Fecal microbiota transplantation for induction of remission, maintenance and rescue in patients with corticosteroid-dependent ulcerative colitis: a long-term follow-up real-world cohort study.

BACKGROUND/AIMS: To study role of fecal microbiota transplantation (FMT) in induction, maintenance, and rescue in patients with corticosteroid-dependent ulcerative colitis (CDUC). METHODS: Patients with active CDUC received 3 fortnightly sessions of colonoscopic induction FMT (iFMT) in addition to standard of care. In patients who achieved clinical remission (CR) or response, prednisolone was tapered from week 4 and azathioprine from week 12. Responders were advised maintenance FMT (mFMT) every 6 months. Those with relapse were offered rescue FMT (rFMT), and low dose prednisolone was added if there was no improvement in 2 weeks. RESULTS: All 27 patients enrolled completed iFMT and were followed up for 39 months (range, 9-71 months). The mean Mayo score decreased from 6.4±2.5 at baseline to 2.6±3.7 at week 4, 2.6±3.4 at week 12, and 2.8±3.8 at week 24 (P<0.05). Corticosteroid-free CR and clinical response at week 12 were seen in 13 patients (48%) and 1 patient (3.7%), respectively. Corticosteroid and azathioprine-free CR at week 24 was seen in 13 patients (48%) and in them histological response was seen in 2 patients (15.2%) at week 4, 5 patients (38.4%) at week 12, and 10 patients (76.9%) at week 24. First relapse was seen in 10 of 13 responders (76.9%) at a median of 14.8 months (range, 6-34 months) after iFMT and was less frequent in patients on mFMT. Relapse was treated successfully with rFMT alone in 4 patients (40%) and rFMT with low dose steroids in 5 patients (50%). CONCLUSIONS: iFMT, mFMT, and rFMT may have a role in treatment of selected patients with CDUC.

Successful colonoscopic fecal microbiota transplantation for active ulcerative colitis: First report from India.

Forty-four-year-old male with ulcerative colitis (UC) for 11 years reported frequent relapse despite daily sulfasalazine 4 g, azathioprine 125 mg, and rectal 5-aminosalicylic acid. Repeated use of corticosteroids led to cataract. At enrollment, he was passing eight stools a day with blood with a Mayo score of 9 (3+1+3+2). Stool was negative for ova/cysts/acid fast bacilli and Clostridium difficile toxin assay. Rectal biopsy showed cryptitis, crypt abscess, and crypt distortion with no inclusion bodies, and cytomegalovirus DNA was negative. Following informed consent and approval from IEC, three sessions of fecal microbiota transplant (FMT) were performed at intervals of 2 weeks. The donor was a 34-year-old relative with no history of gastrointestinal illness, no use of antibiotics over 3 months, and free from transmissible disease as per standard protocol. At colonoscopy, 350 mL of blended and filtered donor stool, drawn into seven syringes of 50 cm3, was instilled from terminal ileum to sigmoid. Follow up sigmoidoscopy and rectal biopsy were done monthly for 6 months. There was symptomatic, colonoscopic, and histopathological improvement with the Mayo scores of 4.1 and 0 at 4.8 and 12 weeks post FMT. Azathioprine and sulfasalazine were tapered sequentially between months 4 and 6 of FMT. He remains in clinical and endoscopic remission 8 months after FMT and 2 months after withdrawal of all medication. Colonoscopic FMT may be effective in inducing drug-free remission in patients with active UC.

First prospective study on brain stem death and attitudes toward organ donation in India.

Organ donation following brain stem death is infrequent in India. There is no prospective study on prevalence of brain stem death and causes of non-donation. Consecutive patients admitted to intensive care unit from Sep 2006 to Sep 2008 were studied prospectively. Families of those with brain stem death were approached for organ donation by transplant coordinator. Extensive awareness drive was launched. Reasons for non-donation, if any, were documented. Of 2820 patients admitted, 994 (35%) were on mechanical ventilator and 657 (23%) died. Brain stem death could be diagnosed in 55, 37 males, median age 46 years (range 7 to 87 years) i.e., 1.9% of all admissions and 8.3% of all deaths. Among neurology and neurosurgery patients brain stem death was seen in 45 of 1037 (4.3%) admissions and 45 of 161 (27.9%) deaths. Complications of brain stem death were hypotension in 49, diabetes insipidus in 17 and hypertension in 5 patients. Of 33 families counselled, 16(48%) consented to organ donation. In 14(42%), organs and tissues retrieved and transplanted included 13 livers, 23 kidneys, 25 corneas and 5 cardiac valves. Consent was more likely in females (10 of 14 as compared to 6 of 19 males, p = 0.037). Consent did not correlate with age of donor or medico-legal issues (p = 0.227 & 0.579 respectively). Trained staff with requisite systems in place produced significant organ donation rates. Religious issues and medico legal concerns were not a major hurdle towards organ donation. Female patients with brain stem were more likely to become organ donors.

Role of ultrathin transnasal esophagogastroduodenoscopy: experience with 50 patients.

Conventional gastroscopes have a diameter of 8.8-12 mm; ultrathin endoscopes have an outer diameter of 5.3-5.9 mm. We share our experience with 50 patients who underwent transnasal esophagogastroduodenoscopy using an ultrathin endoscope. The indications included endoscopyassisted nasogastric tube placement in 25 patients, tight lesions not negotiable with conventional endoscope in 9, restricted mouth opening in 9, corrosive injury in 3, restricted cervical spine movement in 2 and altered sensorium following cerebrovascular accident in 2 patients. Transnasal esophageal intubation failed in 1 patient each with oropharyngeal malignancy and lipoma annularis coli. Wire-guided naso-jejunal tube placement was done in 2 patients and transnasal percutaneous endoscopic gastrostomy was done in 1 patient. Two patients developed self-limiting epistaxis. Ultrathin transnasal esophagogastroduodenoscope is a useful tool in endoscopy units, particularly those dealing with oncology patients. Inability to deliver endotherapy due to small diameter of the working channel is a limitation.

Liver transplantation for porphyria: who, when, and how?

Porphyrias are a heterogenous group of diseases that may result in disabling or life threatening neurovisceral symptoms and/or cutaneous photosensitivity. In acute intermittent porphyria, the clinical features, particularly neurological symptoms, may be life-threatening and disabling. Conventional treatment with human hemin, though effective in reducing symptoms, does not reverse neuropathy when structural nerve damage has occurred and may cause intense phlebitis. Liver transplantation (LT) may be considered as treatment for those with repeated life-threatening acute attacks resulting in poor quality of life, requirement of ventilatory support, and progressive loss of venous access due to hemin infusion. Patients with variegate porphyria (VP) present after puberty with neurovisceral symptoms and skin manifestations. LT resolved VP in the 1 patient reported in the literature. Aminolaevulinic acid dehydratase deficient porphyria is a rare autosomal recessive disorder and a child who presented with failure to thrive and required transfusions and parenteral nutrition did not improve with LT. In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin in the bone marrow. Protoporphyrin is hepatotoxic and pigment loading of hepatocytes and bile canalicular sludging may result in progressive cholestasis and cirrhosis. LT is beneficial for such patients with end-stage liver disease. Perioperative management includes use of filters on operative lights to prevent skin burns and intestinal perforation. Other concerns include development of neuropathy, biliary complications, and recurrent liver disease. This review addresses the rationale, patient selection, evaluation, management issues, and technique of performing LT in various types of porphyria.

Rapid progression of hepatitis C-induced liver failure in renal allograft recipients.

Early mortality due to hepatitis C virus (HCV)-related liver failure in renal allograft recipients in the absence of fibrosing cholestatic hepatitis is reported infrequently. We report six renal allograft recipients with HCV infection who died of rapid progression to liver failure. Of these, 2 were detected anti-HCV positive at screening prior to kidney transplantation and 4 were diagnosed after transplantation following derangement of liver function (HCV RNA positive in all 4, anti-HCV positive in 2). Median interval between kidney transplantation and derangement of liver function was 11.8 months (range 2 to 25) and median interval between transplant and death was 27 months (range 11 to 53). Liver biopsy performed during the terminal illness in 3 patients and post-mortem liver histology in 2 patients showed chronic hepatitis with mean grade of 10.2 (range 9 to 12) and stage 2.4 (range 2 to 3). None had features of fibrosing cholestatic hepatitis.

Management of hepatitis C in HIV infected and other immunocompromised individuals.

Host immunity is important in determining the natural history of HCV infection. Patients with ineffective polyclonal HCV specific CD4+ response are persistently infected and loss of HCV-specific CD4+ T cells is associated with relapse of viraemia. Weak HCV-specific CD4+ response early in the course of chronic hepatitis C correlates with higher rates of fibrosis during subsequent course of the disease. In HIV co-infected patients, the HCV load is higher by an average of 0.5-1 log than the mono-infected patients. Based on the evidence from randomized control trials, the therapy for chronic hepatitis C in HIV co-infected patients is pegylated interferon and ribavirin for 48 weeks irrespective of genotype. In patients with CD4 counts < 200 cells/l and/or plasma HIV RNA above 100,000 copies/ml, it is recommended to administer HAART before HCV therapy. The sustained viral response rate achieved in the HCV/HIV co-infected patients is lower than that for mono-infected patients. Pre-treatment HCV RNA level and the genotype are the best predictors of sustained viral response. Treatment may be discontinued at 12 weeks if there is no early viral response as the likelihood of sustained viral response in this sub-group is only 2%. Biochemical response may not be relevant in HIV/HCV co-infected patients as a third of them have normal pretreatment ALT and normalization of ALT does not correlate with virological clearance. Histological response may not also correlate with virological response as up to 43% of subjects without sustained viral response may show histological improvement at the end of 48 weeks treatment. Liver disease due to HCV in patients with end stage renal disease on maintenance dialysis, is a significant cause of morbidity. The value of aminotransferases in patients on haemodialysis is lower than in the non-uraemic population and the level may not rise above the 'normal' range despite active liver disease. HCV RNA may be required to diagnose HCV infection, as anti-HCV may not be detectable, in such patients. Weekly pegylated interferon may be effective in them. In renal allograft recipients, paired biopsies may show rapid progression of liver disease in the absence of fibrosing cholestatic hepatitis. Interferon is contraindicated in this population due to increased risk of graft rejection. Following liver transplantation, recurrence of HCV is universal and histological evidence of recurrent infection may occur as early as 1 to 8 weeks after transplantation. Combination therapy with pegylated interferon and ribavirin may be effective in them.

Intestinal lipoma: a rare cause of lower gastrointestinal haemorrhage.

Lower gastrointestinal bleeding from submucosal lipomas of the intestine is very rare. We report our experience with 3-patients presenting with lower gastrointestinal haemorrhage who were detected to have no cause other than intestinal lipomas. In two of these patients, the lipoma was in the small intestine and presented with chronic blood loss or recurrent episodes of bleeding. The third patient presented with massive haematochyzia and had a number of lipomas in the cecum and right colon. The diagnosis was established by laparotomy and intraoperative enteroscopy in 2 cases, and by colonoscopy and laparotomy in the third. Surgical excision of the lipoma led to cure in all the patients. We conclude that when laparotomy and intraoperative enteroscopy fail to show any cause for bleeding other than an innocuous-looking lipoma, it should be excised. The literature has been reviewed.