- Alcoholic fatty liver associated with the male gender, being overweight, central obesity
The unsafe use of alcohol or unsafe drinking is observed almost exclusively in males with alcoholic fatty liver being associated at the baseline with the male gender, the state of being overweight, and central obesity while new onset alcoholic fatty liver was associated solely with the male gender, a prospective, community-based study conducted among adults in an urban Sri Lankan community found.
These findings were made in an original article on “Alcohol use and alcoholic fatty liver disease: A prospective, community-based study among adults in an urban community in Sri Lanka” which was authored by M. Niriella, A. Kasturiratne, T. Beddage, S. De Silva, A. Dassanayake, A. Pathmeswaran, A. Wickramasinghe, and H. de Silva (all eight attached to the Kelaniya University's Medical Faculty), and N. Kato (attached to the National Centre for Global Health and Medicine, Japan) and published in the Ceylon Medical Journal's 67th Volume's Second Issue in October, 2022.
Alcohol-related liver disease, per J. Rehm, A.V. Samokhvalov and K.D. Shield's “Global burden of alcoholic liver diseases” and M. Masarone, V. Rosato, M. Dallio, L. Abenavoli, A. Federico, C. Loguercio and M. Persico's “Epidemiology and natural history of alcoholic liver disease”, is one of the most common types of chronic liver disease, accounting for almost 50% of the cases of cirrhosis (scarring/fibrosis of the liver caused by long term liver damage where the scar tissue prevents the liver from working properly) worldwide. Alcohol related liver disease can, as mentioned by Masarone et al. and in H.K. Seitz, R. Bataller, H. Cortez-Pinto, B. Gao, A. Gual, C. Lackner, P. Mathurin, S. Mueller, G. Szabo and H. Tsukamoto's “Alcoholic liver disease”, progress from simple steatosis (alcoholic fatty liver) to alcoholic steatohepatitis, which is characterised by hepatic (liver) inflammation where chronic alcoholic steatohepatitis can eventually lead to progressive fibrosis and the development of cirrhosis and hepatocellular cancer.
Triggering causes
Most individuals with chronic, unsafe, excessive alcohol intake develop the simplest phenotype (an observable trait) alcoholic fatty liver; however, only a subset of individuals will develop the more advanced phenotypes alcoholic steatohepatitis and cirrhosis. Seitz et al. note that genetic, epigenetic (how one's behaviour and environment can cause changes that affect the way one's genes work, and which are reversible but can change how the body reads a deoxyribonucleic acid sequence) and non-genetic factors might explain the considerable inter individual variation in the alcohol related liver disease phenotype.
In Sri Lanka, according to S.M. Senanayake, M.A. Niriella, S.K. Weerasinghe, A. Kasturiratne, J.P. de Alwis, A.P. de Silva, A.S. Dassanayake, and H.J. de Silva's “Survival of patients with alcoholic and cryptogenic (of a disease of obscure or uncertain origin) cirrhosis without liver transplantation: A single centre retrospective study”, alcohol related or cryptogenic or fatty liver-related forms of cirrhosis predominate.
The Ragama Health Study (RHS) is a large, community-based, prospective, cohort study on non-communicable diseases which is a collaboration between the National Centre for Global Health and Medicine, Tokyo, Japan, and the Kelaniya University's Medical Faculty (A.S. Dassanayake, A. Kasturiratne, S. Rajindrajith, U. Kalubowila, S. Chakrawarthi, A.P. De Silva, M. Makaya, T. Mizoue, N. Kato, A.R. Wickremasinghe, and H.J. de Silva's “Prevalence and risk factors for non-alcoholic fatty liver disease among adults in an urban Sri Lankan population”), which aimed to determine unsafe alcohol use and the incidence and risk factors for alcoholic fatty liver in the RHS cohort after seven years of follow-up.
The study population was initially selected by age stratified, random sampling from the electoral lists of the Medical Officer of Health area of Ragama. The population was urban, with a multi-ethnic distribution. They were initially screened in 2007 (aged 35-64 years) and invited for re-evaluation after seven years in 2014 (aged 42-71 years). On both occasions, they were assessed by structured interviews, anthropometric measurements, liver ultrasound, and biochemical and serological (any of the several laboratory procedures carried out on a sample of blood serum which is the clear liquid that separates from the blood when it is allowed to clot, for the purpose of detecting antibodies or antibody like substances that appear specifically in association with certain diseases) tests.
Details regarding the type and amount of alcohol consumed and the duration of drinking were obtained by the direct questioning of the participants using a structured questionnaire. A total of 14 units were defined as 14 single measures of spirit (25 millilitres [ml] of 40% alcohol by volume) or six glasses of wine (175 ml of 13% alcohol by volume) or six pints of ordinary strength beer (568 ml of 4% alcohol by volume). Illicit alcohol was assumed to have a strength of 40% alcohol by volume. The diagnosis of fatty liver was based on established ultrasound criteria (two out of the following three criteria; increased echogenicity [the ability to bounce an echo, e.g. return the signal in ultrasound examinations] of the liver compared to the kidney and the spleen, the obliteration of the vascular architecture of the liver and the deep attenuation of the ultrasonic signal), per S. Saadeh, Z.M. Younossi, E.M. Remer, T. Gramlich, J.P. Ong, M. Hurley, K.D. Mullen, J.N. Cooper and M.J. Sheridan's “The utility of radiological imaging in non-alcoholic fatty liver disease”. Alcoholic fatty liver was diagnosed in the presence of ultrasound criteria for fatty liver, unsafe alcohol consumption (Asian standards: males over 14 units, females over seven units per week, per H.L-Y. Chan, H.J. de Silva, N.W-Y. Leung, L.S-G. Lim, G.C. Farrell, and the Asia-Pacific Working Party on non-alcoholic fatty liver disease. How should we manage patients with non-alcoholic fatty liver disease in 2007?”) and the absence of hepatitis B/C markers. Controls, per Saadesh et al. were individuals with unsafe alcohol consumption but who had no ultrasound criteria of fatty liver. The resolution of fatty liver was defined as those who had no ultrasound criteria of fatty liver.
Life modification results
Those with an initial diagnosis of alcoholic fatty liver in 2007 were encouraged to adopt healthy lifestyle modification and alcohol abstinence and referred for medical care for associated metabolic risk factors such as diabetes, hypertension and dyslipidemia (the imbalance of lipids), as appropriate. They were invited every six months to attend a community clinic for the reinforcement of the healthy lifestyle advice. New onset alcoholic fatty liver were those who did not have alcoholic fatty liver at the baseline in 2007 but developed alcoholic fatty liver at reassessment after seven years in 2014, while continuing unsafe alcohol use.
There were 3,012 participants in the initial study, of whom 2,985 (99.1%) had complete data for analysis. The ethnic breakdown was Sinhalese (96.2%), Tamils (1.3%), Muslims (1.3%), and Burghers (1.3%). This included 1,349 men (45.2%). The mean age was 54.2 years (standard deviation 7.8 years). A total of 2,148 out of 2,985 (72%), including 910 (42.4%) men, participated in the follow-up assessment. Except for a fewer number of males attending the follow-up, the rest of the characteristics were similar among the initial and follow-up cohorts.
At the baseline in 2007, 272 out of 2,985 (9.1%) were unsafe drinkers (males – 270/99.3%, mean age 51.9 years and standard deviation eight years). A total of 86 out of 2,985 (2.9%) of the initial cohort (86 out of 272 [31.6%] of unsafe drinkers) had alcoholic fatty liver (males – 85/98.8%, the mean age 50.2 years and standard deviation 8.6 years). A total of 186 out of 272 (68.4%) had an unsafe alcohol intake but did not have alcoholic fatty liver at the baseline. The male gender, being of a younger age, having an abnormal waist circumference, the presence of diabetes raised triglycerides (type of fat/lipid found in one's blood where when one eats, the body converts any calories it does not need to use right away into triglycerides) and raised alanine aminotransferase (an enzyme found mostly in the liver) were associated with alcoholic fatty liver. A low level of education (not completed secondary education) and a low monthly household income (median – Rs. 25,000) were associated with an unsafe alcohol intake without alcoholic fatty liver. Only the increased waist circumference and raised alanine aminotransferase were independently associated with alcoholic fatty liver at the baseline in 2007.
A total 173 out of 272 (63.6%) who consumed unsafe amounts of alcohol in 2007 presented for follow-up in 2014. Of these 173, 55 already had alcoholic fatty liver in 2007 and 79 had changed their drinking status to ‘safe’ or no alcohol consumption. A total of 39 unsafe drinkers who did not have fatty liver at the baseline in 2007 continued hazardous drinking, and 21 out of 39 (53.8%) (all males, with a mean age of 57.9 years and standard deviation 7.9 years) of them had developed fatty liver after seven years (annual incidence 7.7%). Only the male gender was significantly associated with new onset alcoholic fatty liver. Of the 42 who had alcoholic fatty liver at the baseline, who changed their drinking status from unsafe to safe or no alcohol, six had a resolution of fatty liver in 2014 (annual resolution 2%).
Unsafe alcohol usage
An unsafe alcohol intake was seen in 9.1%, and the problem was almost exclusively in males at the baseline and follow-up. Among the unsafe drinkers, the annual incidence of alcoholic fatty liver was 7.7%. Only the male gender was significantly associated with the development of new onset alcoholic fatty liver. Of those with alcoholic fatty liver at the baseline and who had changed their drinking status from unsafe to safe or no alcohol, few had a resolution of the fatty liver after seven years.
Unsafe alcohol consumption was almost exclusively seen among males. Men are, according to R.W. Wilsnack, S.C. Wilsnack, A.F. Kristjanson, N.D. Vogeltanz-Holm and G. Gmel's “Gender and alcohol consumption patterns from the multinational Gender, Alcohol, and Culture: An International Study project”, more likely to engage in alcohol use and are at a much greater risk of developing alcohol use disorder than women worldwide. I. Obot and R. Room's “Alcohol, gender and drinking problems: Perspectives from low and middle income countries” observes that in Asian countries, women are known to abstain from using alcohol due to social and cultural reasons.
The unsafe alcohol consumption rate observed is slightly higher than previous reports from urban community surveys in Sri Lanka (9.1 versus 5.2% and 6.2% in V. De Silva, D. Samarasinghe and N. Gunawardena's “Alcohol and tobacco use among males in two Districts in Sri Lanka” and H.M. Zavos, S. Siribaddana, H.A. Ball, M.T. Lynskey, A. Sumathipala, F.V. Rijsdijk and M. Hotopf's “The prevalence and correlates of alcohol use and alcohol use disorders: A population based study in Colombo”, respectively). The estimates of the World Health Organisation's “Global status report on alcohol” and health estimated the 12 months prevalence of alcohol use disorder among men in Sri Lanka to be 5.6%.
The community prevalence of alcoholic fatty liver was 2.9%.
Although individuals who had alcoholic fatty liver at the baseline were invited to periodically (every six months) visit a community based clinic for the reinforcement of healthy lifestyle practices to abstain from unsafe alcohol use, those with alcoholic fatty liver at the baseline attended these clinics very infrequently.
The male gender was significantly associated with new onset alcoholic fatty liver. Central obesity, an overweight state and raised alanine aminotransferase were independently associated with alcoholic fatty liver at the baseline. However, the baseline overweight state and central obesity were not associated with new onset alcoholic fatty liver. S. Naveau, V. Giraud, E. Borotto, A. Aubert, F. Capron and J.C. Chaput's “Excess weight risk factor for alcoholic liver disease” and H. Iturriaga, D. Bunout, S. Hirsch, and G. Ugarte's “Overweight as a risk factor or a predictive sign of histological liver damage in alcoholics” have suggested that being overweight is an independent risk factor for the development of alcohol related liver disease. However, a study conducted in Italy did not report an association between the body weight or body mass index and the risk of alcohol related liver disease.
Metabolic abnormalities such as central obesity, being overweight, or having diabetes mellitus and raised triglycerides at the baseline were associated with alcoholic fatty liver. However, of the metabolic abnormalities, only central obesity and the overweight status were independently associated with alcoholic fatty liver at the baseline. The independent association of central and general obesity with alcoholic fatty liver raises the possibility of the disease being an overlap of non-alcoholic fatty liver disease and alcoholic fatty liver. This is in agreement with the new proposed definition of fatty liver disease. Y. Fouad, I. Waked, S. Bollipo, A. Gomaa, Y. Ajlouni, and D. Attia's “What’s in a name? Renaming ‘non-alcoholic fatty liver disease’ to ‘metabolic (dysfunction) associated fatty liver disease’” proposed the term metabolic (dysfunction) associated fatty liver disease as a more appropriate nomenclature for this disease, and a simplified and easily applicable scheme for redefining fatty liver disease.
Unsafe alcohol use was seen in 9.1% of the study population. The prevalence of alcoholic fatty liver among unsafe alcohol users was 31.6%, and after seven years of follow-up, the annual incidence of alcoholic fatty liver among unsafe drinkers was 7.7%.