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Triple combination of interferon a-2b, ribavirin, and amantadine for treatment of chronic hepatitis C
AASLDA1501
April 2000
6786 SEROEPIDEMIOLOGIC STUDY OF ANTI·HEPATITIS A VIRUS IGG DURING 1988-1997 IN CHINJU, KOREA. Hee-Shang Youn, Yun-Kyong Cho, Yang-Suk lung, Eun-leong Kim, Myoung-Bum Choi, Ji-Young Hwang, Hyang-Ok Woo, Gyung-Hyuck Ko, Seung-Chul Baik, Woo-Kon Lee, Myung-Je Cho, Kwang-Ho Rhee, Pediatric, Gyeongsang Natl Univ Coll of Medicine, Chinju, South Korea; Pediatric, Masan Med Ctr, Masan, South Korea; Pediatric, Ulsan Donggang Hosp. Ulsan, South Korea; Pediatric, Masan Samsung Hosp, Masan, South Korea; Pediatric, Chinju, South Korea; Pathology, Chinju, South Korea; Microbiolog y, Chinju, South Korea. Hepatitis A epidemiolgy is changing rapidly, so that the incidence and prevalence data that are a few years old may not be valid today. In Korea, an outbreak of heaptitis A among adolescents and young adults in Taejon, middle part of South Korea, was noted during summer, 1996. A recent report of a shift in anti-hepatitis A IgG antibody prevalence from children to adults in Seoul and Taejon city was very surprising. So we tried to survey the changing pattern of seroprevalence rate of anti-Ha V antibodies among the residents in Chinju, southern central part of Korea over recent 10 years. Serum anti-HAY IgG was measured using the commerciall y available HAVAB radioimmunoassay kit (Abbott laboratories). The sera were collected and stored in deep freezer by age from patients without liver diseases at the Gyeongsang National University Hospital during 19881997. Total 3517 sera were collected and examined . The five two-year groups (l988-1989, 1990-1991, 1992-1993, 1994-1995, 1996-1997) were intentionally made. The age distribution of patients' sera of the each two-year group could be divided into neonates, 3 mo, 9 mo, 15 mo, 21 mo, yearly from 2 to 19 yr, 20-29 yr, 30-39 yr, 40-49 yr, 50-59 yr, and 60-69 yr. The high seropositive rates (over 90%) of anti-HAY IgG among infants did not change for the last 10 years, and these high seropositive rates seemed to represent maternal anti-HAV IgG antibodies transferred through the placenta during pregnancy. The seropositive rates in 15 months-4 years during 1988-1989 was 18%, and it has declined progressively down to 7% for 10 years. The seropositive rates in 5· 9 years during 1988-1989 was 20%, and it has also declined progressively down to 2% for 10 years. The seropositive rates in 10-14 years were 53% during 1988-1989,41 % during 1990-199 1,37% during 1992- 1993, 18% during 1994- 1995, and 4% during 1996-1997. The seropositive rates in 15-19 years were 77% during 19881989, 59% during 1992-1993, 48% during 1994-1995, and 26% during 1996-1997. These changing patterns of seropositive rates of anti-HAY IgG in children and adolescents during 1988-1997 reflect the effect of moving cohort for 10 years. These seroepidemi ological changes of hepatitis A can be attributed to the improvements in socioeconomic, sanitary and hygienic conditions. But, hepatitis A epidemics may occur among adolescents and young adults in our society when our socioeconomic status draws back. So, we should try to find out the plausible preventive modalities against hepatitis A infection among adolescents and young adults at risk. 6787 TRIPLE COMBINATION OF INTERFERON A-2B, RmAVIRIN, AND AMANTADINE FOR TREATMENT OF CHRONIC HEPATI· TIS C. Zobair M. Younossi, Kevin D. Mullen, Sandra Hodnick, Marilyn McCormick, Diane Bringman, David S. Bame s, William D. Carey, Arthur J. McCullough, Kirk Easley, Belinda Yen-Lieberman, Cleveland Clin Fdn, Cleveland, OH; Metrohealth Med Ctr, Cleveland, OH. Retreatment of chronic hepatitis C (non-responders to interferon monotherapy or Rebetron) is quite difficult. Aim: In a pilot study, the efficacy of triple com bination therapy in this group of patients was assessed. Design: I. Twenty patients with chronic hepatitis C, previously treated with interfeon monotherapy followed by 6 months of combination therapy (lntron A 3 MU T.I.W. + Ribavirin 800 mg/d (Group A; n= 10) and Intron A 3 MU T.I.W. + Amantadine 200 mg/d (Group B; n= 10) were enrolled. Patients had no previous virologic or biochemical response to either IFN monotherapy or combination regimens [elevated ALT and HCV RNA (+) by PCR]. 2. After one month of discontinuation of the last regimen, patients were re-started on Intron A 3 MU TIW , Ribavirin 800 mg/d and Amantadine 200 mg/d. 3. Bichemical (ALT), virologic (HCV RNA by PCR), and quality of life (CLDQ and SF-36) endpoints were monitored. Results: 60 % of patients were male with an age of 42.9±4.9, 85% white, 85% with genotype I and 20% with histologic cirrhosis. Their baseline HCV RNA was 1,845,150 ± 1,279,069 copies/ml and their baseline ALT was 130± 100. Of20 patients with week 12 HCV RNA, 9 (45%) had eradicated the virus early. Five patients discontinued treatment (prior to week 24) due to side effects. Of 10 patients with week 24 HCV RNA, 4 (40%) remain negative. Both 12 and 24 week virologic responses were equally divided among those previously treated with Intron A + Ribavirin and those treated
with Intron A +Amantadine. Conclusions: Triple combination therapy seems to be associated with significant early viral eradication in patients who are non-responders to both interferon monotherapy and combination therapy. Data for the follow-ups and sustained response rates are currently being collected.
60 50 40 0;. II C \'
30
R ;';,\ (. )
20 10 0 12 w
24 w
Duration of Thera py Gr A D Gr B
I
6788 INDUCTION VS. STANDARD INTERFERON MONOTHERAPY FOR PATIENTS WITH HCV VIREMIA AND NORMAL ALT. Zobair M. Younossi, Arthur J. McCullough , Nancy Buchler , Barbara Donofrio, Navdeep Boparai, Kevin D. Mullen, William D. Carey, David S. Bames , Terry L. Gramlich, Cleveland Clin Fdn, Cleveland. OH; Metrohealth Med Ctr, Cleveland , au. Efficacy of anti-viral therapy in patients with HCV infection and persistently normal ALT is not established. Aim: In a randomized controlled trial, the efficacy of standard interferon monotherapy was compared to an induction protocol. Design :1. Patients with positive HCV RNA and persistently normal ALT (on 3 occasions) were enrolled and randomized to either standard interferon monotherapy (S: interferon a -2a 3 MU T.I.W) or an induction regimen (I: interferon a-2a 6 MU QD for 4 weeks followed by 3 MU T.I.W.). 2. All patients without early virologic response [HCV RNA ( + ) after 12 weeks of therapy] were discontinued. All others cornpleted a full 48 week course of therapy . 3. Biochemical (ALT), virologic (HCV RNA by PCR), and quality of life (HRQL) (CLDQ and SF-36) endpoints were monitored. Results: I. There were no difference s between the standard interferon monotherapy and induction regimen with respect to age (44±5 vs. 43±6). %males (42 vs, 50). %cirrhotics (0 vs. 3), %geno· type I (73 vs. 82), initial ALT (31± 9 vs, 35±8), initial HCY RNA (1.3± 1.2 million vs. 1.2±0.7 million), and HCY RNA at week 12 of therapy (0.7± 0.8 million vs. 0.52±0.6 million). 2. Baseline liver biopsy showed mild activity and early stage (49% without fibrosis, 39% with mild portal fibrosis, 6% with focal bridging fibrosis, 3% with bridging fibrosis and 3% with cirrhosis ). Although there was a significant drop in HCV RNA with the induction regimen, no one achieved early (l 2 weeks) virologic clearance . After 12 weeks of therapy, only 2 patients in the standard therapy became HCV RNA negative as compared to no one in the induetion regimen (p= 0.23). 3. After 12 weeks of therapy, 33% of patients in the standard therapy vs. 38% of the induction regimen developed abnormal ALT (p=0.62). 4. II % of patients on the standard therapy vs. 6% of those on the induction regimen discontinued early due to side effects. 5. HeV infected individuals had significant HRQL impairment prior to initiation of therapy [as compared to normals and type II diabetics (P<0.05)]. This impairment worsened in some of the HRQL domains during interferon therapy. Conclusion s: Standard interferon monotherapy or induction regimen in patients with HCV viremia and persistently normal ALT is associated with low efficacy and substantial impairment of HRQL.
April 2000
6786 SEROEPIDEMIOLOGIC STUDY OF ANTI·HEPATITIS A VIRUS IGG DURING 1988-1997 IN CHINJU, KOREA. Hee-Shang Youn, Yun-Kyong Cho, Yang-Suk lung, Eun-leong Kim, Myoung-Bum Choi, Ji-Young Hwang, Hyang-Ok Woo, Gyung-Hyuck Ko, Seung-Chul Baik, Woo-Kon Lee, Myung-Je Cho, Kwang-Ho Rhee, Pediatric, Gyeongsang Natl Univ Coll of Medicine, Chinju, South Korea; Pediatric, Masan Med Ctr, Masan, South Korea; Pediatric, Ulsan Donggang Hosp. Ulsan, South Korea; Pediatric, Masan Samsung Hosp, Masan, South Korea; Pediatric, Chinju, South Korea; Pathology, Chinju, South Korea; Microbiolog y, Chinju, South Korea. Hepatitis A epidemiolgy is changing rapidly, so that the incidence and prevalence data that are a few years old may not be valid today. In Korea, an outbreak of heaptitis A among adolescents and young adults in Taejon, middle part of South Korea, was noted during summer, 1996. A recent report of a shift in anti-hepatitis A IgG antibody prevalence from children to adults in Seoul and Taejon city was very surprising. So we tried to survey the changing pattern of seroprevalence rate of anti-Ha V antibodies among the residents in Chinju, southern central part of Korea over recent 10 years. Serum anti-HAY IgG was measured using the commerciall y available HAVAB radioimmunoassay kit (Abbott laboratories). The sera were collected and stored in deep freezer by age from patients without liver diseases at the Gyeongsang National University Hospital during 19881997. Total 3517 sera were collected and examined . The five two-year groups (l988-1989, 1990-1991, 1992-1993, 1994-1995, 1996-1997) were intentionally made. The age distribution of patients' sera of the each two-year group could be divided into neonates, 3 mo, 9 mo, 15 mo, 21 mo, yearly from 2 to 19 yr, 20-29 yr, 30-39 yr, 40-49 yr, 50-59 yr, and 60-69 yr. The high seropositive rates (over 90%) of anti-HAY IgG among infants did not change for the last 10 years, and these high seropositive rates seemed to represent maternal anti-HAV IgG antibodies transferred through the placenta during pregnancy. The seropositive rates in 15 months-4 years during 1988-1989 was 18%, and it has declined progressively down to 7% for 10 years. The seropositive rates in 5· 9 years during 1988-1989 was 20%, and it has also declined progressively down to 2% for 10 years. The seropositive rates in 10-14 years were 53% during 1988-1989,41 % during 1990-199 1,37% during 1992- 1993, 18% during 1994- 1995, and 4% during 1996-1997. The seropositive rates in 15-19 years were 77% during 19881989, 59% during 1992-1993, 48% during 1994-1995, and 26% during 1996-1997. These changing patterns of seropositive rates of anti-HAY IgG in children and adolescents during 1988-1997 reflect the effect of moving cohort for 10 years. These seroepidemi ological changes of hepatitis A can be attributed to the improvements in socioeconomic, sanitary and hygienic conditions. But, hepatitis A epidemics may occur among adolescents and young adults in our society when our socioeconomic status draws back. So, we should try to find out the plausible preventive modalities against hepatitis A infection among adolescents and young adults at risk. 6787 TRIPLE COMBINATION OF INTERFERON A-2B, RmAVIRIN, AND AMANTADINE FOR TREATMENT OF CHRONIC HEPATI· TIS C. Zobair M. Younossi, Kevin D. Mullen, Sandra Hodnick, Marilyn McCormick, Diane Bringman, David S. Bame s, William D. Carey, Arthur J. McCullough, Kirk Easley, Belinda Yen-Lieberman, Cleveland Clin Fdn, Cleveland, OH; Metrohealth Med Ctr, Cleveland, OH. Retreatment of chronic hepatitis C (non-responders to interferon monotherapy or Rebetron) is quite difficult. Aim: In a pilot study, the efficacy of triple com bination therapy in this group of patients was assessed. Design: I. Twenty patients with chronic hepatitis C, previously treated with interfeon monotherapy followed by 6 months of combination therapy (lntron A 3 MU T.I.W. + Ribavirin 800 mg/d (Group A; n= 10) and Intron A 3 MU T.I.W. + Amantadine 200 mg/d (Group B; n= 10) were enrolled. Patients had no previous virologic or biochemical response to either IFN monotherapy or combination regimens [elevated ALT and HCV RNA (+) by PCR]. 2. After one month of discontinuation of the last regimen, patients were re-started on Intron A 3 MU TIW , Ribavirin 800 mg/d and Amantadine 200 mg/d. 3. Bichemical (ALT), virologic (HCV RNA by PCR), and quality of life (CLDQ and SF-36) endpoints were monitored. Results: 60 % of patients were male with an age of 42.9±4.9, 85% white, 85% with genotype I and 20% with histologic cirrhosis. Their baseline HCV RNA was 1,845,150 ± 1,279,069 copies/ml and their baseline ALT was 130± 100. Of20 patients with week 12 HCV RNA, 9 (45%) had eradicated the virus early. Five patients discontinued treatment (prior to week 24) due to side effects. Of 10 patients with week 24 HCV RNA, 4 (40%) remain negative. Both 12 and 24 week virologic responses were equally divided among those previously treated with Intron A + Ribavirin and those treated
with Intron A +Amantadine. Conclusions: Triple combination therapy seems to be associated with significant early viral eradication in patients who are non-responders to both interferon monotherapy and combination therapy. Data for the follow-ups and sustained response rates are currently being collected.
60 50 40 0;. II C \'
30
R ;';,\ (. )
20 10 0 12 w
24 w
Duration of Thera py Gr A D Gr B
I
6788 INDUCTION VS. STANDARD INTERFERON MONOTHERAPY FOR PATIENTS WITH HCV VIREMIA AND NORMAL ALT. Zobair M. Younossi, Arthur J. McCullough , Nancy Buchler , Barbara Donofrio, Navdeep Boparai, Kevin D. Mullen, William D. Carey, David S. Bames , Terry L. Gramlich, Cleveland Clin Fdn, Cleveland. OH; Metrohealth Med Ctr, Cleveland , au. Efficacy of anti-viral therapy in patients with HCV infection and persistently normal ALT is not established. Aim: In a randomized controlled trial, the efficacy of standard interferon monotherapy was compared to an induction protocol. Design :1. Patients with positive HCV RNA and persistently normal ALT (on 3 occasions) were enrolled and randomized to either standard interferon monotherapy (S: interferon a -2a 3 MU T.I.W) or an induction regimen (I: interferon a-2a 6 MU QD for 4 weeks followed by 3 MU T.I.W.). 2. All patients without early virologic response [HCV RNA ( + ) after 12 weeks of therapy] were discontinued. All others cornpleted a full 48 week course of therapy . 3. Biochemical (ALT), virologic (HCV RNA by PCR), and quality of life (HRQL) (CLDQ and SF-36) endpoints were monitored. Results: I. There were no difference s between the standard interferon monotherapy and induction regimen with respect to age (44±5 vs. 43±6). %males (42 vs, 50). %cirrhotics (0 vs. 3), %geno· type I (73 vs. 82), initial ALT (31± 9 vs, 35±8), initial HCY RNA (1.3± 1.2 million vs. 1.2±0.7 million), and HCY RNA at week 12 of therapy (0.7± 0.8 million vs. 0.52±0.6 million). 2. Baseline liver biopsy showed mild activity and early stage (49% without fibrosis, 39% with mild portal fibrosis, 6% with focal bridging fibrosis, 3% with bridging fibrosis and 3% with cirrhosis ). Although there was a significant drop in HCV RNA with the induction regimen, no one achieved early (l 2 weeks) virologic clearance . After 12 weeks of therapy, only 2 patients in the standard therapy became HCV RNA negative as compared to no one in the induetion regimen (p= 0.23). 3. After 12 weeks of therapy, 33% of patients in the standard therapy vs. 38% of the induction regimen developed abnormal ALT (p=0.62). 4. II % of patients on the standard therapy vs. 6% of those on the induction regimen discontinued early due to side effects. 5. HeV infected individuals had significant HRQL impairment prior to initiation of therapy [as compared to normals and type II diabetics (P<0.05)]. This impairment worsened in some of the HRQL domains during interferon therapy. Conclusion s: Standard interferon monotherapy or induction regimen in patients with HCV viremia and persistently normal ALT is associated with low efficacy and substantial impairment of HRQL.