Endoscopic ultrasound-guided biliary drainage for distal malignant biliary obstruction: a prospective 3-year multicenter Egyptian study.

Background/Aim: Malignant biliary obstruction (MBO) is often diagnosed at late stages with mostly unresectable lesions. Recently, EUS-guided biliary drainage (EUS-BD) has gained wide acceptance and appears to be a feasible and safe backup option after ERCP failure in such patients. Herein, we aimed to represent a 3-year multi-center Egyptian experience in the application of this challenging procedure for distal MBO as a salvage technique after failed ERCP. Patients and methods: This was a prospective multi-center study of patients underwent EUS-BD for distal MBO in the duration between December 2018 and December 2021, after ERCP failure. Results: Ninety-one patients (59 males, median age: 61 years) were included in the study. EUS-guided extrahepatic approach including choledocho-duodenostomy (CDS) was done for 48 patients (52.8%), followed by choledecho-antrostomy (CAS) in 4 patients (4.4%). The intrahepatic approach included hepaticogastrostomy (HGS) for 35 patients (38.5%) and antegrade stenting (AG) stenting in 2 patients (2.2%), while Rendezvous (RV) approach was performed in 2 patients (2.2%). Technical and Clinical success were achieved in the majority of cases; 93.4% and 94.1% respectively. Adverse events occurred in 13.2% of patients which were mostly mild (8.2%) to moderate (2.4%). Only one patient died within 48h after the procedure with progression of preceding sepsis and organ failure. Conclusion: EUS-BD is a feasible option, even in developing countries, after a failed ERCP, and it is a relatively safe option in patients with MBO once experienced team and resources were present. Majority of cases in our study have achieved technical and clinical success with relatively low incidence of adverse events.

Sofosbuvir plus Daclatasvir with or without ribavirin for treatment of chronic HCV genotype 4 patients: real-life experience.

INTRODUCTION: New regimens involving direct-acting antiviral agents have recently been approved for the treatment of HCV. Our aim was to assess the efficacy and safety of 12 or 24 weeks of Sofosbuvir 400 mg plus Daclatasvir 60 mg, with or without ribavirin (800-1000 mg) in treating chronic hepatitis C genotype 4 patients. METHODS: This is an open-label observational study that describes the effect of 12 week or 24 weeks of daily oral Sofosbuvir (SOF) 400 mg plus Daclatasvir (DCV) 60 mg with or without ribavirin (RBV) with dose adjustment if indicated. It included the first 1168 patients that fulfilled the inclusion and exclusion criteria and treated in the Egyptian Liver Research Institute and Hospital, Mansoura, Egypt. RESULTS: Sustained viral response after 12 weeks of end of treatment (SVR12) was achieved in 96.6% (95% CI 95.1-98.2%) of the patients receiving 12 weeks of DCV + SOF treatment, in 95.7% (95% CI 93.6-97.8%) of the patients receiving 12 weeks of DCV + SOF + RBV, in 93.3% (95% CI 90.0-96.6%) of those receiving 24 weeks of DCV + SOF, and in 92.2% (95% CI 85.4-98.9%) of patients receiving 24 weeks of DCV + SOF + RBV treatment. SVR12 rate was significantly higher in patients with no cirrhosis receiving DCV + SOF only for 12 weeks or 24 weeks (97.4 and 97.4%, respectively) than in patients with cirrhosis (91.7 and 88.9%, respectively). The most common adverse events were fatigue, headache, insomnia, and anemia. No treatment-related serious adverse events or death were reported in the studied groups. CONCLUSION: Treatment with SOF (400 mg) plus DCV (60 mg), with or without RBV (800-1000 mg) for 12 or 24 weeks, was effective and well tolerated in chronic hepatitis C genotype 4 patients. SVR rates were higher for patients with no cirrhosis. Addition of RBV has benefit only in treatment-experienced group receiving 24 weeks.

Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922). RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001). CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

A simple bedside blood test (Fibrofast; FIB-5) is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis in patients with chronic hepatitis C.

INTRODUCTION: A simple non-invasive score (Fibrofast, FIB-5) was developed using five routine laboratory tests (ALT, AST, alkaline phosphatase, albumin and platelets count) for the detection of significant hepatic fibrosis in patients with chronic hepatitis C. The FIB-4 index is a non-invasive test for the assessment of liver fibrosis, and a score of ≤1.45 enables the correct identification of patients who have non-significant (F0-1) from significant fibrosis (F2-4), and could avoid liver biopsy. The aim of this study was to compare the performance characteristics of FIB-5 and FIB-4 to differentiate between non-significant and significant fibrosis. METHOD: A cross-sectional study included 604 chronic HCV patients. All liver biopsies were scored using the METAVIR system. Both FIB-5 and FIB-4 scores were measured and the performance characteristics were calculated using the ROC curve. RESULTS: The performance characteristics of FIB-5 at ≥7.5 and FIB-4 at ≤1.45 for the differentiation between non-significant fibrosis and significant fibrosis were: specificity 94.4%, PPV 85.7%, and specificity 54.9%, PPV 55.7% respectively. CONCLUSION: FIB-5 score at the new cutoff is superior to FIB-4 index for the differentiation between non-significant and significant fibrosis.

Sofosbuvir-based treatment regimens: real life results of 14 409 chronic HCV genotype 4 patients in Egypt.

BACKGROUND: Chronic hepatitis C virus infection is one of the most important health problems in Egypt. The Ministry of Health's National Treatment Programme introduced sofosbuvir-based therapy in October 2014. AIM: To assess the clinical effectiveness and predictors of response to SOF-based treatment regimens, either dual therapy, with SOF/ribavirin (RBV) for 6 months or triple therapy with SOF/peg-IFN-alfa-2a/RBV for 3 months, in a cohort of patients treated in National Treatment Programme affiliated centres in Egypt. METHODS: Between October 2014 and end of 2014, patients who were eligible for treatment were classified according to their eligibility for interferon therapy: Group 1 (interferon eligible) were treated with triple therapy for 12 weeks and Group 2 (interferon ineligible) were treated with dual therapy for 24 weeks. Difficult to treat patients included those with F3-F4 on Metavir score, Fib-4 >3.25, albumin ≤3.5, total Bilirubin >1.2 mg/dL, INR >1.2 and platelet count <150 000 mm3 . RESULTS: Twelve weeks post-treatment data were available on 14 409 patients; 8742 in group 1 and 5667 in group 2. In group 1, the sustained virological response at week 12 (SVR12) was 94% and in group 2 the SVR12 was 78.7%. Multivariate logistic regression analysis in which treatment failure is the dependent variable was done. Male gender, being a difficult to treat patient and previous interferon therapy were significant predictors of nonresponse in both treatment groups. CONCLUSION: Results of sofosbuvir-based therapies in Egypt achieved similar rates of SVR12 as seen in phase III efficacy studies.

The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

Evaluation of serum procollagen aminoterminal propeptide III, laminin, and hydroxyproline as predictors of severe fibrosis in patients with chronic hepatitis C.

In an attempt to identify biochemical analytes that could enhance the discrimination between the patients with severe liver fibrosis (F3-F4) and mild fibrosis (F1-F2) based on absolute values of biochemical markers, we measured 12 analytes, including procollagen III aminoterminal propeptide (PIIINP), laminin, proline, hydroxylproline, glycine, AST, ALT, alkaline phosphatase, albumin, total bilirubin, total protein, and prothrombin time in 252 individuals with chronic hepatitis C infection (CHC). PIIINP and laminin were determined by radio-immunoassay; the degraded amino acids were determined using high performance liquid chromatography. Statistical analyses were performed by logistic regression, and receiver operating characteristic (ROC) curves. The best linear combination of blood markers was selected by multivariate discriminant analysis (MDA) for construction of the fibrosis discriminant score (FDS). FDS, an index of five markers (PIIINP, laminin, hydroxyproline, prothrombin activity, and AST/ALT) correctly classified 82% of the patients with severe liver fibrosis at a discriminant cut-off score=-0.5 (i.e., less than -0.5 indicated severe liver fibrosis and greater than -0.5 indicated mild liver fibrosis with sensitivity (76%) and specificity (89%). This result was reproduced in a validation study with no significant difference. In conclusion, FDS is useful for identifying severe liver fibrosis in patients with CHC.

Does schistosomiasis interfere with application of Knodell score for assessment of chronic hepatitis C?

BACKGROUND: Schistosoma Mansoni (SM) is a significant etiology of liver disease in Egypt. Chronic hepatitis, predominantly HCV, is a major health problem worldwide. Whether, schistosomal affection could interfere with assessment of necroinflammatory injury and degree of fibrosis in liver biopsy of chronic hepatitis, is not a settled issue. The present study is an attempt to highlight this problem. MATERIAL AND METHODS: 185 individuals--pure schistosomal affection (25 pts), pure HCV (100 pts), and mixed schistosomal and HCV (HCV + SC) (60 pts)--were included. They were selected from among 222 biopsied patients with chronic liver disease attending the liver unit of Internal Medicine Department, Mansoura University July 1999-May 2000. They were subjected to rectal snip and serological test for schistosomiasis, liver functions, HBV, HCV serological markers, serum qualitative and quantitative PCR and liver biopsy. Masson trichrom stain was performed to assess fibrosis. Immunohistochemical staining for HBsAg & HBcAg were performed. Modified Knodell score was applied to assess the biopsy. RESULTS: Five out of the 25 pure schistosomal and only 2 of the mixed group revealed schistosomal granuloma. 30% and 33% of pure HCV and mixed patients, respectively, were found to be cirrhotic. No significant statistical difference was identified between the two groups with respect to necroinflammatory injury and Knodell score (p = 0.81). Additionally, no significant difference was identified related to the stage of fibrosis (p = 0.77). CONCLUSION: Schistosomal hepatic affection does not alter or interfere with assessment of necroinflammatory injury or fibrosis in mixed HCV-schistosomal liver affection.

Gastric variceal ligation: a new technique.

BACKGROUND: Gastric variceal bleeding is a serious complication of portal hypertension. The role of endoscopy in its management is still controversial. However, band ligation of gastric varices has not been evaluated. This study prospectively describes gastric variceal ligation as a new endoscopic technique for the management of different types of gastric varices. METHODS: Gastric variceal ligation was performed in 27 patients with gastric varices: 3 patients had type 1 gastroesophageal varices, 14 had type 2, 8 had isolated gastric varices, and 2 had both type 1 and type 2 gastroesophageal varices. The etiology of portal hypertension was schistosomiasis in 9, post hepatic cirrhosis in 3, and mixed cirrhosis in 15 patients. The Child-Pugh classification was grade A in 6, B in 17, and C in 4 cases. Active variceal bleeding was present in 18 patients, whereas nonbleeding varices were encountered in 9 patients. RESULTS: Emergency gastric variceal ligation arrested bleeding in 16 of 18 patients (88.8%). Recurrent bleeding was noted in 5 of 27 (18.5%). Six patients died (22.2%), 3 due to recurrent bleeding and 2 to liver failure. Variceal obliteration was achieved in all patients who underwent repeated elective sessions. The number of sessions needed for obliteration of varices was significantly less in patients with isolated gastric varices when compared with those with type 1 gastroesophageal varices ( p < 0.04). No serious complications occurred. CONCLUSION: Gastric variceal ligation is a safe and effective treatment for the different types of gastric varices but especially isolated gastric varices.

Sclerotherapy versus sclerotherapy and propranolol in the prevention of rebleeding from oesophageal varices: a randomised study.

BACKGROUND: This trial was carried out to assess the value of propranolol in the prevention of recurrent variceal bleeding when combined with longterm endoscopic sclerotherapy. PATIENTS AND METHODS: Two hundred patients (161 male, 39 female, age range 20-68 years) with portal hypertension resulting mainly from schistosomal periportal fibrosis or posthepatitic cirrhosis presenting with their first episode of haematemesis or melena, or both were included. This was confirmed endoscopically to result from ruptured oesophageal varices. After initial control of bleeding, patients were randomised into two groups: group 1 treated with endoscopic sclerotherapy alone and group 2 treated with sclerotherapy plus propranolol. They were followed up for two years. RESULTS: Group (2) had a lower rebleeding rate (14.3% v 38.6% in group 1), lower variceal recurrence after obliteration (17% v 34% in group 1), longer period between variceal obliteration and recurrence (36 weeks v 21 weeks in group 1); but no change in mortality (12% in both groups). CONCLUSIONS: Patients treated with sclerotherapy should be given propranolol for longterm management.