In mammals, several well-defined metabolic changes occur during infection, many of which are attributable to products of the reticuloendothelial system. Among these changes, a hypertriglyceridaemic state is frequently evident, resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL). We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells). When originally purified from RAW 264.7 (mouse macrophage) cells, cachectin was shown to have a pI of 4.7, a subunit size of relative molecular mass (Mr) 17,000 and to form non-covalent multimers. A receptor for cachectin was identified on non-tumorigenic cultured cells and on normal mouse liver membranes. A new high-yield purification technique has enabled us to determine further details of the structure of mouse cachectin. We now report that a high degree of homology exists between the N-terminal sequence of mouse cachectin and the N-terminal sequence recently determined for human tumour necrosis factor (TNF). Purified cachectin also possesses potent TNF activity in vitro. These findings suggest that the 'cachectin' and 'TNF' activities of murine macrophage conditioned medium are attributable to a single protein, which modulates the metabolic activities of normal as well as neoplastic cells through interaction with specific high-affinity receptors.

Background/Aims Drug-induced and indeterminate Acute Liver Failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced or indeterminate ALF, and whether this benefit varies according to the severity of illness. Methods We conducted a retrospective analysis of autoimmune, indeterminate and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). Results 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% vs. 66%, p=0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of MELD (MELD > 40, survival 30% vs. 57%, p=0.03). In multivariable analysis controlling for steroid use and diagnosis, age (OR 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07) and pH<7.4 (OR 3.09) were significantly associated with mortality. Though steroid use was associated with a marginal benefit in SS overall (35% v. 23%, p=0.047), this benefit did not persistent in multivariable analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and ALT (1.02) were the only significant predictors of SS. Conclusions Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores.

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Background 30-day readmissions for hospitalized patients with cirrhosis are common, particularly for patients with hepatic encephalopathy (HE). Methods We performed a prospective pre-post study from 2010–2013 to assess the impact of a quality improvement (QI) protocol on 30-day readmissions to a transplant center’s liver unit. The intervention included a yearlong control period, a handheld checklist and an “electronic” phase incorporating checklist items into the electronic provider order entry system. The intervention included goal-directed lactulose therapy and universal rifaximin for overt HE as well as prompts for antibiotic prophylaxis of spontaneous bacterial peritonitis (SBP). 30-day readmission trends were compared to non-cirrhotic patients admitted to hospitalists and patients with decompensated cirrhosis at another center. Results 824 patients were admitted 1720 times. The average model for end-stage liver disease score on admission was 17.7 ± 7.4. The electronic phase was associated with 40% lower adjusted odds of 30-day readmission compared to control, both overall and for patients with HE. The proportion of admissions for ≥ grade 2 HE that resulted in a readmission fell from 48.9% (66/135) in the control period to 26.0% (27/104) in the electronic phase (p = 0.0003). Rifaximin use for HE and antibiotic secondary prophylaxis of SBP (on discharge) were associated with lower adjusted odds of readmission (respective OR 0.39 and 0.40). The electronic phase was associated with a lower length of stay (beta coefficient −1.34 95% CI: −2.38 – −0.32, p = 0.01). Conclusion A QI initiative using electronic decision support reduced 30-day readmissions for patients with cirrhosis.