Hepatitis: Stärkel P

Colle I, Adler M, Brenard R, Henrion J, Langlet P, Michielsen P, Orlent H, Reynaert H, Sprengers D, Stärkel P, Van Damme P, Verslype C, Delwaide J, Anonymous00199. · Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, De Pintelaan 185, 9000 Gent, Belgium. · Acta Gastroenterol Belg. · Pubmed #18330099 No free full text.

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Stärkel P. · Department of Gastroenterology, St. Luc University Hospital, Av. Hippocrate 10, 1200 Brussels, Belgium. · Gut. · Pubmed #18334658 No free full text.

This publication has no abstract.

Verslype C, Michielsen P, Adler M, Orlent H, Sprengers D, Delwaide J, D'heygere F, Langlet P, Brenard R, Colle I, Reynaert H, Stärkel P, Henrion J, Anonymous00136. · Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium. · Acta Gastroenterol Belg. · Pubmed #16268417 No free full text.

Abstract: Infection with the hepatitis C virus (HCV) represents an important public health problem and is a leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is a heterogeneous disease. Many patients have mild disease at presentation but not all of them will develop advanced liver disease. However, the identification of these patients with mild hepatitis C who will show progressive disease is difficult and is based on histological criteria and the assessment of co-factors (age, alcohol intake, steatosis). In addition, serum transaminases that are persistently normal on several occasions during 18 months may point to a more benign course. Patients with mild hepatitis C should not be excluded "a priori" from the possibility of being treated, as treatment with pegylated interferon and ribavirin is safe and effective in this group. Overall, the decision to initiate therapy should be individualized and based on the severity of the disease by liver biopsy, the potential of serious side effects, the probability of response and the motivation of the patient.

Robaeys G, Nevens F, Stärkel P, Colle I, Van Eyken P, Bruckers L, Van Ranst M, Buntinx F. · ZOL Campus St.-Jan, Genk, Belgium. · Transplant Proc. · Pubmed #19328933 No free full text.

Abstract: BACKGROUND: End-stage liver disease due to hepatitis C viral (HCV) infection is the most common reason for liver transplantation. One of the major risk factors for infection with HCV is intravenous drug use (IVDU). The pretransplantation characteristics and outcome of liver transplantation in patients with chronic hepatitis C (CHC) infected after IVDU are poorly known. METHODS: We performed a retrospective cohort study in patients with CHC who underwent liver transplantation between 1998 and 2002 in Belgium. Seven patients with and 60 patients without a history of IVDU were compared. RESULTS: Patients with CHC infected after IVDU were primarily men, significantly younger, and affected more by genotype 2 or 3. There was no relapse in substance use. No patients required a second transplantation or developed surgical complications. Progression to fibrosis in the posttransplantation period seemed to be slower. Graft and patient survival, and compliance were similar in both groups. CONCLUSIONS: Compared with patients in the non-IVDU group, patients with CHC infected after IVDU in complete remission have the same compliance, and patient and graft survival after liver transplantation. Therefore, patients with IVDU should not be excluded for liver transplantation because of HCV-induced cirrhosis.

Stärkel P, Saeger CD, Leclercq I, Horsmans Y. · Department and Laboratory of Gastroenterology, St Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium. · Lab Invest. · Pubmed #17318196 links to  free full text

Abstract: In vitro and animal data suggest that hepatitis C virus (HCV) proteins might interfere with signal transducer and activator of transcription 3 (Stat3) signaling. It remains unknown whether Stat3 influences the apoptotic-proliferation balance and how this may relate to liver fibrosis progression in HCV-infected patients. We assessed Stat3 expression and DNA-binding as well as expression of its regulators protein inhibitor of activated Stat 3 (Pias3) and suppressor of cytokine signaling 3 (Socs3) in 65 HCV-infected livers at various stages of fibrosis progression. We then determined the level of expression of the proliferation markers cyclin D1 and proliferating cell nuclear antigen (PCNA) in conjunction with pro- and antiapoptotic markers Bax and Bcl-2 in the same liver samples. With the onset of fibrosis, Stat3 DNA-binding decreased and became almost undetectable in livers with bridging fibrosis or cirrhosis. Stat3 DNA-binding inversely correlated with Pias3 expression and Stat3-Pias3 interaction increased with the progression of fibrosis. Cyclin D1 and PCNA in hepatocytes decreased dramatically during fibrosis progression and levels highly correlated with Stat3 expression. In addition, an antiapoptotic profile due to upregulation of Bcl-2 principally in infiltrating inflammatory cells was observed with progressing fibrosis. In conclusion, fibrosis progression is characterized by a continuous decline in Stat3 DNA-binding activity related to overexpression and progressive interaction of Pias3-Stat3. The decrease in Stat3 activity correlated with reduced hepatocytes proliferation and a positive antiapoptotic balance in infiltrating inflammatory cells that are known mediators of cell damage in HCV.

Leclercq IA, Lebrun VA, Stärkel P, Horsmans YJ. · Laboratory of Gastroenterology, Faculty of Medicine, Université Catholique de Louvain (UCL), Brussels, Belgium. · Lab Invest. · Pubmed #17075577 links to  free full text

Abstract: Hepatic insulin resistance is associated with hepatic steatosis and is thought to play an important role in the pathogenesis of steatohepatitis. Using a murine model of steatohepatitis (mice fed a diet deficient in methionine and choline-MCD diet), we tested the effects of the insulin-sensitising, PPARgamma agonist drug pioglitazone (PGZ) on systemic and intrahepatic insulin sensitivity and on liver pathology. Compared to controls, mice fed the MCD diet develop a significant steatohepatitis, have enhanced glucose tolerance and enhanced systemic response to insulin. PGZ did not affect the systemic insulin sensitivity in control or MCD-fed mice as assessed in vivo by intraperitoneal glucose or insulin dynamic tests. However, PGZ prevented hepatic fat accumulation and steatohepatitis induced by the MCD diet. This effect was associated with an increased mass of adipose tissue and increased expression and release of adiponectin, while hepatic acyl co-enzyme A oxidase and acyl-co-enzyme A carboxylase, regulating hepatic beta-oxidation of fatty acid, remained unchanged. Steatohepatitis in MCD-diet-fed mice was associated with intrahepatic insulin resistance as shown by a reduced phosphorylation of hepatic insulin receptor, and Akt in response to an insulin stimulus. PGZ to MCD-fed mice restored the activation of the insulin receptor and of the Akt pathway in response to insulin. In conclusion, PGZ alleviates steatosis and steatohepatitis induced by the MCD diet, an effect associated with correction of intrahepatic insulin resistance.

Stärkel P, Stoffel M, Lerut J, Horsmans Y. · Department of Gastroenterology, St. Luc University Hospital, Brussels, Belgium. · Liver Transpl. · Pubmed #16184571 links to  free full text

Abstract: Strategies using lamivudine and hepatitis B immunoglobulins (HBIg) for prevention of hepatitis B virus (HBV) reinfection after liver transplantation (LT) are expensive since life-long treatment is needed. We evaluated the possibility to obtain protective hepatitis B surface antigen (HBsAg) antibody (anti-HBs) titers after LT and to discontinue HBIg prophylaxis after a reinforced course of vaccination against HBV using an experimental adjuvant HBsAg / AS04 vaccine (GlaxoSmithKline Biologicals [GSK], Rixensart, Belgium) in patients transplanted for hepatitis B. Fifteen LT patients on stable low-level immunosuppression were vaccinated with a double dose of the vaccine at 0, 1, 2, 6, and 12 months: 5 patients were transplanted for nonviral diseases and 10 patients were transplanted for HBV on HBIg monotherapy. HBIg were continued during baseline vaccination (0, 1, and 2 months) and when anti-HBs titers determined every 6 weeks dropped below 150 IU/L. Overall follow-up was 18 months. Sustained long-term response to vaccination was defined as anti-HBs titers >500 IU/L without further need for HBIg administration during a follow-up period of at least 12 months. Overall sustained response to vaccination was 53% (8 / 15 patients); 80% (4 / 5 patients) in the nonviral disease group and 40% (4 / 10 patients) in the HBV group (2 /2 fulminant and 2/8 chronically infected patients) developed a sustained long-term response and were completely free of HBIg at the end of the 18-month follow-up. No HBV recurrence, rejection episodes, or side effects occurred during the follow-up. In conclusion, protective anti-HBs titers were obtained in a substantial number of LT patients following a reinforced course of HBV vaccination with vaccines containing new immunostimulating adjuvants. Vaccination seems well tolerated and safe and allows long-term discontinuation of HBIg.

Stärkel P, De Saeger C, Leclercq I, Strain A, Horsmans Y. · Department and Laboratory of Gastroenterology, St Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium. · J Hepatol. · Pubmed #16098628 No free full text.

Abstract: BACKGROUND/AIMS: In vitro and animal data suggest that alcohol and hepatitis C virus (HCV) proteins might interfere with Stat3 signaling, a potential regulator of liver cell apoptosis and proliferation. METHODS: We assessed Stat3 expression, activity and the apoptotic-proliferation balance in end-stage HCV and alcoholic liver disease (ALD) in man. Explanted livers of HCV and ALD patients were compared to normal and primary biliary cirrhosis (PBC) livers. RESULTS: Although Stat3 expression and phosphorylation was not altered in HCV and ALD cirrhosis, Stat3 DNA-binding was not detected in all ALD and most HCV samples. Deficient Stat3 DNA-binding was associated with high Pias3 expression, but not with increased Socs3 levels. Bcl-2 was up-regulated in HCV and ALD together with decreased Caspase3 activity. Compared to base-line cell proliferation in normal donor livers, HCV cirrhosis showed a marked reduction in cyclin D1 and PCNA, whereas both markers were only slightly reduced in ALD. CONCLUSIONS: End-stage HCV and ALD cirrhosis is characterized by impaired Stat3 DNA-binding possibly through up-regulation of Pias3. Therefore, impaired activation of Stat3 target genes might contribute to disturbed liver regeneration and repair. The attempt in cirrhotic livers to favor anti-apoptotic over pro-apoptotic pathways is not sufficient to compensate for the low cellular proliferation rates.

Stärkel P, Horsmans Y, Geubel A, Ciccarelli O, Goubau P, Rahier J, Lerut J. · Department of Gastroenterology, Liver transplant program, St. Luc University Hospital, Université Catholique de Louvain, 1200 Brussels, Belgium. · J Hepatol. · Pubmed #11690717 No free full text.

Abstract: BACKGROUND/AIMS: Patients with end-stage liver disease due to chronic hepatitis B infection in whom a YMDD escape hepatitis B virus (HBV) mutant has emerged under lamivudine treatment are generally denied liver transplantation (OLT). METHODS: We report the case of a male patient who was started on prophylactic treatment with lamivudine in the context of recurrent episodes of HBV reactivation during high dose immunosuppressive therapy for relapsing severe pulmonary sarcoidosis. RESULTS: Following the emergence of a YMDD escape mutant virus under lamivudine treatment, he developed subacute liver failure requiring liver transplantation. The patient was treated with a combination of intravenous hepatitis B immune globulin (HBIG) which was started perioperatively and also continued lamivudine after OLT. Twelve months after OLT, there was no evidence of HBV reinfection of the liver graft with the use of HBIG and lamivudine. CONCLUSIONS: This observation suggests that emergence of the YMDD mutation is not a contra-indication to OLT, providing adequate immunoprophylaxis using HBIG and lamivudine combination therapy.