Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis are prone to infection which is a frequent precipitant of hepatic encephalopathy (HE). Clinical studies have examined the importance of inflammation and infection in modulating the manifestation of symptoms of HE in acute liver failure and patients with cirrhosis and minimal/low grade HE. It would be logical to presume that this relationship persists in patients who develop severe HE in cirrhosis although this has not been examined to date. METHODS: We report the findings of a prospective audit of 100 consecutive patients with cirrhosis admitted between Jan 2000 and March 2008 to a liver Intensive Care Unit (ICU) where HE was the primary indication for admission (59% Grade 3; 41% Grade 4). Haematological and microbiological data were collected at ICU admission, and organ scores and outcomes were recorded. RESULTS: 46% of patients had positive cultures taken within ± 48h from admission to ICU [25% blood] and a further 22% were culture negative but had evidence of systemic inflammation (SIRS). SIRS score (p=0.03) and SOFA score (p=0.006) were significantly higher in those patients with Grade 4 HE, who were also less likely to survive (p<0.001). HE grade/coma score did not correlate with ammonia, biochemistry or MELD score. Fifty-two percent of patients survived their ICU stay while the remainder developed progressive multiorgan failure and died; 38% survived to discharge, and 16% were transplanted. CONCLUSIONS: These data support an association between infection/SIRS and not ammonia, in patients with cirrhosis that develop severe HE. The presence or absence of infection/SIRS did not determine survival.

Transcriptional regulation of the mucosal immune system mediated by T-bet.

The immune system faces the arduous task of defending the mucosal surfaces from invading pathogens, but must simultaneously repress responses against commensal organisms and other inert antigens that are abundant in the external environment, as inappropriate immune activation might expose the host to increased risk of autoimmunity. The behavior of individual immune cells is governed by the expression of transcription factors that are responsible for switching immune response genes on and off. T-bet (T-box expressed in T cells) has emerged as one of the key transcription factors responsible for controlling the fate of both innate and adaptive immune cells, and its expression in different immune cells found at mucosal surfaces is capable of dictating the critical balance between permitting robust host immunity and limiting susceptibility to autoimmunity and allergy.

Significant psychological morbidity occurs in irritable bowel syndrome: a case-control study using a pharmacy reimbursement database.

BACKGROUND: Psychological problems are associated with IBS but the strength of this association is unclear. AIM: To assess co-prescribing of antispasmodic and CNS-acting drugs through a nested case-control study. METHODS: A national dispensing database identified patients who were first dispensed antispasmodic medicines for a continuous 3-month period or more during 2006, using 2005 as a run-in period. Each patient was matched with four control patients and excluded if they received drugs indicated for IBD. RESULTS: Four hundred and seven patients commenced antispasmodic drugs during 2006. These patients were matched with 1628 controls. In 2005, patients subsequently prescribed antispasmodics were 2-3 times more likely to receive CNS-acting drugs than controls. In the year following commencement of IBS therapy, patients were 2-4 times more likely than controls to be prescribed CNS-acting drugs including antidepressants (35.4% vs. 9.3%), anxiolytics (27.8% vs. 8.8%), antipsychotics (9.8% vs. 3.3%) and hypno-sedatives (32.7% vs. 11.3%; P < 0.0001). The adjusted OR (95% CI) for antidepressant, anxiolytic, hypnosedative and antipsychotic prescribing in IBS patients were 3.81 (2.79-5.20), 2.84 (2.12-3.81), 2.62 (1.91-3.60) and 2.58 (1.80-3.66), respectively. CONCLUSIONS: Patients prescribed ongoing therapy for presumed IBS are 2-4 times more likely to be prescribed CNS-acting drugs than controls, providing evidence of psychological comorbidity in IBS.