Publications (11)45.4 Total impact
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Article: Hepatitis A virus infection suppresses hepatitis C virus replication and may lead to clearance of HCV.
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ABSTRACT: The significance of hepatitis A virus (HAV) super-infection in patients with chronic hepatitis C had been a matter of debate. While some studies suggested an incidence of fulminant hepatitis A of up to 35%, this could not be confirmed by others. We identified 17 anti-HCV-positive patients with acute hepatitis A from a cohort of 3170 anti-HCV-positive patients recruited at a single center over a period of 12 years. Importantly, none of the anti-HCV-positive patients had a fulminant course of hepatitis A. HCV-RNA was detected by PCR in 84% of the anti-HCV-positive/anti-HAV-IgM-negative patients but only in 65% of anti-HCV-positive patients with acute hepatitis A (p=0.03), indicating suppression of HCV replication during hepatitis A. Previous HAV infection had no effect on HCV replication. After recovery from hepatitis A, an increased HCV replication could be demonstrated for 6 out of 9 patients with serial quantitative HCV-RNA values available while 2 patients remained HCV-RNA negative after clearance of HAV throughout follow-up of at least 2 years. HAV super-infection is associated with decreased HCV-RNA replication which may lead to recovery from HCV in some individuals. Fulminant hepatitis A is not frequent in patients with chronic hepatitis C recruited at a tertiary referral center.Journal of Hepatology 01/2007; 45(6):770-8. · 9.26 Impact Factor -
Article: Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance.
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ABSTRACT: The adipokine resistin has been implicated in obesity and insulin resistance. Liver cirrhosis is associated with decreased body fat mass and insulin resistance. We determined plasma resistin levels in 57 patients with cirrhosis, 13 after liver transplantation, and 30 controls and correlated these with hemodynamic as well as hepatic and systemic metabolic parameters. Patients with cirrhosis had, dependent on the clinical stage, an overall 86% increase in resistin levels (P < 0.001) with hepatic venous resistin being higher than arterial levels (P < 0.001). Circulating resistin was significantly correlated with plasma TNF-alpha levels (r = 0.62, P < 0.001). No correlation was observed between resistin and hepatic hemodynamics, body fat mass, systemic energy metabolism, and the degree of insulin resistance. However, plasma resistin in cirrhosis was negatively associated with hepatic glucose production (r = -0.47, P < 0.01) and positively with circulating free fatty acids (FFA; r = 0.40, P < 0.01) and ketone bodies (r = 0.48, P < 0.001) as well as hepatic ketone body production (r = 0.40, P < 0.01). After liver transplantation, plasma resistin levels remained unchanged, whereas insulin resistance was significantly improved (P < 0.01). These data provide novel insights into the role of resistin in the pathophysiological background of a catabolic disease in humans and also indicate that resistin inhibition may not represent a suitable therapeutic strategy for the treatment of insulin resistance and diabetes in patients with liver cirrhosis.AJP Endocrinology and Metabolism 09/2006; 291(2):E199-206. · 4.75 Impact Factor -
Article: Elevated circulating adiponectin levels in liver cirrhosis are associated with reduced liver function and altered hepatic hemodynamics.
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ABSTRACT: Adiponectin is a novel adipocytokine negatively correlated with parameters of the metabolic syndrome, such as body mass index (BMI), body fat mass (BFM), and circulating insulin levels. Furthermore, metabolic actions directly on the liver have been described. The aim of the present study was to characterize circulating adiponectin levels, hepatic turnover, and the association of adiponectin with key parameters of hepatic as well as systemic metabolism in cirrhosis, a catabolic disease. Circulating adiponectin levels and hepatic turnover were investigated in 20 patients with advanced cirrhosis. Hepatic hemodynamics [portal pressure, liver blood flow, hepatic vascular resistance, indocyanine green (ICG) half-life], body composition, resting energy expenditure, hepatic free fatty acids (FFA) and glucose turnover, and circulating levels of hormones (catecholamines, insulin, glucagon) and proinflammatory cytokines (IL-1beta, TNF-alpha, IL-6) were also assessed. Circulating adiponectin increased dependently on the clinical stage in cirrhosis compared with controls (15.2 +/- 1.7 vs. 8.2 +/- 1.1 microg/ml, respectively, P < 0.01), whereas hepatic extraction decreased. Adiponectin was negatively correlated with parameters of hepatic protein synthesis (prothrombin time: r = -0.62, P = 0.003; albumin: r = -0.72, P < 0.001) but not with transaminases or parameters of lipid metabolism. In addition, circulating adiponectin increased with portal pressure (r = 0.67, P = 0.003), hepatic vascular resistance (r = 0.60, P = 0.008), and effective hepatic blood flow (ICG half-life: r = 0.69, P = 0.001). Adiponectin in cirrhosis was not correlated with BMI, BFM, parameters of energy metabolism, insulin levels, hepatic FFA and glucose turnover, and circulating proinflammatory cytokines. These results demonstrate that 1) adiponectin plasma levels in cirrhosis are significantly elevated, 2) the liver is a major source of adiponectin extraction, and 3) adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function and altered hepatic hemodynamics.AJP Endocrinology and Metabolism 08/2004; 287(1):E82-9. · 4.75 Impact Factor -
Article: Alterations in glucose metabolism associated with liver cirrhosis persist in the clinically stable long-term course after liver transplantation.
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ABSTRACT: With increasing long-term survival rates after orthotopic liver transplantation (OLT), metabolic alterations complicating the clinical course, such as diabetes mellitus (DM), become increasingly important. Liver cirrhosis is associated with severe alterations in glucose metabolism. However, it is currently unclear whether these changes are reversed by successful OLT. We therefore characterized glucose metabolism in patients with liver cirrhosis and normal fasting glucose levels before OLT (cir), in the clinically stable long-term course after OLT (OLT), and control subjects (con) using oral glucose tolerance tests (cir = 100, OLT = 62, con = 32), euglycemic-hyperinsulinemic clamps (cir = 10, OLT = 27, con = 14), and positron emission tomography (PET) scan analysis with 18F-fluorodeoxyglucose (FDG) as a tracer (cir = 7, OLT = 7, con = 5). Fasting insulin and C-peptide levels were significantly elevated in patients with liver cirrhosis compared with both control subjects (P <.001) and patients after OLT (P <.001). After OLT, insulin was normalized, whereas C-peptide remained elevated (P < 0.01). In the patients with liver cirrhosis, 27% had a normal glucose tolerance, 38% had an impaired glucose tolerance (IGT), and 35% were diabetic. After OLT, 34% had a normal glucose tolerance, 29% an IGT, and 37% were diabetic. Comparison of the same patients before and after OLT demonstrated that IGT or diabetes before OLT was the major risk factor for these conditions after OLT, which was independent of either immunosuppression (cyclosporine vs FK506) or low-dose prednisolone. Total glucose uptake was reduced in patients with liver cirrhosis to less than half the values in control subjects (21.2 +/- 2.8 vs 43.7 +/- 2.4 micromol/kg/minute, respectively, P <.001), whereas patients after OLT showed intermediate values (35.7 +/- 1.4 micromol/kg/minute, P < 0.05 vs con, P < 0.01 vs cir). This difference was caused by a reduction in nonoxidative glucose metabolism in patients with liver cirrhosis compared with control subjects (7.4 +/- 1.9 vs 28.7 +/- 1.8 micromol/kg/minute, respectively, P <.01) and patients after OLT (20.1 +/- 1.4 micromol/kg/minute, P < 0.05 vs con and OLT). In the PET study, skeletal muscle glucose uptake was significantly reduced in patients with liver cirrhosis compared with control subjects (3.5 +/- 0.4 vs 11.8 +/- 2.5 micromol/100g/minute, respectively, P <.05). After OLT, muscle glucose uptake improved compared with patients with liver cirrhosis (5.9 +/- 1.0 micromol/100g/minute, P <.05) but remained significantly lower than in control subjects (P <.05). In conclusion, these results demonstrate that preexisting IGT or diabetes are the major risk factors for IGT and diabetes after OLT. This finding was independent of the immunosuppressive medication. The peripheral insulin resistance in cirrhosis is characterized by a decrease in nonoxidative glucose disposal that is improved, but not normalized, after OLT.Liver Transplantation 08/2004; 10(8):1030-40. · 3.39 Impact Factor -
Article: Altered alanine plasma levels despite normalized hepatic alanine extraction in the long-term course after liver transplantation.
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ABSTRACT: The amino acid (AA) metabolism in cirrhosis is deranged, reflected by an altered plasma AA profile. Alanine is a unique AA with predominant production by muscle and the highest hepatic extraction rate. We studied circulating levels and hepatic alanine extraction in 52 patients with advanced cirrhosis, 16 stable patients more than 6 months after orthotopic liver transplant (OLT), and 50 controls. In addition, hepatic hemodynamics (portal pressure, hepatic blood flow, and splanchnic percent indocyanine green extraction) and parameters of hepatic metabolism (splanchnic oxygen uptake and splanchnic glucose production) were assessed. Circulating alanine levels decreased independently of the clinical stage in cirrhosis (262+/-15 micromol/L vs. 330+/-14 micromol/L in controls, P<0.001) and decreased even further after OLT (209+/-10 micromol/L, P<0.001). Hepatic alanine extraction decreased dependently on the clinical stage in cirrhosis (59+/-7 micromol/min) and was normalized after OLT (100+/-10 micromol/min, P<0.001), indicating that decreased plasma alanine levels in OLT patients are the result of changes in extrahepatic metabolism. Hepatic alanine extraction correlated with splanchnic oxygen uptake (r=0.64, P<0.001) and hepatic glucose production (r=0.65, P<0.001). These results demonstrate that significant alterations in muscular AA metabolism persist even in the clinically stable long-term course after OLT when the hepatic AA metabolism is normalized.Transplantation 03/2003; 75(6):804-10. · 4.00 Impact Factor -
Article: Successful treatment of fibrosing cholestatic hepatitis using adefovir dipivoxil in a patient with cirrhosis and renal insufficiency.
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ABSTRACT: Fibrosing cholestatic hepatitis is a deleterious manifestation of hepatitis B virus infection in immunocompromised patients. Without treatment, this condition is usually fatal within weeks of onset. Liver retransplantation has not been successfully performed to date, and treatment intervention was generally unsuccessful before the advent of adefovir dipivoxil. However, concerns have been expressed about the use of this agent in patients who are renally compromised. A 40-year-old liver transplant recipient with hepatitis B virus reinfection, resistance to lamivudine, and fibrosing cholestatic hepatitis complicated by terminal renal impairment and spontaneous bacterial peritonitis was treated with adefovir dipivoxil 10 mg after every dialysis. Since initiating treatment with adefovir dipivoxil 10 mg, a dramatic virologic and clinical improvement was observed in this patient. The patient returned to work full-time within 6 months of starting adefovir dipivoxil without the need for liver retransplantation. Serum HBV DNA (Amplicor HBV; Roche Diagnostics, Basle, Switzerland) decreased by 6 log(10) copies/mL and became negative (< 400 copies/mL) within 8 weeks of treatment and remains negative at the last available assessment. The patient continues to require renal dialysis, but is generally well. Creatinine clearance improved from 8 mL/min to 16 mL/min during the course of treatment. No adverse events related to adefovir dipivoxil were observed. Adefovir dipivoxil resulted in significant clinical improvement in this patient with hepatitis B virus-induced fibrosing cholestatic hepatitis, despite the presence of renal impairment and lamivudine resistance.Liver Transplantation 02/2003; 9(2):191-6. · 3.39 Impact Factor -
Article: Hepatic amino-acid metabolism in liver cirrhosis and in the long-term course after liver transplantation.
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ABSTRACT: The aim of this study was to investigate the impact of orthotopic liver transplantation (OLT) on plasma levels and splanchnic turnover of key amino acids for muscular (branched-chain amino acids: BCAAs) and hepatic metabolism (aromatic amino acids (AAAs) and methionine) in 48 patients with cirrhosis, 14 patients after OLT, and 46 controls. Also, hepatic amino-acid supply and resting energy expenditure were measured. BCAA levels (no hepatic uptake) decreased in cirrhosis (P<0.001) and were improved, although not normalized, after OLT (P<0.001). AAA and methionine levels were raised in cirrhosis (P<0.001) and normalized after OLT (P<0.001). Hepatic supply of these amino acids increased in patients graded Child B and C and decreased significantly after OLT. Splanchnic uptake of AAAs and methionine increased significantly in Child-B and decreased in Child-C patients. After OLT, splanchnic extraction of AAAs and methionine was as in Child A. Circulating AAAs and methionine correlated with indocyanine-green half-life (r=0.71, P<0.001) and resting energy expenditure (r=0.50, P<0.001), indicating that levels of circulating AAAs and methionine in cirrhosis are determined by hepatic and extra-hepatic metabolic factors. This study demonstrates persistent changes in muscular metabolism of BCAAs after OLT, while the hepatic amino-acid metabolism is normalized due to (1) a significant reduction in the rate of peripheral proteolysis, and (2) improved liver function compared with that in patients with cirrhosis.Transplant International 01/2003; 16(1):1-8. · 2.92 Impact Factor -
Article: Lamivudine transiently reduces viral load and improves liver function in liver transplant recipients with fibrosing cholestatic hepatitis.
The American Journal of Gastroenterology 04/2002; 97(3):777-8. · 7.28 Impact Factor -
Article: Plasma amino acids in cirrhosis and after liver transplantation: influence of liver function, hepatic hemodynamics and circulating hormones.
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ABSTRACT: Liver cirrhosis is characterized by substantial changes in amino acid (AA) metabolism, resulting in a deranged plasma AA profile. To investigate the effect of liver transplantation (OLT), we studied arterial AA profiles in 52 patients with advanced cirrhosis, 16 stable patients over 6 months after OLT and 48 controls. Changes in AA levels were correlated with portal pressure (hepatic venous pressure gradient), functional hepatic blood flow (indocyanine green extraction) and circulating hormone levels (catecholamines, insulin, C-peptide). Fourteen of 18 measured AA were significantly altered in cirrhosis and 11 of 18 remained abnormal after OLT compared with controls. Aromatic AA (AAA) and methionine were elevated in cirrhosis (p < 0.001 each), increasing with disease stage, and normalized after OLT. Branched chain AA (BCAA) levels were decreased in cirrhosis (p < 0.001) and were unrelated to disease stage. After OLT, BCAA levels remained subnormal (p < 0.01), although higher than in cirrhosis (p < 0.001). AAA levels increased with decreasing functional hepatic blood flow (r = -0.67; p < 0.001) and increasing portal pressure (r = 0.59; p < 0.001). BCAA levels decreased with increasing catecholamine (r = - 0.54, p < 0.001) and insulin levels (r = - 0.40, p = 0.001). We conclude that despite normal liver function, AA metabolism is only partially normalized after OLT. AAA levels mainly determined by hepatic metabolic function and functional liver blood flow return to normal, while BCAA levels remain subnormal, indicating persistent changes in muscular AA metabolism after OLT.Clinical Transplantation 02/2002; 16(1):9-17. · 1.67 Impact Factor -
Article: Improvement of Acute and Chronic Renal Dysfunction in Liver Transplant Patients After Substitution of Calcineurin Inhibitors By Mycophenolate Mofetil
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ABSTRACT: Background. Renal dysfunction caused by treatment with the calcineurin inhibitors (CNI) is a major problem in the long-term course after liver transplantation. Patients. In 22 liver graft recipients with renal dysfunction and stable graft function between 3 weeks and 12 years after transplantation, CNI were substituted by MMF at a final dose of 1.5-3 g/day between October 1996 and October 1998. Methods. In a prospective non-randomized study, the development of renal function, the side effects of MMF medication, and the stability of liver function were analyzed for a mean follow-up of 15 months. Results. (1) MMF was withdrawn in four patients for major side effects between 1 and 7 months after study entry; eight patients had minor side effects. (2) Six months after study entry, renal function had improved in 17 of the 22 study patients; mean serum creatinine ± SD (μmol/L) was 201±77 at entry and 153±65 after 3 months (P <0.001). (3) Improvement occurred in 11 of 15 patients with creatinine elevation ≥12 months and in 6 of 6 patients with creatinine elevation ≤6 months. (4) One patient developed transient liver dysfunction and a second required retransplantation for progressive cholestasis but without signs of rejection. Conclusions. In patients who undergo liver transplantation, substitution of CNI by MMF leads to improvement of acute as well as chronic renal dysfunction in most cases. Side effects of MMF may be limiting in some patients, and the immunological consequences remain to be studied.Transplantation 05/2000; 69(9):1886-1890. · 4.00 Impact Factor -
Article: Seltene Erstmanifestation und Differentialdiagnose einer primär sklerosierenden Cholangitis
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ABSTRACT: □ HintergrundDie Erstdiagnose einer primärsklerosierenden Cholangitis wird meist bei Männern mittleren Lebensalters gestellt, die zudem an entzündlichen Darmerkrankungen leiden. □ Eigener FallEine junge, bisher gesunde Frau wird wegen eines plötzlich aufgetretenen Ikterus mit hohen Transaminasen und positiver Hepatitis-B-Virus-Serologie aufgenommen. Die bildgebenden Verfahren zeigen auffallende, fokale Raumforderungen der Leber. Nach differentialdiagnostischem Ausschluß einer akuten Virushepatitis und eines primären oder sekundären Lebertumors als Ursache der Symptomatik wird die Diagnose einer primär sklerosierenden Cholangitis gestellt. □ SchlußfolgerungDie Differentialdiagnose einer primär sklerosierenden Cholangitis sollte auch bei untypischer Präsentation bedacht werden. □ BackgroundPrimary sclerosing cholangitis is most often diagnosed in middleaged men who are suffering from inflammatory bowel diseases. □ Case ReportA young, previously healthy woman presents with icterus of acute onset, high transaminases and positive hepatitis B virus serology. Ultrasound and nuclear magnetic resonance images demonstrate multiple liver tumors. After acute viral hepatitis as well as primary or secondary malignant liver tumors have been excluded as underlying diseases, diagnosis of primary sclerosing cholangitis is made. □ ConclusionDifferential diagnosis of primary sclerosing cholangitis should also be considered in cases with untypical primary presentation.04/1997; 92(7):452-456.
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2002–2004
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Medizinische Hochschule Hannover
- Department of Gastroenterology, Hepatology and Endocrinology
Hannover, Lower Saxony, Germany
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