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High dose interferon monotherapy versus combination high dose interferon and ribavirin for initial treatment of chronic hepatitis C
AJG – September, 2000
Abstracts
2511
hospital care would be $15,000. Sensitivity analysis indicated that the probability of asymptomatic patients requiring hospital care and the proportion of organisms susceptible to low-cost oral antibiotics are important factors. For example, if asymptomatic outpatients with untreated SBP had a greater than 20% chance of developing complications which would require hospitalization, routine cultures for SBP would be cost-saving. The specificity of an ascitic fluid albumin less than 1 gm/dL in diagnosing cirrhotic ascites was 100% and the sensitivity 78%. Similarly, with a total protein less than 1.5 gm/dL, specificity was 100%, sensitivity 82%. Conclusions: Even though the prevalence of SBP in outpatient cirrhotics is low, screening for SBP using cell counts, as well as cultures is costeffective. If oral antibiotics are available that can cover the broad spectrum of SBP infections seen in our practice, then routine cultures may not be necessary. In patients of cirrhosis in whom the suspicion of other disease is low, determination of only total protein or albumin in ascitic fluid may be sufficient.
fibromyalgia and depression were recorded as better, worse or the same as such symptoms pre compensation. The results were compared between those followed up for less than two years with those followed up for between two and four years, as were the results for those who were serum PCR positive with those who were serum PCR negative. Results: All 50 had precompensation fatigue; eight had improved, 33 had not changed and nine were worse. Of the 27 with IBS two had improved, 18 had not changed and seven had got worse. The figures for the 19 with arthralgia were zero, 15 and four. Two, eight and eight were the results for the 18 with fibromyalgia, as were six, 11 and four for the 21 with depression. Neither duration post compensation nor serum PCR status influenced the results. Conclusions: Financial compensation was not shown to benefit symptoms in this group of hepatitis C patients. Fatigue and depression were essentially unaltered: IBS, arthralgia and fibromyalgia increased. The mode of infection and its consequences may be the dominant factor in these results.
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High dose interferon monotherapy versus combination high dose interferon and ribavirin for initial treatment of chronic Hepatitis C Aim: Combination therapy using interferon and ribavirin has been shown to be effective in patients with chronic Hepatitis C. However, the optimal dose of interferon is still yet unclear. We performed a multi-center trial of high dose interferon (5MU) as monotherapy vs. combination therapy using interferon alpha (5MU) and oral ribavirin. Method: 49 Naive patients with chronic Hepatitis C and compensated liver disease initiated therapy in double blind placebo control fashion. Group A received interferon alpha 5MU TIW for first 12 weeks in combination with 600 –1200 mg of oral ribavirin in daily divided doses, then the dose of interferon was reduced to 3 MU TIW for the remainder of the treatment period. Group B received interferon alpha (same doses) with placebo. Pre-treatment LFTs, viral RNA, genotype and liver biopsies were done. Follow-up was up to 24 weeks post-treatment. Viral RNA titers were obtained at 24 and 48 weeks of treatment, and 24 weeks after completion of therapy. Follow-up liver biopsies were also performed. Results: Data was analyzed as intention to treat analysis, using Fischer’s exact test. Sustained viral response was seen in 24% (6/25) of group A and in 12% (3/24) of group B (p ⫽ 0.46). There were no statistically significant differences in viral clearance, or normalization of ALT at 24 weeks of therapy, 48 weeks of therapy, and at 24 weeks of follow-up. This lack of statistical difference was still present when subgroup analysis was performed as a function of genotype (genotype 1 vs. non-genotype 1) and as a function of pre-treatment RNA levels (ⱕ2 Mil copies/ml vs. ⱖ2 Mil. copies/ml. Conclusion: Naive Hepatitis C patients who received combination therapy using induction doses of interferon with ribavirin showed no statistically significant differences when compared to patients who received induction doses of interferon monotherapy alone. However a trend toward better response in the combination group was noted. The lack of difference may have simply been due to the sample size of the study. Quality of life and histologic analyses will be reported at the time of meeting.
Genetic testing and pedigree analysis in an exceptional family with Wilson’s disease. How far should we go by genetic analysis? Ga´bor Firneisz1, M.D., La´szlo´ Szo¨nyi2, M.D., Ferenci Pe´ter3, M.D., Pe´ter L. Lakatos1, M.D., De´nes Go¨ro¨g1, M.D., Claudia Polli3, M.D., Ferenc Szalay1, M.D. 1st Dept. Medicine1, 1st Dept. Pediatrics2, Dept. Transplantation4, Semmelweis University, Budapest, Hungary, 4th Dept. Medicine, Allgemneine Krankenhaus3 Wien, Austria.
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Financial compensation did not reduce hepatitis C symptoms in contaminated anti-D immunoglobulin infected patients John F. Fielding, M.D., FACG. Mater Private Hospital, Dublin 7, Ireland.
Hepatofunctional study of ultraviolet-B (302 nm) irradiated goat hepatocytes Chitoor Mohammed Habibullah*, Vijayalakshmi venkateshan V, Naseem Begum Shakeel, Mohammed Aejaz Habeeb, shashi singh S, Rao MN. Centre For Liver Diseases, Deccan College of Medical Sciences, Hyderabad, AP, India.
Purpose: To determine if financial compensation alleviated symptoms in anti-D immunoglobulin associated hepatitis C infected Irish women. Methods: Fifty consecutive anti-D immunoglobulin associated hepatitis C infected women with symptoms, were reviewed between six months and four years following their reception of financial compensation for their illness. They had all been previously seen prior to the reception of compensation. Their symptoms of fatigue, irritable bowel syndrome, arthralgia,
Background: Wilson’s disease (WD)—as an autosomal recessive hereditary disorder—is characterized by “generation-jump” in inheritance trait. We present manifestation of WD throughout two consecutive generations. Patients: Three (3) patients: the mother (W1) and both of her children (W2a; W2b) suffer from WD. W1 and her husband are second cousins. W1 developed tremor of the extremities and ataxic gait at the age of 31 years. WD was diagnosed two years later. Kayser-Fleischer (K-F) rings were present and D-penicillamine (DPA) treatment was started. Three years later W2a (male, 15 years) developed jaundice. Liver biopsy showed a cirrhotic liver. Six months later orthotopic liver transplantation (OLT) was performed. K-F rings were present before the OLT, but no K-F rings were detectable 22 months later. Copper accumulation was detected in the explanted liver. His sister (W2b, 12 years) was screened and was also found to have WD. Methods: The H1069Q gene mutation was detected by rapid semi-nested polymerase chain reaction (PCR). Inheritance of other mutations was examined by haplotype (D13S301, D13S314 and D13S316) analysis. Results: W1 and W2b are compound heterozygous for the H1069Q gene mutation. In contrast, the H1069Q mutation was not found in W2a. Haplotype analysis indicated W2a is homozygous for an yet unidentified mutation (MUTX) and that both W1 and W2b also carry this mutation. Conclusion: Different mutations of the WD-gene may occur within one family. Detailed genetic analysis of such rare families may provide clues or the understanding of the phenotypic-genotypic correlations of WD-gene mutations. Supported in part by OTKA Grant No. 22453 and ETT 510
Purpose: Ultraviolet B (UV-B) irradiation in the range of 280 –320 nm has shown to be a promising immunomodulatory tool in xenogenic hepatocyte transplantation (XHT) with the achievement of long term survival with or without the need for immunosuppression. Most of the studies on XHT have been carried out on model systems such as rodents with very little infor-
Abstracts
2511
hospital care would be $15,000. Sensitivity analysis indicated that the probability of asymptomatic patients requiring hospital care and the proportion of organisms susceptible to low-cost oral antibiotics are important factors. For example, if asymptomatic outpatients with untreated SBP had a greater than 20% chance of developing complications which would require hospitalization, routine cultures for SBP would be cost-saving. The specificity of an ascitic fluid albumin less than 1 gm/dL in diagnosing cirrhotic ascites was 100% and the sensitivity 78%. Similarly, with a total protein less than 1.5 gm/dL, specificity was 100%, sensitivity 82%. Conclusions: Even though the prevalence of SBP in outpatient cirrhotics is low, screening for SBP using cell counts, as well as cultures is costeffective. If oral antibiotics are available that can cover the broad spectrum of SBP infections seen in our practice, then routine cultures may not be necessary. In patients of cirrhosis in whom the suspicion of other disease is low, determination of only total protein or albumin in ascitic fluid may be sufficient.
fibromyalgia and depression were recorded as better, worse or the same as such symptoms pre compensation. The results were compared between those followed up for less than two years with those followed up for between two and four years, as were the results for those who were serum PCR positive with those who were serum PCR negative. Results: All 50 had precompensation fatigue; eight had improved, 33 had not changed and nine were worse. Of the 27 with IBS two had improved, 18 had not changed and seven had got worse. The figures for the 19 with arthralgia were zero, 15 and four. Two, eight and eight were the results for the 18 with fibromyalgia, as were six, 11 and four for the 21 with depression. Neither duration post compensation nor serum PCR status influenced the results. Conclusions: Financial compensation was not shown to benefit symptoms in this group of hepatitis C patients. Fatigue and depression were essentially unaltered: IBS, arthralgia and fibromyalgia increased. The mode of infection and its consequences may be the dominant factor in these results.
341
343
High dose interferon monotherapy versus combination high dose interferon and ribavirin for initial treatment of chronic Hepatitis C Aim: Combination therapy using interferon and ribavirin has been shown to be effective in patients with chronic Hepatitis C. However, the optimal dose of interferon is still yet unclear. We performed a multi-center trial of high dose interferon (5MU) as monotherapy vs. combination therapy using interferon alpha (5MU) and oral ribavirin. Method: 49 Naive patients with chronic Hepatitis C and compensated liver disease initiated therapy in double blind placebo control fashion. Group A received interferon alpha 5MU TIW for first 12 weeks in combination with 600 –1200 mg of oral ribavirin in daily divided doses, then the dose of interferon was reduced to 3 MU TIW for the remainder of the treatment period. Group B received interferon alpha (same doses) with placebo. Pre-treatment LFTs, viral RNA, genotype and liver biopsies were done. Follow-up was up to 24 weeks post-treatment. Viral RNA titers were obtained at 24 and 48 weeks of treatment, and 24 weeks after completion of therapy. Follow-up liver biopsies were also performed. Results: Data was analyzed as intention to treat analysis, using Fischer’s exact test. Sustained viral response was seen in 24% (6/25) of group A and in 12% (3/24) of group B (p ⫽ 0.46). There were no statistically significant differences in viral clearance, or normalization of ALT at 24 weeks of therapy, 48 weeks of therapy, and at 24 weeks of follow-up. This lack of statistical difference was still present when subgroup analysis was performed as a function of genotype (genotype 1 vs. non-genotype 1) and as a function of pre-treatment RNA levels (ⱕ2 Mil copies/ml vs. ⱖ2 Mil. copies/ml. Conclusion: Naive Hepatitis C patients who received combination therapy using induction doses of interferon with ribavirin showed no statistically significant differences when compared to patients who received induction doses of interferon monotherapy alone. However a trend toward better response in the combination group was noted. The lack of difference may have simply been due to the sample size of the study. Quality of life and histologic analyses will be reported at the time of meeting.
Genetic testing and pedigree analysis in an exceptional family with Wilson’s disease. How far should we go by genetic analysis? Ga´bor Firneisz1, M.D., La´szlo´ Szo¨nyi2, M.D., Ferenci Pe´ter3, M.D., Pe´ter L. Lakatos1, M.D., De´nes Go¨ro¨g1, M.D., Claudia Polli3, M.D., Ferenc Szalay1, M.D. 1st Dept. Medicine1, 1st Dept. Pediatrics2, Dept. Transplantation4, Semmelweis University, Budapest, Hungary, 4th Dept. Medicine, Allgemneine Krankenhaus3 Wien, Austria.
342
344
Financial compensation did not reduce hepatitis C symptoms in contaminated anti-D immunoglobulin infected patients John F. Fielding, M.D., FACG. Mater Private Hospital, Dublin 7, Ireland.
Hepatofunctional study of ultraviolet-B (302 nm) irradiated goat hepatocytes Chitoor Mohammed Habibullah*, Vijayalakshmi venkateshan V, Naseem Begum Shakeel, Mohammed Aejaz Habeeb, shashi singh S, Rao MN. Centre For Liver Diseases, Deccan College of Medical Sciences, Hyderabad, AP, India.
Purpose: To determine if financial compensation alleviated symptoms in anti-D immunoglobulin associated hepatitis C infected Irish women. Methods: Fifty consecutive anti-D immunoglobulin associated hepatitis C infected women with symptoms, were reviewed between six months and four years following their reception of financial compensation for their illness. They had all been previously seen prior to the reception of compensation. Their symptoms of fatigue, irritable bowel syndrome, arthralgia,
Background: Wilson’s disease (WD)—as an autosomal recessive hereditary disorder—is characterized by “generation-jump” in inheritance trait. We present manifestation of WD throughout two consecutive generations. Patients: Three (3) patients: the mother (W1) and both of her children (W2a; W2b) suffer from WD. W1 and her husband are second cousins. W1 developed tremor of the extremities and ataxic gait at the age of 31 years. WD was diagnosed two years later. Kayser-Fleischer (K-F) rings were present and D-penicillamine (DPA) treatment was started. Three years later W2a (male, 15 years) developed jaundice. Liver biopsy showed a cirrhotic liver. Six months later orthotopic liver transplantation (OLT) was performed. K-F rings were present before the OLT, but no K-F rings were detectable 22 months later. Copper accumulation was detected in the explanted liver. His sister (W2b, 12 years) was screened and was also found to have WD. Methods: The H1069Q gene mutation was detected by rapid semi-nested polymerase chain reaction (PCR). Inheritance of other mutations was examined by haplotype (D13S301, D13S314 and D13S316) analysis. Results: W1 and W2b are compound heterozygous for the H1069Q gene mutation. In contrast, the H1069Q mutation was not found in W2a. Haplotype analysis indicated W2a is homozygous for an yet unidentified mutation (MUTX) and that both W1 and W2b also carry this mutation. Conclusion: Different mutations of the WD-gene may occur within one family. Detailed genetic analysis of such rare families may provide clues or the understanding of the phenotypic-genotypic correlations of WD-gene mutations. Supported in part by OTKA Grant No. 22453 and ETT 510
Purpose: Ultraviolet B (UV-B) irradiation in the range of 280 –320 nm has shown to be a promising immunomodulatory tool in xenogenic hepatocyte transplantation (XHT) with the achievement of long term survival with or without the need for immunosuppression. Most of the studies on XHT have been carried out on model systems such as rodents with very little infor-