Plain language summary Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis Key messages The prevention and treatment of hepatic encephalopathy, in people with cirrhosis, largely depends on use of the compound lactulose. Rifaximin is not used to treat hepatic encephalopathy, at present, but it is used as an add‐on to lactulose to help prevent hepatic encephalopathy in people whose response to lactulose is inadequate. We found that combining rifaximin with lactulose improved hepatic encephalopathy, reduced the risk of dying, and reduced the risk of developing side effects in addition to preventing future relapses. Its wider use in the management of people with hepatic encephalopathy needs to be considered. What are cirrhosis and hepatic encephalopathy? Cirrhosis is a long‐term condition in which scar tissue (fibrosis) replaces normal liver tissue, often as a result of excess alcohol, being overweight, or having chronic hepatitis B/C infection. People with cirrhosis commonly develop a condition called hepatic encephalopathy which affects their mental function and their neurological function. This condition can have a negative effect on their survival. The exact reason why people with cirrhosis develop hepatic encephalopathy is unknown, but the toxin ammonia, which is produced mainly in the gut, is thought to play an important role. The severity of the symptoms of hepatic encephalopathy ranges from minor difficulties in mental function to obvious changes in movement, mental status, and consciousness. The minor changes in concentration, behaviour, and everyday function are classed as minimal hepatic encephalopathy. The more obvious abnormalities and changes in consciousness are classed as overt hepatic encephalopathy. The overt symptoms may occur in episodes or may be present at all times. How is hepatic encephalopathy treated? The non‐absorbable disaccharides (sugars), lactulose and lactitol, are the most commonly used treatment for hepatic encephalopathy. They reduce ammonia levels in the blood through multiple actions, mainly in the gut. Rifaximin is an antibiotic that is not absorbed into the blood stream but works solely in the gut, where it reduces the production of ammonia by the gut bacteria and ammonia absorption into the blood system. This effect may benefit people with hepatic encephalopathy. What did we want to find out? We wanted to find out if rifaximin could be used to prevent and treat hepatic encephalopathy in people with cirrhosis; whether it does this better than no drug treatment, a dummy pill (placebo), or non‐absorbable disaccharides; whether there may be additional benefit if rifaximin is used together with a non‐absorbable disaccharide; and whether there were any unwanted side effects. What did we do? We searched for studies that looked at rifaximin compared with no treatment, placebo, or non‐absorbable disaccharides in people with cirrhosis with, or at risk for developing, hepatic encephalopathy. We also searched for studies that used rifaximin plus non‐absorbable disaccharides compared with non‐absorbable disaccharides alone. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes. What did we find? We identified 41 clinical studies involving 4545 people, who were randomly allocated to treatment groups. All participants had cirrhosis mainly due to excessive alcohol intake or chronic viral hepatitis. Participants were classed as having acute (13 studies), chronic (7 studies), or minimal (8 studies) hepatic encephalopathy, or were considered to be at risk for its development (13 studies). The studies compared rifaximin with a placebo (12 studies), no intervention (1 study), or lactulose/lactitol (14 studies). In 18 studies, rifaximin was given together with lactulose/lactitol and the results compared to the effect of giving lactulose/lactitol alone. The analyses found that giving rifaximin alone may help improve health‐related quality of life and the performance of tests used to assess mental function in people with minimal hepatic encephalopathy. However, lactulose is probably as effective and is considerably cheaper. There were no differences in the benefits and side effects of rifaximin when directly compared with lactulose/lactitol. However, when rifaximin was given together with lactulose/lactitol, it reduced the risk of death (from 14.8% to 10.1%), reduced the risk of unwanted side effects (from 34.4% to 17.6%), and resulted in improvement in hepatic encephalopathy (from 86.9% to 33.8%) when compared to use of lactulose alone. What are the limitations of the evidence? We are uncertain about or have only moderate confidence in our findings, meaning we cannot make more certain conclusions about the effects of rifaximin. This was mainly because people in the studies might have been aware of which treatment they were getting and not all the studies provided data about the outcomes we were interested in. Also, many studies were too small for us to be certain about their results. More high‐quality studies are needed. How up to date is this evidence? The evidence is up to date to January 2023.
【저자키워드】 humans, Quality of life, Hepatic encephalopathy, Liver cirrhosis, ammonia, rifaximin, Liver Cirrhosis/complications, Disaccharides, Disaccharides/adverse effects, Hepatic Encephalopathy/drug therapy, Rifaximin/therapeutic use,