Granulocyte Colony-Stimulating Factor Use in Decompensated Cirrhosis: Lack of Survival Benefit.

BACKGROUND: Granulocyte colony-stimulating factor (GCSF) has been utilized in decompensated cirrhosis (DC) for improving transplant-free survival (TFS). Data from multiple centers are conflicting with regard to patient outcomes. In this retrospective study, we present our 'real-world experience' of GCSF use in a large group of DC. METHODS: From September 2016 to September 2018, 1231 patients with cirrhosis were screened, of which 754 were found to have decompensation(s). Seventy-three patients with active ascites, jaundice, or both completed GCSF treatment (10 mcg/kg per day for 5 days, followed by 5 mcg/kg/day once every third day for total 12 doses). Per-protocol analysis (n = 56) was performed to study clinical events, liver disease severity, and outcomes at 3, 6, and 12 months after treatment. Modified intention-to-treat (mITT, n = 100) analysis was performed to study overall survival at 180 days. Outcomes were compared with a matched historical control (HC) group (n = 24). RESULTS: Nine (16%, n = 56), 24 (43%, n = 56), and 36 (75%, n = 48) patients died at 3, 6, and 12-month follow-up after GCSF. The commonest cause of death was sepsis (53%) followed by progressive liver failure (33%). Nine percent of patients developed hepatocellular carcinoma on follow-up at the end of 1 year. Acute variceal bleeds, overt hepatic encephalopathy, intensive unit admissions, and liver disease severity scores were higher after treatment at the end of 1 year. The Child-Pugh score >11 and model for end-stage liver disease-sodium score >25 and > 20 predicted worse outcomes at all time points and at 6 and 12 months after GCSF, respectively. Compared to a matched HC group, patients receiving GCSF had higher mortality (75% vs 46%, P = 0.04) at one year. mITT analysis revealed poor overall survival at 6 months compared to HCs (48% vs 75%, P = 0.04). CONCLUSION: Survival in DC was shorter than what was expected in the natural history of the disease after GCSF use.

Erratum: Removal Notice to "Slimming to the Death: Herbalife® Associated Fatal Acute Liver Failure - Heavy Metals, Toxic Compounds, Bacterial Contaminants and Psychotropic Agents in Products Sold in India", [J Clin Exp Hepatol 9 (2019) 268-272].

[This corrects the article DOI: 10.1016/j.jceh.2018.08.002.].

Slimming to the Death: Herbalife®-Associated Fatal Acute Liver Failure-Heavy Metals, Toxic Compounds, Bacterial Contaminants and Psychotropic Agents in Products Sold in India.

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Role of Granulocyte Colony-stimulating Factor Therapy in Cirrhosis, 'Inside Any Deep Asking Is the Answering'.

Liver cirrhosis progresses through multiple clinical stages which culminate in either death or liver transplantation. Availability of organs, timely listing and prompt receipt of donor-livers pose difficulties in improving transplant-listed and transplant outcomes. In this regard, regenerative therapies, particularly with granulocyte colony-stimulating factor (GCSF), has become a lucrative option for improving transplant-free survival. However, the literature is confusing with regards to patient selection and real outcomes. In this exhaustive review, we describe the basics of liver fibrosis and cirrhosis through novel insights from a therapeutic point of view, discuss preclinical studies on GCSF in advanced liver disease to improve on clinical utility, shed light on the pertinent literature of GCSF in advanced cirrhosis, and provide astute inputs on growth factor therapy in decompensated cirrhosis.

Gut Microbiota in Alcoholic Hepatitis is Disparate from Those in Acute Alcoholic Pancreatitis and Biliary Disease.

BACKGROUND: Alcoholic hepatitis (AH) is associated with gut dysbiosis. Comparative gut microbial profiles of acute alcoholic pancreatitis (AAP) and acute biliary disease (ABD) are not demonstrated. We aimed to compare gut microbiota of AH, AAP, and ABD patients with each other and with their respective healthy controls (HCs). METHODS: From December 2016 to September 2017, consecutive patients with AH, AAP, and ABD (acute cholecystitis, acute biliary pancreatitis, and choledocholithiasis with cholangitis) were included in the study. Qualitative and functional stool microbiota comparative analysis was performed between groups, with AH as the reference comparator. RESULTS: Of 3564, 882, and 224 patients with liver disease, pancreatic disease, and biliary disease, respectively, after exclusion, 29 patients with AH and 7 patients each with AAP and ABD and their corresponding HCs were included in the study analysis. The alpha diversity between patients with AH and AAP was found to be significantly different. Significant relative abundance (RA) of Acinetobacter and Moraxella was noted among patients with AAP. Enterobacter, Atopobium, Synergistia, and Devosia were significantly higher in patients with ABD compared to patients with AH, in whom Faecalibacterium and Megamonas were higher. Functional pathways associated with carbohydrate metabolism, phenylpropanoid biosynthesis, and ethylbenzene degradation were significantly higher in AAP when compared to AH. Fatty acid and inositol phosphate metabolism and dioxin degradation were significantly upregulated in patients with ABD while lipid and fatty acid biosynthetic pathways and pathways associated with immune processes were upregulated in patients with AH. CONCLUSIONS: Differential gut dysbiosis is evident in both patients with AH, AAP, and ABD and also in comparison to HCs. The differential microbiota among patients with AH and AAP maybe important in promotion and progression of liver or pancreatic disease among alcohol users and may be a potential therapeutic target, which needs to be confirmed in larger multicenter studies.

A Case Series on Superior Mesenteric Artery Syndrome Surgical Management, Single Institution Experience.

Compression of duodenum by Superior Mesenteric Artery (SMA) causing proximal intestinal obstruction is an uncommon condition. Treatment of this condition involves conservative management initially followed by surgical management in those patients who have persistent symptoms. This case series evaluates surgical management and outcome of six patients after one year, who presented with SMA syndrome and describes a brief review of literature. Three patients underwent open duodenojejunostomy and the rest three underwent laparoscopic duodenojejunostomy. All patients had uneventful postoperative recovery. Postoperative requirement of analgesics was less in laparoscopic group versus open group. All the three patients in laparoscopic group could be mobilised out of bed on the day of the surgery itself. Mean duration of hospital stay was seven days for open surgery group and three days for the laparoscopy group. Outcome in terms of resolution of abdomen pain and vomiting was similar in both the groups. Four patients were asymptomatic after one year of follow up. A high index of clinical suspicion is needed for the diagnosis of SMA syndrome. Laparoscopic approach is feasible, safe, less morbid and effective as compared to open surgery. In the presence of facilities and surgical expertise, laparoscopic duodenojejunostomy should be considered the procedure of choice for SMA syndrome. Majority of patients remain symptom free at one year follow up.