A Randomized Controlled Trial Comparing Nitazoxanide Plus Lactulose With Lactulose Alone in Treatment of Overt Hepatic Encephalopathy.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is a reversible spectrum of neuropsychiatric abnormalities associated with liver dysfunction. Lactulose is a nonabsorbable disaccharide presently used to treat HE. Nitazoxanide (NTZ) has a broad-spectrum activity against urease-producing bacteria, so it decreases ammonia production and is therefore expected to reverse the symptoms of HE. A previous pilot study on HE patients given NTZ and lactulose had encouraging results with regard to amelioration of the clinical picture. Patients showed improvement in mental status and the drug was well-tolerated. Results such as these are encouraging larger studies. The aim of this study was to compare the safety and adequacy of NTZ plus lactulose versus lactulose and placebo in management of overt HE. METHODS: In total, 120 cirrhotic patients suffering from overt HE were randomly designated to take either NTZ plus lactulose (n=60) or lactulose and placebo (n=60). The Clinical Hepatic Encephalopathy Staging Scale (CHESS) score was assessed for all patients on inclusion to the study and 1 week from the start of treatment. RESULTS: Both groups evinced an improvement in CHESS score at 1 week, yet the improvement was significantly better in the NTZ group as the score decreased from 4.15±2.09 to 0.00±0.00 compared with 4.96±2.29 to 1.28±0.91 in patients receiving lactulose and placebo (P-value <0.001). CONCLUSIONS: NTZ significantly decreases the CHESS score and improves mental status in the form of patient alertness, orientation, response to stimulation, and ability to talk. NTZ is safe and well-tolerated apart from infrequent epigastric pain.

Randomized controlled study of a novel triple nitazoxanide (NTZ)-containing therapeutic regimen versus the traditional regimen for eradication of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori infection has become more and more resistant to conventional first-line treatment regimens. So, there is a considerable interest in evaluating new antibiotic combinations and regimens. Nitazoxanide is an anti-infective drug with demonstrated activity against protozoa and anaerobic bacteria including H. pylori. This work is designed to evaluate the efficacy and safety of a unique triple nitazoxanide-containing regimen as a treatment regimen in Egyptian patients with H. pylori infection. METHODS: Two hundred and 24 patients with upper gastrointestinal tract (GIT) dyspeptic symptoms in whom H. pylori -induced GIT disease was confirmed were included in the study. They have been randomized to receive either nitazoxanide 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40 mg twice daily for 14 days or metronidazole 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40  mg twice daily for 14 days. Laboratory evaluation for H. pylori antigen within the stool was performed 6 weeks after cessation of H. pylori treatment regimens to assess the response. RESULTS: The response to treatment was significantly higher in group 1 of nitazoxanide treatment regimen than group 2 of traditional treatment regimen. One hundred and six cases (94.6%) of 112 patients who completed the study in group 1 showed complete cure, while only 63 cases (60.6%) of 104 patients who completed the study in group 2 showed the same response according to per-protocol (PP) analysis (P<.001). The regimen was well tolerated by all the patients enrolled in the study. CONCLUSION: Nitazoxanide-containing triple therapy is a promising therapy for the first-line eradication of H. pylori. (ClinicalTrials.gov Identifier: NCT02422706).

Microbiological risk assessment and resistome analysis from shotgun metagenomics of bovine colostrum microbiome.

Colostrum is known for its nutraceutical qualities, probiotic attributes, and health benefits. The aim of this study was to profile colostrum microbiome from bovine in rural sites of a developing country. The focus was on microbiological safety assessments and antimicrobial resistance, taking into account the risks linked with the consumption of raw colostrum. Shotgun sequencing was employed to analyze microbiome in raw buffalo and cow colostrum. Alpha and beta diversity analyses revealed increased inter and intra-variability within colostrum samples' microbiome from both livestock species. The colostrum microbiome was mainly comprised of bacteria, with over 90% abundance, whereas fungi and viruses were found in minor abundance. Known probiotic species, such as Leuconostoc mesenteroides, Lactococcus lactis, Streptococcus thermophilus, and Lactobacillus paracasei, were found in the colostrum samples. A relatively higher number of pathogenic and opportunistic pathogenic bacteria were identified in colostrum from both animals, including clinically significant bacteria like Clostridium botulinum, Pseudomonas aeruginosa, Escherichia coli, and Listeria monocytogenes. Binning retrieved 11 high-quality metagenome-assembled genomes (MAGs), with three MAGs potentially representing novel species from the genera Psychrobacter and Pantoea. Notably, 175 antimicrobial resistance genes (ARGs) and variants were detected, with 55 of them common to both buffalo and cow colostrum metagenomes. These ARGs confer resistance against aminoglycoside, fluoroquinolone, tetracycline, sulfonamide, and peptide antibiotics. In conclusion, this study describes a thorough overview of microbial communities in buffalo and cow colostrum samples. It emphasizes the importance of hygienic processing and pasteurization in minimizing the potential transmission of harmful microorganisms linked to the consumption of colostrum.

Metagenomic Insights into the Microbiome and Resistance Genes of Traditional Fermented Foods in Arabia.

This study uncovered microbial communities and evaluated the microbiological safety of traditional fermented foods consumed in the Arab region. Samples of dairy and non-dairy fermented foods-mish, jibneh, zabadi, and pickles-were collected from local markets in Saudi Arabia. Using the MiSeq system, samples were sequenced using 16S amplicons and shotgun metagenomics. Alpha and beta diversity indicated inter- and intra-variation in the studied fermented foods' bacterial communities. In the case of mish, the replicates were clustered. Twenty-one genera were found to be significantly different (FDR < 0.05) in abundance in pairwise comparison of fermented foods. Five high-quality, metagenome-assembled genomes (MAGs) of Lactococcus lactis, Lactobacillus helveticus, Pseudoalteromonas nigrifaciens, Streptococcus thermophiles, and Lactobacillus acetotolerans were retrieved from the shotgun sequencing representing the dominant taxa in the studied fermented foods. Additionally, 33 genes that cause antimicrobial resistance (ARGs) against ten different antibiotic classes were detected. Metabolic pathways were abundant in the studied metagenomes, such as amino acid metabolism, carbohydrate metabolism, cofactors, and vitamin biosynthesis. Metagenomic evaluation of Arabian fermented foods, including the identification of probiotics, pathogenic bacteria, and ARGs, illustrates the importance of microbiological analysis in evaluating their health effects.

Amyloid A in Serum and Ascitic Fluid as a Novel Diagnostic Marker of Spontaneous Bacterial Peritonitis.

BACKGROUND: Diagnosis of Spontaneous Bacterial Peritonitis (SBP) depends mainly on ascetic fluid culture which may be negative in spite of the clinical suggestion of SBP and high ascetic fluid neutrophilic count. AIMS: This study aimed to evaluate the biological importance of amyloid A biomarker in both serum and ascetic fluid to diagnose SBP as early as possible and to compare it to other markers (C-reactive protein (CRP), and the neutrophil-to-lymphocyte ratio (NLR)). METHODS: This study included 37 patients with hepatic ascites; twenty-two of them had SBP, and 15 patients did not have SBP. Serum and ascetic fluid amyloid A, ascetic fluid neutrophil, C-reactive protein, and neutrophil-to-lymphocyte ratio were measured in all subjects before the start of antimicrobial chemotherapy to the infected ones. RESULTS: Both the serum and ascetic fluid amyloid and also, CRP were significantly higher in patients infected with ascetic fluid than others. The cut-off point of serum amyloid A for early detection of SBP was 9.25ug/ml with the high sensitivity and specificity. For ascetic amyloid A, the sensitivity and specificity were 90.09% and 60% at cut-off point 2.85ug/ml, respectively. CONCLUSION: Amyloid A in serum and ascitic fluid can be considered as a good biomarker for early diagnosis of SBP.

Genetic Susceptibility in Family Members of Egyptian Hepatitis C Virus Infected Patients: Role of Interleukin-12 B Gene Polymorphism.

AIM: The research was conducted to study 1188 A\C polymorphism of Interleukin (IL)-12B gene for C/C, A/C and A/A genotypes in families of Hepatitis C virus (HCV) infected patients in Egypt. METHODS: Three hundreds HCV patients, 860 family members and 100 healthy subjects were studied. All family members were screened for HCV antibodies by enzyme-linked immunosorbent assay (ELISA). Positive cases were examined using Real-Time polymerase chain reaction (PCR) to confirm the presence of HCV ribonucleic acid (RNA) and detect the viral load. Molecular study of IL-12B gene was carried out on all patients, family members and controls using PCR and restriction enzyme analysis. RESULTS: HCV infection was confirmed in 10.6% of family members. The distribution of IL-12B gene polymorphism in patients was 2.3%, 45.7% and 52% for C/C, A/C and A/A genotypes respectively, in infected family members was 3.3%, 41.7%, 55%, in noninfected family members was 4.5%, 43.5% and 52% for C/C, A/C and A/A genotypes respectively and in control was 5%, 36% and 59% for C/C, A/C and A/A genotypes respectively. The frequency of the C/C, A/C and A/A genotype was not significantly different between the studied groups. CONCLUSION: IL-12B gene polymorphism has no role in intrafamilial susceptibility of HCV transmission. The distribution of the functional 1188 A\C polymorphism of Interleukin (IL)-12B gene for C/C, A/C and A/A genotypes was not significantly different among the studied groups.

Randomized controlled trial of polyethylene glycol versus lactulose for the treatment of overt hepatic encephalopathy.

BACKGROUND: Overt hepatic encephalopathy (HE) is a frequent complication of cirrhosis and one of the most debilitating manifestations that necessitates hospitalization. Although many treatment modalities are being investigated, none of them are satisfactory. So, newer treatment modalities have to be tried. OBJECTIVE: To evaluate the safety and efficacy of polyethylene glycol (PEG) versus lactulose in the management of HE. PATIENTS AND METHODS: This clinical trial included 100 patients with post-hepatitis C cirrhosis who were admitted with HE. Patients were randomized into two equal groups: group I patients received lactulose and group II patients received PEG. The clinico-epidemiological characteristics of patients, Child-Pugh score, and HE scoring algorithm were registered before and 24 h after administration of the drug. Moreover, any suspected adverse effects were recorded. RESULTS: All 100 patients received treatment. Three patients died within 24 h of admission and did not complete the follow-up period. According to intention-to-treat approach, they were considered as treatment failure. On analysis, 36/50 (72%) patients improved one grade or more in HE scoring algorithm score after 24 h of lactulose therapy versus 47/50 (94%) of those on PEG therapy (P<0.05). The time needed for resolution of HE and length of hospital stay were significantly lower in PEG group versus lactulose group (P<0.001). Both therapies were tolerated, and no significant adverse events were reported. CONCLUSION: Both lactulose and PEG were safe and effective in the treatment of HE. PEG significantly decreased the time needed for resolution of HE and significantly shortened the hospital stay.

Helicobacter pylori may be an initiating factor in newly diagnosed ulcerative colitis patients: A pilot study.

AIM: To directly visualize Helicobacter pylori (H. pylori) by the highly sensitive and specific technique of immunohistochemical staining in colonic tissue from patients newly diagnosed with ulcerative colitis (UC). METHODS: Colonoscopic biopsies from thirty patients with newly diagnosed UC and thirty controls were stained with Giemsa stain and immunohistochemical stain for detection of H. pylori in the colonic tissue. Results were confirmed by testing H. pylori Ag in the stool then infected patients were randomized to receive either anti H. pylori treatment or placebo. RESULTS: Twelve/30 (40%) of the UC patients were positive for H. pylori by Giemsa, and 17/30 (56.6%) by immunohistochemistry stain. Among the control group 4/30 (13.3%) and 6/30 (20 %) were positive for H. pylori by Giemsa and immunohistochemistry staining respectively. H. pylori was significantly higher in UC than in controls (P = 0.04 and 0.007). All Giemsa positive patients and controls were positive by immunohistochemical stain. Four cases of the control group positive for H. pylori also showed microscopic features consistent with early UC. CONCLUSION: H. pylori can be detected in colonic mucosa of patients with UC and patients with histological superficial ulcerations and mild infiltration consistent with early UC. There seems to be an association between UC and presence of H. pylori in the colonic tissue. Whether this is a causal relationship or not remains to be discovered.

Randomized-controlled trial of rifaximin versus norfloxacin for secondary prophylaxis of spontaneous bacterial peritonitis.

BACKGROUND AND AIMS: Spontaneous bacterial peritonitis (SBP) is a serious complication of liver cirrhosis with a high recurrence rate and a marked increase in mortality. Norfloxacin is used widely for the secondary prophylaxis of SBP; however, its extensive long-term use has led to an increase in the incidence of quinolone-resistant and Gram-positive SBP. Rifaximin is a nonabsorbable broad-spectrum antibiotic and does not appear to promote emergence of resistance. The aim of this study was to compare the safety and efficacy of rifaximin versus norfloxacin for the secondary prevention of SBP in patients with liver cirrhosis and ascites. MATERIALS AND METHODS: Two hundred and sixty two cirrhotic patients with ascites and a previous episode of SBP were assigned randomly to receive either 1200 mg rifaximin or 400 mg of norfloxacin daily for 6 months. All patients were monitored clinically each month and with ascitic fluid examination at the end of 2 and 6 months if not clinically suspected of recurrence earlier. RESULTS: Recurrence of SBP was significantly lower in the rifaximin group (3.88 vs. 14.13%) compared with the norfloxacin group (P=0.04). The mortality rate was significantly decreased in the rifaximin group (13.74 vs. 24.43%) compared with the norfloxacin group (P=0.044). The causes of death between the two groups did not show a significant difference (P=0.377), but encephalopathy-related deaths were three folds higher in the norfloxacin group. There was a significant decrease in the side effects in the rifaximin group versus the norfloxacin group (P=0.033). CONCLUSION: Rifaximin was more effective than norfloxacin in the secondary prevention of SBP. Encephalopathy-related mortality and side effects were fewer in the rifaximin group.

Pigtail Catheter: A Less Invasive Option for Pleural Drainage in Egyptian Patients with Recurrent Hepatic Hydrothorax.

Background and Aims. Treatment of hepatic hydrothorax is a clinical challenge. Chest tube insertion for hepatic hydrothorax is associated with high complication rates. We assessed the use of pigtail catheter as a safe and practical method for treatment of recurrent hepatic hydrothorax as it had not been assessed before in a large series of patients. Methods. This study was conducted on 60 patients admitted to Tanta University Hospital, Egypt, suffering from recurrent hepatic hydrothorax. The site of pigtail catheter insertion was determined by ultrasound guidance under complete aseptic measures and proper local anesthesia. Insertion was done by pushing the trocar and catheter until reaching the pleural cavity and then the trocar was withdrawn gradually while inserting the catheter which was then connected to a collecting bag via a triple way valve. Results. The use of pigtail catheter was successful in pleural drainage in 48 (80%) patients with hepatic hydrothorax. Complications were few and included pain at the site of insertion in 12 (20%) patients, blockage of the catheter in only 2 (3.3%) patients, and rapid reaccumulation of fluid in 12 (20%) patients. Pleurodesis was performed on 38 patients with no recurrence of fluid within three months of observation. Conclusions. Pigtail catheter insertion is a practical method for treatment of recurrent hepatic hydrothorax with a low rate of complications. This trial is registered with ClinicalTrials.gov Identifier: NCT02119169.

Randomized placebo-controlled study of baclofen in the treatment of muscle cramps in patients with liver cirrhosis.

BACKGROUND AND AIMS: Muscle cramps adversely influence the quality of life of patients with liver cirrhosis. Indeed, to date, a well-established therapy for this complication is still lacking. This is the first randomized placebo-controlled trial of baclofen in the treatment of muscle cramps in patients with liver cirrhosis. PATIENTS AND METHODS: A total of 100 patients with liver cirrhosis and muscle cramps signed an informed consent to participate in this study. They were recruited from the Department of Tropical Medicine-Tanta University Hospital. They were randomized to receive either baclofen or placebo for 3 months. Patients were followed monthly and 1 month after withdrawal. At each visit, the clinicoepidemiological data were recorded, the muscle cramp questionnaire was filled, and any drug-related side effects were reported. RESULTS: In the baclofen group, the frequency of muscle cramps decreased significantly after 1 and 3 months of treatment (P<0.005), with a significant relapse after withdrawal (P<0.001). Patients receiving baclofen showed a significant decrease in the severity and duration of muscle cramps (P<0.001). After 3 months of baclofen therapy at a dose of 30 mg/day, muscle cramps disappeared completely in 72%, reduced in 20%, and led to no change in 8% of patients. No significant changes in the frequency, severity, and duration of muscle cramps were noted in the placebo group. There were few but nonsignificant side effects in the baclofen group compared with the placebo group. CONCLUSION: Baclofen was well tolerated, safe, and effective in the treatment of muscle cramps in patients with liver cirrhosis.

A 2-week Nitazoxanide-based quadruple treatment as a rescue therapy for Helicobacter pylori eradication: A single center experience.

As there are increasing reports of fluoroquinolone resistance on use as a first- or second-line treatment for Helicobacter pylori (H pylori), we aimed at evaluation of the efficacy and safety of nitazoxanide-based regimen as a rescue regimen in Egyptian patients whose previous traditional treatment for H pylori infection failed.In total, 100 patients from the outpatient clinic of the Tropical medicine department, Tanta University hospital in whom the standard triple therapy (clarithromycin-based triple therapy) failed were enrolled in the study. Nitazoxanide (500 mg bid), levofloxacin (500 mg once daily), omeprazole (40 mg bid), and doxycyclin (100 mg twice daily) were prescribed for 14 days. Eradication was confirmed by stool antigen for H pylori 6 weeks after the end of treatment. Among the patients enrolled in the study, 44% of patients were men and the mean age for the participants in the study was 46.41 ±â€Š8.05, 13% of patients were smokers, and 4% of patients had a previous history of upper gastro-intestinal bleeding. A total of 94 patients (94%) completed the study with excellent compliance. Only 1 patient (1%) discontinued treatment due to intolerable side effects and 5 patients (5%) did not achieve good compliance or were lost during follow up. However, 83 patients had successful eradication of H pylori with total eradication rates 83% (95 % CI 75.7-90.3%) and 88.30% (95 % CI 81.8-94.8%) according to an intention-to-treat and per-protocol analysis, respectively. Adverse events were reported in 21% of patients: abdominal pain (6%), nausea (9%) and constipation (12%), (2%) headache, and (1%) dizziness. A 2-week nitazoxanide-based regimen is an effective and safe rescue therapy in Egyptian patients whose previous standard triple therapy has failed.

Correlation of platelets count with endoscopic findings in a cohort of Egyptian patients with liver cirrhosis.

Screening endoscopy is recommended for early detection of esophageal varices (EVs) in cirrhotic patients with portal hypertension. However, this approach is limited by its invasiveness and cost. The aim of the study was to determine if platelet count can predict the presence of EVs, especially large (grade III, IV) EVs in need of prophylactic therapy, in a cohort of Egyptian patients with liver cirrhosis. In all, 110 patients with cirrhosis were prospectively analyzed. The presence of medium or large EVs was correlated with patients' platelet count and FIB-4. Esophageal varices were present in 87 (79.09%) patients. Among those with thrombocytopenia (platelet level below 150,000), 25.97% (20 patients) and 27.27% (21 patients) had EV grade II and EV grade III or IV, respectively. Whereas in patients in whom the platelet count was above 150,000, only 21.21% (7 patients) and 9.09% (3 patients) of patients had grade II EV and EV grade III or IV, respectively. A platelet count cut-off value of 149,000 was found to have specificity of 82% and sensitivity 39% for detection of presence of varices. A FIB-4 cut-off value of 3.175 was found to have an 83.3% sensitivity and 39.5% specificity in detecting large (grade III, IV) EVs. Platelet count is a noninvasive parameter with high accuracy for prediction of EVs. Cirrhotic patients with normal platelet counts (above 150,000), especially in financially deprived developing countries, can avoid screening endoscopy as they are at a low risk for variceal bleeding, and presence of large EVs in these patients is much less common than in those with thrombocytopenia. A 3.175 cut-off value of FIB-4 could be useful as a noninvasive predictor of large varices requiring prophylactic banding in cirrhotic patients.