1289 CHOLESTASIS-ASSOCIATED PRURITUS TREATED WITH UVB PHOTOTHERAPY: REPORT OF 13 CASES

POSTERS 1288 INCREASED EXPRESSION OF TRANSCRIPTION FACTOR FOXO3A AND PROAPOPTOTIC PROTEIN BIM IN PRIMARY BILIARY CIRRHOSIS BUT NOT IN PRIMARY SCLEROSING CHOLANGITIS J. Czyszek1 , M. Milkiewicz1 , E. Elias2 , P. Milkiewicz3 . 1 Medical Biology Laboratory, Pomeranian Medical University, Szczecin, Poland; 2 Liver Unit, Queen Elizabeth Hospital, Birmingham, UK; 3 Liver Unit, Pomeranian Medical University, Szczecin, Poland E-mail: [email protected] Background: Apoptosis, with subsequent aberrant expression of pyruvate dehydrogenase complex (PDC-E2) on cell surface has been postulated to play an important role in the pathogenesis of Primary Biliary Cirrhosis (PBC). More recently, a particular feature of cholangiocytes that leads to prolonged exposure of an intact immunoreactive PDC-E2 to the immune system within apoptotic blebs has been described. Whether this effect is related to specific for PBC, impaired regulation of apoptotic pathways remains to be established. The transcription factor FoxO3a is known to be an upstream activator of Bim (Bcl-2-interacting mediator of cell death) protein which is involved in cellular apoptosis. The aim of the study was to analyze gene expression of transcription factor FoxO3a and Bim in livers of patients with earlyPBC, end-stage PBC, end-stage Primary Sclerosing Cholangitis (PSC) and control liver tissue. Methods: Total RNA was isolated from liver tissues obtained either during routine percutaneous liver biopsies (early-PBC n = 21) or from explanted livers from end-stage diseases (PBC n = 19; PSC n = 8). Liver tissues from large margin resections of HCC were used as controls (n = 19). Gene expressions were evaluated using Quantitative Taq Man real time PCR analysis. Protein levels (not measured in early PBC) were assessed with Western Blot. The study protocol was conformed to the ethical guidelines of the 1975 Declaration of Helsinki by local ethics committee and written consents were obtained from all included subjects. Results: As compared to controls, expression of FoxO3a mRNA showed statistically significant increase in both early-PBC (2.2-fold increase; p = 0.006) and end-stage PBC (4.3-fold increase; p = 0.003). Expression of FoxO3a was significantly higher in patients with more advanced fibrosis (F0–2 vs F3–4, p = 0.042). Also, a substantial up-regulation of Bim mRNA was observed both in early-PBC (8fold increase vs. controls; p = 0.045). and end-stage PBC (8.2-fold increase vs. controls; p = 0.003). Correspondingly, levels of Foxo3a and Bim proteins were significantly enhanced in end-stage PBC. Levels of FoxO3a and Bim mRNAs in PSC were not significantly different from controls. Conclusions: Up-regulation of FoxO3a and Bim observed in PBC but not in PSC may support an involvement of apoptotic pathways in the pathogenesis of this condition. 1289 CHOLESTASIS-ASSOCIATED PRURITUS TREATED WITH UVB PHOTOTHERAPY: REPORT OF 13 CASES S. Decock1 , R. Roelandts2 , D. Cassiman1 , J. Fevery1 , W. Laleman1 , W. Van Steenbergen1 , C. Verslype1 , F. Nevens1 . 1 Hepatology, 2 Dermatology, University Hospitals Leuven, Leuven, Belgium E-mail: sofi[email protected] Introduction: Intractable pruritus is a frequent and disabling complication of cholestasis. The management of cholestasisassociated pruritus remains challenging. Especially the pruritus related to ischemic strictures after liver transplantation is difficult to treat and can be one of the reasons for retransplantation. AASLD guidelines recommend first line therapy of cholestasis-associated pruritus with cholestyramin, second line therapy with rifampicin and third line therapy with opiate antagonists. Ultraviolet B (UVB) phototherapy is successfully used to treat pruritus in patients with atopic dermatitis, aquagenic pruritus, systemic mastocytosis, S508

cutaneous T-cell lymphoma, chronic renal failure, . . . . We report our experience on treatment of cholestasis-associated pruritus with UVB phototherapy. Methods: Thirteen patients (3 men, 10 women, mean age 52 years, range 28–73 years) with pruritus from cholestatic liver disease were treated with UVB phototherapy. Six patients had a chronic cholestatic liver disease (4 PBC, 2 PSC), four patients had cholestatic liver disease post liver transplantation (3 ischemic bile duct strictures and 1 vanishing bile duct syndrome due to ductopenic rejection), three patients had a drug-induced cholestatic hepatitis. In all patients conventional medical treatment had failed to control symptoms of pruritus. All patient were treated with UVB phototherapy. The perception of pruritus was recorded with the aid of a visual analogue scale (VAS) where 0 represented no pruritus and 10 the worst imaginable pruritus. Results: Twelve of thirteen patients (92%) had a more than 50% reduction in perceived pruritus. Mean VAS score before and at the end of treatment decreased from 8.5 to 2.3. The number of phototherapy sessions required varied between 12 to 60 with a mean of 26 (8.5 weeks of treatment). Four patients started a second phototherapy session because of recurrence of pruritus. In all of them again a marked improvement of pruritus was observed. Main side effects seen with UVB phototherapy were erythema and paraesthesias. Treatment had to be interrupted in two patients for that reason. Conclusion: UVB phototherapy appears to be a promising and well tolerated treatment in the therapeutic armamentarium for cholestasis-associated pruritus. The treatment is also succesfull in patients with intractable pruritus after liver transplantation. 1290 TREATMENT OF AUTOIMMUNE HEPATITIS: WHAT IS THE OPTIMAL ENDPOINT ON FOLLOW-UP BIOPSY? H.K. Dhaliwal1 , B. Hoeroldt2 , A. Dube3 , E. Mcfarlane1 , M.A. Karajeh1 , D.C. Gleeson1 . 1 Liver Unit, Sheffield Teaching Hospitals NHS Trust, Sheffield, 2 Gastroenterology, Rotherham General Hospital, Rotherham, 3 Department of Histopathology, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK E-mail: [email protected] Introduction and Aims: We have reported [1] that following immunosuppressive treatment of Autoimmune Hepatitis (AIH), many patients fail to achieve histological remission (necroinflammatory score (NIS) ≤ 3), despite attaining biochemical remission (normal serum ALT). A recent report2 suggests that, following treatment, a NIS ≤ 5 is not associated with fibrosis progression and hence, may be an acceptable treatment outcome [2]. We therefore aimed to assess the associations of NIS on follow-up biopsy within the range 0–5, with change in fibrosis and survival. Methods: We studied 114 patients with AIH by IAIHG criteria (81 definite, 94 female, mean age 48.7±1.7 years), treated initially with reducing dose prednisolone and 1 mg/kg azathioprine, who had achieved normal serum ALT and a NIS between 0 to 5 on followup biopsy (performed at median (range) 2.16 (0.65–13.67) years) after diagnosis (paired diagnostic and follow-up biopsies available in 93 patients). Biopsies were graded using the Ishak system. Results: Fibrosis score between baseline and follow-up biopsy decreased in patients with follow-up NIS 0–3 (mean 3.4±0.24 to 2.7±0.21, n = 59 p = 0.001) but was unchanged in those with followup NIS of 4 or 5 (3.5±0.3 to 3.4±0.3, n = 34 p = 0.846). Fibrosis score on follow up biopsy was higher in patients with NIS 4–5 (n = 40) than with NIS 0–3 (n = 72) (mean 3.3±0.3 vs 2.4±0.2, p = 0.014). Regression of fibrosis was independently associated with lower NIS (p = 0.014) and less portal inflammation (p = 0.006) on followup biopsy, and with longer interval between the two biopsies (p = 0.001). All cause death/transplantation rate was higher in

Journal of Hepatology 2011 vol. 54 | S363–S534