Liver transplantation for alcoholic cirrhosis: Long term follow-up and impact of disease recurrence

Background. Alcoholic liver disease has emerged as a leading indication for hepatic transplantation, although it is a controversial use of resources. We aimed to examine all aspects of liver transplantation associated with alcohol abuse. Methods. Retrospective cohort analysis of 123 alcoholic patients with a median of 7 years follow-up at one center. Results. In addition to alcohol, 43 (35%) patients had another possible factor contributing to cirrhosis. Actuarial patient and graft survival rates were, respectively, 84% and 81% (1 year); 72% and 66% (5 years); and 63% and 59% (7 years). After transplantation, 18 patients (15%) manifested 21 noncutaneous de novo malignancies, which is significantly more than controls (P=0.0001); upper aerodigestive squamous carcinomas were over-represented (P=0.03). Thirteen patients had definitely relapsed and three others were suspected to have relapsed. Relapse was predicted by daily ethanol consumption (P=0.0314), but not by duration of pretransplant sobriety or explant histology. No patient had alcoholic hepatitis after transplantation and neither late onset acute nor chronic rejection was significantly increased. Multiple regression analyses for predictors of graft failure identified major biliary/vascular complications (P=0.01), chronic bile duct injury on biopsy (P=0.002), and pericellular fibrosis on biopsy (P=0.05); graft viral hepatitis was marginally significant (P=0.07) on univariate analysis. Conclusions. Alcoholic liver disease is an excellent indication for liver transplantation in those without coexistent conditions. Recurrent alcoholic liver disease alone is not an important cause of graft pathology or failure. Potential recipients should be heavily screened before transplantation for coexistent conditions (e.g., hepatitis C, metabolic diseases) and other target-organ damage, especially aerodigestive malignancy, which are greater causes of morbidity and mortality than is recurrent alcohol liver disease

A Switch in the Mechanism of Hypertension in the Syndrome of Apparent Mineralocorticoid Excess

The syndrome of apparent mineralocorticoid excess arises from nonfunctional mutations in 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), an enzyme that inactivates cortisol and confers aldosterone specificity on the mineralocorticoid receptor. Loss of 11βHSD2 permits glucocorticoids to activate the mineralocorticoid receptor, and the hypertension in the syndrome is presumed to arise from volume expansion secondary to renal sodium retention. An 11βHSD2 null mouse was generated on an inbred C57BL/6J genetic background, allowing survival to adulthood. 11βHSD2−/− mice had BP approximately 20 mmHg higher on average compared with wild-type mice but were volume contracted, not volume expanded as expected. Initially, impaired sodium excretion associated with increased activity of the epithelial sodium channel was observed. By 80 days of age, however, channel activity was abolished and 11βHSD2−/− mice lost salt. Despite the natriuresis, hypertension remained but was not attributable to intrinsic vascular dysfunction. Instead, urinary catecholamine levels in 11βHSD2−/− mice were double those in wild-type mice, and α1-adrenergic receptor blockade rescued the hypertensive phenotype, suggesting that vasoconstriction contributes to the sustained hypertension in this model. In summary, it is proposed that renal sodium retention remains a key event in apparent mineralocorticoid excess but that the accompanying hypertension changes from a renal to a vascular etiology over time

Hepatic resection for metastatic endometrioid carcinoma

AbstractBackgroundThe role of hepatic resection for gynaecological tumours is not well defined as evidence on the subject is lacking. This article describes a tertiary hepatopancreatobiliary unit's experience with hepatic resection for liver metastases from endometrioid primaries.MethodsFive women in whom liver metastases developed at 11 months to 10 years post-primary resection are presented. These patients subsequently underwent hepatic resection with disease-free survival of 8–66 months post-resection.ResultsOutcomes in this patient series support hepatic resection in the face of isolated liver metastasis.ConclusionsThe authors advocate that patients with hepatic deposits should be referred to specialist hepatobiliary units with a view towards hepatic resection and a subsequent good outcome

Angiotensin-converting enzyme Ii a modifier of hypertensive end organ damage

Severe forms of hypertension are characterized by high blood pressure combined with end organ damage. Through the development and refinement of a transgenic rat model of malignant hypertension incorporating the mouse renin gene, we previously identified a quantitative trait locus on chromosome 10, which affects malignant hypertension severity and morbidity. We next generated an inducible malignant hypertensive model where the timing, severity, and duration of hypertension was placed under the control of the researcher, allowing development of and recovery from end organ damage to be investigated. We have now generated novel consomic Lewis and Fischer rat strains with inducible hypertension and additional strains that are reciprocally congenic for the refined chromosome 10 quantitative trait locus. We have captured a modifier of end organ damage within the congenic region and, using a range of bioinformatic, biochemical and molecular biological techniques, have identified angiotensin-converting enzyme as the modifier of hypertension-induced tissue microvascular injury. Reciprocal differences between angiotensin-converting enzyme and the anti-inflammatory tetrapeptide, N-acetyl-Ser-Asp-Lys-Pro in the kidney, a tissue susceptible to end organ damage, suggest a mechanism for the amelioration of hypertension-dependent damage