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The Cochrane Database of Systematic... Apr 2019Alcoholic hepatitis is a form of alcoholic liver disease characterised by steatosis, necroinflammation, fibrosis, and complications to the liver. Typically, alcoholic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcoholic hepatitis is a form of alcoholic liver disease characterised by steatosis, necroinflammation, fibrosis, and complications to the liver. Typically, alcoholic hepatitis presents in people between 40 and 50 years of age. Alcoholic hepatitis can be resolved if people abstain from drinking, but the risk of death will depend on the severity of the liver damage and abstinence from alcohol. Glucocorticosteroids have been studied extensively in randomised clinical trials to assess their benefits and harms. However, the results have been contradictory.
OBJECTIVES
To assess the benefits and harms of glucocorticosteroids in people with alcoholic hepatitis.
SEARCH METHODS
We identified trials through electronic searches in Cochrane Hepato-Biliary's (CHB) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, and Science Citation Index Expanded. We looked for ongoing or unpublished trials in clinical trials registers and pharmaceutical company sources. We also scanned reference lists of the studies retrieved. The last search was 18 January 2019.
SELECTION CRITERIA
Randomised clinical trials assessing glucocorticosteroids versus placebo or no intervention in people with alcoholic hepatitis, irrespective of year, language of publication, or format. We considered trials with adults diagnosed with alcoholic hepatitis, which could have been established through clinical or biochemical diagnostic criteria or both. We defined alcoholic hepatitis as mild (Maddrey's score less than 32) and severe (Maddrey's score 32 or more). We allowed cointerventions in the trial groups, provided they were similar.
DATA COLLECTION AND ANALYSIS
We followed Cochrane methodology, performing the meta-analyses using Review Manager 5. We presented the results of dichotomous outcomes as risk ratios (RR) and of continuous outcomes as mean difference (MD), with 95% confidence intervals (CI). We used both the fixed-effect and the random-effects models for meta-analyses. Whenever there were significant discrepancies in the results, we reported the more conservative point estimate of the two. We considered a P value of 0.01 or less, two-tailed, as statistically significant if the required information size was reached for our three primary outcomes (all-cause mortality, health-related quality of life, and serious adverse events during treatment) and our post hoc decision to include analyses of mortality at more time points. We presented heterogeneity using the I² statistic. If trialists used intention-to-treat analysis to deal with missing data, we used these data in our primary analysis; otherwise, we used the available data. We assessed the bias risk of the trials using bias risk domains and the certainty of the evidence using GRADE.
MAIN RESULTS
Sixteen trials fulfilled our inclusion criteria. All trials but one were at overall high risk of bias. Fifteen trials (one of which was an abstract) provided data for analysis (927 participants received glucocorticosteroids and 934 participants received placebo or no intervention). Glucocorticosteroids were administered orally or parenterally for a median 28 days (range 3 days to 12 weeks). The participants were between 25 and 70 years old, had different stages of alcoholic liver disease, and 65% were men. Follow-up, when reported, was up to the moment of discharge from the hospital, until they died (median of 63 days), or for at least one year. There was no evidence of effect of glucocorticosteroids on all-cause mortality up to three months following randomisation (random-effects RR 0.90, 95% CI 0.70 to 1.15; participants = 1861; trials = 15; very low-certainty evidence) or on health-related quality of life up to three months, measured with the European Quality of Life - 5 Dimensions - 3 Levels scale (MD -0.04 points, 95% CI -0.11 to 0.03; participants = 377; trial = 1; low-certainty evidence). There was no evidence of effect on the occurrence of serious adverse events during treatment (random-effects RR 1.05, 95% CI 0.85 to 1.29; participants = 1861; trials = 15; very low-certainty evidence), liver-related mortality up to three months following randomisation (random-effects RR 0.89, 95% CI 0.69 to 1.14; participants = 1861; trials = 15; very low-certainty evidence), number of participants with any complications up to three months following randomisation (random-effects RR 1.04, 95% CI 0.86 to 1.27; participants = 1861; very low-certainty evidence), and number of participants of non-serious adverse events up to three months' follow-up after end of treatment (random-effects RR 1.99, 95% CI 0.72 to 5.48; participants = 160; trials = 4; very low-certainty evidence). Based on the information that we collected from the published trial reports, only one of the trials seems not to be industry-funded, and the remaining 15 trials did not report clearly whether they were partly or completely funded by the industry.
AUTHORS' CONCLUSIONS
We are very uncertain about the effect estimate of no difference between glucocorticosteroids and placebo or no intervention on all-cause mortality and serious adverse events during treatment because the certainty of evidence was very low, and low for health-related quality of life. Due to inadequate reporting, we cannot exclude increases in adverse events. As the CIs were wide, we cannot rule out significant benefits or harms of glucocorticosteroids. Therefore, we need placebo-controlled randomised clinical trials, designed according to the SPIRIT guidelines and reported according to the CONSORT guidelines. Future trials ought to report depersonalised individual participant data, so that proper individual participant data meta-analyses of the effects of glucocorticosteroids in subgroups can be conducted.
Topics: Adult; Aged; Female; Glucocorticoids; Hepatitis, Alcoholic; Humans; Male; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 30964545
DOI: 10.1002/14651858.CD001511.pub4 -
Health Technology Assessment... Jan 2015Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious... (Meta-Analysis)
Meta-Analysis Review
Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation.
BACKGROUND
Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established.
OBJECTIVE
To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease.
DATA SOURCES
We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists.
METHODS
We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted.
RESULTS
Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822.
LIMITATIONS
A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments.
CONCLUSIONS
Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42011001561.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antiviral Agents; Biomarkers; Chronic Disease; Cost-Benefit Analysis; Diagnostic Techniques and Procedures; Elasticity Imaging Techniques; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Liver Diseases; Markov Chains; Models, Econometric; Non-alcoholic Fatty Liver Disease; Quality-Adjusted Life Years; Sensitivity and Specificity; Sex Factors
PubMed: 25633908
DOI: 10.3310/hta19090 -
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 -
Ontario Health Technology Assessment... 2015Liver fibrosis is characterized by a buildup of connective tissue due to chronic liver damage. Steatosis is the collection of excessive amounts of fat inside liver... (Review)
Review
BACKGROUND
Liver fibrosis is characterized by a buildup of connective tissue due to chronic liver damage. Steatosis is the collection of excessive amounts of fat inside liver cells. Liver biopsy remains the gold standard for the diagnosis of liver fibrosis and steatosis, but its use as a diagnostic tool is limited by its invasive nature and high cost.
OBJECTIVES
To evaluate the cost-effectiveness and budget impact of transient elastography (TE) with and without controlled attenuation parameter (CAP) for the diagnosis of liver fibrosis or steatosis in patients with hepatitis B, hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease.
DATA SOURCES
An economic literature search was performed using computerized databases. For primary economic and budget impact analyses, we obtained data from various sources, such as the Health Quality Ontario evidence-based analysis, published literature, and the Institute for Clinical Evaluative Sciences.
REVIEW METHODS
A systematic review of existing TE cost-effectiveness studies was conducted, and a primary economic evaluation was undertaken from the perspective of the Ontario Ministry of Health and Long-Term Care. Decision analytic models were used to compare short-term costs and outcomes of TE compared to liver biopsy. Outcomes were expressed as incremental cost per correctly diagnosed cases gained. A budget impact analysis was also conducted.
RESULTS
We included 10 relevant studies that evaluated the cost-effectiveness of TE compared to other noninvasive tests and to liver biopsy; no cost-effectiveness studies of TE with CAP were identified. All studies showed that TE was less expensive but associated with a decrease in the number of correctly diagnosed cases. TE also improved quality-adjusted life-years in patients with hepatitis B and hepatitis C. Our primary economic analysis suggested that TE led to cost savings but was less effective than liver biopsy in the diagnosis of liver fibrosis. TE became more economically attractive with a higher degree of liver fibrosis. TE with CAP was also less expensive and less accurate than liver biopsy.
LIMITATIONS
The model did not take into account long-term costs and consequences associated with TE and liver biopsy and did not include costs to patients and their families, or patient preferences related to diagnostic information.
CONCLUSIONS
TE showed potential cost savings compared to liver biopsy. Further investigation is needed to determine the long-term impacts of TE on morbidity and mortality in Canada and the optimal diagnostic modality for liver fibrosis and steatosis.
Topics: Biopsy; Cost-Benefit Analysis; Elasticity Imaging Techniques; Fatty Liver; Hepatitis B; Hepatitis C; Humans; Liver; Liver Cirrhosis; Liver Diseases, Alcoholic; Models, Statistical; Non-alcoholic Fatty Liver Disease; Ontario
PubMed: 26664666
DOI: No ID Found -
International Immunopharmacology Mar 2023The liver is a well-known metabolic organ that can be susceptible to external stimuli to affect its normal physiological function. Worldwide, the morbidity and mortality... (Review)
Review
The liver is a well-known metabolic organ that can be susceptible to external stimuli to affect its normal physiological function. Worldwide, the morbidity and mortality of liver diseases are skyrocketing every year, causing human health crises. Recently, new approaches such as biotechnology have been introduced to achieve optimal treatment and prognostic management of liver diseases. microRNAs (miRNAs), a kind of small non-coding RNA molecule, have the advantages of biodiversity, wide distribution and numerous members. Among these miRNAs, miR-155 is an important regulator of inflammation, immunity and tumorigenesis. In this review, the PubMed and Web of Science databases were searched from 2009 to 2022. After inclusion and exclusion, 64 articles were selected for a systematic review to comprehensively summarize the mechanisms of miR-155 regulating inflammation, immunity and tumorigenesis in liver diseases and liver cancer, covering in vitro, in vivo and clinical studies. Existing preclinical studies and clinical trials have listed that the up-regulation and down-regulation of miR-155 are significant in alcoholic liver injury, viral hepatitis, autoimmune hepatitis, infectious liver injury, liver transplantation and liver cancer. The immune and inflammation effects of miR-155 are manifested by regulating macrophage polarization, NK cell killing, Th17 cell and Th1/Th2 cell differentiation. Additionally, miR-155 is also committed to participating in the cell cycle, invasion and metastasis, immune escape and other processes to promote and intensify the development of liver cancer. In conclusion, miR-155 is not only a biomarker for the diagnosis and prognosis of liver diseases, but also plays a therapeutic role via regulating immunity, inflammation and tumorigenesis.
Topics: Humans; MicroRNAs; Liver Neoplasms; Inflammation; Carcinogenesis
PubMed: 36753984
DOI: 10.1016/j.intimp.2023.109775 -
Liver International : Official Journal... Apr 2023Alcohol use increases the risk of many conditions in addition to liver disease; patients with alcohol-related liver disease (ALD) are therefore at risk from both... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol use increases the risk of many conditions in addition to liver disease; patients with alcohol-related liver disease (ALD) are therefore at risk from both extra-hepatic and hepatic disease.
AIMS
This review synthesises information about non-liver-related mortality in persons with ALD.
METHODS
A systematic literature review was performed to identify studies describing non-liver outcomes in ALD. Information about overall non-liver mortality was extracted from included studies and sub-categorised into major causes: cardiovascular disease (CVD), non-liver cancer and infection. Single-proportion meta-analysis was done to calculate incidence rates (events/1000 patient-years) and relative risks (RR) compared with control populations.
RESULTS
Thirty-seven studies describing 50 302 individuals with 155 820 patient-years of follow-up were included. Diabetes, CVD and obesity were highly prevalent amongst included patients (5.4%, 10.4% and 20.8% respectively). Outcomes varied across the spectrum of ALD: in alcohol-related fatty liver the rate of non-liver mortality was 43.4/1000 patient-years, whereas in alcoholic hepatitis the rate of non-liver mortality was 22.5/1000 patient-years. The risk of all studied outcomes was higher in ALD compared with control populations: The RR of death from CVD was 2.4 (1.6-3.8), from non-hepatic cancer 2.2 (1.6-2.9) and from infection 8.2 (4.7-14.3).
CONCLUSION
Persons with ALD are at high risk of death from non-liver causes such as cardiovascular disease and non-hepatic cancer.
Topics: Humans; Cardiovascular Diseases; Liver Diseases; Fatty Liver, Alcoholic; Morbidity; Neoplasms; Liver Diseases, Alcoholic
PubMed: 36694995
DOI: 10.1111/liv.15526 -
The American Journal of Tropical... Apr 2022COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver...
COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver manifestations of COVID-19 and discussed the possible underlying pathophysiological mechanisms and their diagnosis and management. Factors that may contribute to hepatic involvement in COVID-19 include direct viral cytopathic effects, exaggerated immune responses/systemic inflammatory response syndrome, hypoxia-induced changes, vascular changes due to coagulopathy, endothelitis, cardiac congestion from right heart failure, and drug-induced liver injury. The majority of COVID-19-associated liver symptoms are mild and self-limiting. Thus management is generally supportive. Liver function tests and abdominal imaging are the primary investigations done in relation to liver involvement in COVID-19 patients. However, imaging findings are nonspecific. Severe acute respiratory syndrome coronavirus 2 RNA has been found in liver biopsies. However, there is limited place for liver biopsy in the clinical context, as it does not influence management. Although, the management is supportive in the majority of patients without previous liver disease, special emphasis is needed in those with nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis B and C infections, and alcoholic liver disease, and in liver transplant recipients.
PubMed: 35203056
DOI: 10.4269/ajtmh.21-1240 -
Liver International : Official Journal... Jun 2017Liver biopsy remains the gold standard for the diagnosis of liver fibrosis, but its use as a diagnostic tool is limited by its invasive nature and high cost. (Review)
Review
BACKGROUND
Liver biopsy remains the gold standard for the diagnosis of liver fibrosis, but its use as a diagnostic tool is limited by its invasive nature and high cost.
OBJECTIVE
The aim of this study was to systematically review the cost-effectiveness of transient elastography (TE) with and without controlled attenuation parameter (CAP) for the diagnosis of liver fibrosis or steatosis in patients with hepatitis B, hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease.
METHODS
An economic literature search was performed. Eligibility criteria included systematic reviews, health technology assessments or economic evaluations of TE compared to liver biopsy and other non-invasive tests. After abstract screening, full-text reports of potentially relevant articles were assessed in duplicate. The methodological quality of the included studies was also appraised.
RESULTS
The database search yielded 253 records; four cost-effectiveness and four cost-utility studies were included. The methodological quality of the included studies varies. High-quality cost-effectiveness studies not only suggested that TE is less costly but also less accurate than liver biopsy. The incremental cost-effectiveness ratio (ICER) of TE improves with a greater level of diagnostic accuracy and a higher degree of liver fibrosis. High-quality cost-utility studies indicated that TE is a cost-effective alternative to biopsy with ICER between $9000 and $14 000 per QALY for patients with hepatitis C. We did not find studies that assessed the cost-effectiveness of TE with CAP for the diagnosis of liver steatosis.
CONCLUSIONS
Transient elastography is an economically attractive alternative to liver biopsy and other non-invasive diagnostic tests especially for patients with a higher degree of liver fibrosis.
Topics: Biopsy; Cost-Benefit Analysis; Elasticity Imaging Techniques; Hepatitis B; Hepatitis C; Humans; Liver Cirrhosis; Liver Diseases, Alcoholic; Non-alcoholic Fatty Liver Disease
PubMed: 27699993
DOI: 10.1111/liv.13260 -
Cureus May 2022Non-alcoholic fatty liver disease (NAFLD) is a broad term encompassing hepatic steatosis and non-alcoholic steatohepatitis (NASH), a form of chronic hepatitis. This may,... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is a broad term encompassing hepatic steatosis and non-alcoholic steatohepatitis (NASH), a form of chronic hepatitis. This may, unfortunately, lead to terminal complications like cirrhosis and hepatocellular carcinoma (HCC). NAFLD is strongly associated with obesity, type 2 diabetes (T2DM), hypertension, and metabolic syndrome. The growing prevalence of NAFLD, its associated conditions, and its complications are alarming. The insulin sensitizer group "thiazolidinediones" has shown some therapeutic benefits in this condition. This systematic review is intended to focus on the clinical efficacy of this group in patients with NAFLD, employing PubMed, Google Scholar, and the Cochrane Library as databases. We discovered 10 randomized control trials (RCTs; nine involving pioglitazone and one involving rosiglitazone) involving 887 participants. All studies varied in duration from 6 to 24 months. Most of the involved trials had a small number of participants, and the intrinsic quality of the studies was mixed. Pioglitazone consistently improved histological parameters and normalized liver transaminases, although evidence supporting the benefits of other drugs in this class was minimal. Thiazolidinediones, particularly pioglitazone, have proven efficacious in patients with NAFLD/NASH. However, more extensive trials need to be carried out to investigate this drug class's benefits further. Unfortunately, this drug has attendant side effects like weight gain and fractures, limiting its widespread use; hence, careful selection for likely candidates is imperative.
PubMed: 35765391
DOI: 10.7759/cureus.25380 -
Addiction Biology Sep 2017Based on the knowledge that alcohol misuse causes a multitude of diseases and increased mortality, this systematic review examines whether a reduction of the individual... (Review)
Review
Based on the knowledge that alcohol misuse causes a multitude of diseases and increased mortality, this systematic review examines whether a reduction of the individual alcohol consumption can contribute to a minimization of health risks within a harm reduction approach. In fact, the reviewed 63 studies indicate that interventions aiming at alcohol reduction (including total abstinence as one possible therapeutic aim) indeed resulted in or were associated with positive effects in harmful, hazardous or alcohol-dependent drinkers. Major benefits were observed for reducing alcohol-associated injuries, recovery of ventricular heart function in alcoholic cardiomyopathy, blood pressure lowering, normalization of biochemical parameter, body weight reduction, histological improvement in pre-cirrhotic alcohol-related liver disease and slowed progression of an already existing alcohol-attributable liver fibrosis. Furthermore, reduced withdrawal symptoms, prevalence of psychiatric episodes and duration of in-patient hospital days, improvement of anxiety and depression symptoms, self-confidence, physical and mental quality of life, fewer alcohol-related adverse consequences as well as lower psychosocial stress levels and better social functioning can result from reduced alcohol intake. The reviewed literature demonstrated remarkable socioeconomic cost benefits in areas such as the medical health-care system or workforce productivity. Individuals with heightened vulnerability further benefit significantly from alcohol reduction (e.g. hypertension, hepatitis C, psychiatric co-morbidities, pregnancy, but also among adolescents and young adults). Concluding, the reviewed studies strongly support and emphasize the importance and benefits of early initial screening for problematic alcohol use followed by brief and other interventions in first contact medical health-care facilities to reduce alcohol intake.
Topics: Adolescent; Alcohol Drinking; Alcohol-Related Disorders; Alcoholism; Anxiety; Blood Pressure; Cardiomyopathy, Alcoholic; Cost-Benefit Analysis; Depression; Disease Progression; Efficiency; Female; Harm Reduction; Health Care Costs; Humans; Liver Diseases, Alcoholic; Male; Pregnancy; Quality of Life; Recovery of Function; Risk Reduction Behavior; Wounds and Injuries
PubMed: 27353220
DOI: 10.1111/adb.12414