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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 -
Nutrients Feb 2023The increasing burden of nonalcoholic fatty liver disease (NAFLD) requires innovative management strategies, but an effective pharmacological agent has yet to be found.... (Review)
Review
The increasing burden of nonalcoholic fatty liver disease (NAFLD) requires innovative management strategies, but an effective pharmacological agent has yet to be found. Apart from weight loss and lifestyle adjustments, one isomer of the vitamin E family-alpha-tocopherol-is currently recommended for nondiabetic steatohepatitis patients. Another member of the vitamin E family, tocotrienol (T3), has anti-inflammatory and antioxidant properties that reach beyond those of alpha-tocopherol, making it a potential agent for use in NAFLD management. This systematic review aimed to provide an overview of the effects of T3 supplementation on NAFLD from both clinical and preclinical perspectives. A literature search was performed in October 2022 using PubMed, Scopus and Web of Science. Original research articles reporting NAFLD outcomes were included in this review. The search located 12 articles (8 animal studies and 4 human studies). The literature reports state that T3 isomers or natural mixtures (derived from palm or annatto) improved NAFLD outcomes (liver histology, ultrasound or liver profile). However, the improvement depended on the severity of NAFLD, study period and type of intervention (isomers/mixture of different compositions). Mechanistically, T3 improved lipid metabolism and prevented liver steatosis, and reduced mitochondrial and endoplasmic reticulum stress, inflammation and ultimately liver fibrosis. In summary, T3 could be a potential agent for use in managing NAFLD, pending more comprehensive preclinical and human studies.
Topics: Animals; Humans; Non-alcoholic Fatty Liver Disease; Tocotrienols; alpha-Tocopherol; Liver; Vitamin E
PubMed: 36839192
DOI: 10.3390/nu15040834 -
Alcohol and Alcoholism (Oxford,... May 2022Chronic alcohol consumption may result in liver injury and chronic liver disease, but other factors are likely to influence disease progression. Malnutrition,...
AIMS
Chronic alcohol consumption may result in liver injury and chronic liver disease, but other factors are likely to influence disease progression. Malnutrition, specifically micronutrient deficiency, is frequently associated with both alcohol use disorder and chronic liver disease. We hypothesize that micronutrient deficiencies may affect the progression of liver disease in this population.
METHODS
Systematic integrative review of the medical literature; electronic search of MEDLINE 1950-2021; studies investigating role of any micronutrient in the acceleration of alcohol-related liver injury in humans or animals. Studies which specifically related to alcoholic hepatitis were excluded. Outcomes were extracted and recorded in tabulated form and discussed narratively.
RESULTS
We identified 46 studies investigating the role of micronutrient deficiencies in the pathogenesis of alcohol-related liver disease. Specific micronutrients which were identified included folic acid or related B vitamins (n = 9 studies), Vitamin D (n = 9 studies), magnesium (n = 8 studies), zinc (n = 8 studies) and selenium (n = 12 including one systematic review). Observational evidence suggests a potential role of magnesium deficiency in accelerating alcohol-related liver injury with weak or negative evidence for other micronutrients.
CONCLUSIONS
Magnesium deficiency may increase the risk of alcohol-related liver injury and adverse liver outcomes. However, currently, there is insufficient evidence to support magnesium supplementation except for clinically relevant magnesium deficiency. Long-term prospective cohort studies assessing the impact of micronutrients on liver disease progression in patients with alcohol use disorder are lacking and may help determine whether there is a causal role for micronutrient deficiencies in alcohol-related liver injury.
Topics: Alcoholism; Dietary Supplements; Disease Progression; Humans; Liver Diseases; Magnesium; Magnesium Deficiency; Malnutrition; Micronutrients; Prospective Studies; Vitamins
PubMed: 34491307
DOI: 10.1093/alcalc/agab060 -
Alimentary Pharmacology & Therapeutics Dec 2009Biomarkers hold great promise for detecting chronic liver disease without the use of liver biopsy. (Review)
Review
BACKGROUND
Biomarkers hold great promise for detecting chronic liver disease without the use of liver biopsy.
AIM
To review the usefulness of cytokeratin (CK) 18 fragments, a marker of hepatocyte apoptosis, to predict the presence of chronic liver injury.
METHODS
Available literature identified from PubMed was reviewed.
RESULTS
Levels of CK18 fragments have been shown to be elevated in hepatocellular carcinoma, viral hepatitis, alcoholic hepatitis, nonalcoholic fatty liver disease and cholestatic liver disease. In the setting of nonalcoholic fatty liver disease, CK18 fragments may distinguish nonalcoholic steatohepatitis from simple fatty liver.
CONCLUSIONS
Undoubtedly, the most promising application of CK18 fragments is currently in nonalcoholic fatty liver disease, and especially for distinguishing patients with nonalcoholic steatohepatitis vs. those with simple steatosis. Further investigations and technical improvements are required to cross the boundary from research to the clinical application of CK18 fragments as a marker of chronic liver disease.
Topics: Apoptosis; Biomarkers; Caspases; Humans; Keratin-18; Liver; Liver Diseases
PubMed: 19769633
DOI: 10.1111/j.1365-2036.2009.04148.x -
The Cochrane Database of Systematic... Nov 2017Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic liver diseases.
OBJECTIVES
To assess the beneficial and harmful effects of vitamin D supplementation in people with chronic liver diseases.
SEARCH METHODS
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched databases of ongoing trials and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. All searches were up to January 2017.
SELECTION CRITERIA
Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D (cholecalciferol) or vitamin D (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration. We contacted authors of the trials to ask for missing information. We conducted random-effects and fixed-effect meta-analyses. For dichotomous outcomes, we calculated risk ratios (RRs), and for continuous outcomes, we calculated mean differences (MD), both with 95% confidence intervals (CI) and Trial Sequential Analyses-adjusted CIs. We calculated Peto odds ratio (OR) for rare events. We considered risk of bias in domains to assess the risk of systematic errors. We conducted Trial Sequential Analyses to control the risk of random errors. We assessed the quality of the evidence with GRADE.
MAIN RESULTS
We included 15 randomised clinical trials with 1034 participants randomised. All trials had a parallel group design. Nine trials were conducted in high-income countries and six trials in middle-income countries. All trials were at high risk of bias. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. All included trials reported the baseline vitamin D status of participants. Participants in six trials had baseline 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), while participants in the remaining nine trials were vitamin D insufficient (less than 20 ng/mL). All trials administered vitamin D orally. Mean duration of vitamin D supplementation was 0.5 years and follow-up was 0.6 years. Eleven trials (831 participants; 40% women; mean age 52 years) tested vitamin D, one trial (18 men; mean age 61 years) with three intervention groups tested vitamin D and 25-dihydroxyvitamin D in separate groups, and three trials (185 participants; 55% women; mean age 55 years) tested 1,25-dihydroxyvitamin D. Seven trials used placebo, and eight trials used no intervention in the control group.The effect of vitamin D on all-cause mortality at the end of follow-up is uncertain because the results were imprecise (Peto OR 0.70, 95% CI 0.09 to 5.38; I = 32%; 15 trials; 1034 participants; very low quality evidence). Trial Sequential Analysis on all-cause mortality was performed based on a mortality rate in the control group of 10%, a relative risk reduction of 28% in the experimental intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 6396 participants. The cumulative Z-curve did not cross the trial sequential monitoring boundary for benefit or harm after the 15th trial, and the Trial Sequential Analyses-adjusted CI was 0.00 to 2534.The effect of vitamin D on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) and on serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants), myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants), and thyroiditis (RR 0.33 95% CI 0.01 to 7.91; 1 trial; 68 participants) is uncertain because the results were imprecise. The evidence on all these outcomes is of very low quality. The effect of vitamin D on non-serious adverse events such as glossitis (RR 3.70, 95% CI 0.16 to 87.6; 1 trial; 65 participants; very low quality of evidence) is uncertain because the result was imprecise.Due to few data, we did not conduct Trial Sequential Analysis on liver-related mortality, and serious and non-serious adverse events.We found no data on liver-related morbidity and health-related quality of life in the randomised trials included in this review.
AUTHORS' CONCLUSIONS
We are uncertain as to whether vitamin D supplements in the form of vitamin D, vitamin D, 1,25-dihydroxyvitamin D, or 25-dihydroxyvitamin D have important effect on all-cause mortality, liver-related mortality, or on serious or non-serious adverse events because the results were imprecise. There is no evidence on the effect of vitamin D supplementation on liver-related morbidity and health-related quality of life. Our conclusions are based on few trials with an insufficient number of participants and on lack of data on clinically important outcomes. In addition, the analysed trials are at high risk of bias with significant intertrial heterogeneity. The overall quality of evidence is very low.
Topics: Administration, Oral; Calcitriol; Cause of Death; Cholecalciferol; Chronic Disease; Ergocalciferols; Female; Hepatitis C, Chronic; Humans; Hydroxycholecalciferols; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 29099543
DOI: 10.1002/14651858.CD011564.pub2 -
The Turkish Journal of Gastroenterology... Jan 2017Growing evidence indicates that nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) share the same risk factors, and that NAFLD may be associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Growing evidence indicates that nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) share the same risk factors, and that NAFLD may be associated with the occurrence of GD. However, overall results remain controversial. The aim of this study is to perform a meta-analysis to assess the relationship between GD and NAFLD.
MATERIALS AND METHODS
Five databases (PubMed, Medline, Embase, Web of Science, and Cochrane Library) were queried, and observational studies that assessed the association between GD and NAFLD were selected. We pooled the prevalence of GD in participants with NAFLD, and compared the prevalence of GD in NAFLD and non-NAFLD groups in four trials.
RESULTS
Twelve studies met our inclusion criteria. The pooled prevalence of GD in cases with NAFLD was 17% (95% CI: 0.12-0.23). Compared with the non-NAFLD group, NAFLD was significantly correlated with GD (OR: 1.40, 95% CI: 1.23-1.59). Additional analyses reveal that participants in the GD group included more females (OR: 1.95, 95% CI: 1.36-2.79), were older (WMD: 6.61, 95% CI: 3.80-9.42), and had higher BMIs (WMD: 1.63, 95% CI: 0.62-2.65) in the population with NAFLD, compared to the non-GD group.
CONCLUSION
GD prevalence in NAFLD patients is higher than that in the general population. Furthermore, the occurrence of GD is significantly associated with the female sex, age and BMI in NAFLD patients.
Topics: Age Factors; Body Mass Index; Gallstones; Humans; Non-alcoholic Fatty Liver Disease; Prevalence; Risk Factors; Sex Factors
PubMed: 27991855
DOI: 10.5152/tjg.2016.0357 -
JHEP Reports : Innovation in Hepatology Dec 2021In an attempt to uncover unmet patient needs, this review aims to synthesise quantitative and qualitative studies on patients' quality of life and their experience of...
BACKGROUND & AIMS
In an attempt to uncover unmet patient needs, this review aims to synthesise quantitative and qualitative studies on patients' quality of life and their experience of having liver disease.
METHODS
Three databases (CINAHL, Embase, and PubMed) were searched from January 2000 to October 2020. The methodological quality and data extraction of both quantitative and qualitative studies were screened and appraised using Joanna Briggs Institute instruments for mixed-method systematic reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A convergent, integrated approach to synthesis and integration was used. Studies including patients with autoimmune and cholestatic liver disease, chronic hepatitis B and C, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma were considered.
RESULTS
The searches produced 5,601 articles, of which 95 (79 quantitative and 16 qualitative) were included in the review. These represented studies from 26 countries and a sample of 37,283 patients. The studies showed that patients´ quality of life was reduced. Unmet needs for information and support and perceived stigmatisation severely affected patients' quality of life.
CONCLUSIONS
Our study suggests changes to improve quality of life. According to patients, this could be achieved by providing better education and information, being aware of patients' need for support, and raising awareness of liver disease among the general population to reduce misconceptions and stigmatisation.
REGISTRATION NUMBER
PROSPERO CRD42020173501.
LAY SUMMARY
Regardless of aetiology, patients with liver diseases have impaired quality of life. This is associated with disease progression, the presence of symptoms, treatment response, and mental, physical, and social factors such as anxiety, confusion, comorbidities, and fatigue, as well as limitations in daily living, including loneliness, low income, stigmatisation, and treatment costs. Patients highlighted the need for information to understand and manage liver disease, and awareness and support from healthcare professionals to better cope with the disease. In addition, there is a need to raise awareness of liver diseases in the general population to reduce negative preconceptions and stigmatisation.
PubMed: 34805816
DOI: 10.1016/j.jhepr.2021.100370 -
World Journal of Gastroenterology Apr 2019Alcohol-related liver disease (ALD) is a leading cause of liver failure and indication for liver transplantation that arises in the setting of alcohol use disorder... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Alcohol-related liver disease (ALD) is a leading cause of liver failure and indication for liver transplantation that arises in the setting of alcohol use disorder (AUD). Previous reviews of transplantation for ALD are limited in scope of outcomes and type of ALD studied. A comprehensive systematic review could improve use of transplantation in ALD and improve future research. We hypothesize that while transplanting ALD may improve mortality and relapse, findings will be limited by pre-specified causes of heterogeneity - assessment and treatment of AUD, definition of ALD, spectrum of ALD studied, assessment and rates of relapse, and study quality and bias.
AIM
To optimize liver transplantation for ALD, understanding existing research to guide future research, we conducted a systematic review with meta-analysis.
METHODS
We conducted a systematic review, comparing liver transplant to no-transplant in patients with ALD, with a primary outcome of both short- and long-term mortality and relapse. We performed a comprehensive search of MEDLINE, EMBASE, Web of Science, and The Cochrane Library databases for peer-reviewed journal articles comparing use of liver transplant in ALD to no-transplant. Two reviewers independently conducted screening, full text review, and data extraction according to the PRISMA guidelines. We report the quality of the evidence according to the GRADE criteria.
RESULTS
We analyzed data from 10 studies. Of 1332 participants, 34.2% (456/1332) had undergone liver transplantation, while 65.8% (876/1332) had not. While random effects meta-analysis suggested transplant in comparison to no-transplant had an association of reduced mortality that did not reach statistical significance, relative risk (RR) = 0.51 (0.25-1.05), but not relapse risk, RR = 0.52 (0.18-1.53), significant heterogeneity limited these findings. When restricted to prospective data, transplant compared to no-transplant significantly reduced mortality, RR = 0.25 (0.13-0.46, < 0.01), and relapse, RR = 0.25 (0.14-0.45, < 0.01), with insignificant heterogeneity but persistent small-study effects. The overall quality of the evidence was Very Low. Heterogeneity analysis suggested that AUD assessment and treatment was often not reported while ALD, relapse assessment and rate, and data collection were institutionally rather than standardly defined.
CONCLUSION
Systematic review of liver transplantation for ALD suggests reduced mortality and relapse in heterogeneous, institution-specific populations with inherent bias. To understand efficacy of transplanting ALD, our research approach must change.
Topics: Disease Progression; End Stage Liver Disease; Humans; Liver Diseases, Alcoholic; Liver Transplantation; Outcome Assessment, Health Care; Recurrence; Research Design; Treatment Outcome
PubMed: 30983822
DOI: 10.3748/wjg.v25.i13.1628 -
Annals of Surgery Open : Perspectives... Jun 2021To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with...
OBJECTIVE
To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with nonalcoholic fatty liver disease (NAFLD) versus other risk factors.
BACKGROUND
Different clinical and tumor characteristics are associated with HCC in the setting of NAFLD in comparison to other risk factors. It is still unclear whether these differences impact patient survival after radical hepatectomies.
METHODS
Randomized controlled trials and observational studies published in the English literature between July 1980 and June 2020 were searched using multiple databases. Patients' baseline characteristics and the hazard ratios (HRs) of the OS and DFS were extracted and meta-analyses were performed.
RESULTS
Fifteen retrospective cohort studies with a total of 7226 patients were included. Among them, 1412 patients (19.5%) had NAFLD and 5814 (80.4%) had other risk factors (eg, viral hepatitis B or C, alcoholic cirrhosis, or cryptogenic cirrhosis). Summary statistics showed that patients with NAFLD had better DFS (HR = 0.81; 95% CI: 0.70-0.94; = 0.006) and OS (HR = 0.78; 95% CI: 0.67-0.90; = 0.001) than the control group. Subgroups analyses also indicated that the OS favored NAFLD patients versus patients with viral hepatitis B or C (HR = 0.80; 95% CI: 0.67-0.96; = 0.017) or alcoholic and cryptogenic cirrhosis (HR = 0.68; 95% CI: 0.47-1.0; = 0.05).
CONCLUSION
After hepatic resections for HCC, NAFLD patients have better DFS and OS than patients with other risk factors. Subgroup analysis and meta-regression suggested that the survival advantage of NAFLD patients was more pronounced in studies published after 2015 and from Asian centers.
PubMed: 37636554
DOI: 10.1097/AS9.0000000000000065 -
Cureus Mar 2023Diabetes is associated with different types of cancers of which hepatocellular carcinoma (HCC) is one among them. In a study comparing patients with diabetes to those... (Review)
Review
Diabetes is associated with different types of cancers of which hepatocellular carcinoma (HCC) is one among them. In a study comparing patients with diabetes to those who do not have diabetes, it was evident that the risk of HCC is found to increase two-fold in diabetic than that in non-diabetic patients. It is clear that carcinogenesis is advanced due to diabetes in the liver by a variety of mechanisms. We searched PubMed and Google Scholar for articles from 2010 to 2021 that have an association between diabetes, nonalcoholic fatty liver disease (NAFLD), and HCC. For the development of HCC, diabetes is likely related at both the molecular and epidemiological levels. Both diabetes mellitus and hepatic malignancy have the worst impact on mankind socioeconomically. There is a significant relationship between diabetes and HCC independent of alcohol consumption and viral hepatitis. It is noteworthy that not only the elderly but also people of all age groups should monitor their hemoglobin A1C levels. Diet restriction and lifestyle modification can reduce the risk of complications like HCC; the increased physical activity itself can have a major influence on health and can manage comorbidities like diabetes, NAFLD, and HCC.
PubMed: 37065332
DOI: 10.7759/cureus.36079