Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt.

OBJECTIVE: We evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with hepatitis C virus (HCV) genotype 4, including those who had failed previous treatment with sofosbuvir regimens. DESIGN: In this open-label, multicentre, phase III study, treatment-naive patients were randomised to receive 8 or 12 weeks of ledipasvir/sofosbuvir±ribavirin. Interferon treatment-experienced patients were randomised to receive 12 weeks of ledipasvir/sofosbuvir±ribavirin, while sofosbuvir-experienced or ledipasvir/sofosbuvir-experienced patients received 12 weeks of ledipasvir/sofosbuvir+ribavirin. Randomisation was stratified by cirrhosis status. The primary endpoint was sustained virological response 12 weeks post-treatment (SVR12). RESULTS: We enrolled 255 patients from four centres in Egypt. Among treatment-naive patients, SVR12 rates were 95% and 90% for those receiving 8 weeks of ledipasvir/sofosbuvir alone and with ribavirin, respectively, and 98% for those receiving 12 weeks of ledipasvir/sofosbuvir both alone and with ribavirin. Among interferon-experienced patients, SVR rates were 94% for those receiving 12 weeks of ledipasvir/sofosbuvir and 100% for those receiving 12 weeks of ledipasvir/sofosbuvir plus ribavirin. All patients previously treated with sofosbuvir regimens who received ledipasvir/sofosbuvir plus ribavirin achieved SVR12. The most common adverse events, headache and fatigue, were more common among patients receiving ribavirin. CONCLUSION: Among non-cirrhotic treatment-naive patients with HCV genotype 4, 8 weeks of ledipasvir/sofosbuvir±ribavirin was highly effective. Twelve weeks of ledipasvir/sofosbuvir±ribavirin was highly effective regardless of presence of cirrhosis or prior treatment experience, including previous treatment with sofosbuvir or ledipasvir/sofosbuvir. TRIAL REGISTRATION NUMBER: NCT02487030.

BAR Score Performance in Predicting Survival after Living Donor Liver Transplantation: A Single-Center Retrospective Study.

METHODS: 146 adult liver transplant recipients were included. Univariate and multivariate analyses were used to determine the independent predictors of survival at 3 months, 1 year, and 5 years. The receiver operating characteristic (ROC) curve for the BAR score was plotted, and the area under the ROC curve (AUROC) was calculated. Kaplan-Meier curve and log-rank test were used to compare survival above and below the best cutoff values. RESULTS: The mean age was 52.45 ± 8.54 years, and 59.6% were males. The survival rates were 89, 78.8, and 72% at 3 months, 1 year, and 5 years, respectively. The BAR score demonstrated a clinically significant value in the prediction of 3-month (AUROC = 0.89), 1-year (AUROC = 0.76), and 5-year survival (AUROC = 0.71). Among the investigated factors associated with survival, BAR score <10 points was the only independent predictor of 3-month (OR 7.34, p < 0.0001), 1-year (OR 3.37, p=0.001), and 5-year survival (OR 2.83, p=0.044). CONCLUSIONS: BAR is a simple and easily applicable scoring system that could significantly predict short- and long-term survival after LDLT. A large multicenter study is warranted to validate our results in the Egyptian population.

Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: Given the poor synthetic function of cirrhotic liver, successful resection for patients with hepatocellular carcinoma (HCC) necessitates the ability to achieve resections with tumor free margins. AIM: To validate post hepatectomy liver failure score (PHLF), compare it to other established systems and to stratify risks in patients with cirrhosis who underwent curative liver resection for HCC. METHODS: Between December 2010 and January 2017, 120 patients underwent curative resection for HCC in patients with cirrhosis were included, the pre-operative, operative and post-operative factors were recorded to stratify patients' risks of decompensation, survival, and PHLF. RESULTS: The preoperative model for end-stage liver disease (MELD) score [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (OR = 2.5, 95%CI: 1.5-4.2, P = 0.001) were significant independent predictors of hepatic decompensation after resection. While the preoperative MELD score [hazard ratio (HR) = 1.37, 95%CI: 1.16-1.62, P < 0.001] and different grades of PHLF (grade A: HR = 2.33, 95%CI: 0.59-9.24; Grade B: HR = 3.15, 95%CI: 1.11-8.95; Grade C: HR = 373.41, 95%CI: 66.23-2105.43; P < 0.001) and HCC recurrence (HR = 11.67, 95%CI: 4.19-32.52, P < 0.001) were significant independent predictors for survival. CONCLUSION: Preoperative MELD score and tumor diameter can independently predict hepatic decompensation. While, preoperative MELD score, different grades of PHLF and HCC recurrence can precisely predict survival.

Long-Term Impact of Hepatitis C Virus Eradication on Liver Stiffness in Egyptian Patients.

Methods: Liver stiffness measurements (LSM) have been serially assessed 1, 3, and 5 years after HCV clearance in 655 patients who have been treated with DAAs. Results: The mean age was 51.44 ± 10 years. 73% of patients were males. 48% were cirrhotics. In noncirrhotics, the mean LSM was significantly decreased from 8.29 ± 2.3 kPa to 4.03 ± 1.0 kPa (p < 0.0001) at the end of the follow-up. Likewise, LSM decreased in cirrhotics from 29.66 ± 14.25 kPa to 22.50 ± 11.16 kPa (p < 0.0001). The proportions of F1, F2, F3, and F4 patients at the baseline were 17.7%, 17.9%, 16.6%, and 47.8%, which became 56.5%, 4.1%, 4.9%, and 34.5%, respectively, with a substantial reversal of cirrhosis in 87 patients (27.7%) at the end of follow-up. Conclusions: There was an overall significant regression of liver stiffness in all patients after sustained HCV eradication. Liver stiffness reflecting mild fibrosis (F0-F2) usually improves shortly after treatment, while measurements reflecting advanced fibrosis (F3-F4) take a longer time to regress to lower fibrosis stages.

Risk factors and management of different types of biliary injuries in blunt abdominal trauma: Single-center retrospective cohort study.

BACKGROUND: Biliary injuries after blunt abdominal traumas are uncommon and difficult to be predicted for early management. The aim of this study is to analyze the risk factors and management of biliary injuries with blunt abdominal trauma. METHOD: Patients with blunt liver trauma in the period between 2009 to May 2019 were included in the study. Patients were divided into 2 groups for comparison; a group of liver parenchymal injury and group with traumatic biliary injuries (TBI). RESULTS: One hundred and eight patients had blunt liver trauma (46 patients with liver parenchymal injury and 62 patients with TBI). TBI were; 55 patients with bile leak, 3 patients with haemobilia, and 4 patients with late obstructive jaundice. Eight patients with major bile leak and 12 patients with minor bile leak had been resolved with a surgical drain or percutaneous pigtail drainage. Nineteen patients (34.5%) with major and minor bile leak underwent successful endoscopic retrograde cholangiopancreatography (ERCP). Sixteen patients (29.1%) underwent surgical repair for bile leak. In Multivariate analysis, the possible risk factors for prediction of biliary injuries were central liver injuries (P = 0.032), high grades liver trauma (P = 0.046), elevated serum level of bilirubin at time of admission (P = 0.019), and elevated gamma glutamyl transferase (GGT) at time of admission (P = 0.017). CONCLUSION: High-grade liver trauma, central parenchymal laceration and elevated serum level of bilirubin and GGT are possible risk factors for the prediction of TBI. Bile leak after blunt trauma can be treated conservatively, while ERCP is indicated after failure of external drainage.

Utility of post-liver transplantation MELD and delta MELD in predicting early and late mortality.

INTRODUCTION: The performance of early post-liver transplantation (post-LT) model for end-stage liver disease (MELD) or even its dynamic changes over time (ΔMELD) in predicting the mortality after LT is still controversial. AIM: The aim of this study was to assess the ability of absolute and ΔMELD calculated at days 7 and 30 after LT to predict 1- and 5-year mortality. PATIENTS AND METHODS: Data of 209 consecutive patients who underwent LT in two centers were reviewed. Patients who received LT for hepatocellular carcinoma were excluded, as well as those who did not survive for at least 1 month. MELD and [INCREMENT]MELD were calculated for each patient at 7 and 30 days after LT. RESULTS: One hundred fifty-six patients were included, mostly male [104 (66.7%)] with a mean age of 51.9±8.8 years. The main indications for transplantation were decompensated hepatitis C virus-related liver cirrhosis [138 (88.5%)] and hepatitis C and B virus co-infection [10 (6.4%)]. Grafts were obtained from 104 living donors and 52 deceased donors. Survival at 1 and 5 years was 89.7 and 85.9%, respectively, with a mean survival of 52.3±1.5 months. In univariate analysis, both absolute and ΔMELD at postoperative days 7 and 30 significantly predicted 1- and 5-year post-LT mortality. In multivariate analysis, MELD at postoperative day 30 was significantly associated with 1- (odds ratio: 1.24, 95% confidence interval: 1.14-1.35, P<0.0001) and 5-year mortality (odds ratio: 1.23, 95% confidence interval: 1.14-1.33, P<0.0001). The area under the curve for MELD at 30 days post-LT in the prediction of mortality was 0.823 (P=0.01) at 1 year and 0.812 (P<0.001) at 5 years. A cutoff of post-LT day 30 MELD less than 10 could predict mortality with a sensitivity and specificity of 90 and 68.1% at 1 year and 81.3 and 69.7% at 5 years, respectively. CONCLUSION: Failure of the MELD score to decline over the first postoperative month to less than 10 is a significant predictor of both early and late post-LT mortality.