Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study.

Researchers around the world are working at record speed to find the best ways to treat and prevent coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy of ivermectin for the treatment of hospitalized mild to moderate COVID-19 infected patients. This was a randomized open-label controlled study that included 164 patients with COVID-19. Patients were randomized into two groups where Group 1 (Ivermectin group) included patients who received ivermectin 12 mg once daily for 3 days with standard care and Group 2 (control group) included patients who received standard protocol of treatment alone for 14 days. The main outcomes were mortality, the length of hospital stay, and the need for mechanical ventilation. All patients were followed up for 1 month. Overall, 82 individuals were randomized to receive ivermectin plus standard of care and 82 to receive standard of care alone. Patients in the ivermectin group had a shorter length of hospital stay (8.82 ± 4.94 days) than the control group (10.97 ± 5.28 days), but this was not statistically significant (p = 0.085). Three patients (3.7%) in each group required mechanical ventilation (p = 1.00). The death rate was three patients in the ivermectin group (3.7%) versus four patients (4.9%) in the control group without any significant difference between the two groups (p = 1.00). Although there was no statistically significant difference in any endpoints by ivermectin doses (12 mg/day for 3 days); there was an observed trend to reducing hospital stay in the ivermectin-treated group.

Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study.

No specific antiviral drugs have been approved for the treatment of COVID-19. This study aimed to evaluate the efficacy of favipiravir in treatment of COVID-19. This was a multicenter randomized controlled study including 96 patients with COVID- 19 who were randomly assigned into a chloroquine (CQ) group and a favipiravir group. None of the patients in the favipiravir group needed mechanical ventilation (p = 0.129). One patient (2.3%) in the favipiravir group and two patients (4.2%) in the CQ group died (p = 1.00). Favipiravir is a promising drug for COVID-19 that decreases the hospital stay and the need for mechanical ventilation.ClinicalTrials.gov Identifier NCT04351295.

A Randomized Controlled Trial Comparing Nitazoxanide Plus Lactulose With Lactulose Alone in Treatment of Overt Hepatic Encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is a reversible spectrum of neuropsychiatric abnormalities associated with liver dysfunction. Lactulose is a nonabsorbable disaccharide presently used to treat HE. Nitazoxanide (NTZ) has a broad-spectrum activity against urease-producing bacteria, so it decreases ammonia production and is therefore expected to reverse the symptoms of HE. A previous pilot study on HE patients given NTZ and lactulose had encouraging results with regard to amelioration of the clinical picture. Patients showed improvement in mental status and the drug was well-tolerated. Results such as these are encouraging larger studies. The aim of this study was to compare the safety and adequacy of NTZ plus lactulose versus lactulose and placebo in management of overt HE. METHODS: In total, 120 cirrhotic patients suffering from overt HE were randomly designated to take either NTZ plus lactulose (n=60) or lactulose and placebo (n=60). The Clinical Hepatic Encephalopathy Staging Scale (CHESS) score was assessed for all patients on inclusion to the study and 1 week from the start of treatment. RESULTS: Both groups evinced an improvement in CHESS score at 1 week, yet the improvement was significantly better in the NTZ group as the score decreased from 4.15±2.09 to 0.00±0.00 compared with 4.96±2.29 to 1.28±0.91 in patients receiving lactulose and placebo (P-value <0.001). CONCLUSIONS: NTZ significantly decreases the CHESS score and improves mental status in the form of patient alertness, orientation, response to stimulation, and ability to talk. NTZ is safe and well-tolerated apart from infrequent epigastric pain.

Efficacy and safety of sofosbuvir plus ribavirin for treatment of cirrhotic patients with genotype 4 hepatitis C virus in real-life clinical practice.

Egypt has the highest hepatitis C virus (HCV) prevalence in the world. Sofosbuvir is a new highly effective drug for treatment of HCV infection. Compared to previous treatments, sofosbuvir-based regimens provide a higher cure rate, fewer side effects, and a two- to fourfold reduced duration of therapy. The aim of this study was to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir plus ribavirin in Egyptian patients with liver cirrhosis due to chronic HCV infection. We studied 2400 cirrhotic Egyptian patients with chronic HCV infection who were treated with dual therapy with sofosbuvir and ribavirin for 24 weeks. Efficacy was determined by assessment of serum HCV RNA. Any adverse events during treatment were recorded. Two thousand four hundred cirrhotic Egyptian patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24 weeks were enrolled in the study. The mean age of the studied group (± SD) was 53.9 ± 6.5 years, 1549 (64.54%) were males, all were cirrhotic patients, 3.41% were treatment-experienced, the baseline mean HCV RNA concentration was 4.33 × 106 IU/mL, and 94.37% of the patients had completed the full course of therapy. The overall SVR12 rate was 71.2%. The most common adverse events were fatigue, myalgia, headache, insomnia, and anemia. One hundred thirty-five (5.63%) patients stopped treatment permanently due to the appearance of complications that prevented continuation of treatment. The sofosbuvir and ribavirin combination is safe and effective in treatment of HCV patients with liver cirrhosis. However, further studies are needed to establish the optimal treatment regimen for those cases.

Randomized controlled trial of scleroligation versus band ligation alone for eradication of gastroesophageal varices.

BACKGROUND AND AIMS: Gastric varices develop in 5% to 33% of patients with portal hypertension. Their most common form is concomitant gastroesophageal varices. Scleroligation (combined sclerotherapy and band ligation) has been used successfully in management of esophageal varices but has not been evaluated previously in the management of gastroesophageal varices. The aim of this work was evaluation of a new scleroligation technique for management of bleeding gastroesophageal varices regarding efficacy, adverse events, variceal recurrence, and survival. METHODS: This study was conducted on 120 cirrhotic patients with bleeding gastroesophageal varices, whom we divided randomly into 2 groups of 60 patients each-a band ligation group and a scleroligation group. RESULTS: The mean number of sessions was lower in the scleroligation group than in the band ligation group (2.22 ± 0.92 and 3.43 ± 0.67, respectively) (P < .001), as were the duration of treatment and total number of bands used. Cost and survival were comparable in the 2 groups. There was no significant difference between the 2 maneuvers regarding adverse events, recurrence rates, or rebleeding rates after obliteration. Recurrence was significantly higher in patients with larger varices, ulceration, and postprocedure pyrexia. Rebleeding was significantly higher among those who experienced postprocedure pyrexia and developed or had worsening of gastric antral vascular ectasia. CONCLUSIONS: Scleroligation appears to achieve a faster rate of eradication with fewer treatment sessions and total number of bands deployed to achieve variceal obliteration than band ligation and is comparable in cost and in adverse event and recurrence rates. (Clinical trial registration number: NCT02646202.).

Anti-Nuclear Cytoplasmic Antibody-Associated Vasculitis: A Probable Adverse Effect of Sofosbuvir Treatment in Chronic Hepatitis C Patients.

Background: Egypt has the largest hepatitis C virus (HCV) epidemic worldwide. Sofosbuvir is an antiviral drug acting by inhibition of the HCV NS5B polymerase. It has shown high efficacy in combination with several other drugs and has a low reported rate of side effects. Objective: The aim of this prospective cohort study was to assess the safety of sofosbuvir-based treatment regimens used to treat chronic hepatitis C infections and to detect any side effects of sofosbuvir not previously reported. Methods: We studied treatment side effects in 3,000 patients with chronic HCV infection treated with sofosbuvir and ribavirin for 24 weeks or treated by pegylated interferon, sofosbuvir, and ribavirin triple therapy for 12 weeks. The endpoint of the study was the end of treatment. Results: Hyperbilirubinemia occurred frequently during treatment in both groups. Treatment was discontinued in 72 cases due to hepatic decompensation and drug complications; 8 of the cases had deep vein thrombosis (DVT) and 7 had cerebral ischemia. Surprisingly, 177/3,000 (5.9%) patients presented with abnormal bleeding, 85 of whom had a vasculitic skin rash. Conclusion: We report the occurrence of previously nonrecorded side effects with sofosbuvir, namely DVT and bleeding disorders associated with anti-nuclear cytoplasmic antibody (ANCA)-associated vasculitis (AAV).We believe this to be the first report of sofosbuvir-induced AAV skin lesions and bleeding disorders.

Assessment of left atrial function by two-dimensional speckle tracking echocardiography in patients with metabolic-associated fatty liver disease.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) and cardiovascular diseases have mutual risk factors that contribute to pathogenic processes, increasing mortality and morbidity. This study aimed to evaluate variations in left ventricular (LV) structure and diastolic function among different subtypes and severity degrees of MAFLD patients, allowing early identification, intervention, and prevention of severe cardiac outcomes in high-risk populations. RESULTS: The cross-sectional study included 142 MAFLD patients and 142 non-MAFLD participants as a control group. All participants underwent abdominal ultrasound, transient elastography, transthoracic echocardiography, tissue Doppler, and strain imaging. The results showed a significant impairment in the diastolic left ventricular function, as assessed with tissue Doppler, and the left atrial (LA) function, as evaluated with strain imaging, in the MAFLD group. Additionally, the left atrial stiffness was significantly higher in the MAFLD group. CONCLUSION: The use of strain imaging facilitated the detection of subtle impairments of the left atrial reservoir, contraction, conduit function, and left ventricular diastolic function in MAFLD patients.

Impact of laparoscopic cholecystectomy on the complexity of endoscopic retrograde cholangiopancreatography.

BACKGROUND AND OBJECTIVES: A scarce number of researches discussed the impact of cholecystectomies on the anatomy of common bile duct (CBD) and intern if this will affect the difficulty of endoscopic retrograde cholangiopancreatography (ERCP). The objective of present study was to assess the impact of complicated cholecystectomy on the complexity and safety of the ERCP procedure. STUDY DESIGN: A total of 100 patients were enrolled after meeting the following inclusion criteria - study group (group A): 50 patients with previous history of complicated laparoscopic cholecystectomy and control group (group B): 50 patients with previous noncomplicated laparoscopic cholecystectomy. ERCP was performed and complexity was judged by a number of cannulation attempts, ERCP time, pancreatic cannulation and post-ERCP pancreatitis. RESULTS: The study revealed prolonged ERCP procedure duration in noncomplicated cholecystectomy (24.2 ± 8.5 min) and it was significantly more prolonged in complicated cholecystectomy (39.6 ± 10.7 min; P = 0.03). The trials of cannulation attempts were significantly higher in the study group with complicated cholecystectomy (P = 0.009). Pancreatic duct cannulation was frequently higher in the complicated cholecystectomy group (P = 0.03). Difficult or failed stone extraction was significantly prevalent in the complicated cholecystectomy group and the occurrence of post-ERCP pancreatitis (PEP) was significantly higher than the control group. CONCLUSION: ERCP after complicated laparoscopic cholecystectomy is more complex with increased duration liability of complications.

The Effect of HCV Eradication after Direct-Acting Antiviral Agents on Hepatic Steatosis: A Prospective Observational Study.

BACKGROUND AND AIM: Eradication of hepatitis C virus (HCV) by direct-acting-antiviral- agents (DAAs) was followed by fibrosis regression, but little is available about hepatic steatosis changes after DAAs. The aim of this work was to assess the prevalence of hepatic steatosis among HCV Egyptian patients and the long term changes occuring after viral eradication. METHODS: This prospective cohort study included 150 HCV patients with significant fibrosis. They were examined by Transient elastography to evaluate liver stiffness measurement (LSM) and hepatic steatosis before treatment, at SVR12 and 1 year after the end of therapy. RESULTS: LSM showed a significant positive correlation to pretreatment of hepatic steatosis. LSM significantly decreased and hepatic steatosis significantly increased both at SVR12 and one year after DAAs. Patients with steatosis showed significantly higher median LSM and controlled attenuation parameter (CAP) values at: baseline, SVR12, and one year after therapy. Also, the pretreatment steatosis and body mass index (BMI) had a significant negative correlation with fibrosis regression one year after therapy in all studied groups. CONCLUSION: Hepatic steatosis is common in HCV Egyptian patients and increases after HCV eradication with DAAs. BMI and CAP values are negatively correlated to hepatic fibrosis regression and positively correlated to steatosis progression one year after DAAs. So, HCV patients with hepatic steatosis may need close follow up for atherosclerotic and HCC risk after DAAs, especially if they are overweight.

The Correlation Between the Autotaxin Enzyme and Pruritus in Egyptian Patients Suffering from Chronic Liver Disease.

BACKGROUND & AIMS: Pruritus associated with liver diseases confines daily activities and causes sleep deprivation in patients with chronic liver diseases. Autotoxin enzyme (ATX) was found to be higher in sera of patients with intrahepatic cholestasis and it was found to be associated with the intensity of itching. The aim of this study was to assess the correlation between the autotaxin enzyme and pruritus in Egyptian patients suffering from chronic liver disease (CLD). METHODS: This cross-sectional study was carried on a total number of 80 patients with chronic liver disease divided into four groups: Group A and B included cirrhotic patients suffering from pruritis with and without cholestasis, while group C and D included patients without pruritis with or without cholestasis and group E included 17 healthy controls. They were subjected to measurement of serum autotoxin concentration by ELISA in addition to routine investigations including liver function tests: Total and direct bilirubin, ALT, AST, Alkaline phosphatase, Gama- glutamyl transferase, and serum albumin. RESULTS: There was a significant increase in autotaxin in the four groups included chronic liver disease patients (P-value <0.001*) compared to control group (group E). Autotoxin level was the only marker that had a significant increase in pruritus groups (groups A & B) compared to non-pruritus groups (groups C & D) with cut off value ≥ 32. CONCLUSION: Serum autotaxin level was elevated in patients with chronic liver diseases with pruritus. Autotaxin enzyme may play a key role in the induction of hepatogenic pruritus. So, autotaxin enzyme inhibitors and lysophosphatidic acid (LPA) receptor blockers could be a future line of treatment of hepatogenic pruritus.

Platelet Count Improvement after Chronic Hepatitis C Treatment among Cirrhotic Patients Who Achieved Sustained Virological Response: Realworld Results from 2186 Patients in Egypt.

BACKGROUND AND AIMS: This study aimed to assess the changes in platelet counts of patients with liver cirrhosis due to chronic HCV, who achieved sustained virological response (SVR) after taking direct acting antivirals (DAAs) in a large cohort study in Egypt. METHODS: This multicenter observational retrospective study was carried out on 2500 chronic hepatitis C virus (HCV) infected patients who achieved (SVR) after treatment with direct acting antiviral drugs (DAA). HCV infection was confirmed by positive PCR for HCV RNA infection. SVR was defined as a negative PCR test for HCV-RNA 12 weeks after completion of DAA therapy. Platelets count was measured before therapy, during therapy, at the end of treatment, and 12 weeks after the end of the treatment. RESULTS: There were 2186 patients enrolled in the study; 1866 (85.4%) were treatment naïve. There were 1006 (46%) males and 1180 (54%) females. Mean age was 50.82± 11.66 years, 2142 (98%.0) patients achieved SVR, 2118 (96.9%) patients had Child -Pugh class A cirrhosis, and 68 (3.1%) had Child -Pugh class B liver cirrhosis. A significant increase in the platelets count was detected at the end of treatment in comparison to the pretreatment levels (P<0.001), and after achieving SVR (P <0.001) when compared to the pretreatment values. CONCLUSION: Improvement of platelets count occurs after HCV therapy with DAAS in patients with liver cirrhosis. These results suggested that HCV eradication may have a role in the improvement of platelet count.

Treatment of Hepatitis C Cirrhotic Patients With Directly Acting Antivirals: A Multicenter Study.

BACKGROUND: With the introduction of sofosbuvir-based regimens, high cure rates and decreased duration has been achieved. Several studies showed variances in SVR rates between different genotypes, with lower rates of SVR among cirrhotic patients. The aim of our study was to assess the safety and effectiveness of sofosbuvir-based antiviral regimens for the treatment of HCVinfected Egyptian cirrhotic patients. METHODS: This was a retrospective, observational, and comparative study. A total of nine hundred and forty-six cirrhotic patients with chronic HCV genotype 4 infection, who were eligible for direct acting drugs (DAAs) therapy, were enrolled. The primary outcome measures were the number of patients with successful eradication of the virus evidenced by SVR at 12 weeks after discontinuation of therapy (SVR12), and the secondary outcome measures were the incidence of adverse effects associated with the tested HCV therapy. RESULTS: Among the 946 patients enrolled in the study, 527 patients (55.7%) were males and 419 patients (44.3%) were females with a mean age of 54.00±8.88 years. 20.2% were diabetics and 19.1% were hypertensive. Patients were classified according to Child-Pugh classifications; 818 patients (86.46%) were Child-Pugh class A cirrhosis, while 28 patients (13.53%) were Child-Pugh class B cirrhosis. The SVR12 rate was 96.93% (917 /946). Treatment response in the Child-Pugh class A cirrhosis was 794 (97%) after 12 weeks, while treatment response in the Child-Pugh class B cirrhosis was 123 (96%). Mild side effects were observed in 76 patients. CONCLUSIONS: Sofosbuvir based regimens were effective and safe in the treatment of cirrhotic patients with chronic hepatitis C genotype 4.

Is Hepatitis B Surface Antigen (HB s Ag) Enough Alone as a Screening Test for HBV Infection in Rheumatic Disease Patients Before Starting Immunosuppressive Therapies? A Cross-sectional Study.

BACKGROUND & OBJECTIVES: Prevalence of hepatitis B virus in patients with rheumatic diseases has been reported differently among studies. The loss of immune control in these patients may result in the reactivation of HBV replication within hepatocytes. Considering the lifelong use of multiple anti-rheumatic drugs, screening for HBV is recommended before starting immunosuppressive or immunomodulatory therapy. The aim of this study was to select the best and simplest test for screening of HBV in rheumatic patients. METHODS: This study was carried out in 102 patients with different rheumatic diseases. Screening to all patients for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies and human immune deficiency virus antibodies (HIV) was done. HBV core antibodies and real time PCR to detect HBV DNA were done. RESULTS: The mean age of the patients was 37.18 ± 12.37 years, 3.9% of them were males and 96.1% were females. HBsAg had 100% Sensitivity, 100% Specificity, 100% PPV, 100% NPV and 99.0% accuracy. While, anti-HBc had 100% Sensitivity, 78% Specificity, 8% PPV, 100% NPV and 78% accuracy in the screening of HBV. CONCLUSIONS: HBs Ag was found to be superior to antiHBc for screening for HBV infection in rheumatic patients.

Predictors for Fibrosis Regression in Chronic HCV Patients after the Treatment with DAAS: Results of a Real-world Cohort Study.

INTRODUCTION: The goal of treatment of chronic hepatitis C (HCV) is viral eradication. However, obtaining histological regression is even more important, because it will reduce the overall morbidity and mortality related to cirrhosis. Introduction of direct-acting antivirals (DAAs) in HCV improves rates of sustained virologic response (SVR). However, fibrosis regression has not been extensively assessed. The aim of this study was to detect the factors affecting fibrosis regression in chronic HCV patients treated with interferon containing regimens versus interferon-free DAA regimens. METHODS: This prospective observational cohort study was conducted at the Tropical Medicine and Infectious Diseases Department, Tanta University, Egypt, between October 2015 and December 2017. Transient elastography (FibroScan®) examination was performed before therapy, at SVR12, 6 months and 1 year after completing therapy for cured patients. RESULTS: Reduction in fibrosis was reported in; 46.7% and 49.3% of patients with moderate fibrosis, and 89% and 78.7% of patients with advanced fibrosis after one year of interferon containing and interferon free DAAs regimens respectively. Using multiple regression analysis; it was found that BMI, degrees of hepatic stiffness and steatosis were related to regression of hepatic fibrosis after therapy. CONCLUSION: DAAs with or without interferon resulted in a significant reduction of liver fibrosis. BMI, steatosis and liver stiffness were independent factors for fibrosis regression in chronic HCV patients treated with DAAs. Further studies are needed to explore the mechanism by which steatosis affects HCV related fibrosis regression after treatment with DAAs.

Orphenadrine in treatment of muscle cramps in cirrhotic patients: a randomized study.

OBJECTIVE: Many patients of liver cirrhosis are complaining of muscle cramps, which are annoying to them. There is no effective treatment for muscle cramps in cirrhotic patients till now. This study purposed to evaluate efficacy and safety of orphenadrine in the treatment of muscle cramps in cirrhotic patients. METHODS: One hundred and twenty four patients who had muscle cramps three or more times weekly were included. They were divided into two arms: 62 patients administrated orphenadrine and 62 administrated placebo. They were followed up till 2 weeks after the end of therapy. Muscle cramps were evaluated using questionnaire as regards severity, duration, and frequency. Also, side effects of orphenadrine were recorded. RESULTS: Frequency, duration of muscle cramps, and pain score improved significantly after 1 month of orphenadrine therapy in comparison to placebo. Few side effects were recorded in the form of dry mouth, drowsiness, and nausea. CONCLUSION: Orphenadrine is considered as promising safe drug for treatment of muscle cramps associated with liver cirrhosis.

Quadruple Therapy Offers High SVR Rates in Patients with HCV Genotype 4 with Previous Treatment Failure.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) have made a revolution in hepatitis C virus (HCV) treatment with promising reduction of HCV infection and disease morbidities. However, unfortunately, treatment failure still occurs in about 5-15% of patients treated with DAA-based combination regimens. The primary aim of the study was to assess the efficacy and safety of a quadruple regimen of (sofosbuvir, daclatasvir, and simeprevir with a weight-based ribavirin) in chronic HCV DAAs-experienced patients. METHODS: This observational, open-label prospective study was carried out on 103 genotype 4 hepatitis C virus-infected patients who failed to achieve SVR12 after sofosbuvir-daclatasvir with or without ribavirin. Patients were treated for three months with sofosbuvir (400 mg), daclatasvir (60 mg), and simeprevir (150 mg) with a weight-based ribavirin dosage (1000-1200 mg/d). Response to treatment was determined by quantitative PCR for HCV at 3 months after the end of treatment (SVR12), and adverse events during the treatment were recorded. RESULTS: SVR was achieved in 100 patients (97.1%) at week 12 after treatment. No dangerous or life-threatening adverse events were recorded. CONCLUSIONS: Retreatment of HCV genotype 4 patients with quadruple therapy is a good therapeutic option and achieves high response rates with minimal side effects.

Outcomes of Treatment and Predictors of Response to Sofosbuvir Plus Simeprevir in Hepatitis C Virus with Genotype-4 Infection.

BACKGROUND & AIMS: Treatment plan of chronic HCV infection has dramatically improved after the introduction of different groups of Direct-Acting Antiviral (DAA) drugs. These drugs have been found to be safe and effective. Sofosbuvir (SOF) plus simeprevir (SMV) regimen has been shown to be tolerable and effective in treatment of patients with HCV genotype 1. The aim of the study was to evaluate the safety and the efficacy of combined sofosbuvir plus simeprevir treatment in genotype 4 chronic HCV patients. METHODS: This open-label multicenter prospective study was carried out on 381 Egyptian patients with chronic hepatitis C virus- infection. Treatment experienced and treatment-naive patients were included. Subjects administrated a regimen of sofosbuvir (400 mg/ day) plus semiprevir (150 mg /day) for twelve weeks. Sustained Virological Response (SVR) was confirmed by undetectable HCV RNA by quantitative PCR 3 months after the end of the treatment. RESULTS: 97.6% (372 /381) of patients had SVR. None of the studied clinical and demographic characteristics were associated with the SVR status. However, patients who failed to achieve SVR showed low albumin level and high total leucocyte. The most common side effects of the studied regimen were headache, fatigue, itching, photosensitivity, and cough. CONCLUSIONS: Twelve weeks' regimen of sofosbuvir plus simeprevir was considered to be safe and tolerable in the treatment of HCV genotype 4; also it was associated with high SVR (97.6%).