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Association of 5-Hydroxytryptamine 3 Receptor Antagonists With the Prognosis of Liver Failure.

ABSTRACT: Liver failure is a severe clinical syndrome with high mortality. 5-Hydroxytryptamine 3 receptor antagonists (5-HT3RAs) can reduce liver damage in animal models. We investigated whether 5-HT3RAs may improve the prognosis of liver failure. We analyzed the 28 and 90 days mortality of liver failure patients in relation to the use of 5-HT3RAs using data from a tertiary hospital in northwest China. According to the use of 5-HT3RAs, 419 patients with liver failure (46 acute, 93 sub-acute, 44 chronic, 236 acute on chronic) were divided into 5-HT3RA group (n = 105) and control group (n = 314). 5-HT3RAs were associated with decreased 28 days (HR 0.18, 95% CI 0.10-0.34, p < 0.001) and 90 days (HR 0.21, 95% CI 0.13-0.33, p < 0.001) mortality. After propensity score matching (PSM) (n = 67 in each group), 5-HT3RAs were still significantly associated with reduced 28 days (HR 0.10, 95%CI 0.04-0.26, p < 0.001) and 90 days (HR 0.16, 95%CI 0.08-0.31, p < 0.001) mortality. 5-HT3RA group patients had significantly higher 28 and 90 days survivals than controls both before and after PSM (all p < 0.001). This study shows that 5-HT3RAs are associated with increased survival of liver failure patients and thus may be used to treat liver failure if the findings are confirmed by additional studies.

SUBMITTER: Chen Y

PROVIDER: S-EPMC8100675 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimWe assessed the efficacy and safety of 5-hydroxytryptamine (5-HT3) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or diarrhea-predominant IBS (IBS-D).MethodsWe searched PubMed, MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials (RCTs) involving adults with non-constipated IBS or IBS-D that compared 5-HT3 receptor antagonists with placebo or other conventional treatment. Dichotomous symptom data were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs) for improving global IBS symptoms, abdominal pain and abnormal bowel habits, or stool consistency symptoms after therapy, and adverse events, including constipation. Meta- analysis was performed with Mantel Haenszel method using Revman 5.3 software.ResultsWe included 21 RCTs; 16 were high quality (Jadad score ≥ 4). The pooled RR of global IBS symptoms improved by 5-HT3 receptor antagonists versus placebo or mebeverine was 1.56 (95% CI: 1.43-1.71); alosetron, ramosetron, and cilansetron had similar treatment effects. The pooled RR of abdominal pain relieved by 5-HT3 receptor antagonists versus placebo was 1.33 (95% CI: 1.26-1.39). The pooled RR showed that 5-HT3 receptor antagonists improved abnormal bowel habits or stool consistency symptoms (RR = 1.63, 95% CI: 1.33, 1.99). The pooled RR of adverse events following 5-HT3 receptor antagonist treatment was 1.15 (95% CI: 1.08, 1.22). Subgroup analysis indicated that alosetron had a high rate of adverse effects (RR = 1.16, 95% CI: 1.08, 1.25); adverse events following ramosetron treatment were not statistically significantly different. 5-HT3 receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT3 receptor antagonist versus placebo was 3.71 (95% CI: 2.98-4.61). However, constipation was likelier in patients with non-constipated IBS after taking 5-HT3 receptor antagonists than in patients with IBS-D only (non-constipated IBS and IBS-D: RR = 5.28 [95% CI: 3.93, 7.08] vs. IBS-D only 3.24 [2.54, 4.12]).ConclusionsRamosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events.

Project description:InductionLiver transplantation (LT) is the only final therapy for patients with acute liver failure (ALF) that cannot be controlled by conservative treatment. Acute pancreatitis (AP) is a recognized complication of ALF. The pathogenesis of AP in ALF patients has not yet been elucidated. The appearance of AP complicates the patients condition and causes a significantly increased risk of mortality.Patient concernsWe report 2 fatal cases who were both admitted with yellowing of skin and sclera with general weakness lasting for 2 weeks.DiagnosisAfter admission, the laboratory examination of case 1 showed liver dysfunction with serum levels of total bilirubin (TB) 270 μmol/l, alanine aminotransferase (ALT) 106 U/l. Abdominal computed tomography (CT) showed pelvic and peritoneal cavity fluids, occupation of left lateral lobe of liver and unclear margin of pancreas. The clinical laboratory findings of case 2 revealed TB 351.1 μmol/l, ALT 252 U/l, blood lactic acid 18 mmol/l, ammonia 209 μmol/l. And abdominal CT showed pancreatic exudation. They were both diagnosed with acute liver failure, hepatic encephalopathy and AP which was confirmed during the operation.InterventionsThey were both received a routine orthotopic LT.OutcomesAfter the surgery, their liver functions recovered well, and they received conventional conservative treatment for pancreatitis. However, the treatment was not adequately effective, and the infection was too serious and both died of multiple organ failure despite emergency rescue efforts on day 21 and day 19 after LT.ConclusionAP is a serious complication that can contribute to prohibitive morbidity and mortality in LT patients. For this reason, the vulnerable state of the pancreas and the scoring system must be defined to help clinicians decide whether a patient is suitable for liver transplantation, and the clinical experience in the treatment of pancreatitis after LT needs to be summarized as an optimal treatment guideline to facilitate better treatment.

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Association of 5-Hydroxytryptamine 3 Receptor Antagonists With the Prognosis of Liver Failure.

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