Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection.

UNLABELLED: Polymorphism in the interleukin-28B (IL28B) gene region, encoding interferon (IFN)-λ3, is strongly predictive of response to antiviral treatment in the nontransplant setting. We sought to determine the prevalence and impact on clinical outcomes of donor and recipient IL28B genotypes among liver transplant recipients. The cohort study included 189 consecutive patients infected with hepatitis C virus (HCV) who underwent liver transplantation between January 1, 1995, and January 1, 2005, at the Mayo Clinic, Rochester, MN. Genotyping of the polymorphism rs12979860 was performed on DNA collected from all donors and recipients in the cohort. Sixty-five patients received IFN-based antiviral therapy. The CC IL28B variant was less common in the chronic HCV-infected recipients than in non-HCV donor livers (33% versus 47%, P = 0.03). IL28B recipient genotype was significantly predictive of fibrosis stage, with TT genotype being associated with more rapid fibrosis (Pearson chi-square P = 0.024 for the comparison G versus A). Donor and recipient IL28B genotype were independently associated with sustained virologic response (P < 0.005). The presence of IL28B CC variant in either the recipient (R) or donor (D) liver was associated with increased rate of sustained virologic response (D-non-CC/R-non-CC = 3/19 [16%] versus D-CC/R-non-CC = 11/22 [50%] versus D-non-CC/R-CC = 5/12 [42%] versus R-CC/D-CC = 6/7 [86%], P = 0.0095). IL28B genotype was not significantly associated with survival (overall/liver-related). CONCLUSION: Recipient IL28B TT genotype is associated with more severe histological recurrence of HCV. Recipient and donor liver IL28B genotype are strongly and independently associated with IFN-based treatment response in patients after orthotopic liver transplantation. The data suggest that CC donor livers might be preferentially allocated to patients with HCV infection.

Malnutrition is prevalent in hospitalized medical patients: are housestaff identifying the malnourished patient?

OBJECTIVE: Malnutrition is highly prevalent in hospitalized patients and is often not identified by the medical staff. Clinical nutrition and nutritional assessment are often neglected components of the curriculum of medical schools. The effect of instruction of nutritional assessment early in medical school on nutritional practice in clinical training is unknown. Four years after the introduction of nutritional assessment in the medical school curriculum, we assessed the knowledge of medical students and residents of nutritional assessment and the practice of this clinical skill in hospitalized medical patients. METHODS: We determined the nutritional status of 69 patients on a general medical ward within 10 d of their hospital admission. Hospital records were reviewed to determine the documentation of nutrition-related issues and practices. A questionnaire was then administered to the housestaff to determine their knowledge of assessment of nutritional status. RESULTS: Significant malnutrition was found in 69% of patients. Only one patient was identified as being malnourished by the housestaff. References to nutritional status were recorded in two patient charts. History of weight loss, appetite status, current oral intake, and functional status were recorded for fewer than 33% of patients. Although measurements of visceral protein stores (albumin and prealbumin) did not correlate with nutritional status, medical students and residents considered these to be the best markers of nutritional status. CONCLUSIONS: Malnutrition is common in hospitalized patients. Instruction of second-year medical students in assessment of nutritional status does not result in improved knowledge or practice of nutritional assessment in the clinical training years as medical housestaff. Additional instruction in nutritional assessment during clinical training needs to be emphasized. Hospitals need to develop standardized protocols for assessment of nutritional status.

Hepatorenal syndrome: diagnostic accuracy, clinical features, and outcome in a tertiary care center.

OBJECTIVES: Hepatorenal syndrome (HRS) is a common and life-threatening entity that is associated with advanced liver disease. There are limited data on predisposing or precipitating factors related to the development of this syndrome. The aims of this study were: 1) to determine the accuracy of the diagnosis of HRS in an urban tertiary care center; 2) to compare features of HRS with those of non-HRS renal failure; and 3) to document the precipitating factors for HRS in this setting. METHODS: We conducted a retrospective chart review of 46 patients at the Health Sciences Center in Winnipeg, Manitoba, who were diagnosed with HRS within the last 10 yr. In addition to assessing the accuracy of the diagnosis of HRS (as defined by the International Ascites Club), we also developed a database that included clinical and biochemical features of these patients' liver disease, possible predisposing factors, precipitating events, etiology of cirrhosis, and mortality rates. A cohort of 19 patients with advanced liver disease and renal failure not ascribed to HRS (non-HRS) served as controls. RESULTS: A total of 46 patients were labeled as having HRS during their hospital stay, of whom 27 (59%) fulfilled International Ascites Club criteria. Their mean age was 51.8 +/- 12.1 yr, and 67% were male. Demographic and biochemical findings in the HRS patients were similar to those of the non-HRS patients. Hepatic encephalopathy (p < 0.03) and jaundice (p < 0.01) more commonly preceeded renal failure in the HRS group than in the controls. The most common predisposing factor for HRS was alcohol abuse. Precipitating factors for HRS included infection in 48% patients, GI bleeding in 33%, and over paracentesis in 27%. Drug-induced renal disease was significantly more common in patients with non-HRS renal failure. Contrary to previous reports, nonsteroidal anti-inflammatory drugs were not common precipitating factors of HRS. Alcohol-related liver disease was the most common underlying etiology of liver disease in all patients who developed renal failure but was proportionally higher in the HRS group. Mortality was almost universal in both groups, regardless of the cause of renal failure. CONCLUSIONS: The diagnostic accuracy (or lack thereof) of HRS highlights the importance of ensuring that diagnostic criteria are met in studies describing the natural history and/or the results of therapeutic intervention in HRS. Alcohol abuse is a common predisposing factor for the development of HRS. Infection, GI bleed, and aggressive paracentesis were the most common precipitating factors for HRS.