Hepatic encephalopathy describes the spectrum of neuropsychiatric changes that may complicate the course of cirrhosis and detrimentally affect outcomes. Ammonia plays a key role in its development. Rifaximin is a non-absorbable antibiotic that inhibits urease-producing bacteria and reduces absorption of dietary and bacterial ammonia.

To evaluate the beneficial and harmful effects of rifaximin versus placebo, no intervention, or non-absorbable disaccharides for: (i) the prevention of hepatic encephalopathy, and (ii) the treatment of minimal and overt hepatic encephalopathy, in people with cirrhosis, both when used alone and when combined with a non-absorbable disaccharide.

We searched the Cochrane Hepato-Biliary Group Clinical Trials Register, CENTRAL, MEDLINE, Embase, three other databases, the reference lists of identified papers, and relevant conference proceedings. We wrote to authors and pharmaceutical companies for information on other published, unpublished, or ongoing trials. Searches were performed to January 2023.

We included randomised clinical trials assessing prevention or treatment of hepatic encephalopathy with rifaximin alone, or with a non-absorbable disaccharide, versus placebo/no intervention, or a non-absorbable disaccharide alone.

Six authors independently searched for studies, extracted data, and validated findings. We assessed the design, bias risk, and participant/intervention characteristics of the included studies. We assessed mortality, serious adverse events, health-related quality of life, hepatic encephalopathy, non-serious adverse events, blood ammonia, Number Connection Test-A, and length of hospital stay.

We included 41 trials involving 4545 people with, or at risk for, developing hepatic encephalopathy. We excluded 89 trials and identified 13 ongoing studies. Some trials involved participants with more than one type of hepatic encephalopathy or more than one treatment comparison. Hepatic encephalopathy was classed as acute (13 trials), chronic (7 trials), or minimal (8 trials), or else participants were considered at risk for its development (13 trials). The control groups received placebo (12 trials), no/standard treatment (1 trial), or a non-absorbable disaccharide (14 trials). Eighteen trials assessed rifaximin plus a non-absorbable disaccharide versus a non-absorbable disaccharide alone. We classified 11 trials as at high risk of overall bias for mortality and 28 for non-mortality outcomes, mainly due to lack of blinding, incomplete outcome data, and selective reporting. Compared to placebo/no intervention, rifaximin likely has no overall effect on mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.50 to 1.38; P = 48, I2 = 0%; 13 trials, 1007 participants; moderate-certainty evidence), and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.99, 95% CI 0.49 to 1.97; P = 0.97, I2 = 0%; 10 trials, 786 participants; low-certainty evidence). However, there is likely a reduction in the overall risk of mortality when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.69, 95% CI 0.55 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) = 22; P = 0.001, I2 = 0%; 14 trials, 1946 participants; moderate-certainty evidence). There is likely no effect on the overall risk of serious adverse events when comparing rifaximin to placebo/no intervention (RR 1.05, 95% CI 0.83 to 1.32; P = 68, I2 = 0%; 9 trials, 801 participants; moderate-certainty evidence) and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.97, 95% CI 0.66 to 1.40; P = 85, I2 = 0%; 8 trials, 681 participants; low-certainty evidence). However, there was very low-certainty evidence that use of rifaximin plus a non-absorbable disaccharide may be associated with a lower risk of serious adverse events than use of a non-absorbable disaccharide alone (RR 0.66, 95% CI 0.45 to 0.98; P = 0.04, I2 = 60%; 7 trials, 1076 participants). Rifaximin likely results in an overall effect on health-related quality of life when compared to placebo/no intervention (mean difference (MD) -1.43, 95% CI -2.87 to 0.02; P = 0.05, I2 = 81%; 4 trials, 214 participants; moderate-certainty evidence), and may benefit health-related quality of life in people with minimal hepatic encephalopathy (MD -2.07, 95% CI -2.79 to -1.35; P < 0.001, I2 = 0%; 3 trials, 176 participants). The overall effect on health-related quality of life when comparing rifaximin to non-absorbable disaccharides is very uncertain (MD -0.33, 95% CI -1.65 to 0.98; P = 0.62, I2 = 0%; 2 trials, 249 participants; very low-certainty evidence). None of the combined rifaximin/non-absorbable disaccharide trials reported on this outcome. There is likely an overall beneficial effect on hepatic encephalopathy when comparing rifaximin to placebo/no intervention (RR 0.56, 95% CI 0.42 to 0.77; NNTB = 5; P < 0.001, I2 = 68%; 13 trials, 1009 participants; moderate-certainty evidence). This effect may be more marked in people with minimal hepatic encephalopathy (RR 0.40, 95% CI 0.31 to 0.52; NNTB = 3; P < 0.001, I2 = 10%; 6 trials, 364 participants) and in prevention trials (RR 0.71, 95% CI 0.56 to 0.91; NNTB = 10; P = 0.007, I2 = 36%; 4 trials, 474 participants). There may be little overall effect on hepatic encephalopathy when comparing rifaximin to non-absorbable disaccharides (RR 0.85, 95% CI 0.69 to 1.05; P = 0.13, I2 = 0%; 13 trials, 921 participants; low-certainty evidence). However, there may be an overall beneficial effect on hepatic encephalopathy when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.58, 95% CI 0.48 to 0.71; NNTB = 5; P < 0.001, I2 = 62%; 17 trials, 2332 participants; low-certainty evidence).

Compared to placebo/no intervention, rifaximin likely improves health-related quality of life in people with minimal hepatic encephalopathy, and may improve hepatic encephalopathy, particularly in populations with minimal hepatic encephalopathy and when it is used for prevention. Rifaximin likely has no overall effect on mortality, serious adverse events, health-related quality of life, or hepatic encephalopathy compared to non-absorbable disaccharides. However, when used in combination with a non-absorbable disaccharide, it likely reduces overall mortality risk, the risk of serious adverse events, improves hepatic encephalopathy, reduces the length of hospital stay, and prevents the occurrence/recurrence of hepatic encephalopathy. The certainty of evidence for these outcomes is very low to moderate; further high-quality trials are needed.

Alcohol use disorder (AUD) is one of the most widespread psychiatric disorders leading to detrimental consequences to people with this disorder and others. Worldwide, the prevalence of heavy episodic drinking (30-day prevalence of at least one occasion of 60 g of pure alcohol intake among current drinkers) is estimated at 20% and the prevalence of AUD at 5% of the adult general population, with highest prevalence in Europe and North America. Therapeutic approaches, including pharmacotherapy, play an important role in treating people with AUD. This is an update of a Cochrane Review first published in 2018.

To evaluate the benefits and harms of baclofen on achieving and maintaining abstinence or reducing alcohol consumption in people with AUD compared to placebo, no treatment or any other pharmacological relapse prevention treatment.

We used standard, extensive Cochrane search methods. The latest search was 22 November 2021.

Randomised controlled trials (RCTs) of at least four weeks' treatment duration and 12 weeks' overall study duration comparing baclofen for AUD treatment with placebo, no treatment or other treatments.

We used standard Cochrane methods. Our primary outcomes were 1. relapse, 2. frequency of use, 3. amount of use, 4. adverse events, 5. dropouts from treatment and 6. dropouts from treatment due to adverse events. Our secondary outcomes were 7. craving, 8. anxiety, 9. depression and 10. frequency of most relevant adverse events.

We included 17 RCTs (1818 participants) with a diagnosis of alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition or International Classification of Diseases 10th edition criteria. Mean age was 46.5 years and 70% were men. Ten studies compared baclofen to placebo or another medication; seven compared two baclofen doses to placebo or another medication. Globally, 15 studies compared baclofen to placebo, two baclofen to acamprosate and two baclofen to naltrexone. In 16 studies, participants received psychosocial treatments. We judged most studies at low risk of selection, performance, detection (subjective outcome), attrition and reporting bias. Ten studies detoxified participants before treatment; in seven studies, participants were still drinking at the beginning of treatment. Treatment duration was 12 weeks for 15 RCTs and longer in two studies. Baclofen daily dose was 30 mg to 300 mg: 10 RCTs used low doses (30 mg or less); eight RCTs medium doses (above 30 and 100 mg or less) and four RCTs high doses (above 100 mg). Compared to placebo, moderate-certainty evidence found that baclofen probably decreases the risk to relapse (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.77 to 0.99; 12 studies, 1057 participants). This result was confirmed among detoxified participants but not among other subgroups of participants. High-certainty evidence found that baclofen increases the percentage of days abstinent (mean difference (MD) 9.07, 95% CI 3.30 to 14.85; 16 studies, 1273 participants). This result was confirmed among all subgroups of participants except non-detoxified or those who received medium doses. There was no difference between baclofen and placebo in the other primary outcomes: heavy drinking days (standardised mean difference (SMD) -0.18, 95% CI -0.48 to 0.11; 13 studies, 840 participants; moderate-certainty evidence); number of drinks per drinking days (MD -0.45, 95% CI -1.20 to 0.30; 9 studies, 392 participants; moderate-certainty evidence); number of participants with at least one adverse event (RR 1.05, 95% CI 0.99 to 1.11; 10 studies, 738 participants; high-certainty evidence); dropouts (RR 0.88, 95% CI 0.74 to 1.03; 17 studies, 1563 participants; high-certainty evidence); dropouts due to adverse events (RR 1.39, 95% CI 0.89 to 2.18; 16 studies, 1499 participants; high-certainty evidence). These results were confirmed by subgroup analyses except than for the dropouts that resulted lower among participants who received high doses of baclofen and studies longer than 12 weeks. Compared to placebo, there was no difference in craving (SMD -0.16, 95% CI -0.37 to 0.04; 17 studies, 1275 participants), anxiety (MD -0.01, 95% CI -0.14 to 0.11; 15 studies, 1123 participants) and depression (SMD 0.07, 95% CI -0.12 to 0.27; 11 studies, 1029 participants). Concerning the specific adverse events, baclofen increases fatigue, dizziness, somnolence/sedation, dry mouth, paraesthesia and muscle spasms/rigidity. There was no difference in the other adverse events. Compared to acamprosate, one study (60 participants) found no differences in any outcomes but the evidence was very uncertain: relapse (RR 1.25, 95% CI 0.71 to 2.20; very low-certainty evidence); number of participants with at least one adverse event (RR 0.63, 95% CI 0.23 to 1.69; very low-certainty evidence); dropouts (RR 0.56, 95% CI 0.21 to 1.46; very low-certainty evidence); dropouts due to adverse events (RR 0.33, 95% CI 0.01 to 7.87; very low-certainty evidence) and craving (MD 5.80, 95% CI -11.84 to 23.44); and all the adverse events evaluated. Compared to naltrexone, baclofen may increase the risk of relapse (RR 2.50, 95% CI 1.12 to 5.56; 1 study, 60 participants; very low-certainty evidence) and decrease the number of participants with at least one adverse event (RR 0.35, 95% CI 0.15 to 0.80; 2 studies, 80 participants; very low-certainty evidence) but the evidence is very uncertain. One study (60 participants) found no difference between baclofen and naltrexone in the dropouts at the end of treatment (RR 1.00, 95% CI 0.32 to 3.10; very low-certainty evidence), craving (MD 2.08, 95% CI -3.71 to 7.87), and all the adverse events evaluated.

Baclofen likely reduces the risk of relapse to any drinking and increases the percentage of abstinent days, mainly among detoxified participants. It does not increase the number of participants with at least one adverse event, those who dropout for any reason or due to adverse events. It probably does not reduce number of heavy drinking days and the number of drinks per drinking days. Current evidence suggests that baclofen may help people with AUD in maintaining abstinence. The results of comparisons of baclofen with acamprosate and naltrexone were mainly based on only one study.

Alcohol use disorder (AUD) and alcohol-related impairments belong to the most widespread psychiatric disorders leading to specific psychophysical, affective and cognitive symptoms and consequences for psychosocial well-being and health. Alcohol consumption is increasingly becoming a problem in many developing regions and AUD prevalence is estimated at 4.1% worldwide, with highest prevalence in European countries (7.5%), and the North America (6.0%). Therapeutic approaches, including pharmacotherapy, play an important role in treating patients with AUD.

To assess the efficacy and safety of baclofen for treating people with AUD, who are currently drinking, with the aim of achieving and maintaining abstinence or reducing alcohol consumption.

We searched the Cochrane Drugs and Alcohol Specialised Register, CENTRAL, MEDLINE, Embase, two further databases and two clinical trials registries, conference proceedings, and the reference lists of retrieved articles. The date of the most recent search was 30 January 2018.

Randomised controlled trials (RCTs) of at least four weeks' treatment duration and 12 weeks' overall study duration comparing baclofen for relapse prevention of AUD with placebo, no treatment or other treatments.

We used standard methodological procedures expected by Cochrane.

We included 12 RCTs (1128 participants). All studies but three recruited fewer than 100 participants. Participants had a diagnosis of alcohol dependence according the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV or the International Classification of Diseases (ICD)-10 criteria who were currently drinking. The mean age of participants was 48 years, and there were more men (69%), than women. All studies compared baclofen to placebo, except for one study that evaluated baclofen versus acamprosate. The included studies considered baclofen at different doses (range 10 mg a day to 150 mg a day). In all but one of the studies, participants in both the baclofen and placebo groups received psychosocial treatment or counselling of various intensity.We judged most of the studies at low risk of selection, performance, detection (subjective outcome), attrition and reporting bias.We did not find any difference between baclofen and placebo for the primary outcomes: relapse-return to any drinking (RR 0.88, 95% CI 0.74 to 1.04; 5 studies, 781 participants, moderate certainty evidence); frequency of use by percentage of days abstinent (MD 0.39, 95% CI -11.51 to 12.29; 6 studies, 465 participants, low certainty evidence) and frequency of use by percentage of heavy drinking days at the end of treatment (MD 0.25, 95% CI -1.25 to 1.76; 3 studies, 186 participants, moderate certainty evidence); number of participants with at least one adverse event (RR 1.04, 95% CI 0.99 to 1.10; 4 studies, 430 participants, high certainty evidence); the dropout rate at the end of treatment (RR 0.98, 95% CI 0.77 to 1.26, 8 studies, 977 participants, high certainty evidence) and dropout due to adverse events (RR 1.11, 95% CI 0.59 to 2.07; 7 studies, 913 participants, high certainty evidence).We found evidence that baclofen increases amount of use (drink per drinking days), (MD 1.55, 95% CI 1.32 to 1.77; 2 studies, 72 participants, low certainty evidence).Among secondary outcomes, there was no difference on craving (MD 1.38, 95% CI -1.28 to 4.03, 5 studies, 469 participants), and anxiety (SMD 0.07, 95% CI -0.14 to 0.28; 5 trials, 509 participants). We found that baclofen increased depression (SMD 0.27, 95% CI 0.05 to 0.48; 3 studies, 387 participants).Concerning the specific adverse events we found that baclofen increased: vertigo (RR 2.16, 95% CI 1.24 to 3.74; 7 studies, 858 participants), somnolence/sedation (RR 1.48, 95%CI 1.11 to 1.96; 8 studies, 946 participants), paraesthesia (RR 4.28, 95% CI 2.11 to 8.67; 4 studies, 593 participants), and muscle spasms/rigidity (RR 1.94, 95%CI 1.08 to 3.48; 3 studies, 551 participants). For all the other adverse events we did not find significant differences between baclofen and placebo.For the comparison baclofen versus acamprosate, we were only able to extract data for one outcome, craving. For this outcome, we found that baclofen increased craving compared with acamprosate (MD 14.62, 95% CI 12.72 to 16.52; 1 study, 49 participants).

None of the primary or secondary outcomes of the review showed evidence of a difference between baclofen and placebo. The high heterogeneity among primary studies results limits the interpretation of the summary estimate, the identification of moderators and mediators of baclofen's effects on alcohol use remains a challenge for further research. Even though some results from RCTs are promising, current evidence remains uncertain regarding the use of baclofen as a first-line treatment for people with AUDs.

The Maastricht IV/Florence Consensus Report and the Second Asia-Pacific Consensus Guidelines strongly recommend eradication of Helicobacter pylori (H. pylori) in patients with previous gastric neoplasia who have undergone gastric surgery. However, the guidelines do not mention optimal timing, eradication regimens, diagnostic tools, and follow-up strategies for patients undergoing gastrectomy and do not indicate if eradication of H. pylori reduces the risk of marginal ulcer or stump cancer in the residual stomach after gastrectomy. The purpose of this review is to provide an update which may help physicians to properly manage H. pylori infection in patients who have undergone gastric surgery. This review focuses on (1) the microenvironment change in the stomach after gastrectomy; (2) the phenomenon of spontaneous clearance of H. pylori after gastrectomy; (3) the effects of H. pylori on gastric atrophy and intestinal metaplasia after gastrectomy; (4) incidence and clinical features of ulcers developing after gastrectomy; (5) does eradication of H. pylori reduce the risk of gastric stump cancer in the residual stomach? (6) does eradication of H. pylori reduce the risk of secondary metachronous gastric cancer in the residual stomach? and (7) optimal timing and regimens for H. pylori eradication, diagnostic tools and follow-up strategies for patients undergoing gastrectomy.