Alcohol-Related Liver Disease: What Do We Know Today?
By Roberto de Carvalho Filho

Alcohol has been part of human history for millennia. From early prehistoric fermentations to modern social rituals, its consumption has become an almost universal habit. But the same substance that symbolizes celebration and social interaction is also one of the leading causes of preventable illness and death worldwide.

Among the various consequences of abusive use, alcohol-related liver disease (ALD) is the most emblematic. It represents a spectrum of injuries that begins with simple fat accumulation in the liver but can progress to inflammation, fibrosis, cirrhosis, and liver cancer. It is the most frequent cause of liver cirrhosis in Western countries and in Brazil.

The global impact of alcohol

Worldwide, the average consumption of pure alcohol is 5.5 liters per person per year, but among those who drink alcoholic beverages, this average rises to 12.4 liters. In Brazil, the average consumption is 7.7 liters per person per year, and 13.3 liters among non-abstainers. According to the World Health Organization’s Global Status Report on Alcohol and Health¹, about 2.6 million people die every year from alcohol-related causes, equivalent to 4.7% of all deaths worldwide.

The COVID-19 pandemic worsened the problem. Studies have shown an increase of more than 30% in hospitalizations for alcoholic liver disease in several medical centers. Isolation, anxiety, and declining social well-being were triggering factors for excessive consumption in many populations.

Despite the growing consumption of alcoholic beverages, data on the prevalence of ALD remain limited. Rates above 10% have been reported in Uganda, Sweden, Italy, and India. There are no precise Brazilian data on the prevalence of the disease, but the Center for Information on Health and Alcohol (CISA) estimated that, in 2022, more than 11,000 annual deaths were directly attributable to alcoholic liver disease². This report confirmed that prevalence is higher among men, although an increase in deaths among women—particularly Black women—was observed. It is important to note that women are biologically more vulnerable to the toxic effects of alcohol than men, because they metabolize ethanol more slowly and have higher blood concentrations after consuming the same dose.

How does alcohol damage the liver?

The liver is the main organ responsible for metabolizing ethanol. When a person drinks, most of the alcohol is converted into acetaldehyde, a highly toxic substance. This process, driven by the enzymes alcohol dehydrogenase (ADH) and CYP2E1, generates free radicals and oxidative stress, profoundly altering hepatic metabolism. Excess NADH produced during ethanol oxidation inhibits the breakdown of fatty acids and promotes fat accumulation — this is how hepatic steatosis, the first stage of ALD, develops. If consumption persists, inflammatory cells are activated and cytokines (TNF-α, IL-6, IL-1β) are released, intensifying liver tissue damage.

In addition to its direct effects, alcohol alters the intestinal microbiota, increases gut permeability, and allows bacteria and endotoxins to reach the liver, worsening inflammation. Over time, repeated inflammatory processes lead to fibrosis, in which normal tissue is replaced by scar tissue that accumulates in the organ.

Some factors make certain individuals more prone to disease progression. One of the most studied is the PNPLA3 gene, whose mutation increases the risk of alcoholic cirrhosis by up to threefold. Other factors—such as female sex, obesity, high-fat diets, and binge drinking—also accelerate liver damage.

Disease stages

Not everyone who drinks heavily develops severe liver injury. Progression depends on the amount, frequency, and duration of consumption, as well as genetic and environmental factors. A family history of alcohol-related cirrhosis and the coexistence of conditions such as diabetes, obesity, hypertension, dyslipidemia, and smoking increase the risk of cirrhosis and its complications. Thus, even small regular amounts of alcohol, when combined with metabolic syndrome, can accelerate this process.

Overall, the clinical spectrum of ALD follows this progression:

How to identify alcohol-related liver disease?

Diagnosing ALD begins with a detailed clinical history, essential to identifying a pattern of abusive alcohol consumption, typically spanning more than 5 to 10 years. Most individuals with ALD (though not all) meet criteria for alcohol use disorder (AUD), such as tolerance and signs of withdrawal (current or past), among others. In some situations, screening tools such as AUDIT-C (Alcohol Use Disorders Identification Test) can be helpful. On physical examination, classic signs of advanced chronic liver disease may be present, such as palmar erythema, telangiectasias, hepatomegaly, jaundice, and ascites. Enlargement of the parotid glands, Dupuytren’s contracture, and certain neurological findings suggest alcoholic etiology.

In laboratory tests, a characteristic finding is an AST/ALT ratio > 1.5, with values generally below 400 U/L. Other alterations include elevated GGT and MCV (mean corpuscular volume). In advanced stages of the disease, coagulopathy (thrombocytopenia and elevated INR), high bilirubin levels, and hypoalbuminemia may occur. Other complementary methods may provide relevant information:

• Abdominal ultrasound: shows liver enlargement and steatosis.
• Liver elastography: measures liver stiffness to estimate fibrosis.
• Liver biopsy: indicated only when the diagnosis is uncertain or when overlap with other diseases is suspected.

Alcoholic hepatitis — one of the most severe forms of ALD — usually presents with recent jaundice, painful hepatomegaly, low-grade fever, leukocytosis, and an AST/ALT ratio > 2 or 3. Diagnosis is generally clinical and laboratory-based, but liver biopsy may be needed when confounding factors exist.

Treatment: abstinence is the foundation!

No medication replaces the benefits of complete abstinence. It is the main factor associated with clinical improvement and reduced mortality. In an Austrian study of 320 cirrhotic patients followed for three years, those who managed to stop drinking had significantly higher survival rates than those who continued³.

Abstinence, however, is rarely simple. It requires continuous support, psychotherapy, and often medications to reduce cravings and prevent relapse. Psychotherapeutic interventions are an essential part of treating AUD associated with ALD. The most commonly used approaches include motivational interviewing, cognitive-behavioral therapy, and dialectical behavior therapy, in addition to complementary strategies such as brief interventions, psychoanalysis, and group therapy, which can enhance adherence and self-awareness, especially when integrated into a structured social and family support network.

Pharmacological treatment of AUD associated with ALD acts as an ally to psychotherapy by reducing compulsive alcohol cravings. The most commonly used medications in Brazil are naltrexone and baclofen, whose efficacy and safety have been demonstrated in clinical studies involving individuals with ALD. Gabapentin and topiramate have shown promising results. Acamprosate, which stabilizes GABA and glutamate neurotransmission, would be another good option, but it is not currently available in Brazil. Disulfiram, although effective due to its aversive reaction to alcohol ingestion, should not be used in patients with suspected ALD because of the high risk of hepatotoxicity. Regardless of the drug used, therapeutic success always depends on continuous medical follow-up and integration with psychosocial interventions.

Liver transplantation: when there is no other option

Liver transplantation is the only curative option for advanced cirrhosis or severe alcoholic hepatitis unresponsive to clinical treatment. For many years, a minimum of six months of abstinence was required before the procedure. Today, this rule is more flexible: the focus is on assessing motivation, family support, and adherence. In a classic study⁴, early transplantation in selected cases of severe refractory alcoholic hepatitis resulted in 77% six-month survival, with relapse in only 15% of cases. More recent studies confirm these positive results, showing that, when well indicated, these patients achieve survival comparable to other transplant indications⁵ ⁶.

Conclusion and future perspectives

Alcohol-related liver disease is a clear example of how a culturally accepted substance can cause silent and profound health damage. The liver “suffers quietly” for a long time, without symptoms, until injuries become irreversible. But there is good news: the liver’s capacity for regeneration is remarkable. When alcohol use is stopped, the healing process begins almost immediately, and improvements can be seen within a few weeks.

ALD is a 100% preventable disease. Prevention begins with health education and early identification of abusive alcohol use. Simple tools such as AUDIT-C can be used in primary care units for risk screening. Public policies that restrict advertising and access, increase costs, and promote alcohol-free social environments have proven effective in many countries and should be adopted.

From a medical perspective, it is important to integrate hepatologists, psychiatrists, nutritionists, and social workers into a continuous care network. The approach should be empathetic and non-stigmatizing, valuing each step the patient takes toward abstinence.

The central message is simple and powerful: there is no level of alcohol consumption that is completely safe for the liver. The less, the better — and the sooner one stops, the greater the chances of liver recovery.

References:

1. World Health Organization. Global status report on alcohol and health and treatment of substance use disorders.Geneva: WHO; 2024. Available from: https://www.who.int/publications/i/item/978924009674
2. CISA – Centro de Informações sobre Saúde e Álcool. DATASUS 2022–2024.
3. Hofer, B. S., Simbrunner, B., Hartl, L., Jachs, M., Bauer, D. J. M., Balcar, L., Paternostro, R., Schwabl, P., Semmler, G., Scheiner, B., Staettermayer, A. F., Trauner, M., Mandorfer, M., & Reiberger, T. (2023). Alcohol Abstinence Improves Prognosis Across All Stages of Portal Hypertension in Alcohol-Related Cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 21(9), 2308–2317.e7. https://doi.org/10.1016/j.cgh.2022.11.033
4. Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, Castel H, et al. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med. 2011;365(19):1790-1800. doi:10.1056/NEJMoa1105703.
5. Louvet, A., Labreuche, J., Moreno, C., Vanlemmens, C., Moirand, R., Féray, C., Dumortier, J., Pageaux, G. P., Bureau, C., Chermak, F., Duvoux, C., Thabut, D., Leroy, V., Carbonell, N., Rolland, B., Salamé, E., Anty, R., Gournay, J., Delwaide, J., Silvain, C., … QuickTrans trial study group (2022). Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study. The lancet. Gastroenterology & hepatology, 7(5), 416–425. https://doi.org/10.1016/S2468-1253(21)00430-1Louvet, A., & Mathurin, P. (2015). Alcoholic liver disease: mechanisms of injury and targeted treatment. Nature reviews. Gastroenterology & hepatology, 12(4), 231–242. https://doi.org/10.1038/nrgastro.2015.35
6. Parker, R., Aithal, G. P., Becker, U., Gleeson, D., Masson, S., Wyatt, J. I., Rowe, I. A., & WALDO study group (2019). Natural history of histologically proven alcohol-related liver disease: A systematic review. Journal of hepatology, 71(3), 586–593. https://doi.org/10.1016/j.jhep.2019.05.020

Other References:

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- Altamirano, J., Miquel, R., Katoonizadeh, A., Abraldes, J. G., Duarte-Rojo, A., Louvet, A., Augustin, S., Mookerjee, R. P., Michelena, J., Smyrk, T. C., Buob, D., Leteurtre, E., Rincón, D., Ruiz, P., García-Pagán, J. C., Guerrero-Marquez, C., Jones, P. D., Barritt, A. S., 4th, Arroyo, V., Bruguera, M., … Bataller, R. (2014). A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology, 146(5), 1231–9.e96. https://doi.org/10.1053/j.gastro.2014.01.018

- Thompson, R., Taddei, T., Kaplan, D., & Rabiee, A. (2024). Safety of naltrexone in patients with cirrhosis. JHEP reports : innovation in hepatology, 6(7), 101095. https://doi.org/10.1016/j.jhepr.2024.101095

- Parker, R., Arab, J. P., Lazarus, J. V., Bataller, R., & Singal, A. K. (2025). Public health policies to prevent alcohol-related liver disease. Nature reviews. Gastroenterology & hepatology, 22(8), 587–594. https://doi.org/10.1038/s41575-025-01084-6