Disordered vascular compliance in haemochromatosis.

BACKGROUND: A relationship may exist between body iron stores, endothelial dysfunction and overall cardiovascular risk. AIMS: To compare vascular compliance, biochemical endothelial function and antioxidant status between patients with homozygous hereditary haemochromatosis and healthy controls. METHODS: Haemochromatosis patients and healthy controls were recruited. Measures of vascular compliance were assessed by applanation tonometry. Serological markers of endothelial function (plasma lipid hydroperoxides, cell adhesion molecules), antioxidant levels (ascorbate, lipid soluble antioxidants) and high-sensitivity C-reactive protein (CRP) were also measured. RESULTS: Thirty-five hereditary haemochromatosis patients (ten females, mean age 54.6) and 36 controls (27 female, mean age 54.0) were recruited. Haemochromatosis patients had significantly higher systolic and diastolic blood pressures. Pulse wave velocity (PWV) was significantly higher in male haemochromatosis patients (9.90 vs. 8.65 m/s, p = 0.048). Following adjustment for age and blood pressure, male haemochromatosis patients continued to have a trend for higher PWVs (+1.37 m/s, p = 0.058). Haemochromatosis patients had significantly lower levels of ascorbate (46.11 vs. 72.68 µmol/L, p = 0.011), retinol (1.17 vs. 1.81 µmol/L, p = 0.001) and g-tocopherol (2.51 vs. 3.14 µmol/L, p = 0.011). However, there was no difference in lipid hydroperoxides (0.46 vs. 0.47 nmol/L, p = 0.94), cell adhesion molecule levels (ICAM: 348.12 vs. 308.03 ng/mL, p = 0.32 and VCAM: 472.78 vs. 461.31 ng/mL, p = 0.79) or high-sensitivity CRP (225.01 vs. 207.13 mg/L, p = 0.32). CONCLUSIONS: Haemochromatosis is associated with higher PWVs in males and diminished antioxidants across the sexes but no evidence of endothelial dysfunction or increased lipid peroxidation.

Paracetamol overdose: the liver unit perspective.

Liver failure resulting from deliberate or accidental paracetamol overdose continues to be an important reason for referral to liver transplant centres. Severe hepatic dysfunction often appears 72-96 h after overdose. Liver injury can be prevented by timely administration of the specific antidote, N-acetylcysteine. Unfortunately, administration of N-acetylcysteine is frequently delayed due to late presentation or late administration. While N-acetylcysteine works best if given within 8 h of overdose, it is beneficial at any time period and should always be given if there is concern about significant overdose, irrespective of interval from time of ingestion. Early discussion with liver transplant unit is suggested if there is any doubt or evidence of liver failure.

Successful pregnancy after liver transplantation in progressive familial intrahepatic cholestasis, type 1.

A woman who had undergone liver transplantation for genetically documented ATP8B1 disease/progressive familial intrahepatic cholestasis, type 1, successfully conceived, carried, and was delivered of a healthy child. The pregnancy and its management are described; implications are discussed.

Current concepts in the assessment and treatment of hepatic encephalopathy.

Hepatic encephalopathy (HE) is defined as a metabolically induced, potentially reversible, functional disturbance of the brain that may occur in acute or chronic liver disease. Standardized nomenclature has been proposed but a standardized approach to the treatment, particularly of persistent, episodic and recurrent encephalopathy associated with liver cirrhosis has not been proposed. This review focuses on the pathogenesis and treatment of HE in patients with cirrhosis. The pathogenesis and treatment of hepatic encephalopathy in fulminant hepatic failure is quite different and is reviewed elsewhere.

Adjuvant therapy used in conjunction with combination therapy for chronic hepatitis C improves sustained virus response rates in genotype 1 patients.

Combination treatment with pegylated interferon (Peg-IFN) and ribavirin remains the gold standard in the treatment of chronic hepatitis C. This therapy is limited by many side-effects including anaemia, neutropenia and reduced quality of life. The use of adjuvant agents to reduce the frequency of dose reductions because of haematological side-effects has been proven to be effective but there are few reports of what effect the use of these adjuvant therapies is having on sustained virological response (SVR). The aim of the study was to assess the clinical impact on sustained virological response of adjuvant therapies during combination therapy with Peg-IFN and ribavirin for chronic hepatitis C. A total of 132 patients, 96 males, were included in the study. The overall SVR was 66.7%, with 50% of genotype 1/4/6 (n = 27/54) patients achieving SVR and 78.2% of genotypes 2/3. The overall SVR of the treatment naïve patients (83/121) was 68.6%. Fifty-one of these patients were genotype 1 with 49.0% (25/51) of this group achieving SVR. The genotype 2/3 group of treatment naïve patients reached an SVR of 82.9% (58/70). Adjuvant therapy was used in 57 patients (43.8%). With the use of supportive adjuvant therapy, we achieved an overall SVR of 66.7% and in treatment naïve patients 68.6%. In genotype 1 patients, SVR rates of up to 46% have been reported in previous studies without the use of erythropoietin and granulocyte colony stimulating factor. We have demonstrated the SVR for genotype 1 can be improved to 50% overall.