Alcohol Policies and Alcohol-related Liver Disease Mortality.
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ABSTRACT:
SUBMITTER: Parikh ND
PROVIDER: S-EPMC8238820 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Alcohol-related liver disease (ALD) represents a major public health problem worldwide. According to the World Health Organization, the highest levels of per capita alcohol consumption are observed in countries of the European Region. Alcohol consumption is also alarmingly increasing in developing countries. ALD is one of the main contributors to the burden of alcohol-attributable deaths and disability. In the United States, severe forms of ALD such alcoholic hepatitis have increased in the last decade and in the United Kingdom, three-quarters of liver-related mortality results from alcohol consumption. Besides genetic factors, there is strong evidence that the amount of alcohol consumed plays a major role in the development of advanced ALD. Establishing effective public health policies is therefore mandatory to reduce the burden of ALD. Since the 90s, major public health institutions and governments have developed a variety of policies in order to reduce the harm caused by excessive drinking. These policies encompass multiple factors, from pricing and taxation to advertising regulation. Measures focused on taxation and price regulation have been shown to be the most effective at reducing alcohol-related mortality. However, there are few studies focused on the effect of public policies on ALD. This review article summarises the factors influencing ALD burden and the role of different public health policies.
| S-EPMC7005647 | biostudies-literature
Project description:OBJECTIVES:Data describing long-term outcomes following ICU for patients with alcohol-related liver disease are scarce. We aimed to report long-term mortality and emergency hospital resource use for patients with alcohol-related liver disease and compare this with two comparator cohorts. DESIGN:Retrospective cohort study linking population registry data. SETTING:All adult general Scottish ICUs (2005-2010) serving 5 million population. PATIENTS:ICU patients with alcohol-related liver disease were compared with an unmatched cohort with Acute Physiology and Chronic Health Evaluation defined diagnoses of severe cardiovascular, respiratory, or renal comorbidity and a matched general ICU cohort. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Outcomes were 5-year mortality, emergency hospital resource use, and emergency hospital readmission. Multivariable regression was used to identify risk factors and adjust for confounders. Of 47,779 ICU admissions, 2,463 patients with alcohol-related liver disease and 3,590 patients with severe comorbidities were identified; 2,391(97.1%) were matched to a general ICU cohort. The alcohol-related liver disease cohort had greater 5-year mortality than comorbid (79.2% vs 75.3%; p < 0.001) and matched general (79.8% vs 63.3%; p < 0.001) cohorts. High liver Sequential Organ Failure Assessment score and three-organ support were associated with 90% 5-year mortality in alcohol-related liver disease patients. After confounder adjustment, alcohol-related liver disease patients had 31% higher hazard of death (adjusted hazard ratio, 1.31; 95% CI, 1.17-1.47; p < 0.001) and used greater resource than the severe comorbid comparator group. Findings were similar compared with the matched cohort. CONCLUSIONS:ICU patients with alcohol-related liver disease have higher 5-year mortality and emergency readmission rates than ICU patients with other severe comorbidities and matched general ICU patients. These data can contribute to shared decision-making for alcohol-related liver disease patients.
| S-EPMC6314466 | biostudies-literature
Project description:Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs. Heavy alcohol misuse leads to alcohol-related liver disease, which is responsible for a significant proportion of alcohol-attributable deaths globally. Other than reducing alcohol consumption, there are currently no effective treatments for alcohol-related liver disease. Oxidative stress refers to an imbalance in the production and elimination of reactive oxygen species and antioxidants. It plays important roles in several aspects of alcohol-related liver disease pathogenesis. Here, we review how chronic alcohol use results in oxidative stress through increased metabolism via the cytochrome P450 2E1 system producing reactive oxygen species, acetaldehyde and protein and DNA adducts. These trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and necrosis. Reactive oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic signaling. There is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic regulation. Increased global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory genes. This review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic regulation. Improved understanding of these processes may identify novel targets for therapy.
| S-EPMC7407918 | biostudies-literature
Project description:Background: Alcohol is the main cause of liver cirrhosis. The objective of this study was to analyze the mortality rates of alcohol-related cirrhosis in Mexico from 2000 to 2017. Methods: Mortality data from alcohol-related cirrhosis were obtained from the National Institute of Statistics and Geography. Rates were adjusted to the World Standard Population and were calculated with a direct method. The differences between genders were evaluated with Student's t-test, while the ANOVA test was used for differences among age groups. A trend analysis was performed with an ln regression of adjusted mortality rates and analyzed with Student's t-test. Results: The mean age-adjusted mortality rate during the study period was 13.28 per 100,000 inhabitants. A significant decrease in mortality rates was observed, from 20.55 to 10.62 per 100,000 inhabitants. All age groups studied showed a significant decrease in mortality. The mortality rate was higher in males than in females. Conclusions: Mortality from alcohol-related cirrhosis decreased in Mexico. Males still have the highest mortality rate.
| S-EPMC7644839 | biostudies-literature
Project description:Fatty liver disease constitutes a spectrum of liver diseases which begin with simple steatosis and may progress to advance stages of steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The two main etiologies are-alcohol related fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). NAFLD is a global health epidemic strongly associated with modern dietary habits and life-style. It is the second most common cause of chronic liver disease in the US after chronic hepatitis C virus (HCV) infection. Approximately 100 million people are affected with this condition in the US alone. Excessive intakes of calories, saturated fat and refined carbohydrates, and sedentary life style have led to explosion of this health epidemic in developing nations as well. ALD is the third most common cause of chronic liver disease in the US. Even though the predominant trigger for onset of steatosis is different in these two conditions, they share common themes in progression from steatosis to the advance stages. Oxidative stress (OS) is considered a very significant contributor to hepatocyte injury in these conditions. Mitochondrial dysfunction contributes to this OS. Role of mitochondrial dysfunction in pathogenesis of fatty liver diseases is emerging but far from completely understood. A better understanding is essential for more effective preventive and therapeutic interventions. Here, we discuss the pathogenesis and therapeutic approaches of NAFLD and ALD from a mitochondrial perspective.
| S-EPMC7792990 | biostudies-literature
Project description:Backgruound and aims: Loss of hepatocyte identity is associated with impaired liver function in alcohol-related hepatitis (AH). However, the mechanisms and the impact of hepatocyte reprogramming in liver disease are poorly understood. Here we show that both hepatocytes expressing KRT7 (hepatobiliary (HB) cells) and ductular reaction cells were increased in decompensated cirrhotic patients and AH, but only HB cells correlated with poor liver function, reduced liver synthetic capacity and poor outcome. Transcriptomic analysis of microdissected HB cells revealed the expression of biliary-specific genes and a mild reduction of hepatocyte metabolism. Functional analysis identified pathways involved in hepatocyte reprogramming together with inflammatory, stemness and cancer gene programs. In this context, CXCR4 pathway was highly enriched in HB cells, and CXCR4 correlated with disease severity and reduced expression of hepatocyte transcription factors and albumin. Mechanistically, TGFβ induced the expression of CXCR4 in primary hepatocytes, and its ligand CXCL12 promoted hepatocyte reprogramming. Liver overexpression of CXCR4 in chronic liver injury decreased hepatocyte gene expression and promoted liver injury. Pharmacological inhibition of CXCR4 reverted hepatocyte loss of identity and reduced ductular reaction and fibrosis progression. Conclusions: This study shows the association of hepatocyte reprogramming with disease progression and poor outcome in AH. Moreover, we identify CXCR4 as a driver of hepatocyte reprogramming as well as a potential therapeutic target in chronic liver injury.
2023-04-06 | GSE199168 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, with a prevalence of 25-30%. Since its first description in 1980, NAFLD has been conceived as a different entity from alcohol-related fatty liver disease (ALD), despite that, both diseases have an overlap in the pathophysiology, share genetic-epigenetic factors, and frequently coexist. Both entities are characterized by a broad spectrum of histological features ranging from isolated steatosis to steatohepatitis and cirrhosis. Distinction between NAFLD and ALD is based on the amount of consumed alcohol, which has been arbitrarily established. In this context, a proposal of positive criteria for NAFLD diagnosis not considering exclusion of alcohol consumption as a prerequisite criterion for diagnosis had emerged, recognizing the possibility of a dual etiology of fatty liver in some individuals. The impact of moderate alcohol use on the severity of NAFLD is ill-defined. Some studies suggest protective effects in moderate doses, but current evidence shows that there is no safe threshold for alcohol consumption for NAFLD. In fact, given the synergistic effect between alcohol consumption, obesity, and metabolic dysfunction, it is likely that alcohol use serves as a significant risk factor for the progression of liver disease in NAFLD and metabolic syndrome. This also affects the incidence of hepatocellular carcinoma. In this review, we summarize the overlapping pathophysiology of NAFLD and ALD, the current data on alcohol consumption in patients with NAFLD, and the effects of metabolic dysfunction and overweight in ALD.
| S-EPMC7468507 | biostudies-literature
Project description:BACKGROUND:Excessive alcohol consumption is a well-established risk factor for liver disease and hepatocellular carcinoma (HCC). Previous studies have found that increased alcohol consumption can lead to lower absorption of folate. Conversely, higher folate intake has been inversely associated with liver damage and HCC. In the current study, we investigate the effect of alcohol consumption and folate intake on HCC incidence and liver disease mortality in the NIH-American Association of Retired Persons Diet and Health Study. METHODS:The study population included 494,743 participants who reported at baseline their dietary intake for the previous year. Alcohol and folate were analyzed with hazards ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards regression models adjusted for age, sex, race, education, smoking, body mass index, and diabetes. HCC incidence (n = 435) was determined through 2006 via linkage with cancer registries, and liver disease mortality (n = 789) was determined through 2008 via linkage to the U.S. Social Security Administration Death Master File and the National Death Index Plus by the National Center for Health Statistics. RESULTS:Consumption of more than three drinks per day was positively associated with both HCC incidence (HR: 1.92; 95%CI: 1.42-2.60) and liver disease mortality (HR: 5.84; 95%CI: 4.81-7.10), whereas folate intake was associated with neither outcome. Folate, however, modified the relationship between alcohol and HCC incidence (Pinteraction = 0.03), but had no effect on the relationship between alcohol and liver disease mortality (Pinteraction = 0.54). CONCLUSIONS:These results suggest that higher folate intake may ameliorate the effect of alcohol consumption on the development of HCC. IMPACT:Folate intake may be beneficial in the prevention of alcohol-associated HCC.
| S-EPMC3596467 | biostudies-literature
Project description:Liver transplant programs in Canada require a period of 6 months of abstinence from alcohol before considering a patient with liver disease secondary to alcohol for transplantation. Although some studies have demonstrated good outcomes following a transplant in carefully selected patients before the 6-month abstinence period has been met, there have been arguments against this, including the claim that the public has a general negative perception of those with alcohol dependence. We performed a multicenter cross-sectional survey to determine the perception of people in British Columbia, Canada, toward liver transplantation in patients with liver disease due to alcohol who have not demonstrated the capacity to remain abstinent from alcohol for 6 months. A total of 304 patient questionnaires were completed, and 83.1% agreed with a period of abstinence of 6 months. In those patients who were unlikely to survive 6 months without a transplant, 34.1% of respondents agreed with, 44.1% did not agree with, and 21.4% were neutral about, early transplantation; 42.8% would have less trust in the process of transplantation if a period of abstinence was not maintained, but relaxing the requirement for an abstinence period would not have an impact on the majority's decision to donate organs. Only 30.5% would support abandoning the abstinence criteria. Conclusion: Among patients followed at general gastroenterology, medicine, or transplant clinics, there is a willingness to relax the criteria in selected patients unlikely to survive without a transplant, although a general consensus remains in support of the existing 6-month alcohol abstinence rule. A larger scale survey of all provinces in Canada would be required to assess support for such a change in policy.
| S-EPMC6671774 | biostudies-literature
Project description:BackgroundAlcohol-related liver disease (ALD) is a leading indication for liver transplantation.MethodsState consumption of spirits, wine, and beer was determined from published sources. Excise and ad valorem alcohol taxes of spirits, wine, and beer were calculated following standard practices and correlated using multiple logistic regression models to 2002 to 2015 ALD transplant listing data from the United Network for Organ Sharing database.Results21.22% (29,161/137,440) of transplant listings were for ALD. Increased consumption of spirits was associated with increased ALD transplant listings (odds ratio [OR]: 1.67; 95% CI: 1.12 to 2.49, p = 0.01), but wine and beer consumption did not have a statistically significant association with ALD transplant listings. Spirits excise taxes on- and off-premise were inversely associated with ALD transplant listing (OR: 0.79 and 0.82, respectively, both p < 0.02). Beer and wine taxes were not significantly associated with ALD transplant listings.ConclusionsTransplant listings for ALD are directly associated with spirit consumption and inversely associated with spirits excise taxes. These findings suggest a possible public health benefit of increasing excise taxes for spirits.
| S-EPMC8061744 | biostudies-literature