Evolution of liver fibrosis after interferon-based anti-hepatitis C virus therapy failure in 3,049 chronic hepatitis C patients without cirrhosis.

BACKGROUND AND STUDY AIMS: Liver fibrosis is the underlying causeof hepatitis C virus (HCV)-related disease progression to endpoints such as cirrhosis, liver failure, and hepatocellular carcinoma. The aim of our study was to assess changes in hepatic fibrosis in patients with chronic HCV who had a fibrosis evaluation at two time points at least six months apart. PATIENTS AND METHODS: This was a retrospective cohort study that included patients who had failed interferon therapy and received HCV retreatment with direct-acting antivirals (DAAs) at least six months later. Patients were evaluated previously for fibrosis according to liver biopsy and fibrosis biomarkers were evaluated before pegylated interferon and ribavirin (PEG/RBV) therapy. Fibrosis was re-evaluated with fibrosis-4 (FIB-4) scores before starting DAAs. RESULTS: A total of 3,049 patients were included [age 43.47 ± 9.07 years, 55.20 % males] and baseline histopathology showed F1, F2, and F3 in 16.86 %, 46.21 %, and 36.93 %, respectively. The mean time interval between the last dose of previously failed IFN-therapy to the first dose of DAAs was 2.38 (±1.07) years. Overall, there was a significant increase in FIB-4 scores at retreatment times (from 11.71 ± 1.13 to 22.26 ± 1.68, p < 0.001). Patients with baseline FIB-4 < 1.45 (n = 1,569) and between 1.45 and 3.25 (n = 1,237) had significant increases in their FIB-4 at the retreatment time point [median difference; 0.41 (0.91) and 0.24 (1.5), p < 0.001, respectively], whereas patients with FIB-4 > 3.25 had significant reduction of their FIB-4 score at a retreatment timepoint [-0.98 (2.93), p ≤ 0.001]. CONCLUSION: Fibrosis progressed in most patients, even within six months for some patients, and this indicates retreatment of non-system vascular resistance patients even if they do not have significant fibrosis.

Impact of Sarcopenia on Short-Term Complications and Survival After Liver Transplant.

OBJECTIVES: Sarcopenia is a common entity in cirrhosis with significant morbidity and mortality. However,the effects of sarcopenia on the risk of complications and survival after liver transplant remain controversial.We aimed to evaluate the effect of sarcopenia on survival and complications after liver transplant. MATERIALS AND METHODS: Our study cohort included 61 adult patients with hepatitis C-related cirrhosis who underwent living donor liver transplant. Pretransplant clinical and anthropometric assessments included body mass index, hand grip, mid-arm circumference, triceps skin fold thickness, and gait speed. Sarcopenia was determined by computed tomography using the skeletal muscle index at the third lumbar vertebra cut-off value of <38.5 cm2/m2 for women and <52.4 cm2/m2 for men; these patients were then followed up for 6 months after transplant to determine survival and complications. RESULTS: At time of liver transplant, sarcopenia was present in 27/61 patients (44.3%). At follow-up after transplant, sarcopenia was found in 14 patients (30.4%) among 46 survivors; all patients who survived were male patients. Among patients with sarcopenia posttransplant, 12 had sarcopenia before transplant and 2 developed sarcopenia after transplant. Liver dysfunction, lower triceps skin fold thickness, recent infections, and sarcopenia pretransplant were associatedwithposttransplant complications, especially infection(42.8%) and prolonged intensive careunit stay. Age and pretransplant sarcopenia were found to be independent predictors of posttransplant mortality. CONCLUSIONS: Sarcopenia is a common entity in patients with cirrhosis who are on liver transplant wait lists and may continue after liver transplant. De novo sarcopenia after liver transplant is also a common finding. Sarcopenia can affect patient outcomes, including prolonged intensive care unit stay and poor short-term survival.

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.

Safety and efficacy of favipiravir versus hydroxychloroquine in management of COVID-19: A randomised controlled trial.

Favipiravir is considered a potential treatment for COVID-19 due its efficacy against different viral infections. We aimed to explore the safety and efficacy of favipiravir in treatment of COVID-19 mild and moderate cases. It was randomized-controlled open-label interventional phase 3 clinical trial [NCT04349241]. 100 patients were recruited from 18th April till 18th May. 50 patients received favipiravir 3200 mg at day 1 followed by 600 mg twice (day 2-day 10). 50 patients received hydroxychloroquine 800 mg at day 1 followed by 200 mg twice (day 2-10) and oral oseltamivir 75 mg/12 h/day for 10 days. Patients were enrolled from Ain Shams University Hospital and Assiut University Hospital. Both arms were comparable as regards demographic characteristics and comorbidities. The average onset of SARS-CoV-2 PCR negativity was 8.1 and 8.3 days in HCQ-arm and favipiravir-arm respectively. 55.1% of those on HCQ-arm turned PCR negative at/or before 7th day from diagnosis compared to 48% in favipiravir-arm (p = 0.7). 4 patients in FVP arm developed transient transaminitis on the other hand heartburn and nausea were reported in about 20 patients in HCQ-arm. Only one patient in HCQ-arm died after developing acute myocarditis resulted in acute heart failure. Favipiravir is a safe effective alternative for hydroxychloroquine in mild or moderate COVID-19 infected patients.

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.

Outcome of Colonoscopic Screening in Potential Liver Transplant Candidates.

BACKGROUND: Screening for neoplastic lesions is mandatory as a part of the evaluation process of potential candidates for liver transplant (LT). This work aimed at identifying the main findings in screening colonoscopy and their risk factors. METHODS: Endoscopic and pathologic findings of the biopsied lesions of 311 potential candidates for living donor liver transplant were collected and analyzed. RESULTS: Colorectal polyps (8.7%) were the most common colonoscopic finding, of which 4.18% were diagnosed as adenomas. Other findings included hemorrhoids (7.7%), portal hypertensive colopathies (3.5%), angiomatous malformations (2.6%), rectal varices (1.6%), and diverticulosis (1.6%). The univariate analysis revealed that the prevalence of colonic adenoma was significant in patients 50 years and older (P = .03; odds ratio, 1.178; 95% CI, 1.016-1.365) and in patients who had hepatocellular carcinoma (P = .043; odds ratio, 6.5; 95% CI, 1.002-42.172). In the multivariate analysis, age was found to be the single best predictor of the presence of adenoma (P = .044; odds ratio, 1.178; 95% CI, 1.005-1.382). CONCLUSION: We can conclude that a screening colonoscopy prior to liver donor liver transplant should be performed at least in every LT candidate 50 years or older. Colonic polyps were the most common findings on screening colonoscopy prior to LT.

Pattern of Vascular Involvement in Egyptian Patients with Budd-Chiari Syndrome: Relation to Etiology and Impact on Clinical Presentation.

INTRODUCTION AND AIM: Budd-Chiari syndrome (BCS) is caused by hepatic venous outflow obstruction. This work aims to analyze the pattern of vascular involvement in Egyptian patients with BCS, demonstrates its relation to etiology and shows its impact on clinical presentation. MATERIAL AND METHODS: The current retrospective study was conducted at The Tropical Medicine Department, Ain Shams University on one hundred Egyptian patients with confirmed diagnosis of primary BCS who were presented to the Budd-Chiari Study Group (BCSG) from April 2014 to May 2016 by collecting clinical, laboratory and radiological data from their medical records. RESULTS: Isolated hepatic vein occlusion (HVO) was the most common pattern of vascular involvement (43%), followed by combined HVO and inferior vena cava (IVC) compression by enlarged caudate lobe (32%), then combined HVO and IVC stenosis/webs (21%), and lastly isolated IVC occlusion (4%). Ascites was more significantly encountered in BCS patients with HVO than in those with isolated inferior vena cava (IVC) occlusion and patent HVs (P = 0.005). Abdominal pain was significantly encountered in patients with occluded three major HVs (P = 0.044). Behcet's disease was significantly detected in isolated IVC occlusion. Protein C deficiency was significantly detected in patients with combined HVO and IVC compression. CONCLUSION: Isolated HVs occlusion was the most common pattern of vascular involvement in Egyptian patients with primary BCS. Vascular pattern of involvement affected the clinical presentation and was related to the underlying thrombophilia in those patients.

Efficacy of loco-regional treatment for hepatocellular carcinoma prior to living donor liver transplantation: a report from a single center in Egypt.

BACKGROUND AND AIM: The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade, bridging or downstaging patients on the waiting list for liver transplantation. This study aimed to analyze the outcomes of LRTs prior to living donor liver transplantation in patients with HCC. METHODS: Sixty-two HCC patients received living donor liver transplantation at Ain Shams Center for Organ Transplantation over a 2-year period. Data from 29 HCC patients were analyzed. Twenty patients (68.97%) met the Milan Criteria and 4 patients (13.8%) exceeded the Milan Criteria, but met the University of California, San Francisco Criteria. Five patients (17.2%) exceeded the University of California, San Francisco Criteria. All patients underwent preoperative LRTs. The protocol of bridging/downstaging, methods, duration of follow-up, the number of patients who were successfully downstaged before liver transplantation (LT), and their outcomes after LT were recorded. RESULTS: There was a decrease in the mean overall size of focal lesions (from mean 5.46 to 4.11 cm) in the last abdominal computed tomography (CT) scan after LRT (p=0.0018). Discrepancies between the radiological findings and histopathology were as follows: in 16 patients (55.17%) the CT findings were consistent with the histopathological examination of the explanted liver. Underestimated tumor stage was documented in 10 patients (34.48%), and was overestimated by CT scan findings in 3 patients (10.34%). The 1-year survival rate was 93%. No patient had HCC recurrence after median follow-up of 21 months (range 1-46 months). CONCLUSION: These results encouraged tumor bridging/downstaging as a potential treatment option among carefully selected patients with HCC beyond conventional criteria for LT. Further studies on a large number of patients are necessary.

Safety, Efficacy, and Tolerability of Sofosbuvir and Ribavirin in Management of Recurrent Hepatitis C Virus Genotype 4 After Living Donor Liver Transplant in Egypt: What Have We Learned so far?

BACKGROUND: Recurrence of HCV after living donor liver transplant (LDLT) is nearly universal, with almost one third of recipients developing cirrhosis and graft failure within 5 years after LDLT. Different studies have been published on the effect of sofosbuvir after liver transplantation on recurrent HCV with different genotypes. OBJECTIVES: The aim of this study was to evaluate the efficacy, safety, and tolerability of sofosbuvir and ribavirin in LDLT recipients with recurrent HCV genotype 4. PATIENTS AND METHODS: Thirty-nine Egyptian LDLT recipients were treated for recurrent HCV after LDLT with nucleos(t)ide analog NS5B polymerase inhibitor, sofosbuvir, and ribavirin without pegylated interferon for 6 months (November 2014 to June 2015) in this intention-to-treat analysis. RESULTS: One recipient died 1 week after starting the treatment, but the remaining 38 patients completed 24 weeks of treatment and were then followed for 12 weeks after end of treatment (EOT). The sustained virological response (SVR) at week 12 after EOT was achieved in 76% (29/38) of recipients. SVR was significantly higher in treatment-naïve patients and in recipients with a low stage of fibrosis. Only 2 (5%) recipients developed severe pancytopenia and acute kidney injury. CONCLUSIONS: We recommend initiating treatment as soon as possible after liver transplantation with newer combinations, such as ledipasvir/sofosbuvir or sofosbuvir/simeprevir, rather than sofosbuvir with Ribavirin, to achieve higher rates of SVR.

Curative resection of pancreatic adenocarcinoma with major venous resection/repair is safe procedure but will not improve survival.

OBJECTIVE: To evaluate the safety and survival benefit of combined curative resection (CR) of the pancreas and major venous resection in the management of borderline resectable pancreatic adenocarcinoma. METHODS: In this IRB approved retrospective cohort study, patients who had pancreatic surgery (n=274) between 1998-2012 were reviewed. One hundred and seventy-five patients had malignant causes, of which 119 underwent CR. One hundred and two patients who did not require venous resection/repair (Group-I) were compared with 17 patients who had major vascular involvement (portal-vein/superior-mesenteric-vein) and underwent a vascular resection/repair (Group-II) during the CR. Demographics, operative and follow-up data were reviewed. RESULT: Type of the operations were: standard Whipple (n=53), pylorus-sparing-Whipple (n=41), total pancreatectomy (n=11), and distal pancreatectomy (n=13). In Group-II, venous involvement was excised and primarily repaired (n=12), or repaired using other veins (n=4) or a synthetic patch (n=1). Group-II had a significantly larger tumor size and more perineural invasion and peripancreatic soft tissue involvement (P<0.05). While complication rate, margin status, and duration of stay were not different between the groups, the median-overall-survival was higher for Group-I (15.34 months) than Group-II patients (7.18 months) (P=0.003). CONCLUSION: Pancreatic CR requiring intra-operative venous resection/repair is feasible and safe, but the survival of the patients who have pancreatic adenocarcinoma with venous involvement is poor irrespective of a successful venous resection.