Primary Prophylaxis to Prevent the Development of Hepatic Encephalopathy in Cirrhotic Patients with Acute Variceal Bleeding

Abstract

Background and Aim Variceal bleeding is the second most important precipitating factor related to the development of episodic hepatic encephalopathy; but to date there are no recommendations to prevent this complication. The aim of this study was to compare if primary prophylaxis with lactulose or L-ornithine L-aspartate or rifaximin, in cirrhotic patients with variceal bleeding, is better than placebo for avoiding the development of hepatic encephalopathy. Methods A randomized, double-blind, placebo-controlled clinical trial (ClinicalTrials.gov identifier: NCT02158182) which included cirrhotic patients with variceal bleeding, without minimal or clinical hepatic encephalopathy at admission. Findings 87 patients were randomized to one of four groups. The basal characteristics were similar between groups. Comparatively with placebo, the frequency with regard to the development of hepatic encephalopathy was as follows: lactulose (54.5% versus 27.3%; OR = 0.3, 95% CI 0.09-1.0; P = 0.06); L-ornithine L-aspartate (54.5% versus 22.7%, OR = 0.2, 95% CI 0.06-0.88; P = 0.03); rifaximin (54.5% versus 23.8%; OR = 0.3, 95% CI 0.07-0.9; P = 0.04). There was no significant difference between the three groups receiving any antiammonium drug (P = 0.94). In the group receiving lactulose, 59.1% had diarrhea, and 45.5% had abdominal discomfort, bloating, and flatulence. Two patients (10%) treated with lactulose and a patient (4.5%) in the placebo group developed spontaneous bacterial peritonitis due to E. coli; one of them died due to recurrent variceal bleeding. There were no other adverse effects. Conclusions Antiammonium drugs, particularly L-ornithine L-aspartate and rifaximin, proved to be effective in preventing the development of hepatic encephalopathy in those cirrhotic patients with variceal bleeding.

The Use of Elobixibat and Lactulose for Bowel Preparation for Colon Capsule Endoscopy

“…Although the use of Gastrografin has been reported [10], we used castor oil because it is inexpensive and is covered by the national health insurance system of Japan. It is thought that the Elobixibat [11] [12] which we used this time goes along the adaptation of the aperient and is not caught on Japanese insurance examination because the lactulose [13] is a health food. Elobixibit is a novel ileal bild acid transportor inhibitor that is expressed in the terminal ileum for treatment of chonic constipation [14].…”

Liver Cirrhosis and Sarcopenia from the Viewpoint of Dysbiosis

“…However, the preventive effects of rifaximin on sarcopenia incidence or progression in LC patients remain unclear. Table 2 demonstrates randomized controlled trials (RCTs) published since 2010 regarding the effects of rifaximin on outcomes in patients with decompensated LC [ 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ]. RCTs with the improvement of sarcopenia as a primary endpoint are not found.…”

Beneficial effects of L-ornithine L-aspartate for prevention of overt hepatic encephalopathy in patients with cirrhosis: a systematic review with meta-analysis

“…However current guidelines for the prevention of OHE under these conditions are scant. In order to address this issue, a placebo-controlled RCT was undertaken in 87 patients with cirrhosis and acute variceal bleeding in order to compare the efficacy of primary prophylaxis using one of three agents namely lactulose, LOLA and rifaximin, compared to placebo (Higuera-de-la- Tijera et al 2018). The primary endpoint was the development of OHE in the 7-day period post-bleeding.…”

“…For intravenous infusion of LOLA, 20 g LOLA for 3 days was employed (Abid et al 2011). The single primary prophylaxis trail employed intravenous LOLA 10 g over a 24 h period for 7 days, (Higuera-de-la- Tijera et al 2018).…”

“…Forest Plot for the efficacy of LOLA versus placebo/no intervention for the prevention of progression of MHE to OHE(Abid et al 2011;Mittal et al 2011;Alvares-da-Silva et al 2014), secondary OHE prophylaxis(Varakanahalli et al 2018), primary OHE prophylaxis (Higuera-de-la-Tijera et al 2018) or post-TIPSS OHE prophylaxis(Bai et al 2014) from results of the appropriate published RCTs. Trials are identified by first author names, number of the reference in parentheses and year of publication p < 0.001.The time to first OHE-related hospital admission was longer in the LOLA group compared to placebo with p < 0.021 with concomitantly greater improvements in HRQOL (SIP scores) (p < 0.001).…”