Combined ns5a & ns5b nucleotide inhibitor therapy for patients with chronic hepatitis c with stage 5 chronic kidney disease on hemodialysis / Terapia inibidora de nucleotídeo NS5A& NS5B combinada para pacientes com hepatite C crônica com doença renal crônica em estágio 5, em hemodiálise

ABSTRACT BACKGROUND: Hepatitis C virus (HCV) infection is the most common hepatotropic viral infection affecting the patients on maintenance hemodialysis. Treatment of chronic HCV infection in stage 4 and 5 CKD includes a combination of elbasvir/grazoprevir and glecaprevir/pibrentasvir, which are not available in many countries. OBJECTIVE: Hence, we have conducted this study to look for the safety and efficacy of sofosbuvir combination therapy in this difficult to treat population. METHODS: We conducted a single-center, prospective, open-label study in which Stage 5 CKD patients on maintenance hemodialysis with HCV infection. Total of 18 patients was included. sofosbuvir with daclatasvir or ledipasvir was used according to genotype for 12 weeks. HCV RNA, genotype, transient elastography (TE) was considered for every patient. HCV RNA was quantified at 4th week, 12th week and 12 weeks post-treatment to look for sustained virologic response (SVR 12). RESULTS: Infection due to genotype 1 was seen in 12 (66.7%) patients followed by genotype 3 in 4 (22.3%) with each patient of genotype 2 and 5. The median value of HCV RNA was 2,35,000 IU/mL. On TE, all had liver stiffness of <9.4 KPa. All patients had HCV RNA of <15 IU/mL at 4th and 12th week of treatment and 12 weeks post-treatment. No significant change in hemoglobin, eGFR and liver stiffness was observed. CONCLUSION: Full dose sofosbuvir i.e. 400 mg, in combination with NS5A inhibitors daclatasvir or ledipasvir is found to be safe and effective in patients with end stage renal disease, who are on maintenance hemodialysis.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é a infecção viral hepática mais comum que afeta pacientes em hemodiálise de manutenção. O tratamento da infecção crônica por HCV no estágio 4 e 5 da doença renal crônica inclui uma combinação de elbasvir/grazoprevir e glecaprevir/pibrentasvir, que não estão disponíveis em muitos países. OBJETIVO: Portanto, realizamos este estudo para procurar a segurança e eficácia da terapia combinada de sofosbuvir nesta população de difícil tratamento. MÉTODOS: Realizamos um estudo de centro único, prospectivo e aberto, no qual pacientes com doença renal crônica em estágio 5 em hemodiálise de manutenção com infecção por HCV. Um total de 18 pacientes foi incluído. Sofosbuvir com daclatasvir ou ledipasvir foi usado de acordo com o genótipo por 12 semanas. O HCV RNA, genótipo, elastografia transitória foi considerado para cada paciente. O HCV RNA foi quantificado na 4ª semana, 12ª semana e 12 semanas após o tratamento para procurar uma resposta virológica sustentada. RESULTADOS: A infecção por genótipo 1 foi observada em 12 (66,7%) pacientes, seguido pelo genótipo 3 em 4 (22,3%), em um paciente do genótipo 2 e em outro, 5. O valor mediano do HCV RNA foi de 2.35.000 IU/mL. Na elastografia transitória, todos tinham rigidez hepática de <9.4 KPa. Todos os pacientes tinham RNA HCV <15 IU/mL na 4ª e 12ª semana de tratamento e 12 semanas após o tratamento. Não foi observada nenhuma alteração significativa na hemoglobina, eGFR e rigidez hepática. CONCLUSÃO: A dose completa sofosbuvir ou seja, 400 mg, em combinação com inibidores NS5A daclatasvir ou ledipasvir foi considerada segura e eficaz em pacientes com doença renal em estágio final, que estão em manutenção hemodiálise.

Effect of Lactobacillus acidophilus & epidermal growth factor on experimentally induced Clostridium difficile infection.

Background & objectives: Clostridium difficile-associated disease (CDAD) remains an important nosocomial ailment. Antimicrobial therapy used for CDAD gives inconsistent results. This experimental study was planned to investigate the beneficial effects of Lactobacillus acidophilus and epidermal growth factor (EGF) for CDAD management. Methods: Among 10 groups of BALB/c mice (6 in each), group 1 served as controls receiving no inoculum. Animals in groups 2-10 received C. difficile, those in groups 3, 6 and 9 received L. acidophilus and those in groups 4, 7 and 10 received EGF after C. difficile inoculation. Animals in groups 5-7 were pre-treated with ampicillin and those in groups 8-10 with lansoprazole prior to C. difficile. The animals were killed and investigated for colonisation by C. difficile and toxin production, myeloperoxidase (MPO) activity and histopathology. Results: Colonisation by C. difficile was found to be significantly different (P<0.001) in the various groups. C. difficile toxin titres and MPO activity were significantly lower in animals given L. acidophilus and EGF after ampicillin (groups 6 and 7) and lansoprazole (groups 9 and 10). The severity of acute inflammation was also significantly less (P<0.05) in caecal and colonic segments of animals in groups 6 and 7 compared to those in group 5. Although the severity of acute inflammation was less in the caecal and colonic segment of animals in groups 9 and 10, the reduction was not significant compared to group 8. Interpretation & conclusions: Our findings showed that the administration of L. acidophilus and EGF reduced the severity of C. difficile infection in the experimental animals.

Acute abdomen due to acute pancreatitis--a rare presentation of leptospirosis.

Even though, Leptospiral infection is not uncommon, it can have different rare presentations. Acute pancreatitis is one such rare gastrointestinal manifestation of acute pancreatitis. Apart from the typical clinical features; elevated serum lipase or elastase-1, along with radiological evidence and positive leptospiral serology confirms this rare association.

Gastric atrophy and intestinal metaplasia in a patient on long-term proton pump inhibitor therapy.

We report the case of a patient with gastroesophageal reflux disease who developed gastric atrophy and intestinal metaplasia (IM) while on 20-year treatment with proton pump inhibitors. This is perhaps the first report in human beings. A 74-year-old man, who presented with heartburn, showed abnormally high gastric pH (average 6.57) on 24-hour dual channel pH-metry even after discontinuing acid suppressive drugs for one month. No significant esophageal acid exposure was noted, which may be related to an impairment of the acid secreting capacity of the stomach (percentage time esophageal pH<4 during 24-h period 0.3%). Upper gastrointestinal endoscopy was normal except for the prominent submucosal vessels in the body and fundus suggesting gastric atrophy. Histopathological examination of multiple biopsies from the body and antrum of stomach showed signs of gastric atrophy and IM. Rapid urease test and histopathology of gastric biopsies were negative for Helicobacter pylori. Anti-H.pylori IgG ELISA however, was positive. Patient was asked to stop all anti-secretory drugs and only prokinetics were prescribed following which his symptoms markedly improved. On follow-up, in April 2007, he developed symptoms of peripheral neuropathy; serum vitamin 812 level was low. He responded to parenteral vitamin 812 therapy. 24-h dual channel pH-metry repeated after one and a half years showed persistently high gastric pH (average pH 6.76). The patient remained well after discontinuing proton pump inhibitors and continuing prokinetics and vitamin B12 injections.

Effect of single oral dose of sodium rabeprazole on the intragastric pH & volume in patients undergoing elective surgery.

BACKGROUND & OBJECTIVE: While evaluating the effectiveness of drugs used for the prophylaxis of acid aspiration of gastric contents, the impact of duodeno-gastric reflux on gastric contents has not been studied earlier. This study was carried out to evaluate the effect of preanaesthetic oral administration of sodium rabeprazole on pH and volume of gastric contents in adult patients undergoing elective surgery by excluding cases contaminated with duodeno-gastric refluxate. METHODS: The patients in group C (control) in the triple blind placebo controlled trial received placebo while group S sodium rabeprazole 20 mg orally at 2100 h, a night before elective surgery. Next day, gastric contents were aspirated with a large bore, multi-orifices gastric tube passed through an endotracheal tube placed blindly in oesophagus after tracheal intubation and analyzed for the presence of bile salts, pH and volume. The pH and volume of gastric contents were the primary and duodeno-gastric reflux secondary outcome measures of the study. RESULTS: The pH and volume of group S-2 were 3.97+/-1.78 and 9.48+/-8.39 ml respectively compared with 1.90+/-0.47 and 19.60+/-18.56 ml of group C-2. Sodium rabeprazole, after excluding contaminated cases with duodeno-gastric refluxate, significantly increased the pH (P<0.001), decreased the volume of gastric contents (P<0.005) and the proportion of the patients (30.76 vs 2.63%) considered at risk compared with placebo (P<0.001) according to the criteria defined (pH < 2.5 and volume > 25 ml). Thirty nine samples (33.33%) out of 117 were contaminated with duodenal contents. Duodenogastric reflux significantly (P<0.001) affected pH and volume of gastric in both groups C-1 vs C-2 and S-1 vs S-2. INTERPRETATION & CONCLUSION: Sodium rabeprazole 20 mg given orally a night before surgery provided adequate prophylaxis for acid aspiration syndrome at the time of induction of anaesthesia and duodeno-gastric reflux significantly affected both the pH and volume of gastric contents.

Efficacy of Levofloxacin-based Triple Therapy as Second-lineHelicobacter pylori Eradication / 대한소화기학회지

BACKROUND/AIMS: Bismuth-based quadruple therapy for second-line eradication treatment achieves the eradication rate ranging from 70% to 81% due to antimicrobial resistance and poor compliance. The aim of this study was to compare the eradication rate of levofloxacin-based triple therapy with that of bismuth-based quadruple therapy in second-line Helicobacter pylori (H. pylori) eradication therapy. METHODS: Seventy-six outpatients with persistent H. pylori infection after first-line triple therapy were enrolled in this prospective randomized trial. The subjects were randomized to receive levofloxacin 300 mg, amoxicillin 1 g, and pantoprazole 20 mg, given twice daily for 7 days (LAP group), or metronidazole 500 mg twice, tetracycline 500 mg four times, and pantoprazole 20 mg twice, bismuth subcitrate 600 mg twice daily for 7 days (MTPB group). Eradication was confirmed with 13C-urea breath test or rapid urease test 4 weeks after the cessation of therapy. RESULTS: Among Seventy-six patients initially included, eleven were lost during follow-up. The eradication rates, expressed as intention to treat (ITT) and per protocol (PP) analyses, were 51.6% and 53.3% in the LAP group, and 48.9% and 62.9% in the MTPB group, respectively. There was no significant difference in H. pylori eradication rates between the two groups (p=0.815 by ITT, p=0.437 by PP). LAP regimen was better tolerated than MTPB regimen with lower incidence of side effects (10.0% versus 31.4%, p=0.03). CONCLUSIONS: H. pylori eradication rates of levofloxacin-based triple therapy and bismuth-based quadruple therapy were not significantly different in second-line H. pylori eradication therapy, and low incidence of side effects was observed in levofloxacin-based triple therapy.

The Effect of Proton Pump Inhibitor on Healing of Post-esophageal Variceal Ligation Ulcers / 대한소화기학회지

BACKGROUNE/AIMS: Esophageal variceal ligation (EVL) is the most preferable method for controling variceal bleeding. However, EVL is associated with complications such as hemorrhage, chest pain, dysphagia, and odynophagia due to post-EVL ulcers in the esophageal mucosa. The aim of this study was to assess the effect of proton pump inhibitor (PPI), pantoprazole on the healing of post-EVL ulcers. METHODS: Forty seven patients were randomly allocated into PPI group and control group. Patients in PPI group received 40 mg of pantoprazole intravenously for 3 days after EVL, then 40 mg of oral pantoprazole for 11 days consecutively. Control patients received intravenous and oral placebo. Endoscopic examinations were performed twice at 7+/-2 days and 14+/-2 days after EVL respectively. Clinical outcomes include the size of ulcers, symptoms reported by patients; chest pain, dysphagia, and odynophagia. RESULTS: Forty seven patients completed the 7 days protocol (PPI/control; 25/22), and twenty six patients completed the 14 days protocol (PPI/control; 16/10). Post-EVL ulcers in PPI group were significantly smaller than those in control group (7 days; 98.7 mm2/119.4 mm2, 14 days; 32.3 mm2/43.8 mm2, p0.05). Nineteen patients (PPI/control; 9/10) did not complete the 14 days protocol due to patients' refusal and adverse outcomes, such as hepatic failure and sepsis with bleeding from post-EVL ulcer occurred in two patients of control group. CONCLUSIONS: PPI treatment following EVL may be effective in healing post-EVL ulcer.

14-day quadruple therapy with ranitidine bismuth citrate after Helicobacter pylori treatment failure in Thailand.

BACKGROUND: A quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline is recommended as a second line therapy after Helicobacter pylori treatment failure. OBJECTIVE: To evaluate the efficacy of 14-day ranitidine bismuth citrate (RBC) base quadruple therapy after H. pylori treatment failure in Thai patients. METHOD AND MATERIAL: Between June 2003-May 2005, thirty-four patients who were H. pylori positive after first line (Omeprazole, Amoxicillin, Clarithromycin or Metronidazole) treatment failure received 14-day quadruple therapy with RBC (400 mg bid), Rabeprazole (20 mg bid), Metronidazole (500 mg tid) and Tetracycline (500 mg qid). Four weeks after completion of treatment, eradication was confirmed with 14C-urea breath test. RESULTS: There were 18 males (52.9%) and 16 females (47.1%) with a mean age of 47.3 +/- 14.6 years. Four patients dropped out due to side effects. Per-protocol eradication rate was 86.7% and the intention-to-treat eradication rate was 76.5%. Adverse effects were found in 38.2% with a bitter taste, nausea, and dizziness. The mean age in the treatment failure group was younger than that in the successful group (35.3 +/- 13.9 vs 51.1 +/- 13.9 years, p = 0.046, 95%CI, 0.3-31.5%). The abdominal symptoms were improved after eradication (82.4%). CONCLUSION: The 14-day quadruple therapy with ranitidine bismuth citrate is effective and well tolerated for the patients who failed with the Helicobacterpylori treatment. The patients with older age may receive a more favorable outcome of the treatment.