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F Nevens

Publications and source records attributed to F Nevens.

At least 19 recordsLinked to original sources
PubMed2006

Review article: non-biological liver support in liver failure.

Liver failure, whether acute or acute-on-chronic, remains an important cause of morbidity and mortality. The lack of liver detoxification, metabolic and regulatory functions of the liver leads to life-threatening complications, such as renal failure, altered immune response, hepatic coma and systemic haemodynamic dysfunction, eventually culminating in multiorgan failure. Current medical therapy involves the management of the precipitating event and treatment of complications until the liver eventually recovers, leaving us with no other treatment options than transplantation if these attempts fail. However, the shortage in cadaveric organs and other transplant-related problems, have prompted the need for alternative methods to provide liver support. As liver failure is often potentially reversible, considerable effort has been invested in the development of liver support systems. Currently, most of the experience is available for non-biological support systems. They represent the focus of this review, which aims to define the goals of liver support, to describe the design of the different existing devices and to analyse the available data to determine their current status in the management of patients with liver failure.

Albumins↗
PubMed2006

A stable model of cirrhotic portal hypertension in the rat: thioacetamide revisited.

BACKGROUND: Cirrhotic animal models are vital to investigate complications of chronic liver disease. We chronologically characterized the effect of thioacetamide, administrated orally and adapted weekly to weight changes, focusing on the optimal moment to obtain all typical features of portal hypertension and cirrhosis. MATERIALS AND METHODS: Male Wistar rats, 200-250 g, were intoxicated for 6, 12 or 18 weeks (n = 8 per group), respectively, and compared with age-matched controls (n = 4 per group). An in-situ perfusion model was used to evaluate intrahepatic resistance and endothelial function. Splanchnic blood flow and portosystemic shunting were assessed by a perivascular flow probe. RESULTS: Rats intoxicated for 6 or 12 weeks had no mortality and histologically showed hepatitis and advanced fibrosis, respectively. At 18 weeks, mortality was 16% (on a total of 56 animals) and only at that moment all animals showed homogenous macronodular cirrhosis with signs of high-grade hepatocellular dysplasia. Portal hypertension was present at 12 weeks (11 +/- 0.4 vs. 5.9 +/- 0.4 mmHg, P < 0.001), but was not associated with the hyperdynamic state until 18 weeks (12.1 +/- 0.8 vs. 5.6 +/- 0.5 mmHg, P < 0.001). At this latter time-point, we also observed increased intrahepatic resistance associated with endothelial dysfunction, hyperresponsiveness to vasoconstrictors, splanchnic hyperaemia and portosystemic shunting. These alterations were associated with increased systemic levels of nitrate/nitrite and thromboxane A(2). CONCLUSION: Thioacetamide, adapted to weekly weight changes, leads to a homogenous, reproducible model of cirrhosis in the rat in 18 weeks, which is associated with all the typical characteristics of portal hypertension, including endothelial dysfunction.

Administration, Oral↗
PubMed2006

The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin.

AIMS: Cytokeratin (CK) 7 and CK19 expression, present in hepatic progenitor cells (HPCs) and in cholangiocytes but not in normal hepatocytes, has been reported in some hepatocellular carcinomas (HCCs); however, the incidence and relevance of this expression in HCC in Caucasians is not known. Therefore, our aim was to study the occurrence and clinicopathological characteristics of HCC expressing CK7 and/or CK19 in 109 Caucasian patients. METHODS AND RESULTS: The expression of hepatocellular differentiation markers (Hepar, canalicular polyclonal carcinoembryonic antigen), biliary/progenitor cell markers (CK7, CK19), alpha-fetoprotein (AFP), p53 and beta-catenin in HCC was semiquantitatively assessed by immunohistochemistry. Of 109 HCCs, 78 were CK7-/CK19- (72%), 13 CK7+/CK19- (12%), seven CK7-/CK19+ (6%), 11 CK7+/CK19+ (10%). CK19 expression was significantly associated with elevated serum AFP (400 ng/ml) (P = 0.023), tumour AFP expression (P < 0.0001), presence in serum of anti-hepatitis B core (P = 0.016), less fibrosis in non-neoplastic parenchyma (P = 0.009) and less nuclear beta-catenin expression (P = 0.021). CK7 expression was significantly associated with elevated serum bilirubin (> 2 mg/dl) (P = 0.0005) and less nuclear beta-catenin expression (P = 0.003). HCC expressing CK19 had a higher rate of recurrence (P = 0.009, hazard ratio 12.5, n = 31) after liver transplantation compared with CK19- tumours. CONCLUSIONS: In our series, 28% of HCCs contained cells expressing CK7 and/or CK19. They potentially derive from HPCs. The higher recurrence rate of CK19+ HCC after transplantation suggests a worse prognosis for these HCCs compared with CK19- HCC.

Adult↗
PubMed2006

Cirrhotic portal hypertension: current and future medical therapy for primary and secondary prevention of variceal bleeding.

Portal hypertension (PHT) is the most common complication of chronic liver disease and develops in the vast majority of patients with cirrhosis. It is characterized by an increase of the portal vein pressure, and leads to the development of gastroesophageal varices, ascites, renal dysfunction and hepatic encephalopathy. Over the years, it has become clear that a decrease in portal pressure is not only protective against the risk of variceal (re)bleeding but is also associated with a lower long-term risk of developing other complications and with an improved long-term survival. At present, non-selective b-blockers remain the medical treatment of choice for both primary and secondary prophylaxis. However, recent advances in the knowledge of the pathophysiology of cirrhotic PHT have directed future therapy towards the increased intrahepatic vascular resistance, which in part is determined by an increased hepatic vascular tone. This increased vasculogenic component provides the motivation to the use of therapies aimed at increasing intrahepatic vasorelaxing capacity on the one hand and at antagonizing excessive intrahepatic vasoconstrictor force on the other hand. This review covers current and future developments in the treatment of PHT with regard to primary and secondary prophylaxis.

Adrenergic beta-Antagonists↗
PubMed2005

Diagnosis and treatment of autoimmune hepatitis at age 65 and older.

AIM: To study features in older patients with autoimmune hepatitis, as this was considered mainly a disease of young females. METHODS: Analysis of 28 patients diagnosed at age > or =65 years compared with 84 younger patients. RESULTS: The incidence was similar at all age decades. The ratio M:F was 1:3 (> or =65 years) vs. 1:2 (<65 years). Presenting symptoms were not different when compared with younger patients and consisted of general malaise and fatigue (36%), jaundice +/- other symptoms (50%), or ascites (11%). Antinuclear antibodies (ANA) > or = 1/80 were positive in 93%, smooth muscle antibodies (SMA) > 1/40 in 50%, anti-liver kidney microsomes (anti-LKM) proved always negative. Histology showed acute necrotizing hepatitis in 19%, severe interphase hepatitis in 15%, chronic hepatitis with plasmo-lymphocytic infiltrate in 30%, cirrhosis in 29% (with active inflammation in one-third); biopsy was refused in 11%. The elderly responded very well to low doses of methylprednisolone (< or =8 mg) and azathioprine (1 mg/kg). This schedule obviates side-effects such as infections seen with higher dosages. CONCLUSION: Autoimmune hepatitis has to be also looked for in the elderly with acute and chronic hepatitis. The steroid therapy should be individualized but kept at a low dose.

Aged↗
PubMed2005

Liver transplantation using cavoportal transposition: an effective treatment in patients with complete splanchnic venous thrombosis.

Complete venous thrombosis of the splanchnic system remains a major challenge in liver transplantation surgery. Some of these patients have been treated successfully by multivisceral transplantation. Cavoportal transposition is another alternative to treat these patients. We reviewed our single-center experience with this technique. Five patients with operatively confirmed complete splanchnic thrombosis were transplanted with the cava portal transposition technique. All survived the procedure; 60% survived long term. This technique is a useful salvage procedure in moribund patients with diffuse portal thrombosis who would otherwise rapidly succumb.

Adult↗
PubMed2005

Liver transplantation using livers from septuagenarian and octogenarian donors: an underused strategy to reduce mortality on the waiting list.

Shortage of liver grafts is the only limiting factor for application of liver transplantation and causes an increasing mortality on the waiting list. Very old donors (>70 to 80 years old) are rarely referred to transplant centers because of the assumption that these livers will not work properly. Alternatively, transplant teams may be reluctant to use these very old livers due to the risk of poor posttransplant outcome. We reviewed our experience with seven liver transplantations using very old donor livers. We found that the results in terms of graft function and patient survival are adequate. Interestingly, the majority of these donors originated from a single referring donor unit (of more than 20 units who belong to our donor network) that systematically refers all brain-dead donors to the transplant center, independent of the age of the potential donor. This implies that many of these donors are left undetected in other units. In conclusion, very old donors should be referred to transplant centers since results of transplantation with these grafts are favorable.

Age Factors↗
PubMed2005

Nodular regenerative hyperplasia, portal vein thrombosis, and avascular hip necrosis due to hyperhomocysteinaemia.

A male patient with portal hypertension, portal vein thrombosis, spontaneous splenorenal shunt formation, and encephalopathy, thought to have post-hepatitis B cirrhosis, is described. His condition deteriorated and necessitated liver transplantation. In the explant liver, nodular regenerative hyperplasia with pronounced vascular lesions both in portal venules and in arterioles was found instead of classical cirrhosis. Two years post-transplant he developed bilateral ischaemic femur head necrosis. The three disorders (portal vein thrombosis, nodular regenerative hyperplasia, and ischaemic hip necrosis) seemed to be due to a common vasculopathy induced by hyperhomocyteinaemia. Genetic studies showed that he carried a mutation in the gene encoding for formation of methylenetetrahydrofolate reductase. Treatment with folic acid combined with pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12) normalised his serum homocysteine levels.

Femur Head Necrosis↗
PubMed2005

Case report: hepatic artery pseudoaneurysm after liver transplantation: definitive treatment with a stent-graft after failed coil embolisation.

A 69-year-old woman presented with massive upper gastrointestinal bleeding owing to a ruptured hepatic pseudoaneurysm located at the surgical arterial anastomosis, 2 months after combined liver and kidney transplantation. Initially the pseudoaneurysm was successfully coiled but 3 weeks later recurrence of her symptoms occurred. Hepatic angiography revealed partial reperfusion of the coiled pseudoaneurysm; definitive treatment was performed by placement of an expanded-polytetrafluoroethylene (e-PTFE) covered coronary stent-graft, completely excluding the pseudoaneurysm. Radiological follow-up studies demonstrate a patent stent-graft functioning normally.

Aneurysm, False↗
PubMed2004

Review article: a critical comparison of drug therapies in currently used therapeutic strategies for variceal haemorrhage.

Vasoactive drugs are safe and easy to administer, and universal treatment is the first-line approach for all patients with suspected variceal bleeding. There are strong arguments that the combination of vasoactive drugs, started as soon as possible, and endotherapy later on is the best therapeutic option, particularly in cases of ongoing bleeding at the time of endoscopy. The main action of vasoactive drugs is to reduce variceal pressure. This can be achieved by diminishing the variceal blood flow and/or by increasing resistance to variceal blood flow inside the varices. Changes in variceal pressure parallel changes in portal pressure. Drugs for the treatment of variceal bleeding can therefore be assessed by measuring the changes in portal pressure, azygos blood flow and variceal pressure. Vasoactive drugs can be divided into two categories: terlipressin (Glypressin), and somatostatin and its analogues, especially octreotide. Terlipressin significantly reduces portal and variceal pressure and azygos flow, is superior to placebo in the control of variceal haemorrhage and improves mortality. It is beneficial when combined with sclerotherapy. It also has the advantage that it might preserve renal function, one of the most important factors affecting the outcome of cirrhosis. As such, terlipressin is the most potent of the various vasoactive drugs. Somatostatin significantly reduces portal and variceal pressure and azygos flow, is superior to placebo in controlling variceal haemorrhage, and improves the success of sclerotherapy. The effect of octreotide is well established for preventing the increase in portal pressure after a meal (similar to blood in the intestines) though the effect of ocreotide on variceal pressure is controversial.

Esophageal and Gastric Varices↗
PubMed2004

Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy.

BACKGROUND: The key end point for treatment efficacy in chronic hepatitis C is absence of detectable virus at six months after treatment. However, the incidence of clinical events during long term follow up of patients with sustained virological response is still poorly documented and may differ between the Eastern and Western world. AIMS: To assess clinical end points during long term follow up of European patients with a sustained virological response to interferon monotherapy. METHODS: Meta-analysis of individual patient data from eight European protocolled follow up studies of interferon treatment for chronic hepatitis C. RESULTS: A total of 286 sustained virological responders and 50 biochemical responders (detectable virus but normal alanine aminotransferase levels) were followed up for 59 months. Fifteen sustained virological responders (5.2%) had cirrhosis before treatment and 112 (39%) had genotype 1. The late virological relapse rate after five years of follow up was 4.7% (95% confidence interval (CI) 2.0-7.4) among sustained virological responders; all late relapses occurred within four years after treatment. Among sustained virological responders, the rate of decompensation after five years of follow up was 1.0% (95% CI 0.0-2.3) and none developed hepatocellular carcinoma (HCC). Survival was comparable with the general population, matched for age and sex, the standard mortality ratio being 1.4 (95% CI 0.3-2.5). Clinical outcome of patients with cirrhosis was similar to other sustained virological responders. For biochemical responders, the rates of development of decompensation and HCC during long term follow up were 9.1% (95% CI 0.5-17.7) and 7.1% (95% CI 0-15.0), respectively. CONCLUSIONS: Five year survival of European sustained virological responders was similar to the overall population, matched for age and sex. No HCCs were detected during long term follow up.

Adolescent↗
PubMed2003

Daily induction combination treatment with alpha 2b interferon and ribavirin or standard combination treatment in naive chronic hepatitis C patients. A multicentre randomized controlled trial.

The standard treatment for patients with chronic hepatitis C is a 6-12-month combination therapy with interferon alpha and ribavirin. Induction treatment could result in a faster early decline of the hepatitis C virus (HCV) load and a better response rate. Naive chronically infected HCV patients (n = 454) were randomized into two arms to receive either induction treatment with interferon alpha 2b 5 million units (MU) subcutaneously (s.c.) daily during a period of 8 weeks (arm A); or treatment with interferon alpha 2b 5 MU s.c. three times a week (TIW) for a period of 8 weeks (arm B). After week 8, interferon treatment in both arms was 3 MU s.c. TIW for a total period of 12 months. In both arms, ribavirin (1000-1200 mg orally per day) was added at week 4. Induction treatment resulted in a higher virological response at week 8 of treatment (66%vs 47%; P < 0.01). However, response at the end of treatment and at 6 months follow-up was not different (53%vs 50%, 41%vs 33%). The occurrence of adverse events and the drop-out rate were similar in both arms. Although an early virological response is observed more frequently in the induction treatment, end of treatment response and sustained responses did not differ.

Adolescent↗
PubMed2003

Oxidative breakdown of octanoic acid is maintained in patients with cirrhosis despite advanced disease.

As an octanoic acid 13CO2 breath test is frequently used to test gastric emptying of solid food, the purpose of the present study was to study whether oxidative breakdown of octanoic acid is affected by severe liver disease. The design of our study was twofold. First, cirrhotic patients (n = 82) of varying severity were compared with healthy controls (n = 17). Values of half-time, time point of maximal expiration and cumulative recovery of octanoic acid breath tests (OBT) were not significantly different between them. Secondly, cirrhotic patients (n = 10) were studied before placement of transjugular intrahepatic portosystemic shunt, 4-7 days later and 1-2 months later. Values of half-time, time point of maximal expiration and cumulative recovery of consecutive OBTs did not change significantly. The OBT may therefore be a suitable test in the future to detect delayed gastric emptying of solids in cirrhotic patients with reduced liver function and portal hypertension.

Adult↗
PubMed2002

Blood antioxidant levels in patients with alcoholic liver disease correlate with the degree of liver impairment and are not specific to alcoholic liver injury itself.

BACKGROUND: Enhanced production of reactive oxygen species may play a pathogenic role in alcoholic liver injury. AIMS: To investigate whether various antioxidant parameters in blood are affected in different stages of alcoholic liver disease and how specific the changes are relative to non-alcoholic cirrhosis. METHODS: Patients with alcohol abuse without cirrhosis (n=14), with alcoholic cirrhosis [Child-Pugh scores A (n=9), B (n=5) and C (n=18)] and with non-alcoholic cirrhosis [Child-Pugh score C (n=6)] and healthy controls (n=13) were studied. Levels of reduced glutathione and glutathione peroxidase activity in blood, erythrocytic superoxide dismutase activity and carotenoids, alpha-tocopherol and malondialdehyde in plasma were measured. RESULTS: Levels of reduced glutathione were significantly decreased in Child-Pugh score C cirrhotics, alcoholic or not in origin, whereas oxidized glutathione and glutathione peroxidase activity were not affected. Superoxide dismutase activity and alpha-tocopherol levels were not significantly different in the various groups. Carotenoid levels were significantly lower in alcoholic cirrhotics (Child-Pugh score C) vs. controls. Malondialdehyde levels were elevated only in cirrhotics Child-Pugh score C, alcoholic or non-alcoholic. CONCLUSIONS: Levels of reduced glutathione and malondialdehyde reflect the degree of liver impairment, more than the relation with alcohol intake. Decreases in several antioxidant levels are not specific to alcoholic liver injury.

Adult↗
PubMed2002

A multicentre, randomized study to evaluate the safety and efficacy of histamine dihydrochloride and interferon-alpha-2b for the treatment of chronic hepatitis C.

Interferon- (IFN-)alpha is currently the standard of care treatment for patients with chronic hepatitis C virus (HCV) infection. A significant part of the benefit of IFN-alpha in chronic hepatitis C is believed to be related to the activation of lymphocytes such as T cells and natural killer (NK) cells, which participate in the elimination of infected cells. Histamine dihydrochloride (HDC) has been shown to potentiate the IFN-alpha-induced activation of T cells and NK cells by a mechanism that involves the protection of these lymphocytes against oxygen radical-induced functional inhibition and apoptosis. This study was designed to examine the efficacy and safety of HDC in combination with IFN-alpha-2b in treatment-naïve patients with chronic HCV infection. All patients received IFN-alpha-2b, 3 MIU, three times weekly via subcutaneous injection, and were randomized to one of four HDC regimens (1 mg of either: once a day, three times a week; once a day, five times a week; twice a day, three times a week or; twice a day, five times a week). The doses of HDC in combination with IFN-alpha-2b resulted in sustained viral response rates ranging from 31% to 38%. Sustained biochemical response rates ranged from 28% to 41% across the four treatment groups. Patients infected with HCV genotype 1, and those with high baseline viral levels, which are characteristics associated with poor prognosis, had sustained virologic response rates ranging from 18% to 42% and 15% to 39%, respectively. Combination treatment was generally well tolerated. We propose that the potential benefit of HDC + IFN therapy for chronic HCV infection should be the focus of further investigation.

Adult↗
PubMed2002

In vivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats.

BACKGROUND: Portal hypertension in cirrhosis results from enhanced intrahepatic resistance to an augmented inflow. The former is partly due to an imbalance between intrahepatic vasoconstriction and vasodilatation. Enhanced endothelin-1 and decreased activity of hepatic constitutive endothelial nitric oxide synthase (NOS 3) was reported in carbon tetrachloride (CCl(4)) cirrhotic rat liver. AIMS: To study whether an increase in hepatic NOS 3 could be obtained in the CCl(4) cirrhotic rat liver by in vivo cDNA transfer and to investigate a possible effect on portal pressure. METHODS: Hepatic NOS 3 immunohistochemistry and western blotting were used to measure the amount of NOS 3 protein. Recombinant adenovirus, carrying cDNA encoding human NOS 3, was injected into the portal vein of CCl(4) cirrhotic rats. Cirrhotic controls received carrier buffer, naked adenovirus, or adenovirus carrying the lac Z gene. RESULTS: NOS 3 immunoreactivity and amount of protein (western blotting) were significantly decreased in CCl(4) cirrhotic livers. Following cDNA transfer, NOS 3 expression and the amount of protein were partially restored. Portal pressure was 11.4 (1.6) mm Hg in untreated cirrhotic (n=9) and 11.8 (0.6) in lac Z transfected (n=4) cirrhotic rats but was reduced to 7.8 (1.0) mm Hg (n=9) five days after NOS 3 cDNA transfer. No changes were observed in systemic haemodynamics, in liver tests or urinary nitrates, or in NOS 3 expression in lung or kidney, indicating a highly selective transfer. CONCLUSIONS: NOS 3 cDNA transfer to cirrhotic rat liver is feasible and the increase in hepatic NOS 3 leads to a marked decrease in portal hypertension without systemic effects. These data indicate a major haemodynamic role of intrahepatic NOS 3 in the pathogenesis of portal hypertension in CCl(4) cirrhosis.

Animals↗
PubMed2001

Variceal band ligation in the management of bleeding oesophageal varices: an overview.

Endotherapy is, in many centres, still the cornerstone in the first-line approach of a patient with variceal haemorrhage. Since the introduction of the multiband ligation, devices, active variceal bleeding is controlled as efficiently as with sclerotherapy, and variceal eradication can be obtained much faster with fewer treatment-related complications. This observation is now supported by several randomized trials. Combining sclerotherapy with band ligation has no additional effect and can even increase the number of side-effects. Therefore, multiband ligation can be considered as a first-step treatment for bleeding oesophageal varices.

Esophageal and Gastric Varices↗