Amr Shaaban Hanafy

Rifaximin and midodrine improve clinical outcome in refractory ascites including renal function, weight loss, and short-term survival.

Backgrounds and aims The occurrence of refractory ascites in nearly 17% of patients with decompensated cirrhosis is an unresolved issue. Advanced liver disease, functional renal impairment, and vascular insensitivity to vasopressors are the main causes of its refractoriness. Therefore, the aim of this study was to evaluate the impact on diuresis, weight loss, and short-term survival if midodrine and rifaximin were added to the diuretic therapy (DT). Materials and methods The study evaluated the eligibility of 650 patients with cirrhosis and refractory ascites who were selected during the period from November 2011 to May 2015. A total of 50 patients were excluded and finally 600 were selected and divided into the following groups: patients exposed to DT (n=200) as a control group, or DT with midodrine and rifaximin group (n=400). Body weight, mean arterial pressure, and glomerular filtration rate were determined. Plasma renin and aldosterone were also determined. Follow-up was performed after 2, 6, and 12 weeks, and then every 2 months for 24 months. Results The mean arterial pressure was significantly higher in the midodrine and rifaximin group (P=0.000), and there was a highly significant weight loss after 12 weeks (12.5 kg) (P=0.000), a highly significant increase in serum sodium, urine output, and urinary sodium excretion (P=0.000), and creatinine clearance was more reduced in the control group. With rifaximin and midodrine, a complete response occurred in 310 (78%) patients, a partial response in 72 (18%), and no response in 18 (4%) versus 30 (15%), 110 (55%), and 60 (30%) in the control group, respectively (P=0.000). Midodrine and rifaximin significantly reduced paracentesis needs when compared with the controls (18 study patients vs. 75 DT-only patients, P=0.000). Conclusion Adding rifaximin and midodrine to DT enhanced diuresis in refractory ascites with improved systemic, renal hemodynamics and short-term survival.

Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non-neoplastic portal vein thrombosis

BACKGROUND AND AIM Anticoagulation therapy is the main line of treatment for acute portal vein thrombosis (PVT) in the absence of cirrhosis. However, the use of this therapy in cirrhotic PVT is still with doubtful evidence. We aimed to evaluate the efficacy and safety of rivaroxaban compared to warfarin for the management of acute non-neoplastic PVT in Hepatitis C virus (HCV)-related compensated cirrhosis. METHODS Out of 578 patients with chronic HCV infection, 80 patients with acute PVT who had undergone splenectomy due to hypersplenism and 4 patients with acute PVT due to portal pyemia were selected. The patients were randomly assigned (1:1) to the study group (n = 40), in which the patients received rivaroxaban 10 mg/12 h, or the control group (n = 40), in which the patients received warfarin. RESULTS In the rivaroxaban group, the resolution of PVT was achieved in 34 patients (85%) within 2.6 ± 0.4 months and delayed, partial recanalization after 6.7 ± 1.2 months (n = 6.15%). Complications such as major bleeding, abnormal liver functions, death, or recurrence did not occur during treatment, and patients in this group showed improved short-term survival rate (20.4 ± 2.2 months) compared to the survival rate in the control group (10.6 ± 1.8 months) in which warfarin achieved complete resolution in 45% of patients. Complications such as severe upper GI tract bleeding (43.3%), hepatic decompensation (22.5%), progression to mesenteric ischemia (12.5%), recurrence (10%), and death (20%) were observed in the control group. The duration until complete resolution of thrombus correlated with age, the extent of the thrombus, creatinine level, and MELD score. The recurrence after complete resolution of thrombus correlated with age, the extent of the thrombus, thrombogenic gene polymorphism, and the use of warfarin. CONCLUSION Rivaroxaban was effective and safe in acute HCV-related non-neoplastic PVT with improved short-term survival rate; ClinicalTrials.gov Identifier: NCT03201367.

Beneficial Effects of Vitamin D on Insulin Sensitivity, Blood Pressure, Abdominal Subcutaneous Fat Thickness, and Weight Loss in Refractory Obesity

IN BRIEF This study explored the impact of correcting vitamin D deficiency on blood pressure, metabolic status, and weight loss in patients with fatigue and obesity refractory to conventional interventions such as diet, exercise, behavioral modification, and pharmacotherapy. Correction of vitamin D deficiency in such patients was found to be significantly associated with weight reduction and improved insulin sensitivity.

Association of thrombogenic genes polymorphisms with hepatocellular carcinoma in HCV Egyptian patients

The rate of development of fibrosis varies among HCV patients and affected by many variables. We aimed to investigate the association between mutations in Factor V, prothrombin gene and thrombospondin 1 polymorphisms with hepatic fibrosis progression rate and development of HCC in patients infected with HCV and if they are potential markers for early prediction of disease progression. A total of 280 HCV-infected patients (70 with mild fibrosis, 70 with advanced fibrosis, 70 cirrhotic patients and 70 HCC patients) and 100 healthy controls were included. Factor V Leiden G1691A, prothrombin G20210A and thrombospondin 1 mutations were analyzed by restriction fragment length polymorphism. We observed that there were no significant differences between Factor V Leiden (G1691A) or TPS-1 (A2210G) polymorphisms in the four patient subgroups and control group. In HCC patients, the frequencies of GA genotype were significantly increased compared with control subject. HCV patients carrying GA genotype were more likely to develop hepatocellular carcinoma (OR=5.4, 95% CI=1.09-27.05; P=0.026).We concluded that the risk of HCC was increased 5-fold in subjects carrying GA genotype of prothrombin G20210A gene. However, there was no evidence for a significant association between thrombogenic genes polymorphisms and progression of fibrosis in HCV Egyptian patients.

Pilot study of orphenadrine as a novel treatment for muscle cramps in patients with liver cirrhosis

Background and aims Muscle cramps markedly affect the quality of life in cirrhotic patients with no available highly effective treatment. The aim of this study was to assess the safety and efficacy of orphenadrine in the treatment of muscle cramps in cirrhotic patients. Methods The study enrolled 30 liver cirrhosis patients complaining of frequent muscle cramps (≥3 per week), who were randomized to receive either orphenadrine 100 mg or calcium carbonate 500 mg twice daily as a control for one month. Severity, frequency, and duration of the muscle cramps were assessed before and after treatment as well as recurrence after washout of the drug for two weeks. Side effects were recorded. Results One month after treatment with orphenadrine; the frequency of muscle cramps decreased significantly to 0.6 ± 0.74 per week compared to 12.53 ± 6.01 at baseline (p < 0.001), the duration of muscle cramps decreased from 1 min to 0.1 min after treatment (p < 0.001). The pain score improved significantly from a score of 8/10 to 0/10 (p < 0.001). The side effects were few, such as dry mouth, drowsiness, and nausea, with no significant difference between their occurrences in the two groups. Conclusion Orphenadrine is safe and effective in treatment of muscle cramps in patients with liver cirrhosis.

Endoscopic management of refractory gastroesophageal reflux disease

Abstract Objective: Despite the therapeutic and surgical interventions for the management of gastroesophageal reflux disease (GERD), yet the high cost and the post-operative complications had led to a significant socioeconomic burden. The aim was to evaluate the safety and efficacy of endoscopic band ligation (EBL) in the management of refractory GERD. Methods: A total of 150 patients with refractory GERD were assigned to an EBL group (banding was done at four quadrants just at the gastroesophageal junction (GEJ) (n = 75) or to a control group (optimized dose of PPI, n = 75). Follow-up for both groups by upper GI endoscopy to evaluate the site of the Z line from the incisors, the width of the GEJ and the coaptation of GEJ around the endoscope on retroflection. PH monitoring was performed every 3 months with GERD- QoL assessment monthly for 1 year. Results: In EBL group; 58 patients (77.3%) needed 1 session, 17 patients (22.7%) needed 2 sessions. 4 rubber bands were utilized in 44 patients (58.7%), 3 rubber bands in 31 patients (41.3%). Follow-up for 1 year revealed a highly significant improvement of the GERD- QoL score, the site of Z line with significant reduction of reflux episodes and symptom index when compared to the medical treatment group. In EBL group; there were no major adverse events including bleeding, post band ulcers, stenosis at one year follow up. Conclusion: The current study provides a novel endoscopic intervention to treat refractory GERD, which is safe, cost-effective, with no major adverse effects at one year follow up.

Randomized trial of preoperative administration of oral pregabalin for postoperative analgesia in patients scheduled for radiofrequency ablation of focal lesions in the liver

Abstract Purpose: The aim of this study was to evaluate the effect of preoperative pregabalin on postoperative analgesia in patients undergoing radiofrequency ablation (RFA) of hepatic focal lesions (HFLs). Methods: This randomised controlled study was carried out on 70 adult patients for whom RFA was indicated to treat hepatocellular carcinoma. They were randomised into two groups: Group I: 35 patients who were given a placebo before the procedure and Group II: 35 patients who were given 150 mg of oral pregabalin one hour before the procedure. The primary outcome was the analgesic effect in the form of postoperative pain severity and the need for opioid analgesics. Results: In the immediate postoperative period there was no significant difference between the two groups on pain assessment by the visual analogue pain scale (VAS Pain; p = 0.84). However, the medians of Group II VAS Pain were significantly (p < 0.001) less than Group I 3,2,1,1,1,0 vs. 4,3,3,2,2,2, respectively when measured every four hours until 24 hours. The number of required doses of rescue analgesia and total required dose of morphine in the first 48 hours postoperatively of Group II were significantly (p < 0.001) less than Group I. Side effects such as nausea and vomiting and delayed discharge were significantly less frequent in Group II when compared with Group I:20vs. 45.7%, 17.1 vs. 45.7% and 11.4 vs. 37.1%, respectively (p = 0.02, 0.01 and 0.01, respectively). Conclusion: Pre-emptive oral pregabalin is safe and effective for postoperative analgesia in patients scheduled for radiofrequency ablation of focal lesions in liver.

Randomized Controlled Study Comparing Use of Propofol Plus Fentanyl versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients with Advanced Liver Disease

Objectives We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy. Methods A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopist rating, and hemodynamic parameters including oxygen saturation, heart rate, mean arterial pressure, incidence of side effect as (bradycardia, hypotension, hypoxia, nausea and vomiting, cough, shivering, or diplopia), time needed for complete recovery, and time needed for discharge. Results There was no statistical significant difference between the studied groups regarding age, sex, weight, Child–Pugh classification score, type and duration of endoscopic intervention, time needed for complete recovery, or time needed for discharge. Complication rates were similar in both groups except for mean arterial blood pressure which was significantly lower in group of patients receiving propofol and fentanyl (P = 0.001). Conclusion The use of either propofol or midazolam in combination to fentanyl is effective in sedation of patients with advanced liver diseases presented for upper GIT endoscope. The trial is registered with ClinicalTrials.gov Identifier: NCT03063866.

Management of different types of gastric varices with band ligation: a 3-year experience

Background and aim Gastric varices (GVs) occur with an incidence of 20% in patients with portal hypertension. The aim of this study was to evaluate the efficacy of endoscopic band ligation (BL) as an option in the management of small-to-moderate nonbleeding GVs in cirrhotic patients. Patients and methods A total of 50 patients (GOV2; n=6, IGV1; n=34, IGV2; n=10) with nonbleeding small-to-moderate-sized GVs without local risk signs of bleeding, such as large size, red-colored elevated areas or red wales, and systemic factors of bleeding risk such as an international normalized ratio of at least 2 and a platelet count of 80 000/µl or less were subjected to endoscopic BL. The patients were followed up every 2 weeks for 1 month and then every 1.5 months for 6 months. The primary outcome was GV eradication, detection of complications such as postprocedural bleeding ulceration and mortality. Results The mean number of BL sessions was 2.2±0.8; post-BL ulceration occurred in two (4%) patients (n=2 in IGV1, P=0.61), bleeding occurred in one (2%) patient (n=1 in IGV1, P=0.79), and epigastric pain occurred in six (12%, n=4 in GOV2, n=2 in IGV1) patients. There was no mortality reported among patients treated with BL. Conclusion Endoscopic BL resulted in better outcome and a lower incidence of complications when used to treat small-to-medium-sized nonbleeding GVs. Further, early eradication can save effort and cost, thus avoiding the future risk of treatment of large or risky GVs with sclerotherapy.

Impact of hepatitis B vaccination on HBsAg kinetics, interferon-inducible protein 10 level and recurrence of viremia

Background and aims Persistent HBs antigenemia >1000 IU/ml has a possibility of viral reactivation and HCC in 8%, so we investigated the effect of HBV vaccine on HBsAg, IP‐10, and recurrence of viremia. Methods Group I: inactive carriers (n = 100). Group II: CHB exposed to nucleos(t)ides (n = 120) till 1 year after HBe seroconversion and HBV DNA disappearance in HBeAg positive (n = 60) or 3 years after DNA disappearance in HBeAg negative patients (n = 60). All showed persistent HBs antigenemia. A control group (n = 100) did not receive HBV vaccine. 30 &mgr;g of HBV vaccine initiated at the determined points of time. 3 months after the last vaccine dose; IP‐10, HBsAb, HOMA‐IR and liver stiffness by fibroscan were evaluated. HBV DNA and HBsAg were detected every 6 months for 3 years post vaccination. Results 46 patients (20.9%) were vaccine nonresponders. 174 patients were responders (79.1%). 62 patients (28.2%) cleared HBsAg, 143 patients showed marked reduction of HBsAg (65%). Recurrence of viremia occurred in 4 vaccinated patients (7.8%) vs. 30 patients in the control group (30%, p = 0.000). The vaccine enhanced IP‐10 which at a cutoff 350 pg/ml helped in HBsAg reduction to a favorable level. The vaccine had no significant effect on HOMA‐IR nor fibroscan value. Conclusions HBV vaccine was efficient in enhancing IP‐10 level with HBsAg clearance, or reduction to a favorable level. ClinicalTrials.gov Identifier: NCT03193775. HighlightsA significant number of patients after disappearance of HBV DNA and HBe seroconversion showed persistent HBs antigenemia and find difficulty in indefinite treatment.With HBsAg level > 1000 IU/ml, the possibility of viral reactivation and hepatocellular carcinoma approaches 8%.HBV vaccine given in 30 &mgr;g of HBV vaccine (0, 1, 6 months), initiated 6 months after HBe seroconversion and disappearance of HBV DNA.It was highly efficient, safe, and cost effective in enhancing HBsAg clearance, causes its reduction to a favorable level less than 1000 IU/ml and halts fibrosis progressionBACKGROUND AND AIMS Persistent HBs antigenemia >1000IU/ml has a possibility of viral reactivation and HCC in 8%, so we investigated the effect of HBV vaccine on HBsAg, IP-10, and recurrence of viremia. METHODS Group I: inactive carriers(n=100). Group II: CHB exposed to nucleos(t)ides (n=120) till 1year after HBe seroconversion and HBV DNA disappearance in HBeAg positive (n=60) or3years after DNA disappearance in HBeAg negativepatients (n=60). All showed persistent HBs antigenemia. A control group (n=100) did not receive HBV vaccine. 30µg of HBV vaccine initiated at the determined points of time. 3months after the last vaccine dose; IP-10, HBsAb, HOMA-IR and liver stiffness by fibroscanwere evaluated. HBV DNA and HBsAg were detected every 6months for 3years post vaccination. RESULTS 46 patients (20.9%) were vaccine nonresponders. 174 patients were responders (79.1%). 62 patients (28.2%)cleared HBsAg, 143 patients showed marked reduction of HBsAg (65%). Recurrence of viremia occurred in 4 vaccinated patients (7.8%) vs. 30 patients in the control group (30%,p=0.000). The vaccine enhanced IP-10 which at a cutoff 350pg/ml helped in HBsAg reduction to a favorable level. The vaccine had no significant effect on HOMA-IR nor fibroscan value. CONCLUSIONS HBV vaccine was efficient in enhancing IP-10 level with HBsAg clearance, or reduction to a favorable level. ClinicalTrials.gov Identifier: NCT03193775.