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Prophylactic lamivudine therapy may prevent immunosuppressive induced HBV reactivation in chronic carriers
Category 6: Viral hepatitis: clinical aspects resistancfe reinfection is supposed to have a milder clinical course, although long term data are not available. Patients: 34 patients with hepatitis-B recurrence after liver transplantation were treated with lamivudine. All patients developed reinfection despite long term passive immunoprophylaxis. 22 of them underwent a former course of famciclovir. All patients were followed up with monthly laboratory values and regular liver biopsies. Results: 20 of 34 patients (59%) developed lamivudine-resistance during the follow up period of 12 to 48 months. 1 and 3 year graft survival rates after diagnosis of lamivudine-resistance were 100% and 75%. Lamivudine-resistance presented in most cases with high viral replication (3012 ± 574 pg/ml one month after lamivudine-resistance), but liver enzymes were only slightly elevated (ALT 45 4- 16 U/l). Only 3 patients (15%) presented with a rapid rise of ALT up to 1500 U/l after 3 months. All others had only mildly elevated liver enzymes within the first 8 months. In case of increased transaminases patients were switched to lamivudine plus interferone-alpha (n = 8) or lamivudine plus famciclovir (n = 6). Most patients tolerated this combination well, and HBV-DNA and liver enzmes decreased. In total 3 patients with larnivudine-resistance died (two malignomas, one HBV-reinfection), and two were retransplanted due to reinfection. Conclusion: Lamivudine-resistant reinfection is mostly characterised by a benign course. In case of lamivudine resistance combination of different antivirals could diminish viral replication, in the future new antivirals like adefovir might expand therapeutic options.
~ - ~ - ] PREVALENCE OF EXTRAHEPATIC MANIFESTATIONS OF HCV INFECTION C. Mazzaro, S. Baracetti, G.S. Carnlello, C. Comar, F. Zorat, G. Pozzato. First Medicine Department, Pordenone Hospital Italy Aim: To assess the prevalence of extrahepatic manifestations of hepatitis C virus (HCV) infection. Material and Methods: We recorded the extrahepatic manifestations of HCV infection by reviewing data obtained during the first visit of 210 patients with chronic HCV infection. Patients with positivity for HbsAg or HIV were excluded. The prevalence of dermatologic, neurologic, nephrologic manifestations, and the presence of cryoglobulins was assessed. Results: Extrahepatic manifestations were found in 84 patients (40%), more frequently in cirrhosis and in females. 73 patients (34%) had type II or III (87.6% and 12.4% respectively) dosable levels of cryoglobulins, among them 30 (41%) showed cryoglobulinemic syndrome with purpura of the lower extremities (72%), weakness (73%) and arthralgias (68%). Peripheral neuropathy was found in 36 cases (17%), Raynaud phenomenon in 35 (17%), and Sicca syndrome in 13 (6%). Elevated levels of rheumatoid factor were found in 56 (27%),. The biochemical evidence (high rheumatoid factor) of MC was observed a mean of 7 years before the clinical manifestation of the disease in 10 patients (5%). Membranoproliferative cryoglobulinemic glomerulonephritis was found in 3 cases (1.4%). Low-grade Non Hodgkin's lymphoma (NHL) was found in 10 patients (4.7%), nine of them showed MC. Three MALT lymphoma of the stomach (1.4%), two diffuse large cell lymphoma (1%), and one chronic lymphocytic leukaemia were found. A monoclonal gammopathy was present in 19 patients (9%), and in one case a IgG k myeloma was found. Autoimmune thiroiditis was observed in 3 patients (1.4%). Conclusion: Extrahepatic manifestations are frequently observed in HCV patients. The most frequent immunologic abnormalities include mixed cryoglobulinemia and monoclonal gammophaty
153
- ~ PROPHYLACTIC LAMIVUDINE THERAPY MAY PREVENT IMMUNOSUPPRESSIVE INDUCED HBV REACTIVATION IN CHRONIC CARRIERS O. Shibolet, Y. Ilan, S. Gilis, D. Shouval, R. Safadi. Liver unit, Division
of Medicine, Hadassah University Hospital Jerusalem, Israel Background: Viral reactivation in HBV carders undergoing immunosuppressive therapy ranges from 14%-50%, with 5% mortality. Our aim is to evaluate Lamivudine prophylaxis in HBV patients treated with immunosuppression. Methods: HBV patients treated with prophylactic Lamivudine prior to immunosuppressive therapy for non-hepatic disorders were reveiwed. Results: Eleven patients were treated with Lamivudine prophylaxis between 1997-2000, (9 men, 2 women, mean age 55, range 38-66 years). Of them, 6 had lymphoma, 2 colonic adenocarcinoma, two had vasculitis and one endophthalmitis. The former 8 patients were treated with chemotherapy, while the rest received steroids. All patients had detectable serum HBsAg, three tested positive for HBeAg and HBV-DNA. 5 presented with elevated transaminases. Lamivudine was administered 1-60 days (mean 15) prior to initiation of immunosuppression and continued 2 w to 24 m (mean 7 m) following treatment. Mean follow-up was 21 m (range 2 w-38 m). All 5 patients who presented with transaminases either improved or remained stable during immunosuppression treatment. No signs of hepatic failure were observed within our study group. Patients with viral replication achieved anti-HBe seroconversion at end of follow-up. None of the patients had serological evidence of HBV reactivation during or after lamivudine prophylaxis. Two patients died of lymphoma complications. Conclusions: Lamivudine prophylaxis in HBV carders receiving immunosuppression may prevent HBV reactivation and hepatic failure and enables full-dose repeated courses of immunosuppression.
~6"]
PREDICTORS FOR STEATOSIS AND FIBROSIS IN CHRONIC HEPATITIS C
J. George, J. Hui, G. Farrell, J. Kench, R. Lin, D. Samarasinghe, C. Liddle. Storr Liver Unit, University of Sydney, Westmead Hospital
Australia Steatosis is frequently observed in liver biopsies from patients with chronic hepatitis C (HCV). However, the factors that lead to steatosis are not well defined. Further, there have been few studies which assess whether steatosis is associated with increased fibrosis. The aim was to assess risk factors for steatosis and fibrosis in chronic HCV. Methods: Data were prospectively collected from 100 consecutive chronic HCV pts who underwent liver biopsies. Clinical parameters studied included age, sex, current and past alcohol intake, previous antiviral treatment, BMI and waist/hip ratio. Blood results included HCV genotype, ALT, fasting total cholesterol, LDL, HDL, triglyceride, glucose level, insulin, insulin resistance (by HOMA), c-peptide, iron saturation and ferritin. Liver biopsies were reviewed independently (JK) and inflammation and fibrosis assessed using the Scheuer score. Steatosis was graded: 0, 1 (<33% hepatocytes affected), 2 (33%~56%), or 3 (>66%). Results: The median age was 42 yr (21-72), with 67% male. 45% were genotype 1 and 37% genotype 3a. Using multivariate analysis, independent predictors of steatosis were: genotype 3a (P = 0.002), C-peptide (P = 0.02) and cholesterol (P = 0.05). Cholesterol levels were inversely associated with the degree of steatosis. Independent predictors of fibrosis were: age (P = 0.002), ALT (P = 0.005), insulin levels (P = 0.005) and portal inflammation (P < 0.0001). Conclusions: (1) Viral factors (Genotype 3a) are the most important predictors of steatosis in chronic HCV. Insulin resistance has a minor role. The mechanism for the negative correlation of cholesterol with steatosis warrants further study. (2) Increased fibrosis was not associated with increased steatosis.
~ - ~ - ] PREVALENCE OF EXTRAHEPATIC MANIFESTATIONS OF HCV INFECTION C. Mazzaro, S. Baracetti, G.S. Carnlello, C. Comar, F. Zorat, G. Pozzato. First Medicine Department, Pordenone Hospital Italy Aim: To assess the prevalence of extrahepatic manifestations of hepatitis C virus (HCV) infection. Material and Methods: We recorded the extrahepatic manifestations of HCV infection by reviewing data obtained during the first visit of 210 patients with chronic HCV infection. Patients with positivity for HbsAg or HIV were excluded. The prevalence of dermatologic, neurologic, nephrologic manifestations, and the presence of cryoglobulins was assessed. Results: Extrahepatic manifestations were found in 84 patients (40%), more frequently in cirrhosis and in females. 73 patients (34%) had type II or III (87.6% and 12.4% respectively) dosable levels of cryoglobulins, among them 30 (41%) showed cryoglobulinemic syndrome with purpura of the lower extremities (72%), weakness (73%) and arthralgias (68%). Peripheral neuropathy was found in 36 cases (17%), Raynaud phenomenon in 35 (17%), and Sicca syndrome in 13 (6%). Elevated levels of rheumatoid factor were found in 56 (27%),. The biochemical evidence (high rheumatoid factor) of MC was observed a mean of 7 years before the clinical manifestation of the disease in 10 patients (5%). Membranoproliferative cryoglobulinemic glomerulonephritis was found in 3 cases (1.4%). Low-grade Non Hodgkin's lymphoma (NHL) was found in 10 patients (4.7%), nine of them showed MC. Three MALT lymphoma of the stomach (1.4%), two diffuse large cell lymphoma (1%), and one chronic lymphocytic leukaemia were found. A monoclonal gammopathy was present in 19 patients (9%), and in one case a IgG k myeloma was found. Autoimmune thiroiditis was observed in 3 patients (1.4%). Conclusion: Extrahepatic manifestations are frequently observed in HCV patients. The most frequent immunologic abnormalities include mixed cryoglobulinemia and monoclonal gammophaty
153
- ~ PROPHYLACTIC LAMIVUDINE THERAPY MAY PREVENT IMMUNOSUPPRESSIVE INDUCED HBV REACTIVATION IN CHRONIC CARRIERS O. Shibolet, Y. Ilan, S. Gilis, D. Shouval, R. Safadi. Liver unit, Division
of Medicine, Hadassah University Hospital Jerusalem, Israel Background: Viral reactivation in HBV carders undergoing immunosuppressive therapy ranges from 14%-50%, with 5% mortality. Our aim is to evaluate Lamivudine prophylaxis in HBV patients treated with immunosuppression. Methods: HBV patients treated with prophylactic Lamivudine prior to immunosuppressive therapy for non-hepatic disorders were reveiwed. Results: Eleven patients were treated with Lamivudine prophylaxis between 1997-2000, (9 men, 2 women, mean age 55, range 38-66 years). Of them, 6 had lymphoma, 2 colonic adenocarcinoma, two had vasculitis and one endophthalmitis. The former 8 patients were treated with chemotherapy, while the rest received steroids. All patients had detectable serum HBsAg, three tested positive for HBeAg and HBV-DNA. 5 presented with elevated transaminases. Lamivudine was administered 1-60 days (mean 15) prior to initiation of immunosuppression and continued 2 w to 24 m (mean 7 m) following treatment. Mean follow-up was 21 m (range 2 w-38 m). All 5 patients who presented with transaminases either improved or remained stable during immunosuppression treatment. No signs of hepatic failure were observed within our study group. Patients with viral replication achieved anti-HBe seroconversion at end of follow-up. None of the patients had serological evidence of HBV reactivation during or after lamivudine prophylaxis. Two patients died of lymphoma complications. Conclusions: Lamivudine prophylaxis in HBV carders receiving immunosuppression may prevent HBV reactivation and hepatic failure and enables full-dose repeated courses of immunosuppression.
~6"]
PREDICTORS FOR STEATOSIS AND FIBROSIS IN CHRONIC HEPATITIS C
J. George, J. Hui, G. Farrell, J. Kench, R. Lin, D. Samarasinghe, C. Liddle. Storr Liver Unit, University of Sydney, Westmead Hospital
Australia Steatosis is frequently observed in liver biopsies from patients with chronic hepatitis C (HCV). However, the factors that lead to steatosis are not well defined. Further, there have been few studies which assess whether steatosis is associated with increased fibrosis. The aim was to assess risk factors for steatosis and fibrosis in chronic HCV. Methods: Data were prospectively collected from 100 consecutive chronic HCV pts who underwent liver biopsies. Clinical parameters studied included age, sex, current and past alcohol intake, previous antiviral treatment, BMI and waist/hip ratio. Blood results included HCV genotype, ALT, fasting total cholesterol, LDL, HDL, triglyceride, glucose level, insulin, insulin resistance (by HOMA), c-peptide, iron saturation and ferritin. Liver biopsies were reviewed independently (JK) and inflammation and fibrosis assessed using the Scheuer score. Steatosis was graded: 0, 1 (<33% hepatocytes affected), 2 (33%~56%), or 3 (>66%). Results: The median age was 42 yr (21-72), with 67% male. 45% were genotype 1 and 37% genotype 3a. Using multivariate analysis, independent predictors of steatosis were: genotype 3a (P = 0.002), C-peptide (P = 0.02) and cholesterol (P = 0.05). Cholesterol levels were inversely associated with the degree of steatosis. Independent predictors of fibrosis were: age (P = 0.002), ALT (P = 0.005), insulin levels (P = 0.005) and portal inflammation (P < 0.0001). Conclusions: (1) Viral factors (Genotype 3a) are the most important predictors of steatosis in chronic HCV. Insulin resistance has a minor role. The mechanism for the negative correlation of cholesterol with steatosis warrants further study. (2) Increased fibrosis was not associated with increased steatosis.