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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 -
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 -
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 -
BMC Gastroenterology Aug 2023The incidence of HBV-negative and HCV-negative hepatocellular carcinoma (NBNC-HCC) is significantly increasing. However, their clinicopathologic features and prognosis... (Meta-Analysis)
Meta-Analysis
Comparison of clinicopathologic characteristics among patients with HBV-positive, HCV-positive and Non-B Non-C hepatocellular carcinoma after hepatectomy: a systematic review and meta-analysis.
BACKGROUND
The incidence of HBV-negative and HCV-negative hepatocellular carcinoma (NBNC-HCC) is significantly increasing. However, their clinicopathologic features and prognosis remain elucidated. Our study aimed to compare the clinicopathologic characteristics and survival outcomes of NBNC-HCC with hepatitis virus-related HCC.
METHOD
A literature review was performed in several databases, including PubMed, Embase, Cochrane Library and Web of Science, to identify the studies comparing NBNC-HCC with HBV-positive HCV-negative HCC (B-HCC), HBV-negative HCV-positive (C-HCC) and/or HBV-positive HCV-positive HCC (BC-HCC). The clinicopathologic characteristics and survival outcomes were extracted and pooled to access the difference.
RESULTS
Thirty-two studies with 26,297 patients were included: 5390 patients in NBNC-HCC group, 9873 patients in B-HCC group, 10,848 patients in C-HCC group and 186 patients in BC-HCC group. Patients in NBNC-HCC group were more liable to be diagnosed at higher ages, but with better liver functions and lighter liver cirrhosis. Comparing to B-HCC and C-HCC groups, although NBNC-HCC group was prone to have larger tumor sizes, it did not have more advanced tumors. Meanwhile, there were no significant differences in both 5-year and 10-year disease-free survival and overall survival between NBNC-HCC group and B-HCC or C-HCC group.
CONCLUSIONS
Our meta-analysis revealed patients with NBNC-HCC had as worse prognosis as those with hepatitis virus-related HCC. More attention should be paid on patients with non-alcoholic steatohepatitis or metabolic syndromes to prevent the incidence of NBNC-HCC.
Topics: Humans; Hepatectomy; Carcinoma, Hepatocellular; Hepatitis B virus; Liver Neoplasms; Hepatitis C
PubMed: 37612653
DOI: 10.1186/s12876-023-02925-x -
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 -
Hepatology International Feb 2024Alcohol consumption is the most important risk factor responsible for the disease burden of liver cirrhosis (LC). Estimates of risk relationships available usually... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol consumption is the most important risk factor responsible for the disease burden of liver cirrhosis (LC). Estimates of risk relationships available usually neither distinguish between different causes such as alcohol-related LC or hepatitis-related LC, nor differentiate between morbidity and mortality as outcome. We aimed to address this research gap and identify dose-response relationships between alcohol consumption and LC, by cause and outcome.
METHODS
A systematic review using PubMed/Medline and Embase was conducted, identifying studies that reported an association between level of alcohol use and LC. Meta-regression models were used to estimate the dose-response relationships and control for heterogeneity.
RESULTS
Totally, 44 studies, and 1 secondary data source, with a total of 5,122,534 participants and 15,150 cases were included. Non-linear dose-response relationships were identified, attenuated for higher levels of consumption. For morbidity, drinking 25 g/day was associated with a RR of 1.81 (95% CI 1.68-1.94) compared to lifetime abstention; 50 g/day and 100 g/day corresponded to 3.54 (95% CI 3.29-3.81) and 8.15 (95% CI 7.46-8.91), respectively. For mortality, for 25 g/day, a RR of 2.65 (95% CI 2.22-3.16); for 50 g/day, a RR of 6.83 (95% CI 5.84-7.97); for 100 g/day, a RR of 16.38 (95% CI 13.81-19.42) were identified. A higher risk for alcohol-related and all-cause LC as compared to hepatitis C-related LC was found.
CONCLUSION
Our results demonstrated higher acceleration for mortality compared to morbidity. The current findings will inform the way we quantify the burden due to LC attributable to alcohol use.
Topics: Humans; Alcohol Drinking; Risk Factors; Liver Cirrhosis; Morbidity; Liver Cirrhosis, Alcoholic
PubMed: 37684424
DOI: 10.1007/s12072-023-10584-z -
Clinical Chemistry and Laboratory... Feb 2024Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels.
METHODS
PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups.
RESULTS
Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval).
CONCLUSIONS
Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.
Topics: Humans; Hepcidins; Ferritins; Liver Cirrhosis; Iron; Non-alcoholic Fatty Liver Disease
PubMed: 37540837
DOI: 10.1515/cclm-2023-0540 -
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 -
Journal of Gastrointestinal Cancer Mar 2024Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, including Australia. The absence of a consensus clinical practice guideline (CPG)...
BACKGROUND
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, including Australia. The absence of a consensus clinical practice guideline (CPG) specific to HCC management poses challenges in reducing morbidity, mortality, and improving patient recovery. This systematic review aims to evaluate the existing evidence and assess the potential of published guidelines, including those with an international scope, to provide guidance for healthcare professionals in Australia.
METHODS
Electronic search of MEDLINE, Embase, Cochrane Library, Google Scholar, and PubMed was conducted. Peer-reviewed English language articles from 2005 to June 2022 were included if they described management of HCC as part of an evidence-based overall management plan or CPG. The quality of the included CPGs was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool.
RESULTS
Twenty-one articles from 16 regions throughout the world were included in this review. All included guidelines (n = 21, 100%) recommended evaluating cirrhosis, hepatitis B, and hepatitis C as potential risk factors of HCC. Obesity and non-alcoholic fatty liver disease were recommended by 19 CPGs (91%) as risk factor for HCC. Fourteen guidelines (67%) endorsed using the BCLC staging system. Eighteen guidelines (86%) recommended a multidisciplinary approach for the management of HCC. Eighteen guidelines (86%) advised that surveillance using ultrasound should be implemented in all cirrhotic patients every 6 months regardless of the cause of cirrhosis. AGREE II mean overall assessment score was 90% indicating that all guidelines included were highly recommended in majority of domains.
CONCLUSIONS
The included CPGs provided a comprehensive approach, emphasizing the evaluation of risk factors, utilization of the BCLC staging system, and the importance of a multidisciplinary approach. Regular surveillance using ultrasound for cirrhotic patients was widely recommended. An understanding of contemporary international CPGs can prioritize aspects of the management of HCC to assist healthcare professionals to develop a national guideline to enable standardized, comprehensive, and evidence-based care for patients with HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Practice Guidelines as Topic; Risk Factors; Australia
PubMed: 37480425
DOI: 10.1007/s12029-023-00961-0 -
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