In the JournalsPerspective

Women at greater risk for developing ALD, liver injury vs. men

Women  may be more likely to develop alcoholic liver disease, even among those who drink less alcohol than men. Further, women who drink similar amounts of alcohol as men may be more likely to develop liver injury, according to research recently published in Alcoholism: Clinical and Experimental Research.

“The adverse effects of heavy alcohol drinking seem to manifest with much higher severity in women,” Vatsalya Vatsalya, MD, MS, PgD, MSc-MHC, in the department of medicine at the University of Louisville in Kentucky, told Healio.com/Hepatology. “For treatment providers, understanding the pattern of heavy drinking is very important to assess the impact of heavy drinking on addiction and organ injury.”

Vatsalya Vatsalya, MD, MS, PgD, MSc-MHC
Vatsalya Vatsalya

Vatsalya and colleagues studied 74 men and 40 women classified as heavy drinkers — none with outward signs of liver injury — aged between 21 and 65 years. Researchers divided patients into two groups based on their alanine aminotransaminase levels:  ≤ 40 IU/L as no liver injury, and ALT > 40 IU/L as mild liver injury. Their sex, BMI, drinking history, fatty acid (FA) and metabolic panels were recorded.

“Our primary aim was to evaluate the changes in FA with mild biochemical liver in [alcohol-dependent] patients via à vis their association with drinking profile,” Vatsalya and colleagues wrote. “Understanding these early changes in FA levels that participate in inflammation and associating these changes with liver injury adds value to our present understanding of the nature of [alcoholic liver disease (ALD)].”

Researchers found after considering drinking history, the ratio of pro-inflammatory vs. anti-inflammatory fatty acid levels tipped toward pro-inflammatory in the women with mild liver injury. They also found increased docosahexaenoic acid in men with liver injury, whereas it was lower in women; increased eicosapentaenoic acid in men with liver injury, but it did not significantly rise in women; increased ALT and aspartate aminotransferase were linked to heavy drinking; women with mild biochemical liver injury had considerably higher AST than men; and notable parallels between AST and heavy drinking days in men and AST and total drinks in women.

Limitations

Researchers wrote that to date, no humans have been tested at the onset of liver inflammation or injury who were then treated using fatty acid supplementation. To fill this void, researchers determined the role a person’s sex plays in inflammation and liver injury. A more racially diverse group — one allowing a more comprehensive statistical analysis — was not available. Researchers were also not privy to patients’ FA food allowances. They addressed this latter limitation.

“[A] previous study suggested that daily macro- and micronutrient intake does not seem to be responsible for the sex-specific susceptibility in the development of ALD,” Vatsalya and colleagues wrote. The patients also appeared well-fed and BMI were on the fringe of being considered overweight average.

“In this study, we found that the between group and sex differences, and the within group and within sex-based associations were significant; however, they were mild to moderate in size, which could indicate that FAs are only one of many factors involved in liver injury/repair,” Vatsalya and colleagues wrote. “However, given the cohort size [more than 100], this study supports the potential importance of FAs involved in liver inflammation/injury/repair.” – by Janel Miller

Disclosure: The researchers report no relevant financial disclosures.

 

Women  may be more likely to develop alcoholic liver disease, even among those who drink less alcohol than men. Further, women who drink similar amounts of alcohol as men may be more likely to develop liver injury, according to research recently published in Alcoholism: Clinical and Experimental Research.

“The adverse effects of heavy alcohol drinking seem to manifest with much higher severity in women,” Vatsalya Vatsalya, MD, MS, PgD, MSc-MHC, in the department of medicine at the University of Louisville in Kentucky, told Healio.com/Hepatology. “For treatment providers, understanding the pattern of heavy drinking is very important to assess the impact of heavy drinking on addiction and organ injury.”

Vatsalya Vatsalya, MD, MS, PgD, MSc-MHC
Vatsalya Vatsalya

Vatsalya and colleagues studied 74 men and 40 women classified as heavy drinkers — none with outward signs of liver injury — aged between 21 and 65 years. Researchers divided patients into two groups based on their alanine aminotransaminase levels:  ≤ 40 IU/L as no liver injury, and ALT > 40 IU/L as mild liver injury. Their sex, BMI, drinking history, fatty acid (FA) and metabolic panels were recorded.

“Our primary aim was to evaluate the changes in FA with mild biochemical liver in [alcohol-dependent] patients via à vis their association with drinking profile,” Vatsalya and colleagues wrote. “Understanding these early changes in FA levels that participate in inflammation and associating these changes with liver injury adds value to our present understanding of the nature of [alcoholic liver disease (ALD)].”

Researchers found after considering drinking history, the ratio of pro-inflammatory vs. anti-inflammatory fatty acid levels tipped toward pro-inflammatory in the women with mild liver injury. They also found increased docosahexaenoic acid in men with liver injury, whereas it was lower in women; increased eicosapentaenoic acid in men with liver injury, but it did not significantly rise in women; increased ALT and aspartate aminotransferase were linked to heavy drinking; women with mild biochemical liver injury had considerably higher AST than men; and notable parallels between AST and heavy drinking days in men and AST and total drinks in women.

Limitations

Researchers wrote that to date, no humans have been tested at the onset of liver inflammation or injury who were then treated using fatty acid supplementation. To fill this void, researchers determined the role a person’s sex plays in inflammation and liver injury. A more racially diverse group — one allowing a more comprehensive statistical analysis — was not available. Researchers were also not privy to patients’ FA food allowances. They addressed this latter limitation.

“[A] previous study suggested that daily macro- and micronutrient intake does not seem to be responsible for the sex-specific susceptibility in the development of ALD,” Vatsalya and colleagues wrote. The patients also appeared well-fed and BMI were on the fringe of being considered overweight average.

“In this study, we found that the between group and sex differences, and the within group and within sex-based associations were significant; however, they were mild to moderate in size, which could indicate that FAs are only one of many factors involved in liver injury/repair,” Vatsalya and colleagues wrote. “However, given the cohort size [more than 100], this study supports the potential importance of FAs involved in liver inflammation/injury/repair.” – by Janel Miller

Disclosure: The researchers report no relevant financial disclosures.

 

    Perspective
    Lorenzo Leggio

    Lorenzo Leggio

    We still don’t fully understand the sex difference on alcohol liver disease. To help find a cure, we need to determine why women have a higher predisposition to develop alcoholic liver damage, to detect biomarkers that can help us to understand the degree of liver damage and to develop treatments.

    Even if we don’t fully understand the reasons why, and even if it isn’t easy to predict among alcoholic patients who is going to have clinically significant liver damage vs. who is not, we do know that there are important factors that can explain this difference. There are hormonal factors, genetic factors, environmental factors and also sex plays a key role. Something we know is that in general women, compared with men, have a higher risk for hepatic damage at lower doses of alcohol exposure. Also, once women have a diagnosis of alcoholic liver disease, they have a more rapid acceleration to liver cirrhosis compared with men. We also know that, paradoxically, sometimes it’s harder for women to qualify for the waiting list to receive a liver transplant.

    This study provides inspiration for different lines of research. One future direction could be to see which data replicate and which become more robust in larger samples. The second direction could be what we call bed-to-bench work — using animal models to understand whether factors like changes in fatty acids involved in inflammation could actually have a role in inflammation and damage to the liver in response to the consumption of heavy quantities of alcohol. A third direction could be using these data to inspire us to develop new treatments for people with liver injury due to alcohol. It’s important we never forget the key goal is to help people stop drinking. They go in parallel. You want to fix a liver when there’s damage but you also want to help these people to achieve abstinence, which in turn helps the liver to recover from the damage, and then make sure that they do not relapse. This is why it is important to encourage and promote collaborations and cross-talk, both in research and clinical practice, among people with different but complementary expertise and skills that span from hepatology and internal medicine to addiction medicine, psychiatry and neuroscience.

    The information the researchers provide goes into the same direction of some of the research done with nonalcoholic fatty liver disease. Their concept of commonality of the mechanisms could underline the reasons why some people develop liver damage. This overlap should not really surprise.  

    • Lorenzo Leggio, MD, PhD, MSc
    • Chief of the Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIAAA and NIDA, National Institutes of Health Bethesda, MD

    Disclosures: Leggio reports no relevant financial disclosures.