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Efficacy of lamivudine to prevent hepatitis reactivation in HBV infected patients treated for non-Hodgkin lymphoma
Category 6: Viral hepatitis: clinical aspects onset between patients with and without BBT. Increasing HBV-DNA levels from VBT-onset to 3 months later were strongly associated with BBT development (RH/1 log: 1.8; P = 0.004); HBV-DNA increase > 1 log from the onset of VBT to 3 months later was observed in all 14 patients with BBT within 6 months after VBT-onset. Conclusions: In H B e A g ( - ) C L D , low baseline viremia levels are a strong predictor of long-term remission under LAM. VBTs are followed by BBTs in practically all patients within 24 months. Serum HBV-DNA increase more than 1 log within 3 months from the onset of VBT to later accurately predicts early (within 6 months) BBT development.
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EFFICACY OF LAMIVUDINE TO PREVENT HEPATITIS REACTIVATION IN HBV INFECTED PATIENTS TREATED FOR NON-HODGKIN LYMPHOMA
Marcello Persico 1, Fedele De Marino 1, Eliana Persico l, Giovanni Di Giacomo 1, Bruno Palmentieri 1, Aristide Morante 1, Amalia De Renzo 2, Roberto Torella 1. l lnternal Medicine and Hepatology Unit, SUN, Naples;
2Haematology Unit, Federico H University, Naples, Italy HBV positive patients affected with b-NHL undergoing chemotherapy may develop acute hepatitis. Lamivudine was shown to be of help in the treatment of HBV-related chronic hepatitis by inhibiting the inverse transcriptase enzyme. Some reports of the literature in a small number of cases show that lamivudine seems to prevent the HBV related acute hepatitis in patients with b-NHL treated with chemotherapy. Aim of the present study was to retrospectively compare HBV positive patients, undergoinig to chemotherapy for b-NHL, who were treated or not treated with lamivudine at the occurrence of the acute hepatitis or who were preventively treated with lamivudine in order to avoid the occurrence of acute hepatitis. 86 patients out of 550 b-NHL affected patients (15.6%) were HCV positive and 21 (3.5%) HBV positive. HCV and HBV patients were tested with routine blood examination test and screened for markers of viral hepatitis using when indicated radioimmunoassay and/or PCR methods. Prevalence of HCV resulted statistically significant for HCV positive patients when compared to control groups (15.6% vs 2.02%; p < 0.000) while HBV did not (3.5% vs 1.3%; ns). Patients (n. 9) treated with lamivudine recovered from acute hepatitis, patients (n. 3) who had not been treated, previous the lamivudine era, died. Patients (n. 3) who were preventively treated with lamivudine did not develop acute hepatitis. Lamivudine therapy in HBV infected b-NHL patients is of efficacy either to recover from HBV-related acute hepatitis and to prevent the occurrence of acute hepatitis in HBV infected patients undrgoing chemotherapy for b-NHL.
I-~A
PROSPECTIVE STUDY OF HIGHLY ELEVATED TRANSAMINASES IN AN URBAN POPULATION
Luc Lasser 1, Philippe Langlet 1, J.P. Mulkay 2, E.M. Talib ~, Patricia Denis 1, J.F. Nyst 1, Claude Jonas 1, Thierry Delaunoit 1, Marc Dereuck 1 , Michel Buset 2 , Erik De Koster I . ~CHU Brugmann,
Brussels; 2CHU St-Pierre, Belgium A recent British study (BS) in a rural population (Gut 1999; 45: 129-133) suggested that viral hepatitis accounts for 3.5% o f A S T > 400 U/L whereas ischaemic/hypoxic hepatitis and extrahepatic biliary obstruction accounts for respectively 1/2 and 1/4 of the cases. We prospectively compared the causes of transaminases higher than tenfold normality in an urban population with those of the BS. Methods: 18 months prospective study (PS) including all patients with at least tenfold increase of AST and/or ALT of liver origin on admission or during hospitalisation using a specially designed computer program. Diagnosis was based on the medical record and by executing all necessary biochemical, radiological and invasive procedures. Results: 78 pts included. In 55% (PS: 43 pts, BS: 17%; p < 0.0001) the cause of raised transaminases was a primary hepatocellular disease with viral hepatitis (PS: 33.2%, BS 3.6%, p < 0.0001) and drug toxicity
243
(PS: 15.1%, BS: 8.7%, p = 0.20, NS) as the major causes. 14 pts (PS: 18%, BS: 24%, p = 0.38 NS) presented a pancreatobiliary cause. Hepatic ischaemia/hypoxia was found in only 12 patients (PS 15.4%, BS 50%, p < 0.0001). Finally hepatic malignancy was found in 4 of the patients (PS 5 %, BS 4%, p = 0.93 NS) and diagnosis was unclear in five patients (PS 6.4%, BS 5%, p = 0.22 NS). Conclusions: In an urban population notably elevated transaminases are most frequently of primary hepatocellular origin with viral hepatitis and drug induced necrosis as the most common causes. Compared to the results obtained in a rural population, hepatic ischemia/hypoxia was a much less frequent cause. Finally, our results are more in harmony with the commonly held view of textbooks.
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VIROLOGICAL AND HISTOPATHOLOGICAL EFFICACY OF ANTI-VIRAL THERAPY IN HCV-RELATED CIRRHOSIS
A.V. Pichard, B. Nalpas, H. Fontaine, M.L. Chaix, F. Carnot, C. Brechot, S. Pol. Liver Unit and lnserm U-370, Necker Hospital, Paris, France Aim: To assess the efficacy of interferon and combined therapy (Interferon + ribavirin) according to HCV genotype in HCV+ve cirrhotics who have been exluded of multicenter trials. Patients: All the 124 HCV + ve cirrhotics (88 men and 36 women, mean age of 54 4- 12 y) who had received one or more antiviral therapy and who were HBsAg-ve, HIV-ve, non alcoholics and non receiving immunosuppressive therapy. HCV genotypes were: la or lb (n = 64); non 1 (n = 50); unknown (n = 10). Methods: Naturalistic design and intent-to-treat analysis. The main endpoint was the HCV RNA status 6 months after treatment discontinuation, a negative and positive HCV RNA corresponding to a response and non response, respectively. Results: 90 and 34 patients were treated by interferon alone (1) and combined therapy (I + R) for 12 months, respectively. Repartition of HCV genotypes did not differ according to treatment. In patients with HCV genotype 1, the rate of response was low (<10%) and similar in both treatment groups. However in patients with non-1 genotype, the rate of response was three times higher in I+R (38.5%) than in the I group (13.9%). Fourty-four non responders, all having been initially treated with 1, were retreated, 11 with 1 and 33 with I + R for 12 months. In patients infected with HCV genotype 1, the rates of response were similar in I (¼ = 20%) and I + R (3/12 = 20%) groups while in patients with HCV non-l, the rate of response was 2-fold higher in I + R (8/18 = 44.4%) as compared to 1 (1/6 = 16.7%). Altogether, at the end of one or two rounds of therapy, 12/61 (19.7%) patients with genotype 1 and 24/49 (48.9%) with non-1 HCV genotype were sustained responders, 50 patients, including 18 responders and 32 non-responders, had a liver histopathological evaluation before and after therapy. Treatment was associated with a significant decrease in the HA1 (mean - 1 . 5 -4- 2.6) which was more striking in the 18 responders ( - 3 . 6 -4- 2.3 vs - 0 . 3 4- 2.5, p < 0.001). The mean fibrosis score did not significantly change following therapy ( - 0 . 3 6 q- 1.1, NS) whatever the type of response; however 6 out of the 50 had a striking fibrosis regression of 2 units at the least which was significantly more frequent in responders than in non-responders (5/15, 27.8% vs 1/32, 3.1%, p = 0.02), indicating reversibility of cirrhosis. Conclusion: In cirrhotic patients infected with non 1 genotype, combined therapy is indicated, even after a first unsuccessful treatement, since leading to a sustained HCV RNA negativation in more than 40% of the cases, associated with a significant decrease in the HAI score and a striking fibrosis regression in about 10%. When infection is due to HCV genotype 1, interferon alone and combined therapy appear to have a similarly low virological efficacy, even when repeated.
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EFFICACY OF LAMIVUDINE TO PREVENT HEPATITIS REACTIVATION IN HBV INFECTED PATIENTS TREATED FOR NON-HODGKIN LYMPHOMA
Marcello Persico 1, Fedele De Marino 1, Eliana Persico l, Giovanni Di Giacomo 1, Bruno Palmentieri 1, Aristide Morante 1, Amalia De Renzo 2, Roberto Torella 1. l lnternal Medicine and Hepatology Unit, SUN, Naples;
2Haematology Unit, Federico H University, Naples, Italy HBV positive patients affected with b-NHL undergoing chemotherapy may develop acute hepatitis. Lamivudine was shown to be of help in the treatment of HBV-related chronic hepatitis by inhibiting the inverse transcriptase enzyme. Some reports of the literature in a small number of cases show that lamivudine seems to prevent the HBV related acute hepatitis in patients with b-NHL treated with chemotherapy. Aim of the present study was to retrospectively compare HBV positive patients, undergoinig to chemotherapy for b-NHL, who were treated or not treated with lamivudine at the occurrence of the acute hepatitis or who were preventively treated with lamivudine in order to avoid the occurrence of acute hepatitis. 86 patients out of 550 b-NHL affected patients (15.6%) were HCV positive and 21 (3.5%) HBV positive. HCV and HBV patients were tested with routine blood examination test and screened for markers of viral hepatitis using when indicated radioimmunoassay and/or PCR methods. Prevalence of HCV resulted statistically significant for HCV positive patients when compared to control groups (15.6% vs 2.02%; p < 0.000) while HBV did not (3.5% vs 1.3%; ns). Patients (n. 9) treated with lamivudine recovered from acute hepatitis, patients (n. 3) who had not been treated, previous the lamivudine era, died. Patients (n. 3) who were preventively treated with lamivudine did not develop acute hepatitis. Lamivudine therapy in HBV infected b-NHL patients is of efficacy either to recover from HBV-related acute hepatitis and to prevent the occurrence of acute hepatitis in HBV infected patients undrgoing chemotherapy for b-NHL.
I-~A
PROSPECTIVE STUDY OF HIGHLY ELEVATED TRANSAMINASES IN AN URBAN POPULATION
Luc Lasser 1, Philippe Langlet 1, J.P. Mulkay 2, E.M. Talib ~, Patricia Denis 1, J.F. Nyst 1, Claude Jonas 1, Thierry Delaunoit 1, Marc Dereuck 1 , Michel Buset 2 , Erik De Koster I . ~CHU Brugmann,
Brussels; 2CHU St-Pierre, Belgium A recent British study (BS) in a rural population (Gut 1999; 45: 129-133) suggested that viral hepatitis accounts for 3.5% o f A S T > 400 U/L whereas ischaemic/hypoxic hepatitis and extrahepatic biliary obstruction accounts for respectively 1/2 and 1/4 of the cases. We prospectively compared the causes of transaminases higher than tenfold normality in an urban population with those of the BS. Methods: 18 months prospective study (PS) including all patients with at least tenfold increase of AST and/or ALT of liver origin on admission or during hospitalisation using a specially designed computer program. Diagnosis was based on the medical record and by executing all necessary biochemical, radiological and invasive procedures. Results: 78 pts included. In 55% (PS: 43 pts, BS: 17%; p < 0.0001) the cause of raised transaminases was a primary hepatocellular disease with viral hepatitis (PS: 33.2%, BS 3.6%, p < 0.0001) and drug toxicity
243
(PS: 15.1%, BS: 8.7%, p = 0.20, NS) as the major causes. 14 pts (PS: 18%, BS: 24%, p = 0.38 NS) presented a pancreatobiliary cause. Hepatic ischaemia/hypoxia was found in only 12 patients (PS 15.4%, BS 50%, p < 0.0001). Finally hepatic malignancy was found in 4 of the patients (PS 5 %, BS 4%, p = 0.93 NS) and diagnosis was unclear in five patients (PS 6.4%, BS 5%, p = 0.22 NS). Conclusions: In an urban population notably elevated transaminases are most frequently of primary hepatocellular origin with viral hepatitis and drug induced necrosis as the most common causes. Compared to the results obtained in a rural population, hepatic ischemia/hypoxia was a much less frequent cause. Finally, our results are more in harmony with the commonly held view of textbooks.
I-~
VIROLOGICAL AND HISTOPATHOLOGICAL EFFICACY OF ANTI-VIRAL THERAPY IN HCV-RELATED CIRRHOSIS
A.V. Pichard, B. Nalpas, H. Fontaine, M.L. Chaix, F. Carnot, C. Brechot, S. Pol. Liver Unit and lnserm U-370, Necker Hospital, Paris, France Aim: To assess the efficacy of interferon and combined therapy (Interferon + ribavirin) according to HCV genotype in HCV+ve cirrhotics who have been exluded of multicenter trials. Patients: All the 124 HCV + ve cirrhotics (88 men and 36 women, mean age of 54 4- 12 y) who had received one or more antiviral therapy and who were HBsAg-ve, HIV-ve, non alcoholics and non receiving immunosuppressive therapy. HCV genotypes were: la or lb (n = 64); non 1 (n = 50); unknown (n = 10). Methods: Naturalistic design and intent-to-treat analysis. The main endpoint was the HCV RNA status 6 months after treatment discontinuation, a negative and positive HCV RNA corresponding to a response and non response, respectively. Results: 90 and 34 patients were treated by interferon alone (1) and combined therapy (I + R) for 12 months, respectively. Repartition of HCV genotypes did not differ according to treatment. In patients with HCV genotype 1, the rate of response was low (<10%) and similar in both treatment groups. However in patients with non-1 genotype, the rate of response was three times higher in I+R (38.5%) than in the I group (13.9%). Fourty-four non responders, all having been initially treated with 1, were retreated, 11 with 1 and 33 with I + R for 12 months. In patients infected with HCV genotype 1, the rates of response were similar in I (¼ = 20%) and I + R (3/12 = 20%) groups while in patients with HCV non-l, the rate of response was 2-fold higher in I + R (8/18 = 44.4%) as compared to 1 (1/6 = 16.7%). Altogether, at the end of one or two rounds of therapy, 12/61 (19.7%) patients with genotype 1 and 24/49 (48.9%) with non-1 HCV genotype were sustained responders, 50 patients, including 18 responders and 32 non-responders, had a liver histopathological evaluation before and after therapy. Treatment was associated with a significant decrease in the HA1 (mean - 1 . 5 -4- 2.6) which was more striking in the 18 responders ( - 3 . 6 -4- 2.3 vs - 0 . 3 4- 2.5, p < 0.001). The mean fibrosis score did not significantly change following therapy ( - 0 . 3 6 q- 1.1, NS) whatever the type of response; however 6 out of the 50 had a striking fibrosis regression of 2 units at the least which was significantly more frequent in responders than in non-responders (5/15, 27.8% vs 1/32, 3.1%, p = 0.02), indicating reversibility of cirrhosis. Conclusion: In cirrhotic patients infected with non 1 genotype, combined therapy is indicated, even after a first unsuccessful treatement, since leading to a sustained HCV RNA negativation in more than 40% of the cases, associated with a significant decrease in the HAI score and a striking fibrosis regression in about 10%. When infection is due to HCV genotype 1, interferon alone and combined therapy appear to have a similarly low virological efficacy, even when repeated.