- Email: [email protected]
Survival Benefit of Vitamin D Replacement on Deficient Decompensated Cirrhosis
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
Methods: 100 decompensated cirrhotic patients (CTP10) of any etiology having deficient vitamin D were randomly divided into two groups of 50 patients each. One group received vitamin D replenishment (Intramuscular cholecalciferol 3,00,000IU as loading dose. Maintenance dose 800IU/day oral) and other group received placebo. The groups were compared for effect of treatment on mortality. Results: The mean age of the patients in the treatment group and control was 46.2 years (14.93) and 43.28 years (12.53) respectively. Most common etiology of decompensated CLD was ethanol in both treatment (n=19; 38%) and control (n=24; 48%) groups. 80% of the patients in both groups had history of jaundice at the baseline screening (p = 0.579). Almost all patients of both groups had complain of ascites (p = 1.00). The proportion of survival in treatment group (69%) was higher as compared to control group (64%), but the difference was not statistically significant (p = 0.389). Also the mean survival days in treatment group was 155 days (95% CI; 142–167, as compared to mean duration of survival in control group ie. 141 days (95% CI; 125–157. The mean survival duration was not statistically significant (p = 0.1687). Conclusion: Vitamin D deficiency is very common in cirrhotic patients regardless of etiology of liver disease. Replenishment of vitamin D along with calcium supplementation showed a trend towards survival improvement in cirrhotic patients. CONFLICTS OF INTEREST The author has none to declare. Corresponding author: Sharad K. Jha. E-mail: [email protected]
Background & Aim: Lactulose is a cornerstone of treatment of hepatic encephalopathy (HE). However, it is often poorly tolerated, over a third of patients being non-compliant. This is one of the major reasons for its limited use for minimal HE(MHE) and primary prophylaxis of HE. Interestingly, Indian patients tolerate lactulose very well with excellent compliance. We aim to understand the perception of Indian patients towards lactulose with a Knowledge, Attitude and Practice(KAP) model. Methods: We recruited 62 patients with cirrhosis on lactulose as primary or secondary prophylaxis for HE. They were questioned regarding their KAP for lactulose. Knowledge was assessed by their understanding of need of lactulose. Attitude constituted of their outlook towards the side effects, and Practice involved their level of compliance with lactulose therapy as assessed by a medication adherence questionnaire. Results: Of the 62 patients surveyed, 46 were males. The mean age was 50.45. Median Child Pugh and MELD scores were 7 and 14 respectively. 31 were on primary prophylaxis for HE. 57 (92%) patients perceived lactulose as an important part of their treatment. 59 (95%) did not have a problem in continuing lactulose. 52 felt 2–3 stools/day was normal for them. 7(11%) occasionally forgot to take lactulose, and 4 confessed they were careless towards medication. 17 (27%) stopped lactulose when they felt better. 12 (29%) stopped medication when poorly tolerated, of which 8 were on primary prophylaxis. The frequency of side-effects reported were similar in patients who received lactulose as primary or secondary prophylaxis (P = 0.12). No patient on secondary prophylaxis reported stopping lactulose due to side effects.
http://dx.doi.org/10.1016/j.jceh.2016.06.178 Table 1 Side Effect Profile Of Lactulose. N = 62
39 LACTULOSE TOLERABILITY AND ADVERSE EFFECT PROFILE IN INDIAN PATIENTS WITH CHRONIC LIVER DISEASE – A KNOWLEDGE, ATTITUDE AND PRACTICE STUDY Sahaj Rathi, Madhu Chopra, Sunil Taneja, Ajay Duseja, Yogesh K. Chawla, Radha K. Dhiman Post Graduate Institute of Medical Education and Research, Chandigarh, India
No Bothersome Bothersome, Poorly bothersome but tolerable leading to tolerated, symptoms missed wish to doses discontinue
Frequency of Stools
44
14
4
0
Bloating/ Gas
45
16
1
0
Taste
53
8
1
0
Nausea
59
3
0
0
Abdominal Pain
59
3
0
0
Journal of Clinical and Experimental Hepatology | July 2016 | Vol. 6 | No. S1 | S33–S58
S55
Cirrhosis and Complications
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
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
Methods: 100 decompensated cirrhotic patients (CTP10) of any etiology having deficient vitamin D were randomly divided into two groups of 50 patients each. One group received vitamin D replenishment (Intramuscular cholecalciferol 3,00,000IU as loading dose. Maintenance dose 800IU/day oral) and other group received placebo. The groups were compared for effect of treatment on mortality. Results: The mean age of the patients in the treatment group and control was 46.2 years (14.93) and 43.28 years (12.53) respectively. Most common etiology of decompensated CLD was ethanol in both treatment (n=19; 38%) and control (n=24; 48%) groups. 80% of the patients in both groups had history of jaundice at the baseline screening (p = 0.579). Almost all patients of both groups had complain of ascites (p = 1.00). The proportion of survival in treatment group (69%) was higher as compared to control group (64%), but the difference was not statistically significant (p = 0.389). Also the mean survival days in treatment group was 155 days (95% CI; 142–167, as compared to mean duration of survival in control group ie. 141 days (95% CI; 125–157. The mean survival duration was not statistically significant (p = 0.1687). Conclusion: Vitamin D deficiency is very common in cirrhotic patients regardless of etiology of liver disease. Replenishment of vitamin D along with calcium supplementation showed a trend towards survival improvement in cirrhotic patients. CONFLICTS OF INTEREST The author has none to declare. Corresponding author: Sharad K. Jha. E-mail: [email protected]
Background & Aim: Lactulose is a cornerstone of treatment of hepatic encephalopathy (HE). However, it is often poorly tolerated, over a third of patients being non-compliant. This is one of the major reasons for its limited use for minimal HE(MHE) and primary prophylaxis of HE. Interestingly, Indian patients tolerate lactulose very well with excellent compliance. We aim to understand the perception of Indian patients towards lactulose with a Knowledge, Attitude and Practice(KAP) model. Methods: We recruited 62 patients with cirrhosis on lactulose as primary or secondary prophylaxis for HE. They were questioned regarding their KAP for lactulose. Knowledge was assessed by their understanding of need of lactulose. Attitude constituted of their outlook towards the side effects, and Practice involved their level of compliance with lactulose therapy as assessed by a medication adherence questionnaire. Results: Of the 62 patients surveyed, 46 were males. The mean age was 50.45. Median Child Pugh and MELD scores were 7 and 14 respectively. 31 were on primary prophylaxis for HE. 57 (92%) patients perceived lactulose as an important part of their treatment. 59 (95%) did not have a problem in continuing lactulose. 52 felt 2–3 stools/day was normal for them. 7(11%) occasionally forgot to take lactulose, and 4 confessed they were careless towards medication. 17 (27%) stopped lactulose when they felt better. 12 (29%) stopped medication when poorly tolerated, of which 8 were on primary prophylaxis. The frequency of side-effects reported were similar in patients who received lactulose as primary or secondary prophylaxis (P = 0.12). No patient on secondary prophylaxis reported stopping lactulose due to side effects.
http://dx.doi.org/10.1016/j.jceh.2016.06.178 Table 1 Side Effect Profile Of Lactulose. N = 62
39 LACTULOSE TOLERABILITY AND ADVERSE EFFECT PROFILE IN INDIAN PATIENTS WITH CHRONIC LIVER DISEASE – A KNOWLEDGE, ATTITUDE AND PRACTICE STUDY Sahaj Rathi, Madhu Chopra, Sunil Taneja, Ajay Duseja, Yogesh K. Chawla, Radha K. Dhiman Post Graduate Institute of Medical Education and Research, Chandigarh, India
No Bothersome Bothersome, Poorly bothersome but tolerable leading to tolerated, symptoms missed wish to doses discontinue
Frequency of Stools
44
14
4
0
Bloating/ Gas
45
16
1
0
Taste
53
8
1
0
Nausea
59
3
0
0
Abdominal Pain
59
3
0
0
Journal of Clinical and Experimental Hepatology | July 2016 | Vol. 6 | No. S1 | S33–S58
S55
Cirrhosis and Complications
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY