Fecal microbiota transplantation compared with prednisolone in severe alcoholic hepatitis patients: a randomized trial.

BACKGROUND: Severe alcoholic hepatitis (SAH) has high 90-day mortality. Prednisolone therapy has shown modest survival benefits over placebo at 28 but not 90 days. Fecal microbial transplantation (FMT) has shown promise in these patients. We compared the efficacy and safety of the two therapies in SAH patients. METHODS: Steroid eligible SAH patients were randomized in an open-label study to prednisolone (n = 60) 40 mg/day for 28 days (assessed at day-7 for continuation) or healthy donor FMT (n = 60) through naso-duodenal tube, daily for seven days. Primary outcome of study was day-90 survival. RESULTS: Patients in prednisolone and FMT arms were comparable at baseline (discriminant function score 65 ± 16.2 and 68 ± 14, MELD score 17.1 and 16.5, respectively). Of 120 patients, 112 [prednisolone-57; FMT-55] completed trial. As per intention-to-treat analysis, 90-day survival was achieved by 56.6% (34/60) patients in prednisolone and 75% (45/60) in FMT group (p = 0.044, FMT HR = 0.528, 95%CI 0.279-0.998). Secondary outcome of 28-day survival [78.33% (47/60) and 88.33% (53/60) (p = 0.243, FMT HR = 0.535, 95%CI 0.213-1.34)] with comparable severity scores over time between both arms. Infections accounted for 11 (19.3%) and 2 (3.6%) deaths in prednisolone and FMT groups, respectively (p = 0.01). Path-tracing showed a slow establishment of microbiota and alpha diversity (Shannon index) improvement by day-28 (p = 0.029). FMT resulted in 23 new taxa by day-28, reduction from baseline in pathogenic taxa [Campylobacter (19-fold, p = 0.035), anaerobes (Parcubacteria, Weisella and Leuconostocaceae)], and increase of Alphaproteobacteria [~ sevenfold, p = 0.047] and Thaumarcheota (known ammonia oxidizer, p = 0.06). Lachnospiraceae (p = 0.008), Prevotella and Viellonella communities in gut favored survival (p < 0.05). CONCLUSION: In severe alcoholic hepatitis, FMT is safe and improves 90-day survival and reduces infections by favorably modulating microbial communities. It can be a useful alternative to prednisolone therapy.

A New Variant of an Old Itch: Novel Missense Variant in ABCB4 Presenting with Intractable Pruritus.

We report a novel homozygous missense variant in ABCB4 gene in a Yemeni child born to consanguineous parents, with a significant family history of liver disease-related deaths, resulting in a progressive familial intrahepatic cholestasis (PFIC) type 3 phenotype requiring liver transplantation for intractable pruritus.

Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in pediatric and adult population: a systematic review and meta-analysis.

Treatment options for hydrocephalus include endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS). Some ambiguity remains regarding indications, safety, and efficacy for these procedures in different clinical scenarios. The objective of the present study was to pool the available evidence to compare outcomes among patients with hydrocephalus undergoing ETV versus VPS. A systematic search of the literature was conducted via PubMed, EMBASE, and Cochrane Library through 11/29/2018 to identify studies evaluating failure and complication rates, following ETV or VPS. Pooled effect estimates were calculated using random effects. Heterogeneity was assessed by the Cochrane Q test and the I2 value. Heterogeneity sources were explored through subgroup analyses and meta-regression. Twenty-three studies (five randomized control trials (RCTs) and 18 observational studies) were meta-analyzed. Comparing ETV to VPS, failure rate was not statistically significantly different with a pooled relative risk (RR) of 1.48, 95%CI (0.85, 2.59) for RCTs and 1.17 (0.89, 1.53) for cohort studies; P-interaction: 0.44. Complication rates were not statistically significantly different between ETV and VPS in RCTs (RR: 1.34, 95%CI: 0.50, 3.59) but were statistically significant for prospective cohort studies (RR: 0.47, 95%CI: 0.30, 0.78); P-interaction: 0.07. Length of hospital stay was no different, when comparing ETV and VPS. These results remained unchanged when stratifying by intervention type and when regressing on age when possible. No significant differences in failure rate were observed between ETV and VPS. ETV was found to have lower complication rates than VPS in prospective cohort studies but not in RCTs. Further research is needed to identify the specific patient populations who may be better suited for one intervention versus another.

Microbiome as a therapeutic target in alcohol-related liver disease.

Alcohol-related liver disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced liver disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related liver disease. A major mechanism by which gut microbiota influence the development of alcohol-related liver disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related liver disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related liver disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related liver disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related liver disease. These approaches are likely to add to the therapeutic options for alcohol-related liver disease independently or in conjunction with steroids.

Efficacy of Granulocyte Colony-stimulating Factor in the Management of Steroid-Nonresponsive Severe Alcoholic Hepatitis: A Double-Blind Randomized Controlled Trial.

Severe alcoholic hepatitis (SAH) is often a progressive disease with high mortality and limited steroid responsiveness. Management options of steroid nonresponsive SAH (day 7 Lille score > 0.45) are limited. We assessed the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in steroid nonresponders. A randomized, double-blind, single-center trial (NCT01820208) was conducted between March 2013 and June 2016 in patients with histologically proven SAH, nonresponsive to 40 mg/day of prednisolone were randomized to G-CSF (12 doses, 300 µg each in 28 days) or placebo. Responders were continued with prednisolone. Of the 430 patients with SAH, 132 received steroid therapy. Of these, 33 (25%) were nonresponders and were randomized to G-CSF or placebo (14 in each group after exclusions). The baseline characteristics of both groups were comparable. The 28-day mortality was comparable between the groups (21.4%, G-CSF; 28.6%, placebo; P = 0.69). At 90 days, in the G-CSF but not in the placebo group, the Model for End-Stage Liver Disease reduced from 24.6 ± 3.9 to 19.4 ± 3.7 (P = 0.002) and Maddrey's discriminant function from 74.8 ± 22.8 to 57.4 ± 31 (P = 0.26). Infections were less common (28% versus 71%; P < 0.001) with lower 90-day mortality (35.7% versus 71.4%; P = 0.04) in the G-CSF than in the placebo group. On Cox regression analysis, receiving G-CSF (hazard ratio, 0.37; SD, 0.14-0.98; P = 0.04), and high baseline serum creatinine (hazard ratio, 4.12; SD, 1.7-10.3; P = 0.002) predicted day-90 outcomes in steroid nonresponsive SAH. Patients tolerated G-CSF without any major adverse events. Conclusion: Approximately one-quarter of patients with SAH do not respond to corticosteroid therapy. Administration of G-CSF is safe and helps to reduce the disease severity and 90-day mortality in these patients.

Clinical profile of severe malaria: study from a tertiary care center in north India.

One hundred and sixty patients having clinical features of severe malaria reported during monsoon season-August-October 2010 at this tertiary care center of north India. Of these 110 (68.75 %) had Plasmodium vivax infection, 30 (18.75 %) were infected with P. falciparum and 20 (12.5 %) had co-infection due to P. vivax and P. falciparum. The diagnosis was made using Rapid Card Test and was confirmed by peripheral smear examination of thick and thin films. Several complications such as acute kidney injury, jaundice, severe anemia, metabolic acidosis, shock, hyperpyrexia, hypoglycemia, generalized tonic-clonic convulsions etc. were found to be more prevalent in patients with P. vivax infection. These symptoms were until recently known to be associated with falciparum malaria.

A case of Staphylococcus toxic shock syndrome presenting with multiple pneumatocoeles in the chest.

Staphylococcus toxic shock syndrome is a severe illness caused by infection with toxin producing Staphylococcus aureus and is associated with a poor outcome. We report a case of Staphylococcus TSS presenting with cough and expectoration along with multiple pneumatoceles visible on the chest radiograph that progressed to acute respiratory distress syndrome with eventual foci in brain. The patient was aggressively managed and recovered completely.

Influenza a infection unmasking an underlying mitral valve stenosis in a 19-year-old boy.

Infection with Influenza virus is uncommon in the present times, though a number of cases were reported during pandemics in 1918 in various regions of America. We report a case where a young male patient presented to the hospital with a clinical picture of acute respiratory distress syndrome that turned out to be a viral pneumonia caused by Influenza A virus and it aggravated an underlying yet undiagnosed mitral valve stenosis.

Pulmonary tuberculosis presenting acutely as paraplegia: an unusual presentation.

Extrapulmonary tuberculosis most commonly involves the bones and the spine. The present case is that of a young boy who presented with acute onset paraplegia without any pre-existant complaints of cough with sputum, fever, night sweats or weight loss.

A case of pulmonary tuberculosis presenting as multiple nodular opacities on a chest x-ray.

Tuberculosis is widely prevalent in India. The presentation of pulmonary tuberculosis as multiple nodular opacities on a chest X-ray is very infrequent. We report such a case in a 30-year-old man, who presented with the complaints of dyspnea and responded to anti-tuberculosis treatment.