A simple PCR-SSOP approach based on a single PCR product has been developed to screen the HFE gene for the haemochromatosis-associated mutations Cys 282 Tyr and His 63 Asp. Using this approach the prevalence of these mutations in a cohort (30) of haemochromatosis patients and normal controls (404) was determined. Ninety percent of the haemochromatosis patients were homozygous for the Cys 282 Tyr mutation. In the normal population we found an increased incidence of the Cys 282 Tyr mutation (17.3%; 95% confidence limits 0.136-0.209) which was also reflected in the higher frequency of Cys 282 Tyr homozygotes (1.24%; 95% confidence limits 0.0016-0.0232). Linkage disequilibrium analysis confirmed the association between A*03 and Cys 282 Tyr. However, strong linkage disequilibrium occurred with the HLA-A*03-associated allele HLA-B*14 but not the HLA-A*03-associated allele HLA-B*07. The His 63 Asp was found to be in linkage disequilibrium with HLA-A*29.

Portopulmonary hypertension (PPHTN) represents a constrictive pulmonary vasculopathy in patients with portal hypertension. Liver transplantation (LT) may be curative and is usually restricted to patients with mild-to-moderate disease severity characterized by a mean pulmonary artery pressure (mPAP Ͻ 35 mm Hg). Patients with severe disease (mPAP Ͼ 50 mm Hg) are usually excluded from transplantation. We describe a patient with severe PPHTN, initiated on sequential and ultimately combination therapy of prostacyclin, sildenafil, and bosentan (PSB) pretransplantation and continued for 2 years posttransplantation. Peak mPAP on PSB therapy was dramatically reduced from 70 mm Hg to 32 mm Hg pretransplantation, and continued therapy facilitated a further fall in mPAP to 28 mm Hg posttransplantation. The pulmonary vascular resistance index fell from 604 to 291 dyne second Ϫ1 cm Ϫ5 . The perioperative mPAP rose to 100 mm Hg following an episode of sepsis and fell with optimization of PSB therapy. In conclusion, this is the first reported patient with severe PPHTN using this combination of vasodilator therapy as a bridge to LT and then as maintenance in the posttransplantation phase. This regimen may enable LT in similar patients in the future, without long-term consequences. Liver Transpl 14: [287][288][289][290][291] 2008. See Editorial on Page 270Portopulmonary hypertension (PPHTN) is defined as the development of pulmonary arterial hypertension associated with liver disease or portal hypertension. 1 The diagnostic criteria for PPHTN are a mean pulmonary artery pressure (mPAP) Ͼ 25 mm Hg at rest, mPAP Ͼ 30 mm Hg during exercise, a normal capillary wedge pressure (Ͻ15 mm Hg), and an elevated pulmonary vascular resistance index (Ͼ240 dyne/second/cm Ϫ5 ) alongside portal hypertension (with or without cirrhosis). [2][3][4][5] The recognized noncirrhotic causes of portal hypertension associated with PPHTN include extrahepatic portal vein obstruction, congenital hepatic fibrosis, nodular regenerative hyperplasia, and hepatoportal sclerosis. [5][6][7] Patients with PPHTN have nonspecific symptoms such as worsening fatigue, dyspnea, and peripheral edema. Men and women are equally affected. 7 No clear relationship exists between severity of liver disease, degree of portal hypertension, and severity of PPHTN. 8,9 Treatment of PPHTN is currently limited by lack of randomized controlled trials, concerns related to drug delivery, safety profiles, and failure of reversibility of the pulmonary disease. 10,11 Vasodilators, in particular, Abbreviations: LT, liver transplantation; mPAP, mean pulmonary artery pressure; NR, normal range; PPHTN, portopulmonary hypertension; PSB, prostacyclin, sildenafil, and bosentan.

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Although coexisting primary biliary cirrhosis (PBC) and celiac sprue have been described, celiac sprue is sufficiently common in western Europe for chance to explain isolated cases. We screened our patients with PBC for celiac sprue using serum immunoglobulin A endomysial antibody (EmA), with confirmation by duodenal biopsy in EmA-positive patients. Of 57 patients, 6 (11%) had EmA. Four agreed to have a biopsy taken, and all had villous atrophy, yielding a minimum prevalence of 1:14 (7%). Apart from anemia in one patient, none of the four had symptoms or routine laboratory abnormalities suggestive of celiac sprue. None had improvement in liver biochemical tests after 12 to 24 months on gluten-free diets despite the disappearance of EmA. Celiac sprue is common among patients with PBC and they should be routinely screened for this condition. Symptoms wrongly attributed to PBC may respond to gluten exclusion, and both conditions are potent risk factors for osteoporosis.

Aim:  Primary biliary cirrhosis (PBC) is a chronic cholestatic disease which is associated with hypercholesterolaemia. Further, cholestatic diseases are associated with deficiencies of anti‐oxidant vitamins. Despite these associations PBC is not associated with an increase in cardiovascular mortality. The aim of this study is to assess if primary biliary cirrhosis is associated with oxidative stress, endothelial dysfunction and alteration of vascular compliance which is a surrogate marker for cardiovascular risk. Methods:  Fifty‐one PBC patients and 34 control subjects were studied. Lipid soluble vitamins A, and E in addition to ascorbate and carotenoids were measured to assess anti‐oxidant status. C‐reactive protein, hydroperoxides and adhesion molecules sICAM‐l/sVCAM‐l were assessed as serological measures of endothelial function. Finally, measures of vascular compliance were assessed by applanation tonometer. Results:  CRP, sICAM and sVCAM were all significantly higher in PBC patients (469.14 vs 207.13, P < 0.001; 768.12 vs 308.03,P < 0.001; 708.40 vs 461.31, P < 0.001) whilst anti‐oxidant vitamin levels were lower in PBC patients, with ascorbate, vitamin E and vitamin A all significantly lower in PBC patients (39.91 vs 72.68, P < 0.001; 2.63 vs 3.14, P = 0.02; 1.08 vs 1.81, P < 0.001). Despite these findings PBC patients have a lower pulse wave velocity than control subjects (8.22 m/s vs 8.78 m/s, P = 0.022). Conclusion:  PBC patients appear to have reduced vascular risk as assessed by pulse wave velocity but concurrently have evidence of endothelial dysfunction, inflammation and anti‐oxidant deficiency.