- Email: [email protected]
P0137 : Safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation. Analysis from a French multicenter, open-label study (ANRS HC29 bocepretransplant)
POSTERS mortality. Systemic hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis. Vasopressin is a key-regulator in hemodynamic homeostasis. Aim of the present study was to assess in patients with AD whether genetic variation of the human arginine vasopressin 1A receptor (AVP1aR) is associated with increased mortality or the development of ACLF, renal or circulatory failure. Methods: Eight single nucleotide polymorphisms (SNPs) of AVP1aR with possible clinical relevance were identified. From 188 cirrhotic patients hospitalized for AD, clinical, laboratory and survival data from the CANONIC database were used. Presence of ACLF was defined according to the modified CLIF-sequential organ failure assessment (SOFA) score. All patients were genotyped for all eight SNPs using polymerase chain reaction followed by restriction fragment length polymorphism or PCR allele-specific amplification primers. Fisher’s exact test and linear regression analysis were used to test for associations between genetic frequencies and dichotomous and continuous variables respectively. Cox proportional hazard analysis adjusted for age was performed to assess the association between AVP1a SNPs and mortality at set time points. P < 0.05 was considered significant. Results: Ninety-three patients without ACLF and 95 patents with ACLF were included. As expected, mortality rate at 12 months of follow-up (FU) was higher in patients with ACLF (59%) than in patients with AD who did not develop ACLF (28%). Mutations in rs7298346 [HR 1.81 (95% CI 1.02–3.23), p = 0.044] and rs7308855 [HR 2.17 (1.17–4.01), p = 0.013] showed a clear trend towards a lower overall survival in all patients at 90 days of FU. For rs 7308855 this trend persisted until 180 days of FU [HR 1.87 (1.00–3.50), p = 0.051]. In addition, T>A mutation in rs7298346 was associated with the presence of renal failure in patients with ACLF (p = 0.025). No association was found between AVP1a SNPs and the occurrence of ACLF or circulatory failure. Conclusions: There is a clear trend of AVP1a SNPs to be associated with increased mortality in patients with acute decompensation of liver disease and with the occurrence of renal failure in ACLF. P0136 ALFAPUMP FOR THE TREATMENT OF REFRACTORY ASCITES IN CIRRHOTIC PATIENTS G. Stirnimann1 , T. Berg2 , L. Spahr3 , S. Zeuzem4 , S. McPherson5 , F. Lammert6 , J. Babatz7 , V. Vargas8 , V. Banz1 , F. Storni1 , A. De Gottardi1 . 1 University Hospital Inselspital, Bern, Switzerland; 2 University Clinic Leipzig, Leipzig, Germany; 3 Geneva University Hospitals, Geneva, Switzerland; 4 University Hospital Frankfurt, Frankfurt, Germany; 5 Freeman Hospital, Newcastle, United Kingdom; 6 Saarland University Medical Center, Homburg, 7 Universit¨ atsklinikum Carl Gustav Carus, Dresden, Germany; 8 Vall d’Hebron University Hospital, Barcelona, Spain E-mail: [email protected] Background and Aims: The automated low flow ascites pump (alfapump) is a novel treatment for the management of refractory ascites in patients contraindicated for or with an ineffective TIPS. The aim of this study was to monitor safety and clinical performance. Methods: From September 2012 data from patients with an alfapump have been collected in an international multicentre prospective registry. Inclusion criteria were refractory or recurrent ascites with no other treatment option than repetitive paracentesis, age >18 years, informed consent, ability to manage the alfapump system. Data points were analysed at baseline before surgery, perioperatively, and after 1, 3, 6, 12 and 18 months during follow-up. Results: In total, 55 patients were included (76% men, 24% women), mean age was 61 (range 44–78). Aetiology of cirrhosis was alcohol (69.1%), chronic hepatitis C virus infection (9.1%), NASH (5.5%) and cryptogenic (5.5%). S352
The median duration of the implantation was 60 min (25th/75th percentile: 50/70) and the median length of hospital stay after implantation was 6 days (3/12). The number of large volume paracenteses per month decreased from 2.17 (1.4/4.3) to 0.0 (0.0/0.43), the volume of each paracentesis decreased from 7.0 litres (5.0/9.0) to 4.6 litres (3.0/6.0). The median volume of ascites pumped was 0.9 litres (0.7/1.1) per day. The most frequent complication was obstruction of the peritoneal catheter in 11 patients, followed by pump failures due to technical problems in 7 patients and infections in 6 patients. Of 55 patients, 17 are ongoing, 18 died, 8 were transplanted, 10 were withdrawn, 1 completed the study and 1 was lost to follow-up. Mean survival was 6.33±5.33 months with a 6 month actuarial survival of 74%. Mean BMI was 25.3 kg/m2 at baseline and 26.1 kg/m2 at 18 months. Serum creatinine levels increased during follow-up from 98 mmol/L (86/117) to 124 mmol/L (107/206) at 18 months. Albumin was administered in 34.5% of patients post implant in the context of paracentesis. Median serum albumin decreased from 30.0 g/L at baseline to 25.0 g/L at 18 months. Mean Child and MELD scores were 8.8 (± 1.4) and 13.4 (± 4.3) at baseline and 8.0 (± 1.4) and 12.7 (± 4.4) at 18 months, respectively. Conclusions: Implantation of alfapump was a safe procedure in patients with refractory ascites due to advanced cirrhosis and was associated with a marked reduction in the need for paracentesis and albumin. P0137 SAFETY OF BOCEPREVIR-BASED TRIPLE THERAPY IN HCV CIRRHOTIC PATIENTS AWAITING LIVER TRANSPLANTATION. ANALYSIS FROM A FRENCH MULTICENTER, OPEN-LABEL STUDY (ANRS HC29 BOCEPRETRANSPLANT) H. Fontaine1 , M. Maynard-Muet2 , C. Bouix3 , D. Botta-Fridlund4 , 9 L. D’Alteroche5 , F. Conti6 , G.-P. Pageaux7 , V. Leroy8 , S. Metivier ´ , R. Anty10 , F. Durand11 , V. Canva12 , P. Lebray13 , L. Alric14 , C. Duvoux15 , V. Petrov-Sanchez16 , F. Beaulieux17 , C. Willems17 , C. Paul16 , P. Pradat17 , J.-C. Duclos-Vallee ´ 18 , D. Samuel18 . 1 Hepatology, Cochin Hospital, Paris, 2 Hepatology, Hˆ opital de la Croix Rousse, Hospices Civils de Lyon, 3 Hepatology, Hˆ opital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, 4 Hepatology and Gastroenterology, Hˆ opital de la Conception, Marseille, 5 Hepatology and Gastroenterology, Trousseau Hospital, Tours, 6 Hepatology, Saint-Antoine Hospital, Paris, 7 F´ed´eration m´edico-chirurgicale des maladies de l’appareil digestif, Saint-Eloi, Montpellier, 8 Hepatology and Gastroenterology, La Tronche Hospital, Grenoble, 9 Hepatology and Gastroenterology, Purpan Hospital, Toulouse, 10 Digestive Center, Hˆ opital de l’Archet, Nice, 11 Hepatology, Beaujon Hospital, APHP, Clichy, 12 Hepatology and Gastroenterology, Claude Huriez Hospital, Lille, 13 Hepatology and Gastroenterology, Piti´e-Salp´etri`ere Hospital, Paris, 14 Pˆ ole digestif, Purpan Hospital, Toulouse, 15 Hepatology and Gastroenterology, Henri Mondor Hospital, Cr´eteil, 16 Unit for Basic and Clinical research on Viral Hepatitis, French National Agency for Research on AIDS and Viral Hepatitis, Paris, 17 Hepatology, Croix-Rousse Hospital, Lyon, 18 Hepatology, Paul Brousse Hospital, Villejuif, France E-mail: [email protected] Background and Aims: To analyze the safety of a boceprevir (BOC)based triple therapy in HCV cirrhotic patients (pts) on waiting-list (WL) for liver transplantation (LT) in a French multicenter, openlabel study. Methods: HCV genotype 1 pts received PEG-IFN-a2a 180 mg/week (W) or PEG-IFN-a2b 1.5 mg/kg/W, weight-based RBV 1000– 1200 mg/d during 48W, and BOC 800 mg/8 hours from W4 to W48 or until LT. Biological and clinical safety was assessed during treatment and 6 months after the end of treatment (EOT). Results on severe adverse events (SAE) occurrence are reported. Results: 51 pts from 15 centers were included (80% males, median age 56 years). Hepatocellular carcinoma (HCC) was present in 59%
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POSTERS of pts, end-stage liver disease in 41%. At inclusion, the median MELD score was 9 (range 6–18); the Child–Pugh score was A in 65% and B in 35%. Treatment median duration was 13W. Therapy was discontinued because of SAE in 20 (39%) or virological inefficacy in 12 (24%). Seven pts (14%) died after a median duration of treatment of 9W because of sepsis (n = 4), HCC progression (n = 1), haemorrhagic shock (n = 1) and cerebral haemorrhage (n = 1). Three deaths were considered as possibly related to treatment. 114 SAE were observed in 43 pts (84%). Most common diagnoses were neutropenia (25%), GGT (20%) or AST elevation (12%), anemia (10%), thrombocytopenia (10%), hepatic encephalopathy (10%) and leucopenia (10%). Severe anemia (Hb <8 g/dL) was observed in 4%. Growth factors were used in 36 pts (71%), erythropoietin, thrombopoietin and G-CSF in 23, 9 and 11 pts, respectively. Undetectable HCV-RNA 24 weeks after the EOT (SVR24) was observed in 8 pts (16%). A LT was performed in 18 pts (35%) after a mean duration on WL and of treatment of 59 and 13 W, respectively. HCV RNA was undetectable in 19% at LT and was still negative after LT in 2 pts (W24 post-LT). Severe infection occurred in 12 pts (24%) including septicemia (n = 7), ascites infection (n = 3) and urinary infection (n = 1). One pt had multiple infections. Child–Pugh score B, low Hb, lymphocytes and albumin levels at baseline were associated with the occurrence of severe infection but multivariate analysis indicated that only low albumin level (<35 g/l) remained an independent predictive factor. Conclusions: Safety of PEG-IFN/RBV/BOC combination is poor in pts awaiting LT, with a high risk of developing severe infection. Moreover, the limited efficacy confirms the necessity of IFN-free combinations in these pts.
use of NADs had a beneficial effect on HE (RR 0.56; 95% CI 0.47– 0.68; participants = 1263; I2 = 51%, 20 trials) both when used to treat the syndrome (RR 0.62; 95% CI 0.48–0.80) or else to prevent its occurrence (RR 0.47; 95% CI 0.37–0.59). The result was confirmed in analyses of high-quality trials. Use of NADs was associated with a reduction in mortality (RR 0.60; 95% CI 0.40–0.91; figure) and the risk of serious adverse events including severe infections and liver-related complications (RR 0.47; 95% CI 0.36–0.62); the risk of diarrhoea and bloating was increased. There were no differential effects in relation to the type of HE or use for treatment or prophylaxis; no clear differences were identified in treatment efficacy or safety between lactulose and lactitol. Overall the sample size was adequate and the findings statistically robust. Conclusions: In patients with cirrhosis, NADs are beneficial for both the treatment and prevention of HE; their use is also associated with a significant reduction in liver-related morbidity and mortality.
P0138 THE EFFECT OF TREATMENT FOR HEPATIC ENCEPHALOPATHY WITH NONABSORBABLE DISACCHARIDES ON MORBIDITY AND MORTALITY IN PATIENTS WITH CIRRHOSIS: SYSTEMATIC REVIEW AND META-ANALYSES L.L. Gluud1 , H. Vilstrup2 , M.Y. Morgan3 . 1 Gastrounit, Hvidovre Hospital, Copenhagen University, Hvidovre, 2 Department of Hepatology and Gastroenterology, Aarhus Kommunehospital, Aarhus, Denmark; 3 UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, United Kingdom E-mail: [email protected]
P0139 PATIENTS EXPERIENCING REPEATED EPISODES OF HEPATIC ENCEPHALOPATHY HAVE INCREASING RISK OF DEATH. A POST HOC ANALYSIS OF RIFAXIMIN-a OPEN LABEL STUDY DATA C.A. Bannister1 , P. Conway2 , A. Radwan2 , C.L. Morgan3 , E. Berni3 , C.J. Currie1 . 1 Cardiff University School of Medicine, Cardiff, 2 Norgine, Uxbridge, 3 Pharmatelligence, Cardiff, United Kingdom E-mail: [email protected]
Background and Aims: The non-absorbable disaccharides (NADs), lactulose and lactitol, have been used to treat hepatic encephalopathy (HE), in patients with cirrhosis since 1966. However, a Cochrane systematic review concluded that there was insufficient high-quality evidence to support their use (Als-Nielsen et al, 2004). The advent of several new treatment trials requires this to be reappraised. The aim of this study was to assess the beneficial and harmful effects of NADs vs. placebo/no intervention in patients with cirrhosis and HE. Methods: Randomized controlled trials published between 1966 and October 2014 were identified using a language/ publication unrestricted electronic search of five data-bases; (ii) a manual search of relevant journals, symposia/conference proceedings; (ii) personal communications with investigators; and (iii) publication cross-referencing. Bias control was assessed using the Cochrane Hepato-Biliary Group domains; key outcome data were extracted. Sources of heterogeneity were sought. Small study effects, random and systematic errors were assessed and futility evaluated in sensitivity, subgroup, regression and trial sequential analyses. Results: In total, 37 trials involving 1628 patients with overt HE (12 trials), minimal HE (14 trials) or else for primary/secondary prophylaxis (11 trials) were identified; the mean duration of treatment was 3 months. Compared with placebo/no intervention,
Background and Aims: Hepatic encephalopathy (HE) is a chronic complication of cirrhosis. In recurrent, overt, episodic HE, which is the most common subcategory, its seriousness is due to the chronic debilitating effects of the recurrent episodes. The aim of this study was to characterise the impact of the number of prior HE episodes on the risk of death. Methods: A post-hoc analysis was carried out using data from 322 patients with a history of HE from a phase 3, open-label study evaluating the long-term safety and tolerability of rifaximin-a 550 mg BID. All eligible patients had a Conn score of 0–2 at enrolment, and either successfully participated in a previous HE study with rifaximin-a (RFHE3001) or were new patients enrolled with ≥1 verifiable episode of HE within the preceding 12 months. Results: 321 of 322 patients (650 observations) aged ≥18 years had all the necessary information required for analysis. The median duration of follow-up was 17 months (IQR 8.9–25.4). Stratifying patient observations by number of prior HE episodes and using the Kaplan–Meier method the year one survival was 0.947 (95% CI; 0.891–1.000), 0.898 (0.845–0.953) and 0.793 (0.735–0.856) and the year two survival was 0.910 (0.822–1.000), 0.808 (0.719–0.909) and 0.783 (0.677–0.0.828) for ‘one’, ’two’ and ’three or more’ prior HE episodes, respectively. Plotting the Kaplan–Meier curves of time to death, stratified by number of prior HE episodes, a clear association between decreased time to death and increased number of prior HE
Journal of Hepatology 2015 vol. 62 | S263–S864
S353
The median duration of the implantation was 60 min (25th/75th percentile: 50/70) and the median length of hospital stay after implantation was 6 days (3/12). The number of large volume paracenteses per month decreased from 2.17 (1.4/4.3) to 0.0 (0.0/0.43), the volume of each paracentesis decreased from 7.0 litres (5.0/9.0) to 4.6 litres (3.0/6.0). The median volume of ascites pumped was 0.9 litres (0.7/1.1) per day. The most frequent complication was obstruction of the peritoneal catheter in 11 patients, followed by pump failures due to technical problems in 7 patients and infections in 6 patients. Of 55 patients, 17 are ongoing, 18 died, 8 were transplanted, 10 were withdrawn, 1 completed the study and 1 was lost to follow-up. Mean survival was 6.33±5.33 months with a 6 month actuarial survival of 74%. Mean BMI was 25.3 kg/m2 at baseline and 26.1 kg/m2 at 18 months. Serum creatinine levels increased during follow-up from 98 mmol/L (86/117) to 124 mmol/L (107/206) at 18 months. Albumin was administered in 34.5% of patients post implant in the context of paracentesis. Median serum albumin decreased from 30.0 g/L at baseline to 25.0 g/L at 18 months. Mean Child and MELD scores were 8.8 (± 1.4) and 13.4 (± 4.3) at baseline and 8.0 (± 1.4) and 12.7 (± 4.4) at 18 months, respectively. Conclusions: Implantation of alfapump was a safe procedure in patients with refractory ascites due to advanced cirrhosis and was associated with a marked reduction in the need for paracentesis and albumin. P0137 SAFETY OF BOCEPREVIR-BASED TRIPLE THERAPY IN HCV CIRRHOTIC PATIENTS AWAITING LIVER TRANSPLANTATION. ANALYSIS FROM A FRENCH MULTICENTER, OPEN-LABEL STUDY (ANRS HC29 BOCEPRETRANSPLANT) H. Fontaine1 , M. Maynard-Muet2 , C. Bouix3 , D. Botta-Fridlund4 , 9 L. D’Alteroche5 , F. Conti6 , G.-P. Pageaux7 , V. Leroy8 , S. Metivier ´ , R. Anty10 , F. Durand11 , V. Canva12 , P. Lebray13 , L. Alric14 , C. Duvoux15 , V. Petrov-Sanchez16 , F. Beaulieux17 , C. Willems17 , C. Paul16 , P. Pradat17 , J.-C. Duclos-Vallee ´ 18 , D. Samuel18 . 1 Hepatology, Cochin Hospital, Paris, 2 Hepatology, Hˆ opital de la Croix Rousse, Hospices Civils de Lyon, 3 Hepatology, Hˆ opital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, 4 Hepatology and Gastroenterology, Hˆ opital de la Conception, Marseille, 5 Hepatology and Gastroenterology, Trousseau Hospital, Tours, 6 Hepatology, Saint-Antoine Hospital, Paris, 7 F´ed´eration m´edico-chirurgicale des maladies de l’appareil digestif, Saint-Eloi, Montpellier, 8 Hepatology and Gastroenterology, La Tronche Hospital, Grenoble, 9 Hepatology and Gastroenterology, Purpan Hospital, Toulouse, 10 Digestive Center, Hˆ opital de l’Archet, Nice, 11 Hepatology, Beaujon Hospital, APHP, Clichy, 12 Hepatology and Gastroenterology, Claude Huriez Hospital, Lille, 13 Hepatology and Gastroenterology, Piti´e-Salp´etri`ere Hospital, Paris, 14 Pˆ ole digestif, Purpan Hospital, Toulouse, 15 Hepatology and Gastroenterology, Henri Mondor Hospital, Cr´eteil, 16 Unit for Basic and Clinical research on Viral Hepatitis, French National Agency for Research on AIDS and Viral Hepatitis, Paris, 17 Hepatology, Croix-Rousse Hospital, Lyon, 18 Hepatology, Paul Brousse Hospital, Villejuif, France E-mail: [email protected] Background and Aims: To analyze the safety of a boceprevir (BOC)based triple therapy in HCV cirrhotic patients (pts) on waiting-list (WL) for liver transplantation (LT) in a French multicenter, openlabel study. Methods: HCV genotype 1 pts received PEG-IFN-a2a 180 mg/week (W) or PEG-IFN-a2b 1.5 mg/kg/W, weight-based RBV 1000– 1200 mg/d during 48W, and BOC 800 mg/8 hours from W4 to W48 or until LT. Biological and clinical safety was assessed during treatment and 6 months after the end of treatment (EOT). Results on severe adverse events (SAE) occurrence are reported. Results: 51 pts from 15 centers were included (80% males, median age 56 years). Hepatocellular carcinoma (HCC) was present in 59%
Journal of Hepatology 2015 vol. 62 | S263–S864
POSTERS of pts, end-stage liver disease in 41%. At inclusion, the median MELD score was 9 (range 6–18); the Child–Pugh score was A in 65% and B in 35%. Treatment median duration was 13W. Therapy was discontinued because of SAE in 20 (39%) or virological inefficacy in 12 (24%). Seven pts (14%) died after a median duration of treatment of 9W because of sepsis (n = 4), HCC progression (n = 1), haemorrhagic shock (n = 1) and cerebral haemorrhage (n = 1). Three deaths were considered as possibly related to treatment. 114 SAE were observed in 43 pts (84%). Most common diagnoses were neutropenia (25%), GGT (20%) or AST elevation (12%), anemia (10%), thrombocytopenia (10%), hepatic encephalopathy (10%) and leucopenia (10%). Severe anemia (Hb <8 g/dL) was observed in 4%. Growth factors were used in 36 pts (71%), erythropoietin, thrombopoietin and G-CSF in 23, 9 and 11 pts, respectively. Undetectable HCV-RNA 24 weeks after the EOT (SVR24) was observed in 8 pts (16%). A LT was performed in 18 pts (35%) after a mean duration on WL and of treatment of 59 and 13 W, respectively. HCV RNA was undetectable in 19% at LT and was still negative after LT in 2 pts (W24 post-LT). Severe infection occurred in 12 pts (24%) including septicemia (n = 7), ascites infection (n = 3) and urinary infection (n = 1). One pt had multiple infections. Child–Pugh score B, low Hb, lymphocytes and albumin levels at baseline were associated with the occurrence of severe infection but multivariate analysis indicated that only low albumin level (<35 g/l) remained an independent predictive factor. Conclusions: Safety of PEG-IFN/RBV/BOC combination is poor in pts awaiting LT, with a high risk of developing severe infection. Moreover, the limited efficacy confirms the necessity of IFN-free combinations in these pts.
use of NADs had a beneficial effect on HE (RR 0.56; 95% CI 0.47– 0.68; participants = 1263; I2 = 51%, 20 trials) both when used to treat the syndrome (RR 0.62; 95% CI 0.48–0.80) or else to prevent its occurrence (RR 0.47; 95% CI 0.37–0.59). The result was confirmed in analyses of high-quality trials. Use of NADs was associated with a reduction in mortality (RR 0.60; 95% CI 0.40–0.91; figure) and the risk of serious adverse events including severe infections and liver-related complications (RR 0.47; 95% CI 0.36–0.62); the risk of diarrhoea and bloating was increased. There were no differential effects in relation to the type of HE or use for treatment or prophylaxis; no clear differences were identified in treatment efficacy or safety between lactulose and lactitol. Overall the sample size was adequate and the findings statistically robust. Conclusions: In patients with cirrhosis, NADs are beneficial for both the treatment and prevention of HE; their use is also associated with a significant reduction in liver-related morbidity and mortality.
P0138 THE EFFECT OF TREATMENT FOR HEPATIC ENCEPHALOPATHY WITH NONABSORBABLE DISACCHARIDES ON MORBIDITY AND MORTALITY IN PATIENTS WITH CIRRHOSIS: SYSTEMATIC REVIEW AND META-ANALYSES L.L. Gluud1 , H. Vilstrup2 , M.Y. Morgan3 . 1 Gastrounit, Hvidovre Hospital, Copenhagen University, Hvidovre, 2 Department of Hepatology and Gastroenterology, Aarhus Kommunehospital, Aarhus, Denmark; 3 UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, United Kingdom E-mail: [email protected]
P0139 PATIENTS EXPERIENCING REPEATED EPISODES OF HEPATIC ENCEPHALOPATHY HAVE INCREASING RISK OF DEATH. A POST HOC ANALYSIS OF RIFAXIMIN-a OPEN LABEL STUDY DATA C.A. Bannister1 , P. Conway2 , A. Radwan2 , C.L. Morgan3 , E. Berni3 , C.J. Currie1 . 1 Cardiff University School of Medicine, Cardiff, 2 Norgine, Uxbridge, 3 Pharmatelligence, Cardiff, United Kingdom E-mail: [email protected]
Background and Aims: The non-absorbable disaccharides (NADs), lactulose and lactitol, have been used to treat hepatic encephalopathy (HE), in patients with cirrhosis since 1966. However, a Cochrane systematic review concluded that there was insufficient high-quality evidence to support their use (Als-Nielsen et al, 2004). The advent of several new treatment trials requires this to be reappraised. The aim of this study was to assess the beneficial and harmful effects of NADs vs. placebo/no intervention in patients with cirrhosis and HE. Methods: Randomized controlled trials published between 1966 and October 2014 were identified using a language/ publication unrestricted electronic search of five data-bases; (ii) a manual search of relevant journals, symposia/conference proceedings; (ii) personal communications with investigators; and (iii) publication cross-referencing. Bias control was assessed using the Cochrane Hepato-Biliary Group domains; key outcome data were extracted. Sources of heterogeneity were sought. Small study effects, random and systematic errors were assessed and futility evaluated in sensitivity, subgroup, regression and trial sequential analyses. Results: In total, 37 trials involving 1628 patients with overt HE (12 trials), minimal HE (14 trials) or else for primary/secondary prophylaxis (11 trials) were identified; the mean duration of treatment was 3 months. Compared with placebo/no intervention,
Background and Aims: Hepatic encephalopathy (HE) is a chronic complication of cirrhosis. In recurrent, overt, episodic HE, which is the most common subcategory, its seriousness is due to the chronic debilitating effects of the recurrent episodes. The aim of this study was to characterise the impact of the number of prior HE episodes on the risk of death. Methods: A post-hoc analysis was carried out using data from 322 patients with a history of HE from a phase 3, open-label study evaluating the long-term safety and tolerability of rifaximin-a 550 mg BID. All eligible patients had a Conn score of 0–2 at enrolment, and either successfully participated in a previous HE study with rifaximin-a (RFHE3001) or were new patients enrolled with ≥1 verifiable episode of HE within the preceding 12 months. Results: 321 of 322 patients (650 observations) aged ≥18 years had all the necessary information required for analysis. The median duration of follow-up was 17 months (IQR 8.9–25.4). Stratifying patient observations by number of prior HE episodes and using the Kaplan–Meier method the year one survival was 0.947 (95% CI; 0.891–1.000), 0.898 (0.845–0.953) and 0.793 (0.735–0.856) and the year two survival was 0.910 (0.822–1.000), 0.808 (0.719–0.909) and 0.783 (0.677–0.0.828) for ‘one’, ’two’ and ’three or more’ prior HE episodes, respectively. Plotting the Kaplan–Meier curves of time to death, stratified by number of prior HE episodes, a clear association between decreased time to death and increased number of prior HE
Journal of Hepatology 2015 vol. 62 | S263–S864
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