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Comparative Effectiveness of Different Pharmacological Interventions for the Treatment of Minimal Hepatic Encephalopathy: A Systematic Review With Network Meta-Analysis
CIRRHOSIS AND COMPLICATIONS
CONFLICTS OF INTEREST The authors have none to declare. Corresponding author: Radha K. Dhiman. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2016.06.103
37 COMPARATIVE EFFECTIVENESS OF DIFFERENT PHARMACOLOGICAL INTERVENTIONS FOR THE TREATMENT OF MINIMAL HEPATIC ENCEPHALOPATHY: A SYSTEMATIC REVIEW WITH NETWORK META-ANALYSIS Radha K. Dhiman, Kiran K. Thumburu, Madhu Chopra, Usha Dutta, Meenu Singh, Sunil Taneja, Ajay Duseja, Yogesh K. Chawla Cirrhosis and Complications
Postgraduate Institute of Medical Education & Research, Chandigarh, India
Background and Aim: Minimal hepatic encephalopathy (HE) is associated with impaired quality of life and increased progression to overt HE. We assessed the comparative effectiveness of pharmacological interventions for the reversal of minimal HE and for prevention of development of overt HE through network meta-analysis combining direct and indirect treatment comparisons of randomized clinical trials (RCTs). Methods: We performed a systematic search of the PubMed, EMBASE, OvidSP and CENTRAL databases for RCTs of adults with minimal HE that compared the effectiveness of active interventions [lactulose, rifaximin, L-ornithine L-aspartate (LOLA), pre-/pro-/ synbiotics (PPS), branched chain amino acids (BCAA), alone or in combination] with each other or placebo. We used Bayesian network metaanalysis to combine direct and indirect evidence to estimate odds ratios (ORs) between treatments, and used grading of recommendations assessment, development and evaluation criteria to appraise quality of evidence. Results: We identified 27 RCTs (2056 patients) comparing 5 different interventions for reversal of minimal HE and 21 RCTs (1162 patients) comparing 4 different interventions for the prevention of development of overt HE. In network meta-analysis, in the order of superiority, rifaximin [OR 8.14; 95% predictive interval (PrI), 4.49–14.74], lactulose (OR 5.64; S54
95% PrI, 3.64–8.73), probiotics + lactulose (OR 4.72; 95% PrI, 1.22–18.28), LOLA (OR, 4.43; 95% PrI, 2.39– 8.22), PPS (OR 4.37; 95% PrI, 2.66–7.19) and BCAA (OR 2.16; 95% PrI, 1.03–4.56), showed significantly higher reversal of minimal HE compared to placebo or no intervention. Between the active treatments, rifaximin is superior to BCAA (OR 0.27; 95% PrI, 0.10–0.69), PPS (OR 0.54; 95% PrI, 0.28–1.03), LOLA (OR 0.54; 95% PrI, 0.26–1.14), probiotics + lactulose (OR 0.58; 95% PrI, 0.14–2.38, lactulose (OR 0.69; 95% PrI, 0.38–1.25). Likewise, LOLA (OR 0.16; 95% PrI, 0.04–0.64), lactulose (OR 0.21; 95% PrI, 0.09–0.48), PPS (OR 0.25; 95% PrI, 0.11–0.59), but not rifaximin (OR 0.44; 95% PrI, 0.09–2.04) significantly reduced the risk of development of overt HE when compared to placebo or no treatment. In the network metaanalysis, for reversal of minimal HE, moderate quality evidence supported that rifaximin followed by lactulose were the most effective interventions. For prevention of overt the HE, lactulose (moderate quality) followed by LOLA (low quality) were the most effective interventions. Conclusion: While rifaximin alone was the most effective intervention for reversal of minimal HE, lactulose (moderate quality) is effective both in reversal of minimal HE and in reducing the risk of development of overt HE. CONFLICTS OF INTEREST The authors have none to declare. Corresponding author: Radha K. Dhiman. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2016.06.104
38 SURVIVAL BENEFIT OF VITAMIN D REPLACEMENT ON DEFICIENT DECOMPENSATED CIRRHOSIS Sharad K. Jha Indira Gandhi Institute of Medical Sciences, Patna, India
Background and Aim: Low levels of vitamin D are associated with adverse outcome in various disorders. However role of Vitamin D deficiency in prognosis of decompensated cirrhosis has not been clearly established. The purpose of this study was to assess the levels of vitamin D in decompensated cirrhotic patients and effect of vitamin D replenishment on the mortality. © 2016, INASL
CONFLICTS OF INTEREST The authors have none to declare. Corresponding author: Radha K. Dhiman. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2016.06.103
37 COMPARATIVE EFFECTIVENESS OF DIFFERENT PHARMACOLOGICAL INTERVENTIONS FOR THE TREATMENT OF MINIMAL HEPATIC ENCEPHALOPATHY: A SYSTEMATIC REVIEW WITH NETWORK META-ANALYSIS Radha K. Dhiman, Kiran K. Thumburu, Madhu Chopra, Usha Dutta, Meenu Singh, Sunil Taneja, Ajay Duseja, Yogesh K. Chawla Cirrhosis and Complications
Postgraduate Institute of Medical Education & Research, Chandigarh, India
Background and Aim: Minimal hepatic encephalopathy (HE) is associated with impaired quality of life and increased progression to overt HE. We assessed the comparative effectiveness of pharmacological interventions for the reversal of minimal HE and for prevention of development of overt HE through network meta-analysis combining direct and indirect treatment comparisons of randomized clinical trials (RCTs). Methods: We performed a systematic search of the PubMed, EMBASE, OvidSP and CENTRAL databases for RCTs of adults with minimal HE that compared the effectiveness of active interventions [lactulose, rifaximin, L-ornithine L-aspartate (LOLA), pre-/pro-/ synbiotics (PPS), branched chain amino acids (BCAA), alone or in combination] with each other or placebo. We used Bayesian network metaanalysis to combine direct and indirect evidence to estimate odds ratios (ORs) between treatments, and used grading of recommendations assessment, development and evaluation criteria to appraise quality of evidence. Results: We identified 27 RCTs (2056 patients) comparing 5 different interventions for reversal of minimal HE and 21 RCTs (1162 patients) comparing 4 different interventions for the prevention of development of overt HE. In network meta-analysis, in the order of superiority, rifaximin [OR 8.14; 95% predictive interval (PrI), 4.49–14.74], lactulose (OR 5.64; S54
95% PrI, 3.64–8.73), probiotics + lactulose (OR 4.72; 95% PrI, 1.22–18.28), LOLA (OR, 4.43; 95% PrI, 2.39– 8.22), PPS (OR 4.37; 95% PrI, 2.66–7.19) and BCAA (OR 2.16; 95% PrI, 1.03–4.56), showed significantly higher reversal of minimal HE compared to placebo or no intervention. Between the active treatments, rifaximin is superior to BCAA (OR 0.27; 95% PrI, 0.10–0.69), PPS (OR 0.54; 95% PrI, 0.28–1.03), LOLA (OR 0.54; 95% PrI, 0.26–1.14), probiotics + lactulose (OR 0.58; 95% PrI, 0.14–2.38, lactulose (OR 0.69; 95% PrI, 0.38–1.25). Likewise, LOLA (OR 0.16; 95% PrI, 0.04–0.64), lactulose (OR 0.21; 95% PrI, 0.09–0.48), PPS (OR 0.25; 95% PrI, 0.11–0.59), but not rifaximin (OR 0.44; 95% PrI, 0.09–2.04) significantly reduced the risk of development of overt HE when compared to placebo or no treatment. In the network metaanalysis, for reversal of minimal HE, moderate quality evidence supported that rifaximin followed by lactulose were the most effective interventions. For prevention of overt the HE, lactulose (moderate quality) followed by LOLA (low quality) were the most effective interventions. Conclusion: While rifaximin alone was the most effective intervention for reversal of minimal HE, lactulose (moderate quality) is effective both in reversal of minimal HE and in reducing the risk of development of overt HE. CONFLICTS OF INTEREST The authors have none to declare. Corresponding author: Radha K. Dhiman. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2016.06.104
38 SURVIVAL BENEFIT OF VITAMIN D REPLACEMENT ON DEFICIENT DECOMPENSATED CIRRHOSIS Sharad K. Jha Indira Gandhi Institute of Medical Sciences, Patna, India
Background and Aim: Low levels of vitamin D are associated with adverse outcome in various disorders. However role of Vitamin D deficiency in prognosis of decompensated cirrhosis has not been clearly established. The purpose of this study was to assess the levels of vitamin D in decompensated cirrhotic patients and effect of vitamin D replenishment on the mortality. © 2016, INASL