- Email: [email protected]
Antiviral treatment of hepatitis C in Italian children
Abstracts / Digestive and Liver Disease 41 (2009) A1–A45
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80 + 181 in 2%, 181 + 204 in 2%, 80 + 180 in 1%, 181 + 202 in 1%, and 202 + 233 in 1%. In all cases, mutated viral strains were detected as a minor population (<10%) mixed with the wild-type sequence. Virological response rates at week 48 were similar in patients with and without baseline mutations. In the few patients with detectable viremia at week 48, the RT/polymerase molecular pattern remained unchanged. Conclusions. ETV monotherapy is an effective treatment option for NUC-naïve patients in field practice, the virological response being similar to registration trials. NUCresistance associated mutations were already detected at baseline in a significant proportion of patients, however without clinical impact.
G3 210/373 (56.3%), and G4 36/94 (38.3%)). SVR was 53.1% at large centers, 48.4% at small centers, however SVR in difficult to treat genotypes was less frequently achieved at large centers (G1a 39% vs. 41%, G1b 27% vs. 35%, G4 38% vs. 41%), where comorbidities were more frequent (51% vs. 39%) with cirrhosis (22% vs. 17%) and age >65 years (27% vs. 15%) being the strongest predictors of non-response. Conclusions. (1) The efficacy of combination therapy with PEG-IFNs and RBV in clinical practice is only slightly lower than to the efficacy observed in registration trials. (2) Loss of efficacy is related to the presence of comorbidities, but not to the clinical setting in which the treatment is performed.
doi:10.1016/j.dld.2008.12.017
doi:10.1016/j.dld.2008.12.018
PEG-IFN FOR HEPATITIS C IN CLINICAL PRACTICE
ANTIVIRAL TREATMENT OF HEPATITIS C IN ITALIAN CHILDREN
F. Rosina a,∗ , M.E. Tosti b , E. Borghesio c , A. Mele b , G. Minoli d , A. Gasbarrini e , F. Pallone f , G. Carosi g , F. Mazzotta h , M. Rizzetto (Study Coordinator) c , the AIFA Study Group
R. Giacchino ∗ , F. Bortolotti, G. Indolfi, G. Verucchi, L. Zancan, C. Cammá, L. D’Antiga, M.G. Marazzi, C. Barbera, M. Resti, M. Guido
a
Gastroenterologia & Epatologia, Ospedale Gradenigo, Turin, Italy b Epidemiologia Clinica e Linee Guida, ISS, Rome, Italy c Gastroenterologia & Epatologia, Università di Torino, Turin, Italy d Gastroenterologia, Ospedale Valduce, Como, Italy e Medicina Interna, Policlinico “A. Gemelli”, Rome, Italy f Medicina Interna, Università Tor Vergata, Rome, Italy g Malattie Infettive, Università di Brescia, Italy h Malattie Infettive, Università di Firenze, Florence, Italy Background. Available efficacy data of combination therapy with PEG-IFNs plus Ribavirin are derived from large registration trials enrolling selected patients without comorbidities. Objectives. To assess the effectiveness of PEG-IFNs in the general population of patients with chronic hepatitis C in Italy. Methods. Observational study with a retrospective and prospective phase conducted in a large sample of Italian primary (small centers enrolling <50 pts/year) and tertiary referral centers (large centers enrolling <50 pts/year). Reported data refer to the retrospective phase which enrolled all patients consecutively prescribed HCV therapy in the 12 months before the beginning of the study. Results. 2311/3500 expected patients (66%) were enrolled (naives 80.2%, relapsers 12.3%, NR 7.5%). Genotypes among the 1829 naïve pts were: G1a 10%, G1b 33%, G2 31%, G3 21%, and G4 5%. Comorbidities were present in 839 pts (46%). SVR was obtained in 924 pts (50.5%) (G1a 71/172 (41.3%), G1b 181/582 (31%), G2 402/546 (73.6%),
Gaslini Hospital Genoa, University of Padua, University of Turin, University of Florence, University of Palermo, University of Bologna and Italian Observatory for HCV Infection and Hepatitis C in Children, Italy Background. Chronic hepatitis C has been described as a mild disease in children, but fibrosis progression and early appearance of end stage liver disease have been recently documented. Thus the problem of therapy has become a challenging issue, especially after the recent results of combination therapy (pegIFN + Ribavirin) in adults. We have retrospectively explored the effective and potential role of treatment in a large cohort of pediatric patients recruited in Northern-Central Italy. Methods. Between 1990 and 2007 a consecutive series of 396 HCV-RNA-positive children aged 1–17 years was recruited in 5 tertiary care centers (Padua, Genoa, Turin, Bologna, and Florence) and followed up for an average period of 10 years after putative exposure. Results. Overall 56% were born of infected mother. During observation 25 children, mostly young and perinatally infected, had spontaneously lost HCV RNA. Eighty-seven (22%) were treated: 75 with IFN monotherapy (25% achieved sustained virologic response [SVR]) and 12 with a combination of peg-IFN and Ribavirin (SVR 92% including 5 of 6 children infected with genotype 1). Infection with HCV genotype 1 was significantly associated with poor response to treatment (p < 0.005) whereas genotype 2 was predictive of SVR (p < 0.005). No serious side effects were observed and no patient stopped treatment for adverse events. Two-thirds of patients received treatment during trials and the remaining were treated on compassionate basis. At last visit 165 HCV-RNA-positive children were beyond the pedi-
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Abstracts / Digestive and Liver Disease 41 (2009) A1–A45
atric age and were addressed to the adult outpatient clinic. Overall 176 (45%) children still HCV-RNA-positive, either untreated or non-responders, are waiting for candidacy to treatment. Conclusions. Long-term persistence of HCV replication up to adult life is expected in more than 80% of untreated children. This virological pattern increases social and economic burden of infection and favours comorbidities. Only therapy can change the prognosis. Although our sample is small, the efficacy of combination therapy is evident even in genotype 1 infection. These observations provide justifiable reasons to pursue antiviral therapy in Italian children with hepatitis C. doi:10.1016/j.dld.2008.12.019 HEPATITIS C VIRUS (HCV) INFECTION IN ELDERLY PATIENTS: A MULTICENTER ITALIAN CROSS-SECTIONAL STUDY F. Conti a,∗ , M.L. Morieri a , A. Gramenzi a , C. Cammà b , A. Grieco c , A. Picciotto d , G. Taliani e , D. Romano f , P. Costa g , M. Rendina f , F. Ancarani h , M. Chiaramonte i , G. Verucchi a , A. Craxì b , M. Bernardi a , P. Andreone a , the AISF HepaElder Study Group a
Università di Bologna, Italy di Palermo, Italy c Università Cattolica, Roma, Italy d Università di Genova, Italy e Università di Roma, Italy f Università di Bari, Italy g Ospedale di Mantova, Italy h Università di Ancona, Italy i Università dell’Aquila, Italy b Università
Background and aim. The prevalence of HCV infection increases with advancing age, but the disease has been poorly studied in the elderly. This nationwide cross-sectional study evaluated some epidemiological, virological and clinical aspects of HCV infection in Italian elderly pts. Methods. The study population included all anti-HCV positive pts aged ≥65 years consecutively referred in a 2-year period to Italian liver centers. For each pt data were recorded using a precoded questionnaire. Results. A total of 1544 pts from 34 centers were enrolled. Their mean age was 72 ± 5 years (from 65 to 92) and the males/females ratio was 0.8. Peak prevalence was observed between 65 and 74 years. No one reported a history of injection drug use and in most cases (75%) the source of infection was unknown. An excessive alcohol intake was recorded in 144 pts (9%). HCV-RNA PCR was performed in 1319 (85%) pts and 1104 (84%) tested positive. Genotype 1 showed the highest prevalence in all geographical areas followed by genotype 2. Chronic hepatitis was observed in 1070 (69%) pts, cirrhosis in 385 (25%) and hepatocellular carcinoma in 76 (5%); the remaining 13 (1%) had a diagnosis of previous infection. The prevalence of cirrhosis and liver cancer
increases with aging. Among pts with liver disease, 41% had normal serum ALT levels. Data on antiviral treatment were available for 1531 pts and among them 775 (51%) never received treatment for HCV, mainly because of advanced age followed by the presence of comorbidities. Among treated pts, the sustained virological response rate was significantly better in pts treated after 65 years than in pt treated before (36% vs. 23%; p < 0.001). However, pts treated after 65 years were mainly infected by genotype 2–3 and mainly treated with pegylated interferons. Conclusion. This study shows that about one-third of elderly pts with HCV infection has a severe liver disease, but often normal ALT levels, confirming the difficulty to exactly stage the disease. Older patients can benefit from treatment and age, per se, cannot be considered a contraindication. doi:10.1016/j.dld.2008.12.020 QUALITY OF DECEASED LIVER DONORS IN ITALY AND THEIR ALLOCATION IN RELATION TO RECIPIENT DISEASE SEVERITY M. Angelico ∗,1 , T. Marianelli 1 , A. Ricci 1 The use of “extended criteria” donors is a challenge to face the shortage of organs for liver transplantation, yet limited data are available in Italy. We investigated this issue within the Liver Match project, a nationwide, AISF/CNT-sponsored observational study conducted at 21 Liver Transplant Centers to assess the impact of donor–recipient matching on transplantation outcomes. Data are collected from the National Transplant Ctr (CNT) database, specifically implemented for this project. Methods. We analyzed the data of 895 liver grafts from deceased heart-beating donors transplanted to adult recipients from June 2007 to September 2008. Expanded criteria donors were defined by one or more of the following: ≥60 years; BMI ≥30; macrovesicular steatosis ≥30%; serum sodium >155 mequiv./L; cold ischemia time ≥10 h; partial/split liver. Donor Risk Index (DRI) was computed according to Feng. Results. Donors with at least one “expanded criteria” were 812 (90.7%). The median DRI was 1.63 (range 0.82–3.08). The median age of donors was 55 years (12–97). Donors aged ≥60 years were 363 (40.6%) and those ≥70 years 188 (21%). The median BMI was 24.9 (15.6–39.5). Donors with BMI 25–29 were 348 (39.2%), BMI ≥ 30 were 83 (9.3%) and BMI ≥ 35 17 (1.9%). Macrovesicular steatosis was found in 42 (6.8%) of 614 biopsied donors. Donors deceased for non-traumatic causes were 650 (72.6%). Among these, 503 (77.4%) died due to cerebral haemorrhage. While in ICU 196 donors (22%) had serum sodium > 155 mequiv./L and 653 (73%) received vasoactive drugs. The median cold 1 On behalf of Liver Match investigators: AISF governing board, CNT governing board, Directors of Italian Liver Transplant Programs and AISF fellowship recipients.
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80 + 181 in 2%, 181 + 204 in 2%, 80 + 180 in 1%, 181 + 202 in 1%, and 202 + 233 in 1%. In all cases, mutated viral strains were detected as a minor population (<10%) mixed with the wild-type sequence. Virological response rates at week 48 were similar in patients with and without baseline mutations. In the few patients with detectable viremia at week 48, the RT/polymerase molecular pattern remained unchanged. Conclusions. ETV monotherapy is an effective treatment option for NUC-naïve patients in field practice, the virological response being similar to registration trials. NUCresistance associated mutations were already detected at baseline in a significant proportion of patients, however without clinical impact.
G3 210/373 (56.3%), and G4 36/94 (38.3%)). SVR was 53.1% at large centers, 48.4% at small centers, however SVR in difficult to treat genotypes was less frequently achieved at large centers (G1a 39% vs. 41%, G1b 27% vs. 35%, G4 38% vs. 41%), where comorbidities were more frequent (51% vs. 39%) with cirrhosis (22% vs. 17%) and age >65 years (27% vs. 15%) being the strongest predictors of non-response. Conclusions. (1) The efficacy of combination therapy with PEG-IFNs and RBV in clinical practice is only slightly lower than to the efficacy observed in registration trials. (2) Loss of efficacy is related to the presence of comorbidities, but not to the clinical setting in which the treatment is performed.
doi:10.1016/j.dld.2008.12.017
doi:10.1016/j.dld.2008.12.018
PEG-IFN FOR HEPATITIS C IN CLINICAL PRACTICE
ANTIVIRAL TREATMENT OF HEPATITIS C IN ITALIAN CHILDREN
F. Rosina a,∗ , M.E. Tosti b , E. Borghesio c , A. Mele b , G. Minoli d , A. Gasbarrini e , F. Pallone f , G. Carosi g , F. Mazzotta h , M. Rizzetto (Study Coordinator) c , the AIFA Study Group
R. Giacchino ∗ , F. Bortolotti, G. Indolfi, G. Verucchi, L. Zancan, C. Cammá, L. D’Antiga, M.G. Marazzi, C. Barbera, M. Resti, M. Guido
a
Gastroenterologia & Epatologia, Ospedale Gradenigo, Turin, Italy b Epidemiologia Clinica e Linee Guida, ISS, Rome, Italy c Gastroenterologia & Epatologia, Università di Torino, Turin, Italy d Gastroenterologia, Ospedale Valduce, Como, Italy e Medicina Interna, Policlinico “A. Gemelli”, Rome, Italy f Medicina Interna, Università Tor Vergata, Rome, Italy g Malattie Infettive, Università di Brescia, Italy h Malattie Infettive, Università di Firenze, Florence, Italy Background. Available efficacy data of combination therapy with PEG-IFNs plus Ribavirin are derived from large registration trials enrolling selected patients without comorbidities. Objectives. To assess the effectiveness of PEG-IFNs in the general population of patients with chronic hepatitis C in Italy. Methods. Observational study with a retrospective and prospective phase conducted in a large sample of Italian primary (small centers enrolling <50 pts/year) and tertiary referral centers (large centers enrolling <50 pts/year). Reported data refer to the retrospective phase which enrolled all patients consecutively prescribed HCV therapy in the 12 months before the beginning of the study. Results. 2311/3500 expected patients (66%) were enrolled (naives 80.2%, relapsers 12.3%, NR 7.5%). Genotypes among the 1829 naïve pts were: G1a 10%, G1b 33%, G2 31%, G3 21%, and G4 5%. Comorbidities were present in 839 pts (46%). SVR was obtained in 924 pts (50.5%) (G1a 71/172 (41.3%), G1b 181/582 (31%), G2 402/546 (73.6%),
Gaslini Hospital Genoa, University of Padua, University of Turin, University of Florence, University of Palermo, University of Bologna and Italian Observatory for HCV Infection and Hepatitis C in Children, Italy Background. Chronic hepatitis C has been described as a mild disease in children, but fibrosis progression and early appearance of end stage liver disease have been recently documented. Thus the problem of therapy has become a challenging issue, especially after the recent results of combination therapy (pegIFN + Ribavirin) in adults. We have retrospectively explored the effective and potential role of treatment in a large cohort of pediatric patients recruited in Northern-Central Italy. Methods. Between 1990 and 2007 a consecutive series of 396 HCV-RNA-positive children aged 1–17 years was recruited in 5 tertiary care centers (Padua, Genoa, Turin, Bologna, and Florence) and followed up for an average period of 10 years after putative exposure. Results. Overall 56% were born of infected mother. During observation 25 children, mostly young and perinatally infected, had spontaneously lost HCV RNA. Eighty-seven (22%) were treated: 75 with IFN monotherapy (25% achieved sustained virologic response [SVR]) and 12 with a combination of peg-IFN and Ribavirin (SVR 92% including 5 of 6 children infected with genotype 1). Infection with HCV genotype 1 was significantly associated with poor response to treatment (p < 0.005) whereas genotype 2 was predictive of SVR (p < 0.005). No serious side effects were observed and no patient stopped treatment for adverse events. Two-thirds of patients received treatment during trials and the remaining were treated on compassionate basis. At last visit 165 HCV-RNA-positive children were beyond the pedi-
A8
Abstracts / Digestive and Liver Disease 41 (2009) A1–A45
atric age and were addressed to the adult outpatient clinic. Overall 176 (45%) children still HCV-RNA-positive, either untreated or non-responders, are waiting for candidacy to treatment. Conclusions. Long-term persistence of HCV replication up to adult life is expected in more than 80% of untreated children. This virological pattern increases social and economic burden of infection and favours comorbidities. Only therapy can change the prognosis. Although our sample is small, the efficacy of combination therapy is evident even in genotype 1 infection. These observations provide justifiable reasons to pursue antiviral therapy in Italian children with hepatitis C. doi:10.1016/j.dld.2008.12.019 HEPATITIS C VIRUS (HCV) INFECTION IN ELDERLY PATIENTS: A MULTICENTER ITALIAN CROSS-SECTIONAL STUDY F. Conti a,∗ , M.L. Morieri a , A. Gramenzi a , C. Cammà b , A. Grieco c , A. Picciotto d , G. Taliani e , D. Romano f , P. Costa g , M. Rendina f , F. Ancarani h , M. Chiaramonte i , G. Verucchi a , A. Craxì b , M. Bernardi a , P. Andreone a , the AISF HepaElder Study Group a
Università di Bologna, Italy di Palermo, Italy c Università Cattolica, Roma, Italy d Università di Genova, Italy e Università di Roma, Italy f Università di Bari, Italy g Ospedale di Mantova, Italy h Università di Ancona, Italy i Università dell’Aquila, Italy b Università
Background and aim. The prevalence of HCV infection increases with advancing age, but the disease has been poorly studied in the elderly. This nationwide cross-sectional study evaluated some epidemiological, virological and clinical aspects of HCV infection in Italian elderly pts. Methods. The study population included all anti-HCV positive pts aged ≥65 years consecutively referred in a 2-year period to Italian liver centers. For each pt data were recorded using a precoded questionnaire. Results. A total of 1544 pts from 34 centers were enrolled. Their mean age was 72 ± 5 years (from 65 to 92) and the males/females ratio was 0.8. Peak prevalence was observed between 65 and 74 years. No one reported a history of injection drug use and in most cases (75%) the source of infection was unknown. An excessive alcohol intake was recorded in 144 pts (9%). HCV-RNA PCR was performed in 1319 (85%) pts and 1104 (84%) tested positive. Genotype 1 showed the highest prevalence in all geographical areas followed by genotype 2. Chronic hepatitis was observed in 1070 (69%) pts, cirrhosis in 385 (25%) and hepatocellular carcinoma in 76 (5%); the remaining 13 (1%) had a diagnosis of previous infection. The prevalence of cirrhosis and liver cancer
increases with aging. Among pts with liver disease, 41% had normal serum ALT levels. Data on antiviral treatment were available for 1531 pts and among them 775 (51%) never received treatment for HCV, mainly because of advanced age followed by the presence of comorbidities. Among treated pts, the sustained virological response rate was significantly better in pts treated after 65 years than in pt treated before (36% vs. 23%; p < 0.001). However, pts treated after 65 years were mainly infected by genotype 2–3 and mainly treated with pegylated interferons. Conclusion. This study shows that about one-third of elderly pts with HCV infection has a severe liver disease, but often normal ALT levels, confirming the difficulty to exactly stage the disease. Older patients can benefit from treatment and age, per se, cannot be considered a contraindication. doi:10.1016/j.dld.2008.12.020 QUALITY OF DECEASED LIVER DONORS IN ITALY AND THEIR ALLOCATION IN RELATION TO RECIPIENT DISEASE SEVERITY M. Angelico ∗,1 , T. Marianelli 1 , A. Ricci 1 The use of “extended criteria” donors is a challenge to face the shortage of organs for liver transplantation, yet limited data are available in Italy. We investigated this issue within the Liver Match project, a nationwide, AISF/CNT-sponsored observational study conducted at 21 Liver Transplant Centers to assess the impact of donor–recipient matching on transplantation outcomes. Data are collected from the National Transplant Ctr (CNT) database, specifically implemented for this project. Methods. We analyzed the data of 895 liver grafts from deceased heart-beating donors transplanted to adult recipients from June 2007 to September 2008. Expanded criteria donors were defined by one or more of the following: ≥60 years; BMI ≥30; macrovesicular steatosis ≥30%; serum sodium >155 mequiv./L; cold ischemia time ≥10 h; partial/split liver. Donor Risk Index (DRI) was computed according to Feng. Results. Donors with at least one “expanded criteria” were 812 (90.7%). The median DRI was 1.63 (range 0.82–3.08). The median age of donors was 55 years (12–97). Donors aged ≥60 years were 363 (40.6%) and those ≥70 years 188 (21%). The median BMI was 24.9 (15.6–39.5). Donors with BMI 25–29 were 348 (39.2%), BMI ≥ 30 were 83 (9.3%) and BMI ≥ 35 17 (1.9%). Macrovesicular steatosis was found in 42 (6.8%) of 614 biopsied donors. Donors deceased for non-traumatic causes were 650 (72.6%). Among these, 503 (77.4%) died due to cerebral haemorrhage. While in ICU 196 donors (22%) had serum sodium > 155 mequiv./L and 653 (73%) received vasoactive drugs. The median cold 1 On behalf of Liver Match investigators: AISF governing board, CNT governing board, Directors of Italian Liver Transplant Programs and AISF fellowship recipients.