Impacts of rifaximin and midodrine on morbidity, mortality, and quality of life in patients with decompensated liver cirrhosis.

BACKGROUND: Vasodilatation and bacterial dislocation are the main contributors to the catastrophic events in patients with decompensated liver cirrhosis (DLC). AIM: The aim of this study was to evaluate the impacts of adding midodrine and rifaximin on morbidity, mortality, and quality of life in patients with DLC. METHODS: This interventional clinical study included 100 consecutively enrolled DLC patients randomized 1 : 1 into two groups. Group A received oral midodrine (5 mg/8 h) and rifaximin (550 mg/12 h) with standard diuretic therapy, while group B received only standard diuretic therapy. Clinical and laboratory data, including the McGill Quality of Life Questionnaire, were evaluated over a 3-month treatment period. RESULTS: In the study group, there was a significant reduction in Child-Pugh and Model for End-Stage Liver Disease scores, international normalized ratio, and mean arterial blood pressure at 2, 6, and 12 weeks (P < 0.05). Ascites, spontaneous bacterial peritonitis incidence, hematemesis, paracentesis need, and hepatic encephalopathy showed improvement after 12 weeks compared with the control group. McGill Quality of Life Questionnaire significantly improved after 6 and 12 weeks (P < 0.05). Survival rates demonstrated a noteworthy improvement (P = 0.014), substantiated by evidence in both univariate and multivariate regression analyses. CONCLUSION: Combined midodrine with rifaximin represents an endowment to patients with DLC with spectacular improvements in synthetic liver functions, along with improved quality of life, and survival.

Evaluation of ABCA1 gene polymorphism as a prognostic index of fibrosis progression in NAFLD patients.

INTRODUCTION: It had been evident that non-alcoholic fatty liver disease (NAFLD) is the new era epidemic. Despite emergence of many drugs on the pipeline that considered candidates to cure NAFLD/NASH, the critical need for defining the cohort liable to fibrosis progression is yet unmet. AIM: Evaluate ABCA1 (rs1800977) genotyping as a noninvasive predictor of liver fibrosis severity. MATERIALS AND METHODS: This study included 118 liver biopsy-proven NAFLD-patients. According to Metavir-fibrosis-staging, cases were divided to early fibrosis (74 cases), and 44 cases with significant fibrosis (>F2), added to 49 healthy control subjects. All patients were subjected to liver function tests, lipids profile, triglyceride TG index, and hepatic steatosis index (HSI) and real-time PCR ABCA1 SNP (rs1800977). RESULTS: Significant differences in transaminases (p > .05), albumin (p < .009), cholesterol (p0.03), low density lipoproteins (LDL) (0.006), triglycerides (p < .001), HSI (p < .001), FIB4 (p < .001) and APRI (p < .001) were reported in those with significant than early fibrosis and control groups. CC was the most prevalent in significant (36.4%) than early fibrosis (13.5%) and control groups (8.2%), with prevalence of C allele in significant fibrosis (p ≤ .003). Univariate analysis revealed that DM (p ≤ .001), TG index (p ≤ .022), cholesterol (p ≤ .03), HSI (p ≤ .006), LDL (p ≤ .02), HDL (p ≤ .01), APRI (p ≤ .02) and CC genotype (p ≤ .005) were the main factors affecting fibrosis progression in NAFLD. However multivariate analysis proved only the role of HSI (p ≤ .005), LDL (p ≤ .02), HDL (p ≤ .003) and CC genotype (p ≤ .03) in predicting fibrosis severity. CONCLUSION: Dyslipidemias, hepatic steatosis index and ABCA1 (rs1800977) gene polymorphism CC genotype; were the only independent predictors of advanced fibrosis in NAFLD-patients.

Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients.

Aim of the study: Despite the ample flow of non-alcoholic fatty liver disease (NAFLD) drugs in the pipeline, lifestyle modifications are still the optimal solution of NAFLD. The aim of the study was to assess short term effects of Ramadan fasting (RF) as a sort of intermittent fasting (IF) on biochemical, radiological, and anthropometric parameters of NAFLD patients. Material and methods: Ninety-eight NAFLD patients were recruited and voluntarily subjected to 16 hours daily fasting for an average of 22-29 days, without special dietary recommendations. Anthropometric, laboratory and radiological parameters were measured before, at 30 days, and one month after fasting (fasting and non-fasting phases). Results: Patients were mostly rural (76%), hypertensive (34.7%), diabetic (43.9%), and female (76.8%), with overt criteria of metabolic syndrome (67.3%). Liver transaminases (ALT and AST) were ameliorated significantly after fasting (p ≤ 0.01), which continued in the following month (p ≤ 0.01) especially in those with elevated ALT before fasting (46%). Eleven patients (24.4%) experienced ALT normalization after one month of fasting, which was further increased to 15 (33.3%) one month later. Lipid profiles (cholesterol, triglycerides, HDL, LDL, cholesterol/HDL risk ratio) were significantly corrected following IF (p ≤ 0.01) and continuing in the next phase (p ≤ 0.010). Body mass index (BMI) lessened following the fasting (p ≤ 0.01), while no remarkable changes were noted regarding waist, hip, and triceps skin fold thickness (p ≤ 0.01). Glycemic indices (HbA1c, postprandial, HOMA-IR) and fibrosis markers (FIB-4 and APRI) were significantly ameliorated (p ≤ 0.01), while reduction in inflammatory markers was not long lasting (p ≤ 0.01). Conclusions: Intermittent fasting led to momentous improvements in ultrasonographic, biochemical, and anthropometric parameters of NAFLD especially in early phases and prediabetics.

A case report of COVID-19 evoked cholangitic liver abscess.

BACKGROUND: Lately, the humanity has been being threatened by the coronavirus disease (COVID-19). The virus-related destructive motives can damage not only the lungs but also the brain, blood vessels, kidneys, and the heart. CASE PRESENTATION: A middle-aged female presented with jaundice post-COVID-19 pneumonia. The patient had past history of cholecystectomy 20 years ago. Both laboratory and imaging data revealed a picture of cholestasis with right lobe liver abscess. Despite drainage and culture-based antibiotics, no improvement ensued. Endoscopic retrograde cholangiopancreatography was done revealing mildly dilated common bile duct (CBD), multiple large stones, mildly dilated central biliary radicals, and an old overlooked stent inside the dilated CBD. Papillotomy and papilloplasty were undertaken followed by stones' extraction with insertion of 2 plastic stents (10 cm× 10 f), and a flow of thick dark bile was inspected. The patient was finally improved and safely discharged. CONCLUSION: Herein, we present the first case of long-retained quiescent biliary stent which was over-headed by a cholangitic abscess in the vicinity of COVID pneumonia.

Prevalence and predictors of post-liver transplantation metabolic bone diseases.

INTRODUCTION: Post-liver transplantation (LTx) bone diseases have been poorly investigated. The frequency of bone diseases (osteopenia and osteoporosis) after LTx is unknown. AIM OF THE STUDY: To define prevalence and risk factors of bone disorders following LTx. MATERIAL AND METHODS: This prospective study was conducted on 100 consecutive adult patients who underwent living donor liver transplantation (LDLT) at the National Liver Institute (NLI) and survived longer than a year. Bone mineral density (BMD) was evaluated by dual-energy X-ray absorption (DEXA), as well as other pre- and postoperative risk factors. RESULTS: The frequencies of osteopenia and osteoporosis were found to be 14% and 8% among post-LTx patients. Seven recipients of the osteoporotic group were males, with mean age, and body mass index (BMI) before and after LTx 49.5 ±7.4 years, 24.1 ±4.7 kg/m2 and 22.8 ±1.5 kg/m2, respectively. A significant association between hepatitis C virus (HCV)-related cirrhosis, liver disease severity according to Child-Turcotte-Pugh (CTP) score, and alcoholism with decreased post-LTx BMD was substantiated (p < 0.05, 0.006). Post-LTx development of diabetes mellitus (DM), weight gain, use of corticosteroids and basiliximab all significantly affected decreased post-LTx BMD (p < 0.05). However, binary regression revealed that post-LTx occurrence of DM (p = 0.012, odds ratio [OR] = 0.099), the severity of liver disease (p = 0.023, OR = 0.217), and HCV (p = 0.011, OR = 0.173) are the main independent predictors of metabolic bone disease (MBD) occurrence one year after LTx. CONCLUSIONS: Post-LTx bone disorders are not infrequent complications and should be more considered in those with HCV-related severe liver disease or developed DM after LTx.

Janus Kinase-2 Mutation Associated Portal Vein Thrombosis Complicating Liver Cirrhosis and Hepatocellular Carcinoma.

BACKGROUND: Portal vein thrombosis (PVT) might be a catastrophic event complicating liver cirrhosis and hepatocellular carcinoma (HCC). AIM: role of JAK2 RS V617F mutation as a risk factor for PVT development in liver cirrhosis and HCC. METHODS: A case control study conducted on 100 PVT patients (76 HCC and 24 liver cirrhosis) additionally, 100 healthy individuals used as a control group. PVT was diagnosed incidentally by Doppler ultrasound during routine follow-up HCC screening. Prothrombin G20210A mutation, MTHFR mutation, Factor V Leiden mutation (VFL), antithrombin III (ATIII), protein C, S, and antiphospholipid antibodies, along with JAK2 RS V617F  mutation by real-time polymerase chain reaction all were analyzed. RESULTS: Patients with PVT were significantly older (p <0.001), thrombocytopenic (p <0.001), with high alkaline phosphatase (p <0.001). JAK2 RS V617F mutation was found in 28/100 (28%) in idiopathic PVT complicating liver cirrhosis and hepatocellular carcinoma. Cases with positive JAK2 rs V617F mutation were significantly accompanied by protein S deficiency (P 0.03), LA absence (p 0.06), and high frequency of ascites (P 0.03). While, the MTHFR heterozygous mutation (p0.001), ATIII (P 0.02), and VFL (P 0.01) were more frequent with negative JAK2 rs V617F mutation. The comparison between demographic data and thrombophilic parameters in PVT cases revealed that no significant differences were recorded except for male gender, Diabetes Mellitus, splenomegaly significantly increased among HCC cases (p <0.05). CONCLUSIONS: JAK2 rs V617F mutation must be considered in any case of PVT with liver cirrhosis and hepatocellular carcinoma without identified thrombophilic risk factors, with potential considerations of evolving myeloproliferative disorders. New diagnostic and therapeutic implications are still awaited.

Role of resistin, IL-6 and NH2-terminal portion proBNP in the pathogenesis of cardiac disease in type 2 diabetes mellitus.

INTRODUCTION: Epidemiological and genetic studies have recorded the association between proinflammatory cytokines and the development of insulin resistance, diabetes, and cardiovascular disease. The role of interleukin 6 (IL-6), NH2-terminal portion pro-brain natriuretic peptide (NT-proBNP) and resistin in the pathogenesis of heart disease in type 2 diabetes mellitus (T2DM) is still a matter of controversy. The current study aimed to evaluate the role of these biomarkers in the development of left ventricular systolic dysfunction and the ability to use them as non-invasive test in the prediction of left ventricular hypertrophy and systolic dysfunction in T2DM. RESEARCH DESIGN AND METHODS: 150 participants were included in this case-control study. Patients were divided into two subgroups according to echocardiographic findings: group 1a included 46 patients with type 2 diabetes mellitus and echocardiographic evidence of abnormal systolic function; group 1b included 54 patients with type 2 diabetes mellitus and with normal echocardiogenic study; and group 2 included 50 apparently healthy controls. Routine laboratory investigations such as complete blood count, liver and renal function tests, and lipid profile, serum IL-6, NT-proBNP, and resistin were measured in all participants. Conventional echocardiography was done with special concern on the assessment of left ventricular systolic function (ejection fraction). RESULTS: There was a significant increase in the level of resistin, NT-proBNP and IL-6 in group 1a patients compared with group 1b and in healthy controls. Echocardiographic parameters showed a significant increase in left ventricular mass index, left ventricle posterior wall thickness, interventricular septum thickness, and left ventricle mass in group 1a compared with group 1b and the control group. The increased left ventricular mass index was associated with higher levels of IL-6, NT-proBNP and resistin. CONCLUSIONS: Proinflammatory cytokines had a clear relation with left ventricular systolic dysfunction and hypertrophy and can be used as early non-invasive markers for detection of left ventricular remodeling and systolic dysfunction in patients with T2DM.

Role of Ribavirin in the Era of Direct-Acting Antiviral Therapies of Chronic Hepatitis C.

BACKGROUND: The efficacy of adding ribavirin (RBV) to direct antivirals (DAAs) in HCV treatment is still debatable, with allegations of insecure profiles. OBJECTIVES: To evaluate safety and efficacy of RBV in the era of DAAs in chronic HCV Egyptian patients. METHODS: In this cohort retrospective study, data of 847 HCV patients treated with different regimens of DAAs with or without RBV were recruited between June 2017 and September 2018. Cases were categorized into five groups: non-cirrhotic (318), compensated (196), decompensated liver cirrhosis (53), post liver transplantation (30), and 250 treatment experienced patients. All patients' demographics and laboratory characteristics were evaluated at baseline, week4, 12, 24 of treatment. Ribavirin was prescribed or banned outside international guideline recommendations of HCV treatment in cases assembled from the private sector.Results: No statistically significant difference between RBV and non-RBV treated patients was documented regarding SVR12 (97.2%, 97.8%) respectively in the whole cohort (p 0.509). On grouping, adding RBV was only significant in the treatment experienced patients (96.8%, 85% in RBV and non-RBV regimens respectively) (p 0.001). Adding RBV to DAA regimens was generally associated with modest adverse events particularly anemia (8.5%), and hepatic decompensation (jaundice and ascites) (0.3%). Bilirubin, INR, and platelet counts all were found to be the most independent predictors of SVR achievement by multivariate analysis (p ≤ 0.05).Conclusion: RBV may still have an augmenting role in treatment experienced patients; permitting effectual shortening of therapy particularly in patients with cirrhosis, with modest side and adverse consequences.

Value of IFNL3 genetic polymorphism in the prediction of HCV treatment response to direct-acting antiviral drugs versus interferon therapy.

Background: Despite the outstanding results of direct-acting antiviral therapies (DAAs) of Hepatitis C infection (HCV), non-responders had to be more defined. Aim: assess the outcome of DAAs in linkage with Interferon lambda 3 (IFNL3) in HCV patients. Methods: This case-control-study was conducted on 495 chronic-HCV (genotype-4a), previously treated Egyptians by either DAAs (responders 195, 120 relapsers) or interferon/ribavirin (IFN/RBV) (140 responders, 60 relapsers), and 98 healthy controls. IFNL3 distribution, clinical and laboratory data were assessed. Results: CT was the most predominant genotype in Egyptians (51%). All genotypes were sensitive to DAAs mainly CT genotype (60%), even TT genotype (resistant to IFN/RBV 40%) had 29.2% sensitivity. CT genotype was predominant in sofosbuvir/Daclatasvir responders (67.6%) (OR = 0.66), while non-CT prevailed in relapsers (56.7%). TT genotype may respond to SOF/Ledi better than other regimens (66.7%). In IFN/RBV relapsers; CT genotype was commoner (50%) than others, while CC genotype predominated in responders (54.3%). The c allele was the commonest in responders to IFN/RBV (71.4%), while the T allele was resistant to treatment (65% in relapsers). Addition of RBV to SOF/DCV reported higher resistance with CT genotype (42.2%-50%) and TT genotype (17.8%-27.8%). Conclusion: This study recommended IFNL3 genotyping to be a prerequisite before stratifying treatment for HCV-4a Egyptians.

Presentations, Causes and Outcomes of Drug-Induced Liver Injury in Egypt.

Drug-induced liver injury (DILI) is a frequent cause of liver injury and acute liver failure. We aimed to review all hospitalized DILI cases in a tertiary Egyptian center from January 2015 through January 2016. Cases with elevated alanine aminotransferase more than 3-fold and/or alkaline phosphatase more than 2-fold the upper limit of normal value were prospectively recruited and followed for one year. Drug history, liver biopsy whenever feasible and application of Roussel Uclaf Causality Assessment Method (RUCAM) were the diagnostic prerequisites after exclusion of other etiologies of acute liver injury. In order of frequency, the incriminated drugs were: Diclofenac (31 cases, 41.3%), amoxicillin-clavulanate (14 cases, 18.7%), halothane toxicity (8 cases, 10.7%), ibuprofen (4 cases, 5.3%), Khat (3 cases, 4%), tramadol (3 cases, 4%), Sofosbuvir with ribavirin (2 cases, 2.7%), and acetylsalicylic acid (2 cases, 2.7%) with one offending drug in 93.3% of cases. Forty-four cases (58.7%) were males; while 56 cases (74.7%) had HCV related chronic liver disease. Thirty-two cases (42.7%) presented with pattern of hepatocellular injury, while 23 cases (30.7%) were with cholestasis, and 20 cases (20.7%) with a mixed hepatocellular/cholestatic injury. One case received a transplant (0.75%), 7 cases died (9.3%), 23 cases (30.6%) developed liver decompensation (hepatic encephalopathy and ascites), and 44 cases completely resolved (58.7%). In conclusion, Diclofenac is the commonest offender in DILI occurrence in an Egyptian cohort. Age and prothrombin concentration were the only predictors of unfavorable outcomes of DILI.