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Expert Review of Gastroenterology &... Jun 2024Alcoholic liver disease (ALD) encompasses a spectrum of liver conditions, including liver steatosis, alcoholic hepatitis (AH), fibrosis, cirrhosis, and hepatocellular... (Review)
Review
INTRODUCTION
Alcoholic liver disease (ALD) encompasses a spectrum of liver conditions, including liver steatosis, alcoholic hepatitis (AH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). microRNAs (miRNAs) have garnered significant interest as potential biomarkers for ALD.
METHODS
We searched PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) systemically from inception to June 2024. All extracted data was stratified according to the stages of ALD. The vote-counting strategy performed a meta-analysis on miRNA expression profiles.
RESULTS
We included 40 studies. In serum of individuals with alcohol-use vs. no alcohol-use, miRNA-122 and miRNA-155 were upregulated, and miRNA-146a was downregulated. In patients with ALD vs. healthy controls, miRNA-122 and miRNA-155 were also upregulated and miRNA-146a was downregulated. However, in patients with AH vs. healthy individuals, only the serum miRNA-122 level was upregulated. Due to insufficient data on diagnostic accuracy, we failed to conclude the ability of miRNAs to distinguish different stages of ALD-related liver fibrosis. The results for ALD-related HCC were also insufficient and controversial.
CONCLUSIONS
Circulating miRNA-122 was the most promising biomarker to manage individuals with ALD. More studies were needed for the diagnostic accuracy of miRNAs in ALD.
REGISTRATION
This protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (www.crd.york.ac.uk/prospero/) with registration number CRD42023391931.
PubMed: 38937981
DOI: 10.1080/17474124.2024.2374470 -
Emergency Radiology Jun 2024Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic... (Review)
Review
Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for ectopic variceal management. A comprehensive search through PubMed, Scopus, Web of Science, and Embase was conducted until January 16, 2023, using relevant keywords. Case reports and case series with fewer than 10 patients on TIPS for ectopic variceal management were included. The quality assessment followed the Joanna Briggs Institute checklist for case reports. This systematic review evaluated 43 studies involving 50 patients with ectopic varices undergoing TIPS. Patients had a mean age of 54.3 years, half were female, and two were pregnant. Alcoholic liver disease (48%) and hepatitis C infection (26%) were common causes of portal hypertension. Ascites and splenomegaly were reported in 32% and 28% of the patients, respectively. Rectal, oral, and stomal variceal bleeding accounted for 62%, 16%, and 22% of the patients, respectively. Ectopic varices were mainly located in the duodenum (28%) and rectum (26%) regions. Complications affected 42% of the patients, re-bleeding in eleven and hepatic encephalopathy in seven. The follow-up lasted 12 months on average, and finally, 5 received a liver transplant. Mortality post-TIPS was 18%. Despite complications and a notable mortality rate, favorable outcomes were observed in almost half of the patients with ectopic variceal bleeding managed with TIPS. Further research is warranted to refine strategies and improve patient outcomes.
PubMed: 38935315
DOI: 10.1007/s10140-024-02258-6 -
Hepatology Communications Apr 2024The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We systematically reviewed the literature to answer these questions.
METHODS
Four databases were searched for studies describing the precision of clinical criteria (National Institute on Alcohol Abuse and Alcoholism, European Association for Study of Liver, or classical) and the role of histology in AH. The precision(positive predictive value) of criteria was pooled through random-effects meta-analysis, and its variation was investigated through subgroups and meta-regression of study-level factors with their percent contribution to variation (R2). The risk of bias among studies was evaluated through the QUADAS2 tool (PROSPERO-ID-CRD4203457250).
RESULTS
Of 4320 studies, 18 in the systematic review and 15 (10/5: low/high risk of bias, N=1639) were included in the meta-analysis. The pooled precision of clinical criteria was 80.2% (95% CI: 69.7-89.7, I2:93%, p < 0.01), higher in studies with severe AH (mean-Model for End-Stage Liver Disease > 20) versus moderate AH (mean-Model for End-Stage Liver Disease < 20): 92% versus 67.1%, p < 0.01, and in studies with serum bilirubin cutoff 5 versus 3 mg/dL (88.5% vs.78.8%, p = 0.01). The factors contributing to variation in precision were Model for End-Stage Liver Disease (R2:72.7%), upper gastrointestinal bleed (R2:56.3%), aspartate aminotransferase:aspartate aminotransferase ratio (R2:100%), clinical criteria (R2:40.9%), bilirubin (R2:22.5%), and Mallory body on histology (R2:19.1%).The net inter-pathologist agreement for histologic findings of AH was variable (0.33-0.97), best among 2 studies describing AH through simple and uniform criteria, including steatosis, ballooning, and neutrophilic inflammation. Few studies reported the utility of histology in estimating steroid responsiveness (N = 1) and patient prognosis (N = 4); however, very broad septa, pericellular fibrosis, and cholestasis were associated with mortality. Bilirubinostasis was associated with infection in 1 study.
CONCLUSIONS
Clinical criteria are reasonably precise for diagnosing severe AH, while there is an unmet need for better criteria for diagnosing moderate AH. Histologic diagnosis of AH should be simple and uniform.
Topics: Humans; End Stage Liver Disease; Severity of Illness Index; Hepatitis, Alcoholic; Aspartate Aminotransferases; Bilirubin
PubMed: 38497934
DOI: 10.1097/HC9.0000000000000404 -
Hepatology Communications Apr 2024Alcohol-associated liver disease (ALD), encompassing alcohol-associated hepatitis and alcohol-associated cirrhosis, is rising in the United States. Racial and ethnic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol-associated liver disease (ALD), encompassing alcohol-associated hepatitis and alcohol-associated cirrhosis, is rising in the United States. Racial and ethnic disparities are evident within ALD; however, the precise nature of these disparities is poorly defined.
METHODS
We conducted a search of the PubMed/MEDLINE and EMBASE databases to identify studies published from inception through September 2023 that reported ALD incidence, prevalence, and mortality within the United States, stratified by race and ethnicity. We calculated pooled prevalence and incidence by race and ethnicity, including risk ratios and ORs for ALD pooled prevalence and alcohol-associated hepatitis/alcohol-associated cirrhosis pooled proportions, and OR for ALD mortality using the DerSimonian and Laird method for random-effect models.
RESULTS
We identified 25 relevant studies (16 for quantitative meta-analysis), comprising 76,867,544 patients. ALD prevalence was highest in Hispanic (4.5%), followed by White (3.1%) and Black (1.4%) individuals. Pooled risk ratios of ALD prevalence were 1.64 (95% CI: 1.12-2.39) for Hispanic and 0.59 (95% CI: 0.35-0.87) for Black compared to White individuals. Mortality among those with ALD did not significantly differ between White and Hispanic (OR: 1.54, 95% CI: 0.9-2.5; I2=0%), Black (OR: 1.2, 95% CI: 0.8-1.6; I2=0%), or Native American (OR: 2.41, 95% CI: 0.9-2.9) individuals, while there was a significant difference between White and Asian (OR: 0.1; 95% CI: 0.03-0.5) individuals. Most data were cross-sectional and assessed to be of poor or fair quality.
CONCLUSIONS
Differences were observed in ALD epidemiology, including higher prevalence among Hispanic and lower prevalence among Black individuals, although there were smaller differences in ALD mortality. Differences in ALD prevalence and prognosis remain poorly defined based on existing data, highlighting a need for higher-quality epidemiological studies in this area.
Topics: Humans; Ethnicity; Hepatitis, Alcoholic; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; United States; Racial Groups; Health Status Disparities
PubMed: 38497931
DOI: 10.1097/HC9.0000000000000409 -
International Journal of Molecular... Feb 2024Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and... (Review)
Review
Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and neuroprotective properties. It exhibits the potential to prevent or slow the progression of various diseases, ranging from malignant tumors and viral infections to neurodegenerative disorders and ischemic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral hepatitis stand as prominent causes of morbidity and mortality in chronic liver diseases globally. The literature has substantiated CBD's potential therapeutic effects across diverse liver diseases in in vivo and in vitro models. However, the precise mechanism of action remains elusive, and an absence of evidence hinders its translation into clinical practice. This comprehensive review emphasizes the wealth of data linking CBD to liver diseases. Importantly, we delve into a detailed discussion of the receptors through which CBD might exert its effects, including cannabinoid receptors, CB1 and CB2, peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptor 55 (GPR55), transient receptor potential channels (TRPs), and their intricate connections with liver diseases. In conclusion, we address new questions that warrant further investigation in this evolving field.
Topics: Humans; Cannabidiol; Receptors, Cannabinoid; Cannabis; Digestive System Diseases; Liver Diseases, Alcoholic; Receptor, Cannabinoid, CB1
PubMed: 38397045
DOI: 10.3390/ijms25042370 -
The Cochrane Database of Systematic... Jan 2024Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and...
BACKGROUND
Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and portal hypertension. The prognosis is dismal, often with a survival of weeks to months. Hepatorenal syndrome is characterised by the development of intense splanchnic vasodilation favouring ascites and hypotension leading to renal vasoconstriction and acute renal failure. Therefore, treatment attempts focus on improving arterial pressure through the use of vasopressors, paracentesis, and increasing renal perfusion pressure. Several authors have reported that the placement of transjugular intrahepatic portosystemic shunts (TIPS) may be a therapeutic option because it decreases portal pressure and improves arterial and renal pressures. However, the evidence is not clearly documented and TIPS may cause adverse events. Accordingly, it is necessary to evaluate the evidence of the benefits and harms of TIPS to assess its value in people with hepatorenal syndrome.
OBJECTIVES
To evaluate the benefits and harms of transjugular intrahepatic portosystemic shunts (TIPS) in adults with hepatorenal syndrome compared with sham, no intervention, conventional treatment, or other treatments.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 2 June 2023.
SELECTION CRITERIA
We included only randomised clinical trials with a parallel-group design, which compared the TIPS placement with sham, no intervention, conventional therapy, or other therapies, in adults aged 18 years or older, regardless of sex or ethnicity, diagnosed with chronic liver disease and hepatorenal syndrome. We excluded trials of adults with kidney failure due to causes not related to hepatorenal syndrome, and we also excluded data from quasi-randomised, cross-over, and observational study designs as we did not design a separate search for such studies.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. morbidity due to any cause, and 3. serious adverse events. Our secondary outcomes were 1. health-related quality of life, 2. non-serious adverse events, 3. participants who did not receive a liver transplant, 4. participants without improvement in kidney function, and 5. length of hospitalisation. We performed fixed-effect and random-effects meta-analyses using risk ratio (RR) or Peto odds ratio (Peto OR), with 95% confidence intervals (CI) for the dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) for the continuous outcomes. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included two randomised clinical trials comparing TIPS placement (64 participants) versus conventional treatment (paracentesis plus albumin 8 g/L of removed ascites) (66 participants). The co-interventions used in the trials were dietary treatment (sodium less than 60 mmoL/day), spironolactone (300 mg/day to 400 mg/day), and furosemide (120 mg/day). Follow-up was up to 24 months. Both were multicentre trials from Spain and the USA, and Germany, conducted between 1993 and 2002. Most participants were men (aged 18 to 75 years). We are uncertain about the effect of TIPS placement compared with conventional treatment, during the first 24 months of follow-up, on all-cause mortality (RR 0.88, 95% CI 0.55 to 1.38; 2 trials, 130 participants; I = 58%; very low-certainty evidence) and on the development of any serious adverse event (RR 1.60, 95% CI 0.10 to 24.59; 2 trials, 130 participants; I = 78%; very low-certainty evidence). The use of TIPS may or may not result in a decrease in overall morbidity such as bacterial peritonitis, encephalopathy, or refractory ascites, during the first 24 months of follow-up, compared with the conventional treatment (RR 0.95, 95% CI 0.77 to 1.18; 2 trials, 130 participants; I = 0%; low-certainty evidence). We are uncertain about the effect of TIPS placement versus conventional treatment on the number of people who did not receive a liver transplant (RR 1.03, 95% CI 0.93 to 1.14; 2 trials, 130 participants; I = 0%; very low-certainty evidence) or on the length of hospitalisation (MD -20.0 days, 95% CI -39.92 to -0.08; 1 trial, 60 participants; very low-certainty evidence). Kidney function may improve in participants with TIPS placement (RR 0.53, 95% CI 0.27 to 1.02; 1 trial, 70 participants; low-certainty evidence). No trials reported health-related quality of life, non-serious adverse events, or number of participants with improvement in liver function associated with the TIPS placement. Funding No trials reported sources of commercial funding or conflicts of interest between researchers. Ongoing studies We found one ongoing trial comparing TIPS with conventional therapy (terlipressin plus albumin) and listed one study as awaiting classification as no full-text article could be found.
AUTHORS' CONCLUSIONS
TIPS placement was compared with conventional treatment, with a follow-up of 24 months, in adults with hepatorenal syndrome type 2. Based on two trials with insufficient sample size and trial limitations, we assessed the overall certainty of evidence as low or very low. We are unsure if TIPS may decrease all-cause mortality, serious adverse events, the number of people who did not receive a liver transplant, and the days of hospitalisation because of the very low-certainty evidence. We are unsure if TIPS, compared with conventional treatment, has better effects on overall morbidity (bacterial peritonitis, encephalopathy, or refractory ascites). TIPS may improve kidney function, but the certainty of evidence is low. The trials included no data on health-related quality of life, non-serious adverse events, and liver function associated with the TIPS placement. We identified one ongoing trial and one study awaiting classification which may contribute to the review when information becomes available.
Topics: Adult; Humans; Albumins; Ascites; Brain Diseases; Hepatorenal Syndrome; Peritonitis; Portasystemic Shunt, Transjugular Intrahepatic; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38235907
DOI: 10.1002/14651858.CD011039.pub2 -
Molecular Nutrition & Food Research Jan 2024Akkermansia muciniphila (A. muciniphila) are Gram negative commensal bacteria, degrading mucin in the intestinal mucosa, modulating intestinal permeability and... (Review)
Review
SCOPE
Akkermansia muciniphila (A. muciniphila) are Gram negative commensal bacteria, degrading mucin in the intestinal mucosa, modulating intestinal permeability and inflammation in the digestive tract, liver, and blood. Some components can promote the relative abundance of A. muciniphila in the gut microbiota, but lower levels of A. muciniphila are more commonly found in people with obesity, diabetes, metabolic syndromes, or inflammatory digestive diseases. Over-intake of ethanol can also induce a decrease of A. muciniphila, associated with dysregulation of microbial metabolite production, impaired intestinal permeability, induction of chronic inflammation, and production of cytokines.
METHODS AND RESULTS
Using a PRISMA search strategy, a review is performed on the bacteriological characteristics of A. muciniphila, the factors capable of modulating its relative abundance in the digestive tract and its probiotic use in alcohol-related liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma, hepatic transplantation, partial hepatectomy).
CONCLUSION
Several studies have shown that supplementation with A. muciniphila can improve ethanol-related hepatic pathologies, and highlight the interest in using this bacterial species as a probiotic.
Topics: Humans; Verrucomicrobia; Liver Diseases; Inflammation; Ethanol; Akkermansia
PubMed: 38059838
DOI: 10.1002/mnfr.202300510 -
Clinical Therapeutics Dec 2023Alcohol-associated hepatitis (AH) is a unique presentation of cholestatic steatohepatitis with liver dysfunction and malaise preceded by heavy alcohol intake. Although...
PURPOSE
Alcohol-associated hepatitis (AH) is a unique presentation of cholestatic steatohepatitis with liver dysfunction and malaise preceded by heavy alcohol intake. Although AH exists on a spectrum, in its most severe form, 28-day mortality approaches 50%. Clinical trials of therapeutic interventions over the last 50 years have yielded few durable therapies, none of which convey benefit beyond the short term.
METHODS
A qualitative systematic review was performed via searches of PubMed, the International Clinical Trials Registry Platform, and ClinicalTrials.gov for therapeutic interventions for AH.
FINDINGS
Prior to 2005, clinical trial results for AH were identified within PubMed. From 2005 to the present, trials were well catalogued within online registries and included information regarding trial status (eg, complete, terminated, actively enrolling). Most clinical trials for AH have used existing medications broadly targeting pathogenic themes of AH (eg, inflammation, cell death) in an off-label manner. The trend of initially promising pilot studies answered by larger trials showing lack of efficacy or safety signals have ended the hopes of many new therapeutics. The emergence of theragnostics to identify patients who may benefit from existing therapies and trials of agents with novel mechanisms of action, including epigenetic modifications and hyaluronic acid signaling targeted to AH pathogenesis, are currently under investigation.
IMPLICATIONS
This review of AH treatments details the historical interventions and clinical trials that have led to the current treatment algorithm and active studies shaping the therapeutic pipeline for AH.
Topics: Humans; Hepatitis, Alcoholic; Clinical Trials as Topic
PubMed: 37980219
DOI: 10.1016/j.clinthera.2023.10.013 -
World Journal of Gastroenterology Oct 2023Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy. However, previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease. The diagnostic value of transient elastography for autoimmune liver diseases (AILDs) is worth studying.
AIM
To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD.
METHODS
The PubMed, Cochrane Library and EMBASE databases were searched. Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs [autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC)] were included. The summary area under the receiver operating characteristic curve (AUROC), diagnostic odds ratio, sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis.
RESULTS
A total of 60 articles were included in this study, and the number of patients with AIH, PBC and PSC was 1594, 3126 and 501, respectively. The summary AUROC of transient elastography in the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in patients with AIH were 0.84, 0.88 and 0.90, respectively, while those in patients with PBC were 0.93, 0.93 and 0.91, respectively. The AUROC of cirrhosis for patients with PSC was 0.95. However, other noninvasive indices (aspartate aminotransferase to platelet ratio index, aspartate aminotransferase/alanine aminotransferase ratio, fibrosis-4 index) had corresponding AUROCs less than 0.80.
CONCLUSION
Transient elastography exerts better diagnostic accuracy in AILD patients, especially in PBC patients. The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.
Topics: Humans; Elasticity Imaging Techniques; Liver Cirrhosis; Fibrosis; Hepatitis, Autoimmune; ROC Curve; Non-alcoholic Fatty Liver Disease; Aspartate Aminotransferases; Liver
PubMed: 37900994
DOI: 10.3748/wjg.v29.i39.5503 -
Journal of Crohn's & Colitis Mar 2024Inflammatory bowel disease [IBD] comprises an immune-mediated group of chronic gastrointestinal disorders. Patients with IBD may experience extraintestinal... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Inflammatory bowel disease [IBD] comprises an immune-mediated group of chronic gastrointestinal disorders. Patients with IBD may experience extraintestinal manifestations, such as hepatobiliary complications. This meta-analysis aims to assess the prevalence of different hepatic manifestations in IBD patients.
METHODS
For this systematic review and meta-analysis, PubMed, Scopus, Web of Science, and Embase were searched until July 20, 2022, by specifying keywords for IBD, hepatic manifestations, and study type. Full texts of cohort studies in English that examined the prevalence of different hepatic manifestations were included in this study. The primary outcome was the overall prevalence of hepatic manifestations in IBD patients. For the statistical analysis, a proportion by random effect model meta-analysis was performed. The registration number for the protocol of this study in PROSPERO is CRD42022369595.
RESULTS
From the 4421 articles retrieved from the primary search, 118 met the inclusion criteria and were included in the final analysis. After a pooled analysis of 1 729 128 patients, the overall prevalence of hepatic manifestations was 3.49% (95% confidence interval [CI]: 3.31-3.68%; I2: 99.55%). The pooled prevalence of non-alcoholic fatty liver disease in 228 216 patients was 26.1% [95% CI: 22.1-30.2%; I2: 99.018%]. After pooled analysis of 9642 patients, the prevalence of primary sclerosing cholangitis was 1.67% [95% CI: 1.47-1.88%; I2: 99.10%]. The pooled prevalence of biliary stones was 4.1% [95% CI: 3.6-4.7%; I2: 97.43%]. Autoimmune hepatitis (0.51% [95% CI: 0.26-0.75%]; I2: 85.36%) and portal vein thrombosis (0.21% [95% CI: 0.08-0.33%]; I2: 97.95%) are considered as rare manifestations.
CONCLUSION
This study summarizes the prevalence and importance of different hepatic manifestations in IBD patients. These findings are crucial for the management of extraintestinal manifestations, especially hepatic manifestations, in IBD patients.
Topics: Humans; Inflammatory Bowel Diseases; Prevalence; Research Design; Liver Diseases
PubMed: 37695111
DOI: 10.1093/ecco-jcc/jjad157