Hepatology : official journal of the American Association for the Study of Liver Diseases
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Few data exist concerning survival after the diagnosis of hepatopulmonary syndrome (HPS). Although orthotopic liver transplantation (OLT) frequently results in complete resolution of HPS, the relationship between transplantation and survival has not been described. The study rationale was to describe long-term survival in patients with HPS. ⋯ Baseline PaO(2)
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The contribution of hereditary and environmental factors to the pathogenesis of symptomatic gallstone disease is still unclear. We estimated the relative importance of genetic and environmental factors by analyzing a large population of twins. For this purpose, the Swedish Twin Registry was linked with the Swedish inpatient-discharge and causes of death registries for symptomatic gallstone disease and gallstone surgery-related diagnoses in 43,141 twin pairs born between 1900 and 1958. ⋯ Of note, there were no significant sex differences in heritability. In the full model, genetic effects accounted for 25% (95% CI, 9%-40%), shared environmental effects for 13% (95% CI, 1%-25%), and unique environmental effects for 62% (95% CI, 56%-68%) of the phenotypic variance among twins. In conclusion, our results show heritability to be a major susceptibility factor for symptomatic gallstone disease, consistent with results from previous, much smaller studies.
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Mutations of the bile salt export pump (BSEP) or the multidrug resistance P-glycoprotein 3 (MDR3) are linked to impaired bile salt homeostasis and lead to progressive familial intrahepatic cholestasis (PFIC)-2 and -3, respectively. The regulation of bile salt transporters in PFIC is not known. Expression of hepatobiliary transporters in livers of ten patients with a PFIC phenotype was studied by quantitative reverse transcription polymerase chain reaction, Western blotting, and immunofluorescence microscopy. ⋯ In conclusion, PFIC-2 may be reliably diagnosed by immunofluorescence, whereas the diagnosis of PFIC-3 requires gene-sequencing. Several mechanisms may contribute to elevated plasma bile salts in PFIC: reduced bile salt uptake via NTCP, OATP1B1, and OATP1B3, decreased BSEP-dependent secretion into bile, and increased transport back into plasma by MRP4. Upregulation of MRP4, but not of MRP3, might represent an important escape mechanism for bile salt extrusion in PFIC.