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.

Outcomes of severe pregnancy-related liver disease: refining the role of transplantation.

Severe liver disease in pregnancy is generally considered to have a favorable prognosis. The limited data available have not yielded disease-specific prognostic criteria or guidance on who should undergo liver transplantation (LT). We retrospectively evaluated 54 admissions with pregnancy-related liver disease to (1) evaluate if any admission parameters were associated with death and/or transplantation and (2) identify maternal complications. Eighteen had acute fatty liver of pregnancy and 32 had hypertension/eclampsia related disease. Seven patients (13%) died and four (7%) underwent LT. Survival rates were 43/48 if not listed for LT and 4/6 if listed. Of the four transplanted, three survived. Patients who died and/or underwent LT were more likely to have encephalopathy (p = 0.04) and hyperlactaemia (p = 0.03). Serum lactate was the best discriminant (ROC AUC 0.84). An admission lactate greater than 2.8mg/dL had 73% sensitivity and 75% specificity for predicting death or LT. The addition of encephalopathy to this parameter increased sensitivity and specificity to 90% and 86%, respectively. The King's College criteria were not effective in predicting outcome. This study confirms the overall favorable prognosis in pregnancy-related liver failure but indicates that elevated lactate levels in the presence of encephalopathy best identify patients at greatest risk of death or LT.

Review article: the modern management of autoimmune hepatitis.

BACKGROUND: The management of autoimmune hepatitis (AIH) continues to be refined. However, several issues remain unresolved, primarily as a consequence of the low incidence of the disease. This factor has contributed both to a lack of understanding of and a paucity of large scale clinical trials involving therapeutic agents. AIM: To summarize the latest evidence regarding the pathogenesis, diagnosis, therapy and long-term management of AIH with a focus on clinical aspects of the disease. METHOD: We searched PUBMED for articles pertaining to AIH, its pathogenesis, treatment and clinical outcomes, combined with the authors' own knowledge of the literature. RESULTS: Standard therapy (corticosteroids and azathioprine) is effective in more than 80% of patients which renders study of novel agents difficult. Budesonide appears to show equivalence to prednisolone. Available, but limited, data suggest that mycophenolate mofetil, tacrolimus and ciclosporin are all variably effective second line agents. Patients with AIH and cirrhosis are at risk of hepatocellular carcinoma (HCC) and require screening. Patients with end stage liver disease represent excellent candidates for liver transplantation. CONCLUSIONS: Despite ongoing limitations in the understanding of pathogenesis and difficulties in evaluating novel therapies, the management of AIH continues to evolve slowly. Multi-centre collaboration is necessary to obtain sufficient patient numbers to undertake good quality therapeutic studies.

Role of cognitive function in assessing informed consent for endoscopy.

BACKGROUND: Patient understanding of the consent process is often suboptimal and the reasons for this are poorly understood. In particular the role of cognitive function in assessing the level of understanding of consent has not been evaluated. AIMS: This study aims to assess the level of patient understanding of the informed consent process and the role of cognitive function in those with low levels of understanding. METHODS: The study was prospective, interviewing patients immediately after they had given consent but before undergoing their procedure. Understanding of the reason for the procedure, the risks attendant upon it, details of the procedure itself and post procedure care was scored with the total representing overall level of understanding. A mini mental state examination (MMSE) was then performed with the score recorded. RESULTS: 100 patients were interviewed. A low level of understanding was shown in 36%. Ninety two patients had a MMSE score greater than 24. All patients with a high level of understanding had MMSE scores greater then 24 compared with 78% of those with a low level of understanding. All patients (n = 8) who displayed a MMSE score less than 24 had a low level of understanding. Men displayed poorer levels of understanding than women. A subnormal MMSE only identified 22% of those with low levels of understanding. CONCLUSIONS: Understanding of the consent process is suboptimal. Adequate cognitive function does not predict a high level of understanding of the informed consent process while cognitive impairment precludes it. It is evident, however that factors other than cognitive dysfunction are at play when attempting to explain low levels of understanding.