- Email: [email protected]
Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis: A Double Blind Randomized Controlled Trial of l -Ornithine l -Aspartate Vs Placebo
CIRRHOSIS AND COMPLICATIONS
Results: Minimal hepatic encephalopathy was diagnosed in 41 of 70 patients, a prevalence of 58.5% of MHE was observed in cirrhosis of liver in our study group. Conclusion: This study was conducted to study the prevalence of MHE in the cirrhosis of liver. MHE which adversely effects the quality of live, appropriate management of MHE can improve the quality of life and also Treatment not only results in improvement in cognitive and psychomotor deficits but also in health related quality of life (HRQOL). An early identification of MHE may improve the HRQOL and the prognosis of these patients.
CONFLICTS OF INTEREST The authors have none to declare. http://dx.doi.org/10.1016/j.jceh.2017.05.113
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CIRRHOSIS AND COMPLICATIONS
TO ASSESS OUTCOME OF SLOW LOW-DOSE CONTINUOUS ALBUMIN, FUROSEMIDE ± TERLIPRESSIN SIFA (±T) INFUSION IN PATIENTS OF CIRRHOSIS WITH HEPATIC HYDROTHORAX Manjunath Hatti, Kamlesh Kumar, Alok Kumar, Gaurav Pande ∗ , V.P. Krishna, Prabhat N. Sharma, Vivek Saraswat Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
E-mail address: [email protected] (G. Pande). Background and Aim: Management of hepatic hydrothorax is challenging in view of limited treatment options specially medical management. The study was done to assess efficacy and safety of SIFA (±T) as a response-guided protocol in patients of cirrhosis with hydrothorax. Methods: 27 consecutive patients of cirrhosis with hepatic hydrothorax [(Arm I (n = 15); Arm II (n = 12)] were included. Baseline standard workup including, (hemogram, biochemistry, urine analysis and ascitic fluid examination) along with 24 h urinary sodium (UNa+ )/potassium (UK)/creatinine (Ucre), CXR and ECG were done. Arm I patients received furosemide infusion at 2 mg/h, albumin 2 g/h (20–40 g/d). As per clinical response and lab parameters, graded increase of furosemide was done by 1 mg/12 h if UNa+ < 80 meq/d. After 48 h, if UNa+ was <80 meq/d, terlipressin infusion was added @4 mg/24 h after correction of anemia (≥8 g/dl) and obtaining baseline ECG (repeated 12 hourly) and response-guided increase (1 mg/12 hourly) was done (maximum up to 8 mg/24 h). Arm II patients received SMT. S60
Results: A total 27 patients (Arm I n = 15; Arm II n = 12) of ACLF with hepatic hydrothorax were included. Baseline parameters were comparable among both Arm. All patients in Arm I responded over a median period of 8.6 ± 2.7 days whereas only 41% (5/12) patients responded to SMT in Arm II. Baseline parameters of Arm I patients were: age 44.2 ± 11.4, serum creatinine 1.19 ± 0.53, serum sodium 125.6 ± 8.4, UNa+ 26.02 ± 13.4, CTP-score 10.68 ± 1.42, MELD-score 28.5 ± 4.7. At the end of treatment serum creatinine 0.88 ± 0.48, serum Na 133.47 ± 5.25, maximum (max) UNa+ 192.50 ± 94.35. Baseline urine output (UO) was 475 ± 215 ml, whereas maximum UO was 3280 ± 780 ml while on treatment. 3 patients in terlipressin group had nonspecific mild pain abdomen. 2 patient developed t-wave inversion on terlipressin. All these resolved spontaneously. No other significant adverse events were noted in any group. Conclusions: Response-guided use of furosemide, albumin ± terlipressin is relatively safe and effective treatment options for hepatic hydrothorax.
CONFLICTS OF INTEREST The authors have none to declare. http://dx.doi.org/10.1016/j.jceh.2017.05.114
27 SECONDARY PROPHYLAXIS OF HEPATIC ENCEPHALOPATHY IN CIRRHOSIS: A DOUBLE BLIND RANDOMIZED CONTROLLED TRIAL OF L-ORNITHINE L-ASPARTATE VS PLACEBO Shivakumar Varakanahalli ∗ , Barjesh C. Sharma, Amol S. Dahale G B Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
E-mail address: [email protected] (S. Varakanahalli). Background and Aim: Hepatic encephalopathy is associated with a poor prognosis. l-Ornithine l-aspartate has been useful in treatment of hepatic encephalopathy. There is no study on the prevention of recurrence of encephalopathy with l-ornithine l-aspartate. Methods: We conducted a double blind randomized controlled trial at a tertiary center OPD clinic. Consecutive cirrhotic patients who recovered from HE were randomized to receive LOLA (6 g thrice daily) or similar amount of placebo by computer based random numbers for 6 months. Patients were assessed by number connection tests or figure connection tests (if illiterate), digit symbol © 2017, INASL
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
test, serial dotting test, line tracing test, critical flicker frequency test, arterial ammonia and Sickness impact profile scores at inclusion. Primary end point was development of overt HE. Results: Of 306 patients, 150 patients were enrolled. HE recurred in 9/73 (12.3%) and in 20/72 (27.7%) patients receiving LOLA and placebo respectively, P = 0.02 and hazard ratio = 0.389 (95% CI = 0.174–0.870). Mortality was similar in both groups (6.8% vs 13.8% P = 0.18). At 6 months follow up, there was significant change in the PHES (2.53 ± 2.18 vs −0.01 ± 1.92, P < 0.001), ammonia (−23.58 ± 14.8 vs 1.41 ± 13.34 mol/L P < 0.001) and CFF (5.85 ± 4.82 vs 0.58 ± 4.53 P < 0.001) in patients treated with LOLA compared to placebo. The health related quality of life also improved in LOLA group compared to placebo (−7.89 ± 5.52 vs −0.95 ± 4.25 P = 0.001). On multivariate analysis only MELD score predicted the recurrence of overt HE with odds ratio 2.21 (95% CI: 1.526–3.204 P < 0.001). Conclusions: LOLA is effective in the secondary prophylaxis of HE and is associated with significant improvements in PHES, ammonia and CFF scores and HRQOL (Figure 1 and Table 1).
Table 1 Delta Change in Parameters in LOLA and Placebo Groups at 3 Months and 6 Months Compared to Baseline. LOLA PHES 3 PHES 6 CFF 3 CFF 6 NH3 3 NH3 6 SIP 3 SIP 6
Change Placebo
1.28 ± 1.67 2.53 ± 2.18 3.28 ± 3.65 5.85 ± 4.82 −12.92 ± 9.04 −23.58 ± 14.8 −4.56 ± 3.27 −7.89 ± 5.52
0.30 ± 1.97 −0.01 ± 1.92 0.39 ± 3.59 0.59 ± 4.53 −0.66 ± 10.72 1.41 ± 13.34 −0.74 ± 3.21 −0.95 vs 4.25
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Abbreviations: CTP: Child Turcotte Pugh score; MELD: model for end stage liver disease; PHES: pychometric hepatic encephalopathy scores; CFF: critical flicker frequency. = Delta = change in value of parameters from baseline; 3 is at 3 months and 6 is at 6 months follow up; − value denotes decrease from the baseline and + value denotes increase from baseline.
CONFLICTS OF INTEREST The authors have none to declare. http://dx.doi.org/10.1016/j.jceh.2017.05.115
PREVALENCE OF MALNUTRITION ACROSS VARYING SEVERITY OF CIRRHOSIS IS ASSOCIATED WITH DIETARY INSUFFICIENCY Shraddha Salunkhe 1 , Meena Godhia 1 , Abhinav Jain 2 , Akash Shukla 2 , Shobna Bhatia 2,∗ 1 SVT College, Mumbai City, India 2 Seth GS Medical College, Mumbai, India
E-mail address: [email protected] (S. Bhatia).
Figure 1. Kaplan–Meier analysis for recurrence of hepatic encephalopathy between LOLA and placebo groups.
Background and Aim: Malnutrition is prevalent in cirrhosis and associated with increased number of complications and increased short and long term mortality. Diminished nutrient intake and self imposed dietary restrictions contribute to malnutrition in this population. Methods: A consecutive 100 cirrhotic outdoor patients (age 47.5[11.1] years; 12 women) were enrolled. The nutritional assessment was done using subjective global assessment, anthropometric measurements like body mass index (BMI), triceps skinfold thickness and mid arm muscle circumference (MAMC). Intake of macronutrients was estimated by 72-h dietary recall and compared to the Recommended Daily Allowance (RDA). Results: The etiology of cirrhosis was alcohol in 34%. According to the classification of Child–Pugh, 12% were A, 58% were B and 30% were C. Mean BMI (corrected for ascites) amongst Child–Pugh class A, B and C was 21.9 ± 3.45, 21.3 ± 4.50 and 20.5 ± 3.79 kg/m2 , respectively = 0.56. Mean MAMC amongst Child–Pugh
Journal of Clinical and Experimental Hepatology July 2017 Vol. 7 No. S2
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Results: Minimal hepatic encephalopathy was diagnosed in 41 of 70 patients, a prevalence of 58.5% of MHE was observed in cirrhosis of liver in our study group. Conclusion: This study was conducted to study the prevalence of MHE in the cirrhosis of liver. MHE which adversely effects the quality of live, appropriate management of MHE can improve the quality of life and also Treatment not only results in improvement in cognitive and psychomotor deficits but also in health related quality of life (HRQOL). An early identification of MHE may improve the HRQOL and the prognosis of these patients.
CONFLICTS OF INTEREST The authors have none to declare. http://dx.doi.org/10.1016/j.jceh.2017.05.113
26
CIRRHOSIS AND COMPLICATIONS
TO ASSESS OUTCOME OF SLOW LOW-DOSE CONTINUOUS ALBUMIN, FUROSEMIDE ± TERLIPRESSIN SIFA (±T) INFUSION IN PATIENTS OF CIRRHOSIS WITH HEPATIC HYDROTHORAX Manjunath Hatti, Kamlesh Kumar, Alok Kumar, Gaurav Pande ∗ , V.P. Krishna, Prabhat N. Sharma, Vivek Saraswat Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
E-mail address: [email protected] (G. Pande). Background and Aim: Management of hepatic hydrothorax is challenging in view of limited treatment options specially medical management. The study was done to assess efficacy and safety of SIFA (±T) as a response-guided protocol in patients of cirrhosis with hydrothorax. Methods: 27 consecutive patients of cirrhosis with hepatic hydrothorax [(Arm I (n = 15); Arm II (n = 12)] were included. Baseline standard workup including, (hemogram, biochemistry, urine analysis and ascitic fluid examination) along with 24 h urinary sodium (UNa+ )/potassium (UK)/creatinine (Ucre), CXR and ECG were done. Arm I patients received furosemide infusion at 2 mg/h, albumin 2 g/h (20–40 g/d). As per clinical response and lab parameters, graded increase of furosemide was done by 1 mg/12 h if UNa+ < 80 meq/d. After 48 h, if UNa+ was <80 meq/d, terlipressin infusion was added @4 mg/24 h after correction of anemia (≥8 g/dl) and obtaining baseline ECG (repeated 12 hourly) and response-guided increase (1 mg/12 hourly) was done (maximum up to 8 mg/24 h). Arm II patients received SMT. S60
Results: A total 27 patients (Arm I n = 15; Arm II n = 12) of ACLF with hepatic hydrothorax were included. Baseline parameters were comparable among both Arm. All patients in Arm I responded over a median period of 8.6 ± 2.7 days whereas only 41% (5/12) patients responded to SMT in Arm II. Baseline parameters of Arm I patients were: age 44.2 ± 11.4, serum creatinine 1.19 ± 0.53, serum sodium 125.6 ± 8.4, UNa+ 26.02 ± 13.4, CTP-score 10.68 ± 1.42, MELD-score 28.5 ± 4.7. At the end of treatment serum creatinine 0.88 ± 0.48, serum Na 133.47 ± 5.25, maximum (max) UNa+ 192.50 ± 94.35. Baseline urine output (UO) was 475 ± 215 ml, whereas maximum UO was 3280 ± 780 ml while on treatment. 3 patients in terlipressin group had nonspecific mild pain abdomen. 2 patient developed t-wave inversion on terlipressin. All these resolved spontaneously. No other significant adverse events were noted in any group. Conclusions: Response-guided use of furosemide, albumin ± terlipressin is relatively safe and effective treatment options for hepatic hydrothorax.
CONFLICTS OF INTEREST The authors have none to declare. http://dx.doi.org/10.1016/j.jceh.2017.05.114
27 SECONDARY PROPHYLAXIS OF HEPATIC ENCEPHALOPATHY IN CIRRHOSIS: A DOUBLE BLIND RANDOMIZED CONTROLLED TRIAL OF L-ORNITHINE L-ASPARTATE VS PLACEBO Shivakumar Varakanahalli ∗ , Barjesh C. Sharma, Amol S. Dahale G B Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
E-mail address: [email protected] (S. Varakanahalli). Background and Aim: Hepatic encephalopathy is associated with a poor prognosis. l-Ornithine l-aspartate has been useful in treatment of hepatic encephalopathy. There is no study on the prevention of recurrence of encephalopathy with l-ornithine l-aspartate. Methods: We conducted a double blind randomized controlled trial at a tertiary center OPD clinic. Consecutive cirrhotic patients who recovered from HE were randomized to receive LOLA (6 g thrice daily) or similar amount of placebo by computer based random numbers for 6 months. Patients were assessed by number connection tests or figure connection tests (if illiterate), digit symbol © 2017, INASL
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
test, serial dotting test, line tracing test, critical flicker frequency test, arterial ammonia and Sickness impact profile scores at inclusion. Primary end point was development of overt HE. Results: Of 306 patients, 150 patients were enrolled. HE recurred in 9/73 (12.3%) and in 20/72 (27.7%) patients receiving LOLA and placebo respectively, P = 0.02 and hazard ratio = 0.389 (95% CI = 0.174–0.870). Mortality was similar in both groups (6.8% vs 13.8% P = 0.18). At 6 months follow up, there was significant change in the PHES (2.53 ± 2.18 vs −0.01 ± 1.92, P < 0.001), ammonia (−23.58 ± 14.8 vs 1.41 ± 13.34 mol/L P < 0.001) and CFF (5.85 ± 4.82 vs 0.58 ± 4.53 P < 0.001) in patients treated with LOLA compared to placebo. The health related quality of life also improved in LOLA group compared to placebo (−7.89 ± 5.52 vs −0.95 ± 4.25 P = 0.001). On multivariate analysis only MELD score predicted the recurrence of overt HE with odds ratio 2.21 (95% CI: 1.526–3.204 P < 0.001). Conclusions: LOLA is effective in the secondary prophylaxis of HE and is associated with significant improvements in PHES, ammonia and CFF scores and HRQOL (Figure 1 and Table 1).
Table 1 Delta Change in Parameters in LOLA and Placebo Groups at 3 Months and 6 Months Compared to Baseline. LOLA PHES 3 PHES 6 CFF 3 CFF 6 NH3 3 NH3 6 SIP 3 SIP 6
Change Placebo
1.28 ± 1.67 2.53 ± 2.18 3.28 ± 3.65 5.85 ± 4.82 −12.92 ± 9.04 −23.58 ± 14.8 −4.56 ± 3.27 −7.89 ± 5.52
0.30 ± 1.97 −0.01 ± 1.92 0.39 ± 3.59 0.59 ± 4.53 −0.66 ± 10.72 1.41 ± 13.34 −0.74 ± 3.21 −0.95 vs 4.25
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Abbreviations: CTP: Child Turcotte Pugh score; MELD: model for end stage liver disease; PHES: pychometric hepatic encephalopathy scores; CFF: critical flicker frequency. = Delta = change in value of parameters from baseline; 3 is at 3 months and 6 is at 6 months follow up; − value denotes decrease from the baseline and + value denotes increase from baseline.
CONFLICTS OF INTEREST The authors have none to declare. http://dx.doi.org/10.1016/j.jceh.2017.05.115
PREVALENCE OF MALNUTRITION ACROSS VARYING SEVERITY OF CIRRHOSIS IS ASSOCIATED WITH DIETARY INSUFFICIENCY Shraddha Salunkhe 1 , Meena Godhia 1 , Abhinav Jain 2 , Akash Shukla 2 , Shobna Bhatia 2,∗ 1 SVT College, Mumbai City, India 2 Seth GS Medical College, Mumbai, India
E-mail address: [email protected] (S. Bhatia).
Figure 1. Kaplan–Meier analysis for recurrence of hepatic encephalopathy between LOLA and placebo groups.
Background and Aim: Malnutrition is prevalent in cirrhosis and associated with increased number of complications and increased short and long term mortality. Diminished nutrient intake and self imposed dietary restrictions contribute to malnutrition in this population. Methods: A consecutive 100 cirrhotic outdoor patients (age 47.5[11.1] years; 12 women) were enrolled. The nutritional assessment was done using subjective global assessment, anthropometric measurements like body mass index (BMI), triceps skinfold thickness and mid arm muscle circumference (MAMC). Intake of macronutrients was estimated by 72-h dietary recall and compared to the Recommended Daily Allowance (RDA). Results: The etiology of cirrhosis was alcohol in 34%. According to the classification of Child–Pugh, 12% were A, 58% were B and 30% were C. Mean BMI (corrected for ascites) amongst Child–Pugh class A, B and C was 21.9 ± 3.45, 21.3 ± 4.50 and 20.5 ± 3.79 kg/m2 , respectively = 0.56. Mean MAMC amongst Child–Pugh
Journal of Clinical and Experimental Hepatology July 2017 Vol. 7 No. S2
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CIRRHOSIS AND COMPLICATIONS
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