Simultaneous Determination of Lamivudine, Zidovudine and ...
Lamivudine treatment in precore HBV mutants
1
Results: This analysis included 65 Caucasians (C 39%), 55 African Americans (AA 33%) and 45 Mexican Americans (MA 27%). The group composed of 144 males (87%) and 21 females (13%). HCCs were identified in 33 (22.9%) males and none of the females. Among them, 27 (82%) tumors were associated with cirrhotic livers. There was a much higher proportion of Mexican Americans with HCC: 13 MA (28.9%) compared to 11 C (16.9%) and 9 AA (16.4%). When examining the hepatic iron deposition in non-HCC patients, iron was significantly more com- monly found in males than females (67.6% vs. 42.9%; p 0.03). There was no significant difference in the overall presence of hepatic iron among males with or without HCC (70% vs. 68.5%). However, when the zonal distribution of iron was examined in these specimens, MA without HCC had a significantly lower rate of sinusoidal iron deposition compared to the other two groups (MA 38% vs. C 62% vs. AA 74%; p 0.012) while the hepatocytic and portal iron distributions were similar in all three races. Interestingly, the frequency of sinusoidal iron deposition was preferentially increased from 38% to 50% in MA with HCC but not in the other two racial groups. Furthermore, iron deposition within the tumor tissue was observed in six (46%) MA, but only one C (9%) one AA (11%). Conclusions: The significantly increased prevalence of HCC in males compared to females with HCV infection could be attributed to a higher rate of hepatic iron deposition in males. Mexican American males had the highest rate of HCC. Consistent with previous observation, there was an increased frequency of sinusoidal iron in HCC among Mexican American males. The increased frequency of iron deposition in the tumor tissues may also explain their higher prevalence of HCC. These observations suggest that genetic factors may influence hepatic iron distribution and the patho- genesis of hepatocellular carcinoma in HCV infection. 439 Precore heterogeneity and acute liver injury due to hepatitis B virus (HBV) Premashish Kar DM, FACG, Surinder S Rana MBBS, Bhudev C Das PhD. Department of Medicine and Institute of cytology and preventive oncology (ICMR) Maulana Azad Medical college, New Delhi, India 110002. The role of the most commonly described precore mutant (point mutation from guanine to adenine at nucleotide 83 of the precore region) in patho- genesis of acute liver injury is not clear. We studied the association between precore mutant and acute liver injury by detecting and estimating the proportion of the specific precore mutant in serum samples of 12 patients with acute viral hepatitis (AVH) and 7 patients of fulminant hepatitis (FH) using polymerase chain reaction (PCR) coupled ligase chain reaction (LCR). After DNA extraction from the serum samples, a segment of HBV DNA spanning 309 nucleotides was amplified by PCR. To detect the precore mutant, LCR was done on the DNA amplified by PCR. To estimate the proportion of mutant virus in individual patients, the signals generated by the LCR bands were measured densitometrically. The results of LCR were confirmed by getting PCR product from 3 samples sequenced. Mutant HBV was detected in all the 19 patients, coexisting with the wild type of HBV but the proportion of mutant HBV was significantly higher in patients with FH as compared to patients with AVH. However, none of the patients with FH had HBV that was 100% mutant. Our results suggest that the precore mutant of HBV is associated with the development of FH, but it may not by itself account for the development of the disease. It is likely that this genetic variation along with other variations like core mutations are important and the clinical outcome is determined by these viral factors in conjunction with the host factor. Furthermore, since we were able to detect mixed population of HBV in all the patients with acute liver injury, we propose that acute liver injury could be caused by infection with mixed population of HBV whereas infection with pure wild or pure mutant would probably cause subclinical infection. However, further studies involving large sample size are needed to test this hypothesis. 440 Interferon monotherapy: still a valuable strategy for acute hepatitis C Susana Lopes, M.D., Guilherme Macedo, M.D., FACG; Fernando Arau ´jo, M.D.; Tome ´ Ribeiro, M.D., PhD. Gastrenterology Unit, Hospital S. Joa ˜o, Porto, Portugal. Introduction: The consensus meetings on hepatitis C treatment, reassured the efficacy and the advantage of combined therapy with interferon and ribavirin. Acute hepatitis C is accepted as an indication for treatment, although there is not enough studies defining dose and treatment schedules. Material and methods: Non controlled, open pilot trial, with interferon administered to patients with acute hepatitis C. Diagnosis was based on transaminases elevation, 10 times above normal limit, associated with anti HCV or HCV PCR positivity, with serological, immunological, and bio- chemical exclusion of other causes of acute hepatitis. Interferon was administered subcutaneously, 3 times a week, 5MU, for 6 months. Results: We have analysed 8 patients (6 men), that fulfilled diagnostic criteria. In 7, we had pre treatment histology (demonstrative of acute hepatitis). All of them had transaminases above 300 UI, and the infection was acquired by iv drug abuse in 3 patients, renal transplantation in 1 patient, sexual transmission in 1, dental care in 1, and sporadic in 2. In all of them transaminases returned to normal during the first 4 months of therapy. In patients with follow up of more than one year (7), only one patient (of sporadic transmission, genotype 1b) had PCR and transami- nases elevation. Side effects were negligiable, and we had no need to reduce or stop interferon therapy. Conclusion: Patients with acute hepatitis C, should be treated with interferon, given its good tolerability and efficacy, and might prevent disease progression towards cirrhosis. 441 Lamivudine treatment in precore HBV mutants Guilherme Macedo M.D., FACG, Susana Lopes, M.D., Pedro MoutinhoRibeiro M.D., Fernando Arau ´jo M.D., Tome ´ Ribeiro M.D., PhD. Gastrenterology Unit, Hospital S. Joa ˜o, Porto, Portugal. The proportion of chronic liver disease associated with precore HBV mutant infection, has been rising, particularly in southern european coun- tries. Interferon, in this setting, is associated with a low rate of sustained response, and lamivudine, in preliminary studies has demonstrated a sig- nificative complete sustained response rate. Aim: To evaluate the response rate to lamivudine treatment of precore HBV mutants infected patients. Material and methods: Patients with chronic active infection with precore HBV mutant (HBV DNA 2,5 pg/ml, anti HBe positive, liver histology with necroinflammatory activity/fibrosis, and transaminases 2N), were treated with 150 mg/day lamivudine, for 6 months. Results: From 25 patients (18 men) included for treatment protocol, 18 (72%) had negative DNA in the 6th month of therapy and normal transami- nases. In five patients (20%), DNA was not detectable but transaminases were abnormal (partial response). In 2 patients, there was detectable DNA (8%). No adverse side effects were observed, nor biochemical changes, attributable to lamivudine. Conclusion: Lamivudine demonstrated a significative supressive effect on the replication of precore HBV mutant. COLON 442 Prevalence of medication-associated constipation Olaitan A Adeniji, M.D., and Jack A Di Palma, M.D., FACG*. 1 Division of Gastroenterology, University of South Alabama, Mobile, AL. S140 Abstracts AJG – Vol. 96, No. 9, Suppl., 2001
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Transcript of Lamivudine treatment in precore HBV mutants
Results: This analysis included 65 Caucasians (C � 39%), 55 AfricanAmericans (AA � 33%) and 45 Mexican Americans (MA � 27%). Thegroup composed of 144 males (87%) and 21 females (13%). HCCs wereidentified in 33 (22.9%) males and none of the females. Among them, 27(82%) tumors were associated with cirrhotic livers. There was a muchhigher proportion of Mexican Americans with HCC: 13 MA (28.9%)compared to 11 C (16.9%) and 9 AA (16.4%). When examining the hepaticiron deposition in non-HCC patients, iron was significantly more com-monly found in males than females (67.6% vs. 42.9%; p � 0.03). Therewas no significant difference in the overall presence of hepatic iron amongmales with or without HCC (70% vs. 68.5%). However, when the zonaldistribution of iron was examined in these specimens, MA without HCChad a significantly lower rate of sinusoidal iron deposition compared to theother two groups (MA 38% vs. C 62% vs. AA 74%; p � 0.012) while thehepatocytic and portal iron distributions were similar in all three races.Interestingly, the frequency of sinusoidal iron deposition was preferentiallyincreased from 38% to 50% in MA with HCC but not in the other two racialgroups. Furthermore, iron deposition within the tumor tissue was observedin six (46%) MA, but only one C (9%) one AA (11%).Conclusions: The significantly increased prevalence of HCC in malescompared to females with HCV infection could be attributed to a higherrate of hepatic iron deposition in males. Mexican American males had thehighest rate of HCC. Consistent with previous observation, there was anincreased frequency of sinusoidal iron in HCC among Mexican Americanmales. The increased frequency of iron deposition in the tumor tissues mayalso explain their higher prevalence of HCC. These observations suggestthat genetic factors may influence hepatic iron distribution and the patho-genesis of hepatocellular carcinoma in HCV infection.
439
Precore heterogeneity and acute liver injury due to hepatitis B virus(HBV)Premashish Kar DM, FACG, Surinder S Rana MBBS, Bhudev C DasPhD. Department of Medicine and Institute of cytology and preventiveoncology (ICMR) Maulana Azad Medical college, New Delhi, India110002.
The role of the most commonly described precore mutant (point mutationfrom guanine to adenine at nucleotide 83 of the precore region) in patho-genesis of acute liver injury is not clear. We studied the associationbetween precore mutant and acute liver injury by detecting and estimatingthe proportion of the specific precore mutant in serum samples of 12patients with acute viral hepatitis (AVH) and 7 patients of fulminanthepatitis (FH) using polymerase chain reaction (PCR) coupled ligase chainreaction (LCR). After DNA extraction from the serum samples, a segmentof HBV DNA spanning 309 nucleotides was amplified by PCR. To detectthe precore mutant, LCR was done on the DNA amplified by PCR. Toestimate the proportion of mutant virus in individual patients, the signalsgenerated by the LCR bands were measured densitometrically. The resultsof LCR were confirmed by getting PCR product from 3 samples sequenced.Mutant HBV was detected in all the 19 patients, coexisting with the wildtype of HBV but the proportion of mutant HBV was significantly higher inpatients with FH as compared to patients with AVH. However, none of thepatients with FH had HBV that was 100% mutant. Our results suggest thatthe precore mutant of HBV is associated with the development of FH, butit may not by itself account for the development of the disease. It is likelythat this genetic variation along with other variations like core mutationsare important and the clinical outcome is determined by these viral factorsin conjunction with the host factor. Furthermore, since we were able todetect mixed population of HBV in all the patients with acute liver injury,we propose that acute liver injury could be caused by infection with mixedpopulation of HBV whereas infection with pure wild or pure mutant wouldprobably cause subclinical infection. However, further studies involvinglarge sample size are needed to test this hypothesis.
440
Interferon monotherapy: still a valuable strategy for acute hepatitisCSusana Lopes, M.D., Guilherme Macedo, M.D., FACG; FernandoAraujo, M.D.; Tome Ribeiro, M.D., PhD. Gastrenterology Unit,Hospital S. Joao, Porto, Portugal.
Introduction: The consensus meetings on hepatitis C treatment, reassuredthe efficacy and the advantage of combined therapy with interferon andribavirin. Acute hepatitis C is accepted as an indication for treatment,although there is not enough studies defining dose and treatment schedules.Material and methods: Non controlled, open pilot trial, with � interferonadministered to patients with acute hepatitis C. Diagnosis was based ontransaminases elevation, 10 times above normal limit, associated with antiHCV or HCV PCR positivity, with serological, immunological, and bio-chemical exclusion of other causes of acute hepatitis. Interferon wasadministered subcutaneously, 3 times a week, 5MU, for 6 months.Results: We have analysed 8 patients (6 men), that fulfilled diagnosticcriteria. In 7, we had pre treatment histology (demonstrative of acutehepatitis). All of them had transaminases above 300 UI, and the infectionwas acquired by iv drug abuse in 3 patients, renal transplantation in 1patient, sexual transmission in 1, dental care in 1, and sporadic in 2. In allof them transaminases returned to normal during the first 4 months oftherapy. In patients with follow up of more than one year (7), only onepatient (of sporadic transmission, genotype 1b) had PCR � and transami-nases elevation. Side effects were negligiable, and we had no need toreduce or stop interferon therapy.Conclusion: Patients with acute hepatitis C, should be treated with �interferon, given its good tolerability and efficacy, and might preventdisease progression towards cirrhosis.
441
Lamivudine treatment in precore HBV mutantsGuilherme Macedo M.D., FACG, Susana Lopes, M.D., PedroMoutinhoRibeiro M.D., Fernando Araujo M.D., Tome Ribeiro M.D.,PhD. Gastrenterology Unit, Hospital S. Joao, Porto, Portugal.
The proportion of chronic liver disease associated with precore HBVmutant infection, has been rising, particularly in southern european coun-tries. Interferon, in this setting, is associated with a low rate of sustainedresponse, and lamivudine, in preliminary studies has demonstrated a sig-nificative complete sustained response rate.Aim: To evaluate the response rate to lamivudine treatment of precoreHBV mutants infected patients.Material and methods: Patients with chronic active infection with precoreHBV mutant (HBV DNA � 2,5 pg/ml, anti HBe positive, liver histologywith necroinflammatory activity/fibrosis, and transaminases � 2N), weretreated with 150 mg/day lamivudine, for 6 months.Results: From 25 patients (18 men) included for treatment protocol, 18(72%) had negative DNA in the 6th month of therapy and normal transami-nases. In five patients (20%), DNA was not detectable but transaminaseswere abnormal (partial response). In 2 patients, there was detectable DNA(8%). No adverse side effects were observed, nor biochemical changes,attributable to lamivudine.Conclusion: Lamivudine demonstrated a significative supressive effect onthe replication of precore HBV mutant.
COLON
442
Prevalence of medication-associated constipationOlaitan A Adeniji, M.D., and Jack A Di Palma, M.D., FACG*.1Division of Gastroenterology, University of South Alabama, Mobile,AL.
S140 Abstracts AJG – Vol. 96, No. 9, Suppl., 2001
