Alcohol-Related Liver Disease or Nonalcohol-Related Fatty Liver Disease: What’s The Difference?

Author: Christine Zink, MD

Historically, liver disease has been associated with alcohol use. However, two different diseases (alcohol-related liver disease [ALD] and nonalcohol-related fatty liver disease [NAFLD]) have similar pathological effects on the liver, ranging from simple liver inflammation to chronic cirrhosis and hepatocellular carcinoma. Alcohol-related and nonalcohol-related fatty liver disease cause serious problems worldwide, but risk factors associated with the disorders, predictors of outcomes, and treatments on the horizon can differ. Therefore, the primary care clinician must understand the differences between these two entities.

This article will highlight the differences between ALD and NAFLD and discuss risk factors associated with each entity, diagnosis of disease, and outcomes. The article will also briefly touch on current treatments and new therapies coming in the future. Here are the key takeaways:

  • Alcohol-related liver disease develops in people with heavy alcohol intake, and nonalcohol-related fatty liver disease develops in people with heavy caloric intake1
  • It is challenging to differentiate alcohol-related liver disease from nonalcohol-related fatty liver disease based on presentation, and typically, the diagnosis stems from questions surrounding alcohol use1
  • Most people with alcohol-related and nonalcohol-related liver disease do not develop cirrhosis or hepatocellular carcinoma1
  • The 5-year survival rates for people with alcohol-related and nonalcoholic-related liver disease and inflammation are the same.1 However, people with alcohol-related liver disease are more likely to develop cirrhosis1
  • Treatment for alcohol-related liver disease includes abstinence from alcohol, nutritional therapy, and corticosteroids2
  • The treatment of nonalcohol-related liver disease mainly involves weight loss with lifestyle modifications along with the addition of treatments for diabetes2

Risk Factors

Alcohol-related liver disease

As stated in the name of the disease, ALD develops in people with alcohol use disorders.1 Generally, ALD occurs in patients between ages 45 and 70, and it is much more common in males.1

Nonalcohol-related liver disease

NAFLD typically develops in people with obesity. Approximately 75-92% of people with obesity and 60-70% of people with diabetes (related to obesity) have NAFLD.2 NAFLD is the liver manifestation of metabolic syndrome, a group of conditions that raise a person’s risk for insulin resistance and diabetes, high blood pressure, coronary artery disease, and stroke.1 Since NAFLD is related to weight, it is found in all ages, including almost 10% of children in the United States, based on one study.3 Across the globe, NAFLD is more common in males.1

Genetic factors also seem to be involved in the risk of development of ALD and NAFLD, but research is still ongoing to determine the roles of certain genes.1,2

Diagnosis

Pathophysiology

Both ALD and NAFLD affect hepatocytes leading to tissue damage, and it can be difficult to differentiate them clinically. Direct cellular inflammation seems to play a more significant role in ALD, whereas NAFLD is associated with fatty degeneration of liver cells, leading to lipotoxicity and inflammation.1,4 People with ALD can develop alcohol-related steatohepatitis (ASH) and cirrhosis. People with NAFLD can develop nonalcohol-related steatohepatitis (NASH) and cirrhosis.

Clinical Diagnosis

Typically, the differentiation between the two diseases comes down to determining whether a patient has a history of chronic alcohol use or alcohol use disorder. However, people are not always reliable when answering questions about alcohol. Therefore, clinical parameters have been developed to create a diagnostic tool called the ALD/NAFLD index. This tool considers a patient’s sex, body mass index, liver function studies, and mean corpuscular volume to determine the most likely cause of liver disease.1 That said, liver biopsy is the gold standard diagnostic test, but it is invasive, costly, and painful.1

Outcomes and Survival

Outcomes

ALD and NAFLD cause a significant disease burden globally, but most people do not go on to develop cirrhosis or hepatocellular carcinoma. A long-term study observed that approximately 22% of patients with ALD and 1.2% with NAFLD develop cirrhosis.5 Similarly, people with ALD are more likely to develop hepatocellular carcinoma (about 7% at 5-10 years) than those with NAFLD (approximately 0-3% at 20 years).1

Alcohol-related liver disease

In patients with ALD, the risk of severe liver disease increases as the amount of alcohol ingested increases.1 Additionally, studies have found that consuming spirits instead of beer or wine increases mortality from cirrhosis.1 Finally, studies show that daily heavy drinking is more closely associated with ALD than episodic or binge drinking.1

Nonalcohol-related liver disease

Similarly, high total caloric intake increases the risk of severe liver disease in patients with NAFLD.1 Studies have shown that a greater intake of soft drinks and meats increases the disease risk.1

Survival

The 5-year survival rates in people with ALD and associated ASH and people with NAFLD and NASH are similar at 74% and 75%, respectively.1 People who undergo liver transplantation also have similar post-transplant survival rates. However, post-transplant mortality is more often due to malignancy in people with ALD and cardiovascular disease in people with NAFLD.1

Treatments

Alcohol-related liver disease

The treatment for ALD has not changed in decades and revolves around abstinence from alcohol, nutritional therapy, and corticosteroids.2 However, 40% of patients are unresponsive to corticosteroids, and no further treatment options exist.2 Furthermore, people with severe liver disease can develop complications when taking corticosteroids, such as infection, gastrointestinal bleeding, and hepatorenal syndrome. People who are poor candidates for using corticosteroids can use pentoxifylline, a second-line agent.2

Nonalcohol-related liver disease

The treatment of NAFLD mainly involves weight loss with lifestyle modifications along with the addition of treatments for diabetes, like thiazolidinediones or glucagon-like peptide 1 agonists.2 Studies have shown that weight reduction by 3-5% reduces steatosis, and 5-7% weight loss resolves NASH.2 However, diet and exercise programs can be challenging to maintain. The addition of a thiazolidinedione helps to treat diabetes but also has been shown to improve steatohepatitis and aminotransferase levels.2

Recently, clinicians have praised the use of a glucagon-like peptide 1 agonist, liraglutide, since the medication treats type 2 diabetes and affords people weight loss. Recent evidence has shown that liraglutide can also be therapeutic for NAFLD.2 Finally, experts also recommend treating with lipid-lowering agents since metabolic syndrome is characterized by hypercholesterolemia and hypertriglyceridemia.2 However, studies have been mixed on the actual utility of lipid-lowering agents for treating NAFLD.2

Liver transplantation is the definitive therapy for end-stage liver disease, particularly for patients with ALD who do not respond to steroid therapy.2 Transplantation is a controversial issue in patients with alcohol use disorders. Recidivism following transplant occurs in 10% to 50% of people.2 However, most transplant programs require people to abstain from alcohol for months before the surgery to enhance post-transplant treatment success.

Future Treatment Options

Several therapeutic studies for ALD are underway, and they include the evaluation of probiotics and antibiotics to normalize the gut flora, the use of other antioxidants, such as S-adenosylmethionine and betaine, to potentially improve liver injury, and the targeting of specific chemokines and interleukins that contribute to liver disease.2 New therapies are also being tried to treat NASH. One potential avenue of treatment includes targeting certain enzymes and kinases involved in cell death, inflammation, and fibrosis.2 For example, emricasan is a pancaspase protease inhibitor that can inhibit these processes, and preliminary studies show therapeutic liver improvement.2 Several other agents are undergoing further evaluation, including inhibitors of apoptosis signal-regulating kinase 1 (ASK1), p38 mitogen-activated kinase (MAPK), and chemokine receptors CCR2 and CCR5.2

You can learn more about NAFLD in our CME/CE program NAFLD 2022 Guidelines: New Opportunities to Improve Care in Obesity and Type II Diabetes. Also, visit Pri-Med for even more of the best CME/CE educational opportunities.

 

 

References

1. Toshikuni N, Tsutsumi M, Arisawa T. Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(26):8393-8406.

2. Singh S, Osna NA, Kharbanda KK. Treatment options for alcoholic and non-alcoholic fatty liver disease: A review. World J Gastroenterol. 2017;23(36):6549-6570.

3. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118(4):1388-1393.

4. Idalsoaga F, Kulkarni AV, Mousa OY, Arrese M, Arab JP. Non-alcoholic fatty liver disease and alcohol-related liver disease: two intertwined entities. Front Med (Lausanne). 2020;7:448.

5. Dam-Larsen S, Becker U, Franzmann MB, Larsen K, Christoffersen P, Bendtsen F. Final results of a long-term, clinical follow-up in fatty liver patients. Scand J Gastroenterol. 2009;44(10):1236-1243.