Complications and clinical outcome of hepatic artery embolisation in patients with hereditary haemorrhagic telangiectasia

BACKGROUND: Hepatic artery embolisation (HAE) in patients with hereditary haemorrhagic telangiectasia (HHT) is controversial because of the associated complications and unproven long-term benefit. We present our results in 20 such patients over a time span of 17 years. METHODS: Staged HAE was performed using polyvinyl alcohol (PVA) particles and coils. Complications, clinical symptoms and cardiac output were assessed before and after therapy as well as at the end of follow-up (median 92 months, range 26–208 months). RESULTS: Two patients died within 30 days following HAE (10 %). Four further deaths resulted from causes unrelated to HAE. Ischaemic cholangitis, cholecystitis and focal hepatic necrosis with biliary sepsis necessitated re-intervention in four patients. In all but one patient, clinical symptoms resolved with mean cardiac output falling from 11.84 ± 3.22 l/min pre-treatment to 8.13 ± 2.67 l/min at the end of follow-up (P < 0.001). One patient required liver transplantation for de novo symptoms of portal hypertension 4 years after primary symptoms had been cured by HAE. CONCLUSION: The 30-day mortality of HAE in patients with HHT is 10 %. The rate of complications requiring re-intervention is 20 %. Clinical response at long-term follow-up is satisfactory. KEY POINTS: • Hepatic artery embolisation (HAE) in hereditary haemorrhagic telangiectasia (HHT) provides long-term benefit. • Mortalities of HAE and liver transplantation in HHT patients are comparable. • In HHT, complications of HAE are lower than those of liver transplantation. • Complications of HAE can be further reduced by refinement of technique. • Complications include ischaemic cholangitis, hepatic necrosis, biliary sepsis and death

Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups) after 30–40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects

Brain function and metabolism in patients with long-term tacrolimus therapy after kidney transplantation in comparison to patients after liver transplantation.

BACKGROUND:About 50% of the patients 5-7 years after kidney transplantation show impairment of memory, attention and executive function. Tacrolimus frequently induces neurological complications in the first few weeks after transplantation. Furthermore, tacrolimus treatment is associated with impaired cognitive function in the long-term in patients after liver transplantation. We hypothesize that long-term tacrolimus therapy is associated with cognitive dysfunction and alterations of brain structure and metabolism in patients after kidney transplantation. METHODS:Twenty-one patients 10 years after kidney transplantation underwent cognitive testing, magnetic resonance imaging and whole brain 31-phosphor magnetic resonance spectroscopy for the assessment of brain function, structure and energy metabolism. Using a cross-sectional study design the results were compared to those of patients 1 (n = 11) and 5 years (n = 10) after kidney transplantation, and healthy controls (n = 17). To further analyze the share of transplantation, tacrolimus therapy and kidney dysfunction on the results patients after liver transplantation (n = 9) were selected as a patient control group. RESULTS:Patients 1 and 10 years after kidney transplantation (p = 0.02) similar to patients 10 years after liver transplantation (p<0.01) showed significantly worse cognitive function than healthy controls. In contrast to patients after liver transplantation patients after kidney transplantation showed significantly reduced adenosine triphosphate levels in the brain compared to healthy controls (p≤0.01). Patients 1 and 5 years after kidney transplantation had significantly increased periventricular hyperintensities compared to healthy controls (p<0.05). CONCLUSIONS:Our data indicate that cognitive impairment in the long-term after liver and kidney transplantation cannot exclusively be explained by CNI neurotoxicity

Cerebral metabolite alterations in patients with posttransplant encephalopathy after liver transplantation.

BackgroundIn the first weeks after liver transplantation about 30% of the patients develop a posttransplant encephalopathy. A posttransplant encephalopathy comprises metabolic-toxic caused symptoms such as disorientation, confusion, hallucinations, cognitive dysfunction and seizures. We hypothesize that alterations of cerebral metabolites before liver transplantation predispose posttransplant encephalopathy development after liver transplantation.Methods31 patients with chronic liver disease underwent magnetic resonance spectroscopy (MRS) before liver transplantation to assess glutamine/glutamate (Glx), myo-Inositol (mI), choline (Cho), creatine/phosphocreatine- and N-acetyl-aspartate/N-acetyl-aspartate-glutamate concentrations in the thalamus, lentiform nucleus and white matter. Of these, 14 patients underwent MRS additionally after liver transplantation. Furthermore, 15 patients received MRS only after liver transplantation. Patients' data were compared to 20 healthy age adjusted controls.ResultsPatients showed significantly increased Glx and decreased mI and Cho concentrations compared to controls before liver transplantation (p≤0.01). The MRS values before liver transplantation of patients with posttransplant encephalopathy showed no significant difference compared to patients without posttransplant encephalopathy. Patients after liver transplantation showed increased Glx concentrations (p≤0.01) compared to controls, however, patients with and without posttransplant encephalopathy did not differ. Patients with posttransplant encephalopathy who underwent MRS before and after liver transplantation showed a significant mI increase in all three brain regions (pConclusionPatients with and without posttransplant encephalopathy showed no significant difference in cerebral metabolites before liver transplantation. However, the paired sub-analysis indicates that the extent of cerebral metabolite alterations in patients with liver cirrhosis might be critical for the development of posttransplant encephalopathy after liver transplantation

Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option

Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation

Purpose!#!Calcineurin inhibitors (CNI) can cause long-term impairment of brain function. Possible pathomechanisms include alterations of the cerebral immune system. This study used positron emission tomography (PET) imaging with the translocator protein (TSPO) ligand !##!Methods!#!PET was performed in 22 liver-transplanted patients (3 CNI free, 9 with low-dose CNI, 10 with standard-dose CNI immunosuppression) and 9 healthy controls. The total distribution volume (V!##!Results!#!In controls, V!##!Conclusion!#!Our results provide evidence of chronic suppression of microglial activity in liver-transplanted patients under CNI therapy especially in patients with high sensitivity to CNI toxicity