- Email: [email protected]
A reduction in the hepatic venous pressure gradient (HVPG) prevents clinical outcomes in compensated and decompensated cirrhosis: a meta-analysis
POSTER PRESENTATIONS 13
Royal Melbourne Hospital, Parkville, Australia; 14St. Michael’s Medical Center, Newark; 15Johns Hopkins University School of Medicine, Baltimore, United States E-mail: [email protected] Background and Aims: Pangenotypic, once-daily glecaprevir (identified by AbbVie and Enanta) co-formulated with pibrentasvir (G/P) has demonstrated high rates of sustained virologic response (HCV RNA < lower limit of quantification [LLOQ]) at 12 weeks posttreatment (SVR12) in patients with hepatitis C virus (HCV) genotype (GT) 1-6 infection. This phase 3 study evaluated the efficacy and safety of G/P in patients with chronic HCV GT1–6 infection and HIV-1 co-infection, including patients with compensated cirrhosis. Methods: EXPEDITION-2 (NCT02738138) is a phase 3, multicenter, open-label study evaluating G/P (300 mg/120 mg) treatment in HCV/ HIV-1 co-infected adults without or with compensated cirrhosis for 8 or 12 weeks, respectively. Patients were either HCV treatment-naïve or experienced with interferon (IFN), pegylated IFN ± ribavirin, or sofosbuvir + ribavirin ± pegylated IFN. GT3 treatment-experienced patients were excluded. The primary endpoint was the proportion of patients with SVR12. Results: In total, 153 patients were enrolled, including 16 (10%) with cirrhosis. Baseline demographics are shown in Table 1. Rates of response at post-treatment week 4 (SVR4) were 98.7% (151/153, 95% CI 95.4–99.6). One patient with GT3a infection and cirrhosis had ontreatment virologic failure at treatment week 8. The most common adverse events (AEs) were fatigue (18/153; 12%) and nausea (13/153; 9%). Three patients (2%) had serious AEs, both unrelated to G/P. One patient with cirrhosis had serious AEs of cerebrovascular accident and cerebral hemorrhage on Day 23 that led to treatment discontinuation; this patient had HCV RNA
Characteristic
Without Cirrhosis 8 Weeks N = 137
With Cirrhosis 12 Weeks N = 16
113 (83) 84/12/22/16/0/3 45 (23–74)
15 (94) 10/1/4/1/0/0 50 (35–62)
103 (77) 24 (18) 26 (19) 23 (17) 3 (2) 6.2 (4.0–7.4)
15 (94) 1 (6) 2 (13) 2 (13) 0 6.1 (4.4–7.0)
9/137 (7) 39 (29) 62 (45) 27 (20) 92 (67)
0 6 (38) 5 (31) 5 (31) 9 (56)
Male, n (%) Genotype 1/2/3/4/5/6, n Age, median (range), years Race, n (%)* White Black HCV treatment-experienced Interferon-based Sofosbuvir-based HCV RNA, median (range), log10 IU/milliliter Antiretroviral therapy-naive Raltegravir anchor ARV, n (%) Dolutegravir anchor ARV, n (%) Rilpivirine anchor ARV, n (%) CD4+ cell count ≥500 cells/mm3, n (%) *Race was self-reported
Table 2: Laboratory Abnormalities*
Event, n (%) ALT, grade ≥3 (>5 × ULN) AST, grade ≥3 (>5 × ULN) Total bilirubin, grade ≥3 (>3 × ULN) *Grade must be more extreme than baseline
Without Cirrhosis 8 Weeks N = 137
With Cirrhosis 12 Weeks N = 16
0 0 1 (0.7)
0 0 0
Conclusions: G/P for 8 weeks in non-cirrhotic and 12 weeks in cirrhotic patients is a well-tolerated treatment for HCV/HIV-1 coinfection with high SVR4 rates to date, regardless of baseline HCV RNA or prior IFN or sofosbuvir treatment experience. Full SVR12 rates and available data on baseline NS3 and NS5A polymorphisms will be presented. LBP-523 A reduction in the hepatic venous pressure gradient (HVPG) prevents clinical outcomes in compensated and decompensated cirrhosis: a meta-analysis L. Turco1, C. Villanueva2, V. La Mura3, J.C. Garcia-Pagan4, T. Reiberger5, J. Genesca6, R.J. Groszmann7, B.C. Sharma8, C. Merkel9, C. Bureau10, E. Alvarado2, J.G. Abraldes11, A. Albillos12, R. Banares13, M. Peck-Radosavljevic14, S. Augustin15, S. Sarin16, J. Bosch4, G. Garcia-Tsao7. 1Division of Gastroenterology, Azienda OspedalieroUniversitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy; 2Department of Gastroenterology, Hospital de Sant Pau, Barcelona. Autonomous University, Barcelona, Spain; 3First Division of Internal Medicine, IRCCS Policlinico San Donato, University of Milan, Milano, Italy; 4Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; 6Liver Unit, Liver Disease Laboratory, Internal Medicine Department, Vall d’Hebron Institut Recerca (VHIR)-HUVH), Barcelona, Spain; 7Section of Digestive Diseases, VA-Connecticut Healthcare System, Yale School of Medicine, New Haven, United States; 8Department of Gastroenterology, Pant Institute of Postgraduate Medical Education and Research, New Delhi, India; 9 Hepatic Hemodynamic Laboratory and Clinica Medica 5, Department of Medicine, University of Padua, Padua, Italy; 10Service d’hépato-gastroentérologie CHU, Toulouse Hôpital Purpan et Université Paul Sabatier, Toulouse, France; 11Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), University of Alberta, CEGIIR, Edmonton, Canada; 12Hospital Ramon y Cajal; 13Department of Gastroenterology, Hospital General Universitario Gregorio Marañon, Madrid, Spain; 14Medical University of Vienna, Vienna, Austria; 15Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; 16 Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, Off Abdul Gaffar Khan Marg, New Delhi, India E-mail: [email protected] Background and Aims: Cirrhosis consists of two distinct prognostic stages, compensated and decompensated. A reduction in HVPG by pharmacological therapy has been shown to decrease variceal hemorrhage (VH) and death in a meta-analysis of several studies (D’Amico, Gastroenterology 2006). Because these studies combined compensated and decompensated patients, we aimed to determine whether HVPG reductions are equally predictive of outcomes in these two different stages. Methods: Since data could not be extracted from published studies, we obtained data from investigators of 15 studies that assessed HVPG response in the setting of trials of primary ( patients without prior VH) or secondary ( patients with VH) prophylaxis in which patients received non-selective beta-blockers as main therapy and for whom clinically relevant outcomes were available. We used history or presence of ascites as the event defining cirrhosis decompensation. Results: Data from 1,113 unique patients was obtained. Metaanalyses were performed separately for those with and without ascites. Except for 120 patients (11%) in whom response was defined as a HVPG decrease >10% or to <12 mmHg, in all others HVPG response was defined as a decrease to <12 mmHg or >20% from baseline. a. Patients without ascites (“compensated”, n = 661): HVPG responders (50%) had a significantly lower rate of events (ascites, VH or encephalopathy) than nonresponders (Figure, upper panel) with significant heterogeneity ( p = 0.05) that disappeared after
Journal of Hepatology 2017 vol. 66 | S95–S332
S103
POSTER PRESENTATIONS
Figure: (abstract: LBP-523) stratifying by type of trial ( primary vs. secondary prophylaxis). Death/transplant rates were lower among responders (OR 0.49 [95% CI 0.33–0.72]). b. Patients with ascites (“decompensated”, n = 452) HVPG responders (42%) had a significantly lower rate of events (VH, refractory ascites, spontaneous bacterial peritonitis or hepatorenal syndrome) than non-responders, without significant heterogeneity. Death/ transplant rates were lower among responders (OR (0.26 [95% CI 0.17–0.41). Conclusions: This study demonstrates, for the first time, that HVPG responders are less likely to develop clinically relevant outcomes in both patients with and without ascites LBP-524 Severe periodontitis predicts higher cirrhosis mortality L.L. Grønkjær1, P. Holmstrup2, S. Schou3, P. Jepsen1,4, H. Vilstrup1. 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus; 2Section of Periodontology, Microbiology, and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences; 3Section for Oral and Maxillofacial Surgery, Department of Odontology, Faculty of Health and Medical Sciences, S104
University of Copenhagen, Copenhagen; 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark E-mail: [email protected] Background and Aims: Periodontitis is prevalent in patients with cirrhosis and may lead to systemic infections which are strong risk factors for the patients’ high morbidity and mortality. Our aim was to determine the association of periodontitis with all-cause and cirrhosis-related mortality in a prospective cohort study. Methods: A total of 184 patients were enrolled consecutively and followed for one year. Blood samples, sociodemographics, and disease-related data were collected, and a detailed clinical oral examination was performed. Severe periodontitis was defined by standard criteria comprising 2 or more sites with clinical attachment level of 6 mm or more on different teeth and 1 or more sites with probing depth of 5 mm or more. All-cause and cirrhosis-related mortality was recorded. The association of periodontitis with mortality were explored by Kaplan-Meier survival plots and Cox proportional hazards regression adjusted for age, gender, cirrhosis etiology, Child-Pugh score, Model of End-Stage Liver Disease score, smoker status, present alcohol use, comorbidity, and nutritional risk score.
Journal of Hepatology 2017 vol. 66 | S95–S332
Royal Melbourne Hospital, Parkville, Australia; 14St. Michael’s Medical Center, Newark; 15Johns Hopkins University School of Medicine, Baltimore, United States E-mail: [email protected] Background and Aims: Pangenotypic, once-daily glecaprevir (identified by AbbVie and Enanta) co-formulated with pibrentasvir (G/P) has demonstrated high rates of sustained virologic response (HCV RNA < lower limit of quantification [LLOQ]) at 12 weeks posttreatment (SVR12) in patients with hepatitis C virus (HCV) genotype (GT) 1-6 infection. This phase 3 study evaluated the efficacy and safety of G/P in patients with chronic HCV GT1–6 infection and HIV-1 co-infection, including patients with compensated cirrhosis. Methods: EXPEDITION-2 (NCT02738138) is a phase 3, multicenter, open-label study evaluating G/P (300 mg/120 mg) treatment in HCV/ HIV-1 co-infected adults without or with compensated cirrhosis for 8 or 12 weeks, respectively. Patients were either HCV treatment-naïve or experienced with interferon (IFN), pegylated IFN ± ribavirin, or sofosbuvir + ribavirin ± pegylated IFN. GT3 treatment-experienced patients were excluded. The primary endpoint was the proportion of patients with SVR12. Results: In total, 153 patients were enrolled, including 16 (10%) with cirrhosis. Baseline demographics are shown in Table 1. Rates of response at post-treatment week 4 (SVR4) were 98.7% (151/153, 95% CI 95.4–99.6). One patient with GT3a infection and cirrhosis had ontreatment virologic failure at treatment week 8. The most common adverse events (AEs) were fatigue (18/153; 12%) and nausea (13/153; 9%). Three patients (2%) had serious AEs, both unrelated to G/P. One patient with cirrhosis had serious AEs of cerebrovascular accident and cerebral hemorrhage on Day 23 that led to treatment discontinuation; this patient had HCV RNA
Characteristic
Without Cirrhosis 8 Weeks N = 137
With Cirrhosis 12 Weeks N = 16
113 (83) 84/12/22/16/0/3 45 (23–74)
15 (94) 10/1/4/1/0/0 50 (35–62)
103 (77) 24 (18) 26 (19) 23 (17) 3 (2) 6.2 (4.0–7.4)
15 (94) 1 (6) 2 (13) 2 (13) 0 6.1 (4.4–7.0)
9/137 (7) 39 (29) 62 (45) 27 (20) 92 (67)
0 6 (38) 5 (31) 5 (31) 9 (56)
Male, n (%) Genotype 1/2/3/4/5/6, n Age, median (range), years Race, n (%)* White Black HCV treatment-experienced Interferon-based Sofosbuvir-based HCV RNA, median (range), log10 IU/milliliter Antiretroviral therapy-naive Raltegravir anchor ARV, n (%) Dolutegravir anchor ARV, n (%) Rilpivirine anchor ARV, n (%) CD4+ cell count ≥500 cells/mm3, n (%) *Race was self-reported
Table 2: Laboratory Abnormalities*
Event, n (%) ALT, grade ≥3 (>5 × ULN) AST, grade ≥3 (>5 × ULN) Total bilirubin, grade ≥3 (>3 × ULN) *Grade must be more extreme than baseline
Without Cirrhosis 8 Weeks N = 137
With Cirrhosis 12 Weeks N = 16
0 0 1 (0.7)
0 0 0
Conclusions: G/P for 8 weeks in non-cirrhotic and 12 weeks in cirrhotic patients is a well-tolerated treatment for HCV/HIV-1 coinfection with high SVR4 rates to date, regardless of baseline HCV RNA or prior IFN or sofosbuvir treatment experience. Full SVR12 rates and available data on baseline NS3 and NS5A polymorphisms will be presented. LBP-523 A reduction in the hepatic venous pressure gradient (HVPG) prevents clinical outcomes in compensated and decompensated cirrhosis: a meta-analysis L. Turco1, C. Villanueva2, V. La Mura3, J.C. Garcia-Pagan4, T. Reiberger5, J. Genesca6, R.J. Groszmann7, B.C. Sharma8, C. Merkel9, C. Bureau10, E. Alvarado2, J.G. Abraldes11, A. Albillos12, R. Banares13, M. Peck-Radosavljevic14, S. Augustin15, S. Sarin16, J. Bosch4, G. Garcia-Tsao7. 1Division of Gastroenterology, Azienda OspedalieroUniversitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy; 2Department of Gastroenterology, Hospital de Sant Pau, Barcelona. Autonomous University, Barcelona, Spain; 3First Division of Internal Medicine, IRCCS Policlinico San Donato, University of Milan, Milano, Italy; 4Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; 6Liver Unit, Liver Disease Laboratory, Internal Medicine Department, Vall d’Hebron Institut Recerca (VHIR)-HUVH), Barcelona, Spain; 7Section of Digestive Diseases, VA-Connecticut Healthcare System, Yale School of Medicine, New Haven, United States; 8Department of Gastroenterology, Pant Institute of Postgraduate Medical Education and Research, New Delhi, India; 9 Hepatic Hemodynamic Laboratory and Clinica Medica 5, Department of Medicine, University of Padua, Padua, Italy; 10Service d’hépato-gastroentérologie CHU, Toulouse Hôpital Purpan et Université Paul Sabatier, Toulouse, France; 11Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), University of Alberta, CEGIIR, Edmonton, Canada; 12Hospital Ramon y Cajal; 13Department of Gastroenterology, Hospital General Universitario Gregorio Marañon, Madrid, Spain; 14Medical University of Vienna, Vienna, Austria; 15Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; 16 Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, Off Abdul Gaffar Khan Marg, New Delhi, India E-mail: [email protected] Background and Aims: Cirrhosis consists of two distinct prognostic stages, compensated and decompensated. A reduction in HVPG by pharmacological therapy has been shown to decrease variceal hemorrhage (VH) and death in a meta-analysis of several studies (D’Amico, Gastroenterology 2006). Because these studies combined compensated and decompensated patients, we aimed to determine whether HVPG reductions are equally predictive of outcomes in these two different stages. Methods: Since data could not be extracted from published studies, we obtained data from investigators of 15 studies that assessed HVPG response in the setting of trials of primary ( patients without prior VH) or secondary ( patients with VH) prophylaxis in which patients received non-selective beta-blockers as main therapy and for whom clinically relevant outcomes were available. We used history or presence of ascites as the event defining cirrhosis decompensation. Results: Data from 1,113 unique patients was obtained. Metaanalyses were performed separately for those with and without ascites. Except for 120 patients (11%) in whom response was defined as a HVPG decrease >10% or to <12 mmHg, in all others HVPG response was defined as a decrease to <12 mmHg or >20% from baseline. a. Patients without ascites (“compensated”, n = 661): HVPG responders (50%) had a significantly lower rate of events (ascites, VH or encephalopathy) than nonresponders (Figure, upper panel) with significant heterogeneity ( p = 0.05) that disappeared after
Journal of Hepatology 2017 vol. 66 | S95–S332
S103
POSTER PRESENTATIONS
Figure: (abstract: LBP-523) stratifying by type of trial ( primary vs. secondary prophylaxis). Death/transplant rates were lower among responders (OR 0.49 [95% CI 0.33–0.72]). b. Patients with ascites (“decompensated”, n = 452) HVPG responders (42%) had a significantly lower rate of events (VH, refractory ascites, spontaneous bacterial peritonitis or hepatorenal syndrome) than non-responders, without significant heterogeneity. Death/ transplant rates were lower among responders (OR (0.26 [95% CI 0.17–0.41). Conclusions: This study demonstrates, for the first time, that HVPG responders are less likely to develop clinically relevant outcomes in both patients with and without ascites LBP-524 Severe periodontitis predicts higher cirrhosis mortality L.L. Grønkjær1, P. Holmstrup2, S. Schou3, P. Jepsen1,4, H. Vilstrup1. 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus; 2Section of Periodontology, Microbiology, and Community Dentistry, Department of Odontology, Faculty of Health and Medical Sciences; 3Section for Oral and Maxillofacial Surgery, Department of Odontology, Faculty of Health and Medical Sciences, S104
University of Copenhagen, Copenhagen; 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark E-mail: [email protected] Background and Aims: Periodontitis is prevalent in patients with cirrhosis and may lead to systemic infections which are strong risk factors for the patients’ high morbidity and mortality. Our aim was to determine the association of periodontitis with all-cause and cirrhosis-related mortality in a prospective cohort study. Methods: A total of 184 patients were enrolled consecutively and followed for one year. Blood samples, sociodemographics, and disease-related data were collected, and a detailed clinical oral examination was performed. Severe periodontitis was defined by standard criteria comprising 2 or more sites with clinical attachment level of 6 mm or more on different teeth and 1 or more sites with probing depth of 5 mm or more. All-cause and cirrhosis-related mortality was recorded. The association of periodontitis with mortality were explored by Kaplan-Meier survival plots and Cox proportional hazards regression adjusted for age, gender, cirrhosis etiology, Child-Pugh score, Model of End-Stage Liver Disease score, smoker status, present alcohol use, comorbidity, and nutritional risk score.
Journal of Hepatology 2017 vol. 66 | S95–S332