Steven Masson

All‐cause and liver‐related mortality risk factors in excessive drinkers: Analysis of data from the UK biobank

Publisher: Wiley

Date: 19-11-2022

DOI: 10.1111/ACER.14968

Abstract: High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol. We obtained information from the UK Biobank on approximately 500,000 participants aged 40–70 years at baseline assessment in 2006–2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis. Mortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89–2.17) for all causes, 1.89 (1.69–2.12) for any cancer, 1.87 (1.61–2.17) for any circulatory disease, and 9.40 (7.00–12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake diagnosed alcohol dependence, harmful use, or withdrawal syndrome and current smoking at assessment. People with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.

Genome‐wide Association Study and Meta‐analysis on Alcohol‐Associated Liver Cirrhosis Identifies Genetic Risk Factors

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 29-04-2021

DOI: 10.1002/HEP.31535

Abstract: Only a minority of heavy drinkers progress to alcohol‐associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy‐drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome‐wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta‐analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome‐wide significant risk association of rs738409 in patatin‐like phospholipase domain containing 3 ( PNPLA3 ) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10 −17 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10 −10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas‐associated factor family member 2 ( FAF2 ) (OR = 0.61 [del(T) allele], P = 2.56 × 10 −8 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta‐analysis (without conditioning) confirmed genome‐wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13 . Two other previously known loci ( SERPINA1 and SUGP1/TM6SF2 ) were also genome‐wide significant in the meta‐analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.

Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser

Publisher: Elsevier BV

Date: 09-2013

DOI: 10.1016/J.JCV.2013.05.003

Abstract: Highly active antiretroviral therapy has revolutionised HIV management. However, many of these drugs are potentially hepatotoxic. Here, we report the first adult case of efavirenz induced acute liver failure successfully treated by liver transplantation. Furthermore, genetic analysis revealed our patient to be a slow efavirenz metaboliser, contributing to the severity of clinical presentation.

Cholestasis secondary to anabolic steroid use in young men

Publisher: BMJ

Date: 02-02-2012

DOI: 10.1136/BMJ.E468

Clinical but not histological factors predict long‐term prognosis in patients with histologically advanced non‐decompensated alcoholic liver disease

Publisher: Wiley

Date: 08-07-2013

DOI: 10.1111/LIV.12242

Abstract: Alcoholic liver disease (ALD) is a significant threat to public health and a leading cause of death. Despite this, the long-term clinical course and predictive factors of survival in histologically advanced ALD are not well described. The aim of this study was to identify clinical and histological factors that predict long-term (15-year) survival in outpatients with histologically advanced non-decompensated ALD. Patients (n = 134) with biopsy-proven histologically advanced (stage III or IV) ALD were followed up for 15 years or until death or orthotopic liver transplantation. At baseline, clinical and laboratory data were collected. On biopsy, the degree of fibrosis as well as other histological features (fat type and severity, lymphocyte and neutrophil infiltration) were scored semiquantitatively. Most patients were male (72%) with a median age 51 (46-57). Overall, the 5-, 10- and 15-year survival was 63, 36 and 24% respectively. In multivariate analysis, persistent drinking (P = 0.01), smoking (P = 0.03), age (P = 0.01) and serum albumin at baseline (P = 0.001) were associated with significantly increased risk of death. Persistent drinking was associated with the highest risk. No histological features, including whether the stage of ALD was bridging fibrosis or cirrhosis, correlated with prognosis. In outpatients with biopsy-proven histologically advanced non-decompensated ALD, clinical but not histological factors determine prognosis. Persistent alcohol intake is the strongest predictor and smoking habit, age and serum albumin are also independently prognostic. Abstinence from alcohol and smoking cessation should be the priorities in the long-term management of ALD.

Improving survival in alcohol-related hepatitis: what's new?

Publisher: BMJ

Date: 10-08-2023

DOI: 10.1136/FLGASTRO-2022-102362

Abstract: Alcohol-related hepatitis (AH) is the most florid presentation of alcohol-related liver disease and carries a high short-term and long-term mortality rate. Specific treatment options remain inadequate. The current management approach for AH focuses on early identification, careful screening and treatment of infection, as well as identification of those patients who may benefit from corticosteroid therapy based on validated prognostic scoring systems. In recent years, there has been growing interest in exploring novel therapies for AH, which may offer alternative treatment options beyond the traditional approaches. Additionally, early liver transplantation (LT) has emerged as a promising option in selected cases with growing evidence supporting its role. In this review, we will discuss the current evidence base for the assessment and treatment of AH, and how these advances are shaping practice to improve outcomes in the UK.

Impact of 5 years of hepatitis C testing and treatment in the North East of England prisons

Publisher: Wiley

Date: 12-09-2023

DOI: 10.1111/JVH.13887

White cell count and platelet count associate with histological alcoholic hepatitis in jaundiced harmful drinkers

Publisher: Springer Science and Business Media LLC

Date: 26-03-2013

DOI: 10.1186/1471-230X-13-55

Abstract: Patients with suspected alcoholic hepatitis and a Discriminant Function ≥32 underwent liver biopsy to confirm the diagnosis. Of these (n = 58), 43 had histological features of alcoholic hepatitis and 15 (25%) did not. We aimed to determine the laboratory features that differentiated those patients with a histological diagnosis of alcoholic hepatitis from those without, and assess potential clinical utility. Laboratory investigations at presentation for each of the histologically confirmed cases of alcoholic hepatitis (n = 43) were compared to those without (n = 15) to determine whether there were differences between the two groups. Univariate analysis was by Mann Whitney U Test and Multivariate analysis was by a stepwise approach. White cell count (16.2 ± 10.5 v 6.9 ± 3.5 (× 10 9 /L) p = 0.0001) and platelet count (178 ± 81 v 98.4 ± 43 (× 10 9 /L) p = 0.0005) were higher in the patients with histological features of alcoholic hepatitis than in those without. The area under the ROC curve for AH diagnosis was estimated to be 0.83 (0.73, 0.94) and 0.81 (0.69, 0.93) for white cell count and platelet count respectively. Clinicians cannot accurately differentiate patients with or without alcoholic hepatitis without liver biopsy. This is critically important when deciding on specific therapies such as corticosteroids or when interpreting data from future trials in which biopsy is not mandated. In situations where liver biopsy is unsuitable or unavailable the white cell and platelet counts can be used to determine the likelihood of histological alcoholic hepatitis and guide treatment.

Effects of Exercise on Liver Fat and Metabolism in Alcohol Drinkers

Publisher: Elsevier BV

Date: 10-2017

DOI: 10.1016/J.CGH.2017.05.001

Abstract: Exercise is an important component of obesity-associated disorders and has been shown to reduce markers of nonalcoholic fatty liver disease (NAFLD). However, little is known about how these effects are influenced by alcohol intake. The authors performed a randomized controlled trial to investigate the effects of exercise on hepatic triglyceride content (HTGC) and metabolism in overweight or obese patients who consume alcohol. The authors performed a prospective study of 27 patients (mean 54 ± 11 years of age, body mass index [BMI] 31 ± 4 kg/m After 12 weeks, there was no significant difference between the exercise and control groups in HTGC (reduction of 0.1% ± 2.1% in exercisers vs increase of 0.5 ± 2.1% in control group P > .05). At week 12, the exercise group had significant reductions in subcutaneous fat (loss of 23 ± 28 cm In a randomized controlled trial of obese in iduals who consume alcohol, exercise significantly improved body composition and reduced hepatocyte apoptosis (cytokeratin 18), but did not reduce HTGC. This finding could indicate that alcohol consumption reduces the effects of exercise on NAFLD observed in previous studies. Clinical care teams should look to use exercise as part of the management strategy for people consuming alcohol, but optimal benefit may be as an adjunct to alcohol reduction and weight management strategies. (ISRCTN.com, Number: ISRCTN90597099).

The degree of hepatic steatosis associates with impaired cardiac and autonomic function

Publisher: Elsevier BV

Date: 06-2019

DOI: 10.1016/J.JHEP.2019.01.035

Abstract: Cardiovascular disease is the principle cause of death in patients with elevated liver fat unrelated to alcohol consumption, more so than liver-related morbidity and mortality. The aim of this study was to evaluate the relationship between liver fat and cardiac and autonomic function, as well as to assess how impairment in cardiac and autonomic function is influenced by metabolic risk factors. Cardiovascular and autonomic function were assessed in 96 sedentary in iduals: i) non-alcoholic fatty liver disease (NAFLD) (n = 46, hepatic steatosis >5% by magnetic resonance spectroscopy), ii) Hepatic steatosis and alcohol (dual aetiology fatty liver disease [DAFLD]) (n = 16, hepatic steatosis >5%, consuming >20 g/day of alcohol) and iii) CONTROL (n = 34, no cardiac, liver or metabolic disorders, <20 g/day of alcohol). Patients with NAFLD and DAFLD had significantly impaired cardiac and autonomic function when compared with controls. Diastolic variability and systolic variability (LF/HF-sBP [n/1] 2.3 (1.7) and 2.3 (1.5) vs. 3.4 (1.5), p <0.01) were impaired in patients with NAFLD and DAFLD when compared to controls, with DAFLD in iduals showing a decrease in diastolic variability relative to NAFLD patients. Hepatic steatosis and fasting glucose were negatively correlated with stroke volume index. Fibrosis stage was significantly negatively associated with mean blood pressure (r = -0.47, p = 0.02), diastolic variability (r = -0.58, p ≤0.01) and systolic variability (r = -0.42, p = 0.04). Hepatic steatosis was independently associated with cardiac function (p ≤0.01) TNF-α (p ≤0.05) and CK-18 (p ≤0.05) were independently associated with autonomic function. Cardiac and autonomic impairments appear to be dependent on level of liver fat, metabolic dysfunction, inflammation and fibrosis staging, and to a lesser extent alcohol intake. Interventions should be sought to moderate the excess cardiovascular risk in patients with NAFLD or DAFLD. Increased levels of fat in the liver impair the ability of the cardiovascular system to work properly. The amount of fat in the liver, metabolic control, inflammation and alcohol are all linked to the degree that the cardiovascular system is affected.

Multigenerational epigenetic adaptation of the hepatic wound-healing response

Publisher: Springer Science and Business Media LLC

Date: 09-2012

DOI: 10.1038/NM.2893

Newcastle Upon Tyne Hospital

Location: United Kingdom of Great Britain and Northern Ireland

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The University Of Edinburgh

Location: United Kingdom of Great Britain and Northern Ireland

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Newcastle University

Location: United Kingdom of Great Britain and Northern Ireland

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University Of Edinburgh

Location: No location found

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