Efficacy and safety of basiliximab as initial immunosuppression in liver transplantation: A single center study.

INTRODUCTION AND AIM: The interleukin-2 receptor antagonist; basiliximab is used to allow delayed introduction of Calcineurin inhibitors (CNI) after liver transplantation and thus delay their renal insult. However, there is only little evidence for the safety and the efficacy of this regimen. This study aimed to evaluate the effectiveness and safety of basiliximab induction in liver transplantation. MATERIALS AND METHODS: This study included 89 patients who were classified into two groups: standard triple immunosuppression (IS) regimen of steroid, tacrolimus (TAC) and mycophenolate mofetil (MMF) (n = 47) and induction IS regimen of basiliximab, low dose steroids and MMF with delayed introduction of CNI (n = 42). All patients were followed after liver transplantation for at least six months or until death. RESULTS: There were no significant differences in patient survival, graft dysfunction, infection rate or type, or wound healing between both groups. The acute rejection rate was equivalent in both groups. Renal dysfunction in the first six months post-transplant was less in the basiliximab group in comparison to the other group (7.1% and 19.1% respectively). CONCLUSION: Basiliximab-induced IS protocol is a safe regimen that reduces medium-term renal dysfunction and achieves similar survival without increasing the acute rejection or infection rate in liver transplantation recipients.

Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness Measurements in Apparently Healthy Individuals.

BACKGROUND & AIMS: Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis. METHODS: We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index <30 kg/m2 were examined with the medium probe and those with a body mass index ≥30 kg/m2 were examined with the extra-large probe. Linear regression models were conducted after adjusting for potential confounding factors of LSMs. We performed several sensitivity analyses. RESULTS: We established LSM ranges for healthy individuals measured with both probes-these did not change significantly in sensitivity analyses of individuals with platelets ≥150,000/mm3 and levels of alanine aminotransferase ≤33 IU/L in men or ≤25 IU/L in women. In multivariate analysis, factors that modified LSMs with statistical significance included diabetes, dyslipidemia, waist circumference, level of aspartate aminotransferase, and systolic blood pressure at examination time. Significant increases in LSMs were associated with the metabolic syndrome in individuals examined by either probe. Diabetes in obese individuals increased the risk of LSMs in the range associated with advanced fibrosis. CONCLUSIONS: In a systematic review and meta-analysis of data from individual participants, we established a comprehensive set of LSM ranges, measured by TE in large cohorts of healthy individuals and persons susceptible to hepatic fibrosis. Regression analyses identified factors associated with increased LSMs obtained by TE with the medium and extra-large probes.

Impact of terlipressin infusion during and after live donor liver transplantation on incidence of acute kidney injury and neutrophil gelatinase-associated lipocalin serum levels: A randomized controlled trial.

BACKGROUND AND AIM: Acute kidney injury (AKI) with liver transplantation (LT) is not uncommon. Impact of terlipressin infusion on AKI, hemodynamics, and plasma concentration of neutrophil gelatinase-associated lipocalin (NGAL) was studied. METHODS: Patients (n=50) were randomized (NCT02059460, USA) into two equal groups: terlipressin vs Controls. Terlipressin (1-4 µg/kg/h) was administrated for 5 days. Intraoperative transesophageal Doppler for hemodynamic management. Renal functions, peak portal vein blood flow velocity (PPV), and hepatic artery resistive index (HARI) were recorded. Plasma NGAL (pNGAL) was measured baseline, 2 and 24 hours postreperfusion. RESULTS: Hepatitis C virus (HCV) was the main etiology. Age, sex, model of end-stage liver disease (MELD), and renal functions were comparable. Postoperative AKI incidence and NGAL concentrations were comparable (P>.05) between terlipressin and controls groups (44% vs 48% and 112.5±9 vs 93.1±8 ng/mL), respectively, but intraoperative NGAL in both groups increased significantly 2 hours postreperfusion (P<.05). The three NGAL readings were comparable (P>.05) between AKI (n=23) and non-AKI developers (n=27). Mean arterial blood pressure (MAP) was maintained in both groups with less systemic vascular resistance (SVR) fluctuations with terlipressin. Median norepinephrine consumption was lower in terlipressin vs controls (8 vs 12 mg; P=.04). The PPV and HARI were not affected by terlipressin at any stage (P>.05). CONCLUSION: Postliver transplant AKI was not prevented by terlipressin use nor predicted by NGAL levels.

IL28B, TLR7 SNPs, and cytomegalovirus infection are risk factors for advanced liver disease in chronic hepatitis C patients.

BACKGROUND: Chronic hepatitis C (CHC) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). This study aimed to study the association of IL28B, toll-like receptor (TLR) 7, cytomegalovirus and advanced liver disease. METHODS: Four groups were included; control (n = 125, 25.9%), CHC (n = 114, 23.6%), liver cirrhosis (n = 120, 24.8%), and HCC (n = 124, 25.7%). RESULTS: In CHC group, patients were mainly F1 (60%) followed by F2. IL28B genotype CC percentage was higher in control group than the CHC and cirrhosis groups. CT and TT genotypes were higher in the CHC and cirrhosis groups than control group. The C allele was higher in the control group than the CHC, cirrhosis and HCC groups and the opposite with the T allele. Control and CHC had same TLR7 alleles. Cirrhosis patients and HCC had lower TLR 7 A allele and higher G allele than the control group. Both cirrhosis and HCC groups had statistically significant higher percentage of the AG and GG genotypes than the control group. Patients with HCC had higher cytomegalovirus infection percentage than cirrhosis and CHC group (38.7% vs 20% vs 16.7%), respectively. CONCLUSION: IL28B, TLR7 SNPs and cytomegalovirus infection are risk factors for advanced liver disease in hepatitis C patients.

Direct acting antivirals are associated with more liver stiffness regression than pegylated interferon therapy in chronic hepatitis C patients.

OBJECTIVES: Extent of post-treatment fibrosis change in patients with different stages of fibrosis not fully known. We aimed to study changes in liver fibrosis in chronic hepatitis C patients who were treated with pegylated interferon/ribavirin (PEG/RBV) or direct acting antivirals (DAAs). METHODS: Retrospective evaluation of results of transient elastography (TE) was done before and 1 year after end of treatment for patients treated with PEG/RBV (n = 268) and DAAs (n = 245). RESULTS: The average age was 45.54 ± 10.64 years; mainly males. All patients in the DAAs group achieved sustained virological response (SVR), unlike 56.3% of the patients in the PEG/RBV group. F3-F4 fibrosis was predominant in the PEG/RBV nonresponder patients (51.3%) and DAAs responders (57.1%). TE decreased 1 year after end of treatment (p = 0.001) in the viral responders of the PEG/RBV group (7.44 ± 4.02 vs. 10.24 ± 7.29 kPa) and DAAs group (12.12 ± 9.21 vs. 16.81 ± 12.84 kPa) respectively. The delta TE change in the DAAs responders was higher than the PEG/RBV responders (p = 0.001) and PEG/RBV nonresponders (p = 0.001). The percentage of patients with liver fibrosis regression was higher in DAAs responders (52.5%) than in PEG/RBV responders (23.3%). CONCLUSION: Treatment with DAAs is associated with fibrosis improvement more than treatment with PEG/RBV in chronic hepatitis C patients.

MELD-Sarcopenia is Better than ALBI and MELD Score in Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation.

BACKGROUND: The albumin bilirubin (ALBI) score and model of end stage liver disease (MELD) are prognostic in patients with hepatocellular carcinoma (HCC). Aim was to compare MELD-sarcopenia to MELD and ALBI scores in patients with HCC awaiting liver transplantation. METHODS: patients with HCC (n=262) were included and followed up for 12 months. Baseline MELD, ALBI and MELD-sarcopenia models were calculated. RESULTS: The average age was 59.61 ±8.09 years. Most patients were males (69.5%), CTP class A (55.7%) and BCLC stage B (54.2%). Hepatitis C virus was the main cause of liver cirrhosis in most patients (88.9%). The average MELD, MELD-sarcopenia and median ALBI score were 10.65 ±2.54, 15.11 ±6.22 and -2.12 (0.74) respectively. Sarcopenia patients had higher MELD, ALBI and MELD-sarcopenia values. Patients with sarcopenia had lower survival (10.09 months) than those without (11.72 months). The ALBI, MELD and MELD-sarcopenia were associated with mortality. ALBI had AUROC of 0.717 (95% CI: 0.659 - 0.771), MELD had AUROC of 0.656 (95% CI: 0.595 - 0.713) and MELD-sarcopenia had AUROC of 0.798 (95% CI: 0.744 - 0.845). The ALBI and MELD scores had comparable AUROC (p=0.081). The MELD-sarcopenia had superior AUROC than MELD (p=0.001) and ALBI (p=0.05). CONCLUSION: MELD-sarcopenia is better prognostic model than the ALBI and MELD scores in HCC patients awaiting liver transplantation.
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Baseline Sarcopenia is Associated with Lack of Response to Therapy, Liver Decompensation and High Mortality in Hepatocellular Carcinoma Patients.

OBJECTIVE: hepatocellular carcinoma (HCC) is a dreadful complication of liver cirrhosis. Aim was to study the effect of sarcopenia on the survival in patients with HCC. METHODS: we included 262 patients and were followed up for 12 months. Sarcopenia was calculated by skeletal muscle index (SMI). Sarcopenia was defined by SMI ≤39 cm2/m2 for women and ≤50 cm2/m2 for men. RESULTS: patients with sarcopenia (n= 113, 43.1%) were older, mainly males, Child-Pugh class B and smokers. Patients with sarcopenia had lower survival than those without (10.09 vs. 11.72 months). Survival was also lower in Barcelona clinic liver cancer stage C than B and A (9.02 vs. 11.21 vs. 11.89 months). Age and sarcopenia were hazardous of mortality (p <0.05). There was statistically significant difference of serial SMI in patients without baseline sarcopenia unlike patients with baseline sarcopenia. On follow up patients with sarcopenia had higher incidence of ascites (45% vs. 20.4%), spontaneous bacterial peritonitis (21.7% vs. 11.6%), hepatic encephalopathy (28% vs. 11.5%) and bleeding (22.9% vs. 12.7%). Totally patients with sarcopenia had higher incidence of progressive HCC (39% vs. 25.5%). CONCLUSION: Sarcopenia is associated with lack of response to therapy, liver decompensation and higher mortality in hepatocellular carcinoma patients.
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Laparoscopic cholecystectomy in patients with liver cirrhosis: 8 years experience in a tertiary center. A retrospective cohort study.

With improved laparoscopic techniques, experience, and availability of newer tools and instruments like ultrasonic shears; laparoscopic cholecystectomy (LC) became a feasible option in cirrhotic patients, the aim of this study was to analyze the outcome of LC in cirrhotic patients. METHODS: We retrospectively analyzed 213 cirrhotic patients underwent LC, in the period from 2011 to 2019; the overall male/female ratio was 114/99. RESULTS: The most frequent Child-Turcotte-Pugh (CTP) score was A, The most frequent cause of cirrhosis was hepatitis C virus (HCV), while biliary colic was the most frequent presentation. The harmonic device was used in 39.9% of patients, with a significant correlation between it and lower operative bleeding, lower blood and plasma transfusion rates, higher operative adhesions rates, lower conversion to open surgery and 30-day complication rates, shorter operative time and post-operative hospital stays where operative adhesions and times were independently correlated. The 30-day morbidity and mortality were 22.1% and 2.3% respectively while overall survival was 91.5%, higher CTP, and model for end-stage liver disease (MELD) scores, higher mean international normalization ratio (INR) value, lower mean platelet count, higher operative bleeding, higher blood, and plasma transfusion rates, longer mean operative time and postoperative hospital stays were significantly correlated with all conversion to open surgery, 30-day morbidities and mortalities. CONCLUSION: LC can be safely performed in cirrhotic patients. However, higher CTP and MELD scores, operative bleeding, more blood and plasma transfusion units, longer operative time, lower platelet count, and higher INR values are predictors of poor outcome that can be improved by proper patient selection and meticulous peri-operative care and by using Harmonic scalpel shears.

Elastography and serum markers of fibrosis versus liver biopsy in 1270 Egyptian patients with hepatitis C.

BACKGROUND: Chronic hepatitis C (CHC) is a leading cause of liver fibrosis. OBJECTIVE: To compare utility of liver transient elastography, AST-to-platelet ratio index (APRI), fibrosis-4 index (FIB4), Forns Index and Goteborg University cirrhosis index (GUCI) in predicting fibrosis stage assessed by liver biopsy in Egyptian CHC patients. METHODS: One thousand two-hundred and seventy CHC patients undergoing liver biopsy in preparation for therapy and 40 healthy potential living liver donors had transient elastography and calculation of APRI, FIB4, Forns and GUCI scores on the same day or day preceding the biopsy. RESULTS: Mean age was 39.89 (17-60 years) and most were males (70.7%). All donors had F0 fibrosis, most patients had F1-F2 fibrosis (n = 1011, 79.6%) and 259 (20.4%) had F3-F4 fibrosis. Patients with F3-F4 fibrosis had higher median values of APRI (0.99 vs. 0.46), FIB4 (2.15 vs. 0.95) and Forns (7.34 vs. 4.79) indices, GUCI score (1.16 vs. 0.49) and transient elastography (19.2 vs. 6.2 kPa) (all P = 0.001). For F1 discrimination, AUROC of transient elastography was higher than both Forns and GUCI scores (P = 0.001). APRI, FIB4 and GUCI had lower AUROC than transient elastography for predicting fibrosis stage in F2 and F3 patients (P = 0.001). Transient elastography had the best area under receiver operating characteristic curve for predicting fibrosis stage in F4 patients (P = 0.001). The transient elastography cutoff values (kPa) were F1 (>4.8), F2 (>8.3), F3 (>10.1) and F4 (>13.4). Age, APRI, FIB4, Forns, GUCI and transient elastography were independent predictors of F3-F4 fibrosis. CONCLUSION: Liver elastography is superior to APRI, FIB4, Forns and GUCI scores in predicting fibrosis in CHC patients.

Predictive value of omental thickness on ultrasonography for diagnosis of unexplained ascites, an Egyptian centre study.

Etiology of ascites of unknown origin varies with geographic area and ethnic origin. Tuberculous peritonitis and peritoneal carcinomatosis constitute a considerable proportion of patients. Differentiation between both is a major challenge. The role of omental thickness (OT) by ultrasonography to predict risk of malignancy in unexplained ascites. This prospective study was done at Kasr Alainy School of Medicine, Cairo University and included 100 adults with unexplained ascites and thickened omentum (>15 mm) on ultrasonography. An expert performed ultrasonography to assess peritoneum and peritoneal cavity and measure OT. Ascites was assessed regarding volume, echogenicity, and loculation. The ascitic fluid was analyzed to measure lactate dehydrogenase, adenosine deaminase, and total leukocytic count. Laparoscopic exploration with biopsy was done for final diagnosis that divided the patients into; TB Group (n = 44) and peritoneal carcinomatosis group (n = 56). Main Outcome Measures were to determine degree of omental thickness as a predictor of malignancy risk in unexplained ascites and other ultrasonographic features to predict malignancy risk including omental echogenicity and results of diagnostic ascitic tapping. We found that OT was greater in the PC group compared to the TB group (24.6 ± 4.6 mm vs. 17.9 ± 3.0 mm, respectively, p < 0.001). Higher frequency of hypoechogenicity, irregular peritoneal surface, omental cakes, and lymph nodes was seen in PC Group. ADA, TLC, and relative lymphocyte count were higher in TB group. Omental thickness ≥19.5 mm has a sensitivity of 89.3%, specificity of 84.1% to diagnose PC. We can conclude that omental thickness >19 mm is a sensitive and specific predictor of malignancy in patients with unexplained ascites.

Insulin resistance is not a risk factor for oesophageal varices development in hepatitis C.

Chronic hepatitis C (HCV) patients commonly have insulin resistance which is a risk factor for disease progression. Oesophageal varices may bleed with high mortality. We aimed to assess the relationship between insulin resistance and oesophageal varices. HCV-related compensated liver cirrhosis patients (n = 146) underwent gastroscopy and homeostasis model assessment (HOMA)-IR, HOMA-ß and HOMA-S calculations. Their average age was 54.98 years; most (84.9%) patients were men and non-diabetic (60.3%). Patients with oesophageal varices had higher median Model for End-Stage Liver Disease (MELD) scores and comparable Child-Pugh class. Patients with and without oesophageal varices had comparable (P > 0.05) HOMA scores and insulin resistance percentage of 82.9% versus 85.5%. We therefore conclude that insulin resistance is unrelated to the presence of oesophageal varices.

HCV treatment with direct acting antivirals improves the insulin sensitivity.

Background: There is strong link between hepatitis C virus (HCV) infection and the insulin resistance panel. Homeostatic model assessment (HOMA) ß is an indirect measurement of insulin secretion from pancreatic ß cells, while HOMA-S accounts for insulin sensitivity. Aim: We examined the impact of HCV treatment with direct acting antivirals (DAAs) on HOMA-ß and HOMA-S results. Methods: HOMA-IR, HOMA-ß, and HOMA-S were calculated before and 12 weeks after treatment in 511 treatment eligible patients with HCV. Five DAA treatment protocols were used. Values before and after treatment were compared. Results: The mean age of patients was 50.63 years with a 3.2:1 male: female ratio. A total of 29.7% of patients were treatment experienced and 24.7% had diabetes. HCV sustained virological response (SVR) was achieved in 91% of patients. Unlike non-responders, SVR patients showed significantly decreased post-treatment HOMA-Β. Delta HOMA-Β was comparable between groups. HOMA-S increased significantly in patients with SVR compared to in non-responders, as did delta HOMA-S. HOMA-S and HOMA-ß improved significantly under 5 and 2 DAA protocols, respectively. The treatment status did not affect the HOMA-ß and S dynamics during treatment. Conclusions: Insulin sensitivity improved markedly in patients who achieved HCV SVR.

Insulin resistance does not impair response of chronic hepatitis C virus to direct-acting antivirals, and improves with the treatment.

BACKGROUND: Insulin resistance (IR) is a common complication in chronic hepatitis C virus (HCV) patients. The impact of IR on outcome of therapy with direct antivirals has not been studied. AIM: The aim was to assess the impact of direct-acting antiviral (DAA) therapy on IR status in chronic HCV patients. PATIENTS AND METHODS: A total of 511 patients [mean age: 50.7±10.4 years, 29.7% pegylated interferon and ribavirin (RBV) experienced] were enrolled. Patients with uncontrolled diabetes, decompensated liver disease, or previous nonresponse to DAAs were excluded. Homeostatic model assessment (HOMA) was calculated before and 12 weeks after treatment, and IR was defined as HOMA greater than 1.9. Patients were treated according to the treating physician's choice, and received 12 weeks of either ombitasvir/ritonavir/paritaprevir/RBV (n=28); sofosbuvir (SOF)/simeprevir (n=36); SOF/ravidasvir (n=101); SOF/pegylated interferon/RBV (n=192); or 24 weeks of SOF/RBV (n=154). RESULTS: Most patients received IR pretreatment (80.6%); 51.3% had fibrosis stage F4 and 24.7% had diabetes. A sustained virological response (SVR) at 12 weeks after treatment (SVR12) was achieved in 465 (91%) patients. SVR12 was achieved in 90.5% of patients with IR and in 92.9% of patients without IR (P=0.560), and pretreatment HOMA was not different in responders and nonresponders (P=0.098). The number of patients with IR decreased significantly in patients who achieved an SVR much more than in nonresponders (P<0.0001) and HOMA improved significantly more in patients with SVR than in nonresponders (P=0.001). All treatment protocols were associated with a comparable improvement in HOMA (P=0.101). Predictors of SVR12 included age, platelets, and liver stiffness, but not pretreatment IR. CONCLUSION: IR does not impair the response of patients with HCV treated with DAAs, and improves significantly in patients who achieve an SVR.

Validation of modified albumin-bilirubin-TNM score as a prognostic model to evaluate patients with hepatocellular carcinoma.

BACKGROUND: An ideal staging system for hepatocellular carcinoma (HCC) should rely on the hepatic reserve function and tumor burden. With the improvement in diagnostic and treatment strategies for HCC, in addition to recent treatment of viral hepatitis, finding a suitable assessment tool for hepatic reserve has become mandatory. AIM: To validate a recently proposed modified albumin-bilirubin-TNM (mALBI-T) grade as a prognostic model for patients with HCC in Egypt. METHODS: For patients diagnosed with HCC, Child-Turcotte-Pugh (CTP) score, Barcelona Clinic Liver Cancer (BCLC) stage, albumin-bilirubin (ALBI), plateltet-albumin-bilirubin (PALBI), ALBI-based BCLC, ALBI-T and mALBI-T grades were estimated. Patients were followed from time of diagnosis to date of death or date of data collection if they remained alive. Overall survival and received treatments were determined. Survival data were analyzed. RESULTS: A total of 1910 patients were included (mean age, 57 years; 1575 males). At presentation, 50.6% had CTP A, 36.1% had CTP B and 13.4 % had CTP C; 12% had ALBI grade 1, 62.3% had ALBI grade 2 and 24.7% had ALBI grade 3. Overall median survival was 13 mo; survival was better in patients with ALBI 1 than in those with ALBI 2 and 3 (28.6 vs 14 and 5.8 mo, respectively, P < 0.001). Patients with ALBI-T grades 0 and 1 had better survival than those with ALBI-T grades 2, 3, 4 and 5 (P < 0.001). The modified ALBI-T showed better stratification and significant improvement in prediction of survival. CONCLUSION: ALBI-T grade is a superior prognostic tool that selects patients with HCC who have better liver reservoir and tumor stage. mALBI-T is a better prognostic model in patients with HCC.

Predictors of early recipient mortality after living donor liver transplantation in a tertiary care center in Egypt.

BACKGROUND: Living donor liver transplantation (LDLT) has evolved into a widely accepted therapeutic option. Many different risk factors may affect early mortality after LDLT. OBJECTIVES: Analyze risk factors that can affect early (<6 months) mortality of patients after LDLT in a single center. DESIGN: Retrospective chart review of patients who underwent LDLT. SETTING: University hospital. PATIENTS AND METHODS: Adult cirrhotic patients who underwent LDLT were classified by early (first 6 months) or late mortality. A full pre, intra- and post-operative evaluation had been done on all patients including a full history, examination and investigations to identify risk factors that might affect mortality post-LDLT. MAIN OUTCOME MEASURES: Determination of pre-, intra- or postoperative factors that might affect recipient mortality post-LDLT. SAMPLE SIZE: 123. RESULTS: Pre-operative factors that increased early mortality in a univariate analysis were higher model for end-stage liver disease (MELD) scores, lower graft-recipient weigh ratio (GRWR), older donor age, and recurrent spontaneous bacterial peritonitis. Intraoperative factors included more transfusion units of blood, plasma, platelets and cryoprecipitate, a longer time for cold and warm ischemia, and a longer anhepatic phase among others. Postoperative factors included a longer ICU or hospital stay and abnormal postoperative laboratory data. In the final logistic regression model, the most significant factors were pre-operative GRWR, length of hospital stay, units of intraoperative blood transfusion, postoperative alanine aminotransferase, postoperative total leukocyte count, and MELD score. CONCLUSION: LDLT outcomes might be improved by attempting to resolve clinical factors that have been identified as contributors to early post-LDLT mortality. LIMITATIONS: More risk factors, such as those relevant to patient portal vein hemodynamics, should be included in an analysis of predictors of early mortality. CONFLICT OF INTEREST: None.

Surgical (Open and laparoscopic) management of large difficult CBD stones after different sessions of endoscopic failure: A retrospective cohort study.

OBJECTIVES: For complicated common bile duct stones (CBDS) that cannot be extracted by endoscopic retrograde cholangiopancreatography (ERCP), management can be safely by open or laparoscopic CBD exploration (CBDE). The study aimed to assess these surgical procedures after endoscopic failure. METHODS: We analyzed 85 patients underwent surgical management of difficult CBDS after ERCP failure, in the period from 2013 to 2018. RESULTS: Sixty-seven (78.8%) and 18(21.2%) of our patients underwent single and multiple ERCP sessions respectively. An impacted large stone was the most frequent cause of ERCP failure (60%). Laparoscopic CBDE(LCBDE), open CBDE(OCBDE) and the converted cases were 24.7% (n = 21), 70.6% (n = 60), and 4.7% (n = 4) respectively. Stone clearance rate post LCBDE and OCBDE reached 95.2% and 95% respectively, Eleven (12.9%) of our patients had postoperative complications without mortality. By comparing LCBDE and OCBDE; there was a significant association between the former and longer operative time. On comparing, T-tube and 1ry CBD closure in both OCBDE and LCBDE, there was significantly longer operative time, and post-operative hospital stays in the former. Furthermore, in OCBDE group, choledocoscopy had an independent direction to 1ry CBD repair and significant association with higher stone clearance rate, shorter operative time, and post-operative hospital stay. CONCLUSION: Large difficult CBDS can be managed either by open surgery or laparoscopically with acceptable comparable outcomes with no need for multiple ERCP sessions due to their related morbidities; furthermore, Open choledocoscopy has a good impact on stone clearance rate with direction towards doing primary repair that is better than T-tube regarding operative time and post-operative hospital stay.

Platelets-to-lymphocyte ratio is a good predictor of liver fibrosis and insulin resistance in hepatitis C virus-related liver disease.

BACKGROUND: Hepatitis C virus (HCV) is a global health problem that is complicated by liver fibrosis and insulin resistance (IR). AIM: The aim of this study was to validate neutrophils-to-lymphocytes ratio (NLR) and platelets-to-lymphocytes ratio (PLR) as indirect biomarkers of liver fibrosis and IR in HCV patients. PATIENTS AND METHODS: One hundred and fifty patients were enrolled. Physical examination, BMI, liver function tests, serum creatinine, complete blood count, serum HCV RNA count by PCR, and abdominal ultrasonography were performed. Transient elastography measurement using FibroScan was performed. Patients were classified into those with mild fibrosis (F1-F3) and significant fibrosis (F4). IR was defined as homeostasis model assessment of IR more than 2. NLR and PLR were calculated. RESULTS: The average age of the patients was 47.21±10.51 years, mainly men (n=119; 79.3%), and 87.3% (n=131) had IR and 44.7% (n=67) had significant fibrosis. PLR was lower in patients with IR (74.95±37.90 vs. 94.71±31.45; P=0.032) unlike the NLR, which was comparable (P>0.05). Patients with significant fibrosis had lower PLR (66.43±39.38 vs. 86.35±33.85; P=0.001) unlike NLR (P>0.05). PLR (cutoff≥77.47) had 78.9% sensitivity, 60.3% specificity, 22.4% positive predictive value, and 95.2% negative predictive value for non-IR (P=0.008). At a cutoff of at least 63.71, PLR had 73.5% sensitivity, 61.2% specificity, 70.1% positive predictive value, and 65.1% negative predictive value for nonsignificant fibrosis (P=0.001). Age and PLR (odds ratio=0.99; 95% confidence interval=0.976-0.999) were predictors of IR, whereas age, total bilirubin, serum albumin, liver stiffness, and PLR (odds ratio=0.98; 95% confidence interval=0.974-0.994) were predictors of significant fibrosis. CONCLUSION: PLR is useful in distinguishing the patients with significant fibrosis or IR unlike NLR.

High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C.

BACKGROUND: Direct acting antivirals (DAAs) are highly effective for treatment of hepatitis C (HCV) but brand products are priced beyond the means of most low and middle income countries (LMICs). Although a few DAAs are offered at reduced prices in access programs, they are still beyond affordability in limited resource settings with a large HCV infected population. Cheap generics might fill this economic need, but studies comparing their clinical efficacy to that of original products are limited. AIM: To compare efficacy of brand and generic DAAs used in the national treatment program in Egypt. METHODS: HCV treatment eligible patients (n=971) were enrolled. They were treated with 12 weeks of either sofosbuvir-daclatasvir (SOF-DCV) or SOF-ledipasvir (SOF-LDV). Ribavirin (RBV) was added to patients with cirrhosis and to SOF experienced patients. Patients with cirrhosis who were RBV intolerant were treated for 24 weeks without RBV. RESULTS: Most patients were males (61.4%), treatment naïve (88.6%), without cirrhosis (61.7%), and the mean age was 51.3±11.31 years. Baseline characteristics were not different in patients treated with brand or generic medications regarding age, liver tests, creatinine, platelets, MELD score, baseline HCV-RNA and transient elastography. Overall sustained virologic response (SVR) rate was 98.1%, which was similar for generic and brand drugs (98.2% vs. 98.1%; p=1), and similar with both regimens used (SOF-DCV±RBV: brand: 98.1%, generic 97.8%; p=0.729, SOF-LDV±RBV: brand 98.2%, generic 100%; p=0.729). AST and ALT decreased significantly with initiation of therapy with both generic and original drugs. CONCLUSION: Generic and brand DAAs are equally effective for achieving SVR and improving aminotransferases.

Combined spontaneous bacterial empyema and peritonitis in cirrhotic patients with ascites and hepatic hydrothorax.

BACKGROUND AND STUDY AIMS: Spontaneous bacterial empyema (SBEM) is an underestimated condition in patients with ascites and hepatic hydrothorax with a high mortality. This study aimed to find whether spontaneous bacterial peritonitis (SBP) is a prerequisite for SBEM. PATIENTS AND METHODS: 3000 HCV-related cirrhotic patients with ascites and hydrothorax were screened for the presence of SBP (ascitic fluid neutrophils >250/mm3) and SBEM (positive pleural fluid culture and neutrophils >250/mm3 or negative pleural fluid culture and neutrophils >500/mm3 with no evidence of pneumonia/parapneumonic effusion on chest radiograph or CT). RESULTS: The prevalence of SBEM in cirrhotic patients was 1.2% (36/3000) unlike SBP (1.6%; 48/3000). SBEM was detected in 51.4% of the patients with hepatic hydrothorax (36/70). A total of 70 patients had concomitant ascites and hydrothorax, namely SBP (n=17), SBEM (n=5), and dual SBP and SBEM (n=31), whereas 17 patients had sterile concomitant ascites and hydrothorax. Age, sex, liver function, kidney function tests, complete blood count, INR, MELD, MELD-Na, blood chemistry, and culture/sensitivity for ascitic and pleural fluid were statistically not different (p>0.05) between SBP and dual SBP and SBEM patients. Escherichia coli and Klebsiella pneumoniae were detected in the culture. From univariate analysis, no predictors of dual SBP and SBEM were detected. CONCLUSION: SBEM is a part of SBP in cirrhotic patients with ascites and hydrothorax.