results. RESULTS: Results of 297,965 patients showed that HBsAg was positive in 2,347 (0.8%) patients. Patients with HBV/HCV were 57% females and had a mean age of 51 ± 13 years. Patients with positive HBsAg showed significantly more tobacco consumption, intravenous drug abuse, hypertension, and diabetes. No significant difference was noted in HCV viremia between patients with HCV and those with HBV/HCV. Only 14% of patients with HBV/HCV had cirrhosis compared with the 9% of those with HCV; two of them had HCC. CONCLUSION: Although Egypt has a heavy HCV burden, the overall prevalence of HBV is low among patients with HCV infection. Comorbid conditions seem to favor coinfection.

Value of pancreatic cyst fluid SPINK1 and glucose in differentiating potentially malignant cysts from those of benign nature: A prospective cohort study.

Background: Diagnosis of malignant pancreatic cystic lesions (PCLs) is challenging as there is no investigation that offers both high diagnostic sensitivity and specificity for a definite diagnosis. Accurate diagnosis of cyst type is vital in order to not miss opportunities for early treatment of potentially malignant lesions and to avoid unnecessary surgeries. Serine protease inhibitor Kazal type I (SPINK1) and glucose are promising cyst fluid markers for differentiation of mucinous from non-mucinous cysts. We aim to validate the value of SPINK1 and glucose in detecting potentially malignant PCLs. Methods: A prospective study was conducted on 80 patients presenting with PCLs. Endoscopic ultrasound (EUS) evaluation of detailed cyst morphology and EUS with fine needle aspiration (FNA) were done. Fluid analysis for carcinoembryonic antigen (CEA), glucose and SPINK1 and cytopathology were done. We compared these data with the final diagnosis based on cytopathological and postoperative histopathological examination. Results: Cyst fluid SPINK1 was significantly higher in malignant or potentially malignant cysts compared to benign cysts (0.91 vs 0.47 ng/ml; P = 0.001). Also, glucose was significantly lower in malignant or potentially malignant cysts compared to benign cysts (21.5 vs 68.5 mg/dl; P = 0.0001). Glucose and SPINK1 had the best sensitivity and specificity for differentiating mucinous from non-mucinous cysts with 84.78% and 73.53% (AUC 0.76; 95% CI [0.65-0.88]; cutoff value = 42 mg/dl), and 70.59% and 65.22% (AUC 0.72; 95% CI [0.64-0.86]; cutoff value = 0.58 ug/L) respectively. CEA level >192 ng/ml, high SPINK1 level and lymph node enlargement were the independent predictors of malignant cysts. Conclusion: Cyst fluid SPINK1 and glucose are promising diagnostic markers for the diagnosis of potentially malignant PCLs.

Egyptian revalidation of non-invasive parameters for predicting esophageal varices in cirrhotic patients: A retrospective study.

BACKGROUND AND STUDY AIMS: In resource-limited countries, non-invasive tests for assessing liver fibrosis are a potential alternative to costly endoscopic screening for esophageal varices. We aimed to validate several non-invasive parameters for predicting the presence of varices. PATIENTS AND METHODS: Between September 2006 and August 2017, a total of 46,014 patients who underwent upper gastrointestinal endoscopy as one of the perquisites for receiving hepatitis C virus (HCV) therapy were enrolled and divided into group I (without varices) and group II (with varices). Non-invasive parameters of fibrosis, namely Lok index, Bonacini score, liver stiffness, FIB-4, Baveno, and extended Baveno criteria, were validated. RESULTS: Lok index, Bonacini score, liver stiffness, and FIB-4 had areas under the receiver operating characteristic curve (AUCs) of >0.6 (all P < 0.01 for the null hypothesis that the AUC was 0.5) for determination of the presence/absence of varices, with cutoff values of 0.80, 6.5, 21.9 kPa, and 2.94, and sensitivities of 74%, 74%, 66%, and 83%, respectively. The expanded Baveno VI criteria performed better than the Baveno VI criteria (spared endoscopy rate 81% versus 63%). CONCLUSION: The use of non-invasive methods is of limited value in predicting esophageal varices. The limited accuracy of ≤60% may delay the use of appropriate primary prophylaxis against variceal bleeding in a large proportion of cirrhotic patients.

The egyptian clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.

The landscape of chronic liver disease in Egypt has drastically changed over the past few decades. The prevalence of metabolic-associated fatty liver disease (MAFLD) has risen to alarming levels. Despite the magnitude of the problem, no regional guidelines have been developed to tackle this disease. This document provides the clinical practice guidelines of the key Egyptian opinion leaders on MAFLD screening, diagnosis, and management, and covers various aspects in the management of MAFLD. The document considers our local situations and the burden of clinical management for the healthcare sector and is proposed for daily clinical practical use. Particular reference to special groups was done whenever necessary.

Real-life experience of treating HCV co-infection among HIV-infected population in Egypt: single-center experience.

BACKGROUND: Liver disease has emerged as a leading cause of death among PLHIV coinfected with HCV. METHODS: A retrospective study involving all HCV viremic patients coinfected with HIV who presented to HCV/HIV multidisciplinary clinics located at Embaba fever hospital. Patients were assigned to receive DAAs according to the national treatment guidelines. The primary endpoint was SVR12. RESULTS: Of the 519 patients enrolled, 38.73% LTFU; either not initiated (n = 170) or did not complete the treatment (n = 31). The main identified reasons behind LTFU were schedule conflict (19%) or hospitalization (13%). Among 318 patients who completed their DAAs course, nine patients had a relapse after the end of treatment and 97% had attained SVR12. There were significant differences among different virological response groups in baseline factors including smoking (p = 0.005), history of dental procedure (p = 0.007), CD4 count (p = 0.007), and HIV viral load (p = <0.001). Among responders (n = 309), there was a significant reduction of baseline hemoglobin and significant improvement of baseline platelets (p = 0.005) at on-treatment week 8. Baseline necro-inflammatory markers showed significant improvement across follow-up time points (p < 0.001). CONCLUSIONS: DAAs are an effective and safe choice to treat HCV in PLHIV. Social stigma could be a major cause for lacking adherence to follow-up visits.Abbreviations: ALT: Alanine Aminotransferase; ARV: Antiretroviral treatment; AST: Aspartate Aminotransferase; DAAs: Direct acting antivirals; ARVs: antiretroviral therapy; EMR: Eastern Mediterranean region; HCV: Hepatitis C virus; kPa: Kilopascal; LTFU: Patient lost to follow up; NCCVH: The National Committee for Control of Viral Hepatitis; PWID: People who inject drugs; SVR: Sustained virological response;UNAIDS: The Joint United Nations Programme on HIV/AIDS.

The outcome of re-treatment of relapsed hepatitis C virus infection in a resource-limited setting.

The aim of this study was to compare efficacy and safety of different combination regimens in re-treatment of HCV in the setting of inaccessibility of resistance testing. This real-life prospective study included 86 chronic HCV infected patients who experienced failure of treatment treated at Faculty of Medicine Ain shams Research Institute (MASRI) since 2018. 64% of the patients were males, with median age 50.2 years. They were re-treated using 1 of 3 proposed regimens of DAA combinations. One group received PAR/OMB/SOF/RBV for 12 weeks, another group received SOF/DAC/SIM/RBV for 12 weeks and a third received SOF/DAC/RBV for 24 weeks. Response to different regimens was assessed by comparing sustained virologic response (SVR) of each. Monitoring the occurrence of adverse events was performed. SVR was achieved in all but 3 patients (96.5% SVR), one in the SOF/DAC/SIM/RBV group and two in the SOF/DAC/RBV group. The group receiving RBV had more anaemia and hyperbilirubinemia. The first treatment regimen used was a significant predictor to SVR achievement. This study presents alternative treatment regimens for re-treatment of HCV patients in areas with limited resources in the case of non-availability of other regimens as velpatasvir, voxilaprevir, grazoprevir, elbasvir.

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.

Hepatitis C virus infection and global kidney health: the consensus proceedings of the International Federation of Kidney Foundations.

Hepatitis C virus (HCV) infection is an important cause of major morbidities including chronic liver disease, liver cancer, and acute kidney injury (AKI) as well as chronic kidney disease (CKD). HCV can affect kidney health; among CKD and AKI patients with HCV infection, the clinical outcomes are worse. The prevalence of HCV infection is exceptionally high among dialysis and kidney transplant patients throughout the globe. It is estimated that 5% to 25% or more of dialysis dependent patients are affected by chronic HCV, based on the region of the world. Almost half of all deaths in CKD patients, including HCV-infected patients, are due to cardiovascular disease, and HCV infected patients have higher mortality. Given the importance and impact of the HCV epidemic on CKD and global kidney health, and the status of Egypt as the nation with highest prevalence of HCV infection in the world along with its leading initiatives to eradicate HCV, the International Federation of Kidney Foundations (IFKF) convened a consensus conference in Cairo in December 2017. This article reflects the opinions and recommendations of the contributing experts and reiterates that with the current availability of highly effective and well tolerated pharmacotherapy; CKD patients should be given priority for treatment of HCV, as an important step towards the elimination of viral hepatitis as a public health problem by 2030 according to World Health Organization and IFKF. Every country should have an action plan with the goal to improve kidney health and CKD patient outcomes.

Fibro-indices versus liver stiffness for prediction of significant fibrosis in hepatitis B virus-infected Egyptian patients; a single-center experience.

Background: Liver fibrosis assessment is a key factor for disease management in hepatitis B virus (HBV). Several serum biomarkers have been introduced for noninvasive fibrosis assessment. This study aims to evaluate the validity of simple noninvasive indices, namely Fibrosis-4 score (FIB4), aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), Goteborg University Cirrhosis Index (GUCI), and fibrosis index in evaluation of liver fibrosis in chronic HBV.Methods: 226 patients with chronic HBV genotype D were included. FIB4, APRI, GUCI, and fibrosis index were performed. Receiver operating characteristic (ROC) curves were used to predict ≥F2 fibrosis.Results: The mean age of patients was 39.00 years and 72.27% of patients were treatment naïve. Patients with ≥F2 hepatic fibrosis had significantly higher FIB-4 (1.58 ± 1.46 vs. 1.15 ± 1.09), APRI (0.68 ± 0.71 vs. 0.43 ± 0.37), GUCI score (0.75 ± 0.94 vs. 0.42 ± 0.29) and Fibrosis index (2.18 ± 0.84 vs. 1.84 ± 0.69). All studied indices were able to diagnose ≥F2 fibrosis. APRI had the highest area under the ROC (AUROC) of 0.67. Predictivity of all indices was higher in on-treatment vs naive patients.Conclusion: FIB4, APRI, and GUCI scores are acceptable, noninvasive, and cheap simple indices that can be helpful on treatment follow-up of fibrosis regression in the setting of low socioeconomic conditions compared to the relatively expensive fibroscan modality.

Retreatment of chronic hepatitis C virus genotype-4 patients after non-structural protein 5A inhibitors' failure: efficacy and safety of different regimens.

BACKGROUND: Nonstructural protein 5A (NS5A) is an important regimen for the treatment of chronic hepatitis C virus (HCV) genotype-4 infected patients. Retreatments for NS5A virologic failure are limited. The aim of this study is to provide real-life data regarding the effectiveness and safety of retreatment with different regimens after NS5A regimen virologic failure in GT4 patients. PATIENTS AND METHODS: A total of 524 HCV patients (mean age 48 ± 11 years, 71% males), with virologic failure to sofosbuvir+daclatasvir, n = 450 and sofosbuvir/ledipasvir, n = 74 were included in this study. Patients were retreated with sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin, n = 278 and sofosbuvir + simeprevir + daclatasvir + ribavirin, n = 246. Response was evaluated 12 weeks after the end of treatment (SVR12). RESULTS: Overall, SVR12 was 95.2% [95% confidence interval (CI) 93.3%-97.1%]. In sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir + simeprevir + daclatasvir + ribavirin, SVR12s were 94.9% (95% CI 92.5%-97.4%) and 95.5% (95% CI 92.8%-98%), respectively. In liver cirrhosis patients, SVR12s were 96.4% (95% CI 90.7%-100%) and 98% (95% CI 94.9%-100%), respectively. Relapse in the sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin was n = 14 patients, and n = 11 patients in sofosbuvir + simeprevir + daclatasvir + ribavirin. Three patients developed hepatic encephalopathy, haematemesis, lower limb oedema, and one patient died in the SOF + OBV/PTV/RTV + RIB. In the sofosbuvir + simeprevir + daclatasvir + ribavirin, three patients developed hepatocellular carcinoma and one patient died. No treatment discontinuation due to anaemia. CONCLUSION: Salvage treatment for NS5A-treatment failure is effective and well tolerated in genotype-4 patients, in both noncirrhotic and compensated cirrhotic groups.

Sofosbuvir-containing regimens are safe and effective in the treatment of HCV patients with moderate to severe renal impairment.

BACKGROUND AND AIMS: This study aimed to assess the safety and efficacy of sofosbuvir (SOF)-based regimens in patients with moderate to severe renal impairment; a subject which has been questioned by many investigators with conflicting results. METHODS: This is a real-life multicentre retrospective cohort study on 4944 chronic Hepatitis C virus (HCV) patients with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m2 ) who received SOF-based therapy in specialized treatment centres affiliated to the National Committee for the Control of Viral Hepatitis in Egypt. The efficacy and safety of SOF-based regimens was assessed. RESULTS: Week 12 virological response rates were 97.5%, 96.7%, 85.7% and 80% in the total cohort, patients with eGFR <30 mL/min/1.73 m2 , patients with associated hepatic decompensation and patients on dialysis respectively. Various treatment regimens did not statistically affect the response rates. Treatment experience, cirrhosis and diabetes were predictors of treatment failure on multivariate analysis. Serious adverse events occurred in 0.1% of cases. Forty patients (0.8%) discontinued treatment. CONCLUSION: Sofosbuvir-based regimens are effective and safe for treating patients with chronic HCV and moderate to severe CKD, and in those with associated hepatic decompensation.

Real life application of FIB-4 & APRI during mass treatment of HCV genotype 4 with directly acting anti-viral agents in Egyptian patients, an observational study.

Background: Non-invasive prediction of significant liver fibrosis and gastro-esophageal varices during mass treatment for HCV is crucial.The aim is to validate the accuracy of FIB-4 & APRI for predicting significant fibrosis in chronic HCV patients during mass treatment with directly acting anti-viral agents (DAAs) & their validity for predicting varices.Methods: We did a search in a database of 21,617 patients with chronic HCV infection recruited to one of the national HCV treatment centers to find out those with fibrosis assessment by recent liver biopsies &/or liver stiffness to serve as a gold standard. The diagnostic accuracy of FIB-4 and APRI values were assessed against the gold standard. Demographics and relevant laboratory data of 3144 patients (14.5%) were retrieved.Results: Significant fibrosis (F3-F4) was detected in 1585 (50.4%). AUROCs for detecting significant fibrosis (F3-F4) were 0.76 (0.75-0.78) for FIB-4 and 0.72 (0.72-0.75) for APRI. To diagnose liver cirrhosis, AUROCs were higher; 0.82 (0.80-0.83) for FIB-4 and 0.78 (0.76-0.79) for APRI, p < 0.001. Prediction of gastro-oesophageal varices; AUROC for FIB-4 and APRI, were 0.65 and 0.62 respectively.Conclusion: FIB-4 and APRI are reliable methods in predicting cirrhosis during mass HCV treatment. Their role in predicting gastro-oesophageal varices is less remarkable.

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.

Efficacy and safety of sofosbuvir-based therapy in hepatitis C virus recurrence post living donor liver transplant: A real life egyptian experience.

BACKGROUND AND AIM: Direct acting antiviral has offered treatment of hepatitis C virus (HCV) recurrence post liver transplantation (LT) with an all-oral regimen for short duration, excellent safety profile, and high sustained virological response (SVR). The aim of this study was to evaluate the efficacy and safety of sofosbuvir (SOF)-based regimens in the real world among a cohort of Egyptian patients with recurrent HCV post living donor LT (LDLT). METHODS: Patients with HCV-G4 recurrence post-LDLT were recruited from National Committee of Control of Viral Hepatitis, Egypt, from November 2014 to May 2017. They received different SOF-based regimens according to the treatment protocols available during this period. Patients' outcome and Adverse effects (AE) were evaluated. RESULTS: One hundred ninety patients (170 males, mean age 56.8 ± 7.9 years) were included. Calcineurin inhibitors were the main immunosuppression used (173 patients). Out of 190, 119 (62.6%) received SOF/ribavirin (RBV), 38 (20%) SOF/simeprevir (SMV), 22 (11.6%) SOF/daclatasvir (DSV)/ ± RBV, and 11 (5.8%) received SOF/LDV/ ± RBV. Overall SVR12 was 89.5%, 84.9% in SOF/RBV group, 94.7% in SOF/SMV, 100% in SOF/DCV, and 100% in SOF/LDV with no statistically significant difference ( P = 0.104). The AE reported were as follows: anemia (n = 65, 34.4%) mainly in SOF/RBV group, transient hyperbilirubinemia during SOF/SMV in 13 patients (34%), mild Acute cellular rejection in eight patients (4.2%), and hepatocellular carcinoma in two patients (1%) mainly driven by underlying liver condition. Two deaths were unlikely related to HCV therapy. CONCLUSION: Different SOF-based regimens were effective with high SVR12 rates in a difficult-to-treat population, recurrent HCV post LDLT.

Improvement of liver stiffness measurement, acoustic radiation force impulse measurements, and noninvasive fibrosis markers after direct-acting antivirals for hepatitis C virus G4 recurrence post living donor liver transplantation: Egyptian cohort.

Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct-acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single-center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir-based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir-based treatment resulted in an early improvement in parameters of liver fibrosis in post-LT patients with hepatitis C recurrence.

Spur-of-the-Moment Modification in National Treatment Policies Leads to a Surprising HCV Viral Suppression in All Treated Patients: Real-Life Egyptian Experience.

The aim of this study was to retrospectively analyze the outcome of an unscheduled change in national Egyptian policies for the treatment of hepatitis C virus (HCV), which was transpired as a result of a reduction in interferon supplies, and to manage patients who already started interferon-based therapy. After completing a priming 4-weeks course of sofosbuvir/pegylated interferon/ribavirin (SOF/PEG IFN/RBV), a 12-weeks course of sofosbuvir/daclatasvir (SOF/DCV) combination was initiated. We evaluated the sustained virologic response at 12 weeks posttreatment (SVR12) for 2 groups of patients; Group 1, which included patients who had the previous regimen with IFN priming, and group 2, which included the first consecutive group of patients who received SOF/DCV for 12 weeks from the start without IFN priming. All group 1 patients (1,214 patients) achieved SVR12 (100%) and this was statistically significant when compared with the overall SVR12 in group 2 [8,869 patients with sustained virologic response [SVR] of 98.9%] (P value <0.001). No serious adverse events were reported in both groups. In this real-life treatment experience, interferon-based directly acting antiviral treatment with SOF/PEG IFN/RBV as a priming for 4 weeks, followed by SOF/DCV combination for 12 weeks, led to HCV viral suppression in all treated patients.