New research suggests otherwise, according to a Keck Medicine of USC study published today in Clinical Gastroenterology and Hepatology. 

Researchers discovered that people with metabolic dysfunction–associated steatotic liver disease (MASLD), the most common liver condition in the country affecting one-in-three adults, face significantly higher risk of liver fibrosis, or harmful scarring of the liver, if they engage in episodic heavy drinking. Episodic heavy drinking is four or more drinks in one day for women and five or more drinks in one day for men, at least once a month.  

Those who consume large amounts of alcohol in a single day at least once per month are three times more likely to develop advanced liver fibrosis than individuals who spread out the same total alcohol intake over time, according to the findings. 

Younger adults and men were more likely to report episodic heavy drinking, and the more drinks consumed at one time, the more liver fibrosis people tended to have. 

“This study is a huge wake-up call because traditionally, physicians have tended to look at the total amount of alcohol consumed, not how it is consumed, when determining the risk to the liver,” said Brian P. Lee, MD, MAS, a hepatologist and liver transplant specialist with Keck Medicine and principal investigator of the study. “Our research suggests that the public needs to be much more aware of the danger of occasional heavy drinking and should avoid it even if they drink moderately the rest of the time.”  

How the study was conducted 

Lee and his colleagues used data from the nationally representative National Health and Nutrition Examination Survey, a long-running health survey of the United States population. They included data from more than 8,000 adults, collected between 2017 and 2023. In particular, they looked at the link between episodic heavy drinking and advanced liver fibrosis to understand how drinking patterns — not just total drinks — may cause harm even to moderate drinkers, which is considered seven drinks a week for women and 14 or less for men.  

The research team focused on MASLD because of its prevalence among Americans. MASLD affects people with excess weight, obesity or other metabolic conditions, such as Type 2 diabetes, high blood pressure or high cholesterol, and is on the rise. Additionally, while MASLD is not defined as alcohol-related, Lee and his colleagues wanted to explore if alcohol did in fact play some role in the condition. 

More than one-half of the adults included in the study reported episodic heavy drinking and almost 16% of patients with MASLD were episodic heavy drinkers. 

The researchers compared people with MASLD with the same age, sex and average weekly alcohol consumption, segmenting some as episodic heavy drinkers and others as non-episodic heavy drinkers, to reach their conclusion that episodic heavy drinkers with MASLD had nearly three times higher odds of experiencing advanced liver fibrosis.  

Lee speculates that episodic heavy drinking can harm the liver both directly and indirectly. Drinking large amounts of alcohol at once can overwhelm the liver and increase inflammation, which leads to scarring and damage. People with MASLD may be particularly at risk, as Lee’s previous research has shown that obesity, high blood pressure and other conditions associated with MASLD can more than double liver disease risk. 

Alcohol-related liver disease has more than doubled in the last two decades, according to Lee. He believes this trend is driven by pandemic-era surges in drinking and an increase in people with risk factors for MASLD, like obesity and diabetes.  

“Although this study focused on patients with MASLD, these findings may also be pertinent to a broader patient population,” said Lee. “With more than half of adults reporting some episodic heavy drinking, this issue deserves further attention from both physicians and researchers to help better understand, prevent and treat liver disease.” 

Now, a new study published in Liver International from Keck Medicine of USC reveals that tetrachloroethylene (PCE), a chemical used in dry cleaning and found in consumer products such as adhesives for arts and crafts, spot cleaners and stainless steel polish, may also be harmful to the liver.

Exposure to PCE was shown to triple the risk of significant liver fibrosis, an excessive amount of scar tissue in the liver that can lead to liver cancer, liver failure or death.

Additionally, the more exposure people had to the chemical, the more likely they were to develop significant liver fibrosis.

“This study, the first to examine the association between PCE levels in humans and significant liver fibrosis, underscores the underreported role environmental factors may play in liver health,” said Brian P. Lee, MD, MAS, a hepatologist and liver transplant specialist with Keck Medicine and lead author of the study. “The findings suggest that exposure to PCE may be the reason why one person develops liver disease while someone with the exact same health and demographic profile does not.”  

Where PCE can be found

PCE is a human-made, colorless liquid used in dry cleaning, household goods and industrial settings to remove grease and for other purposes.

People are typically exposed to PCE through the air — for example, the chemical can be slowly released into the air over time from clothes that have been dry cleaned. PCE can also be present in drinking water from contaminated sites due to spills and improper disposal of PCE that can seep into the soil and then into the groundwater.

The International Agency for Research on Cancer has classified PCE as a probable carcinogen and linked it to bladder cancer, multiple myeloma and non-Hodgkin lymphoma. Other studies showed that exposure to PCE increased the risk of liver cancer, said Lee.

Due to its toxicity, the United States Environmental Protection Agency has launched a 10-year phaseout for the use of PCE in dry cleaning as well as banned or placed workplace controls on other uses of PCE. However, the chemical may remain present in some applications and in countries without similar regulations.

The more PCE exposure, the greater the risk of liver disease

Lee and his fellow researchers used data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of the United States population, to reach their conclusions. They tracked PCE exposure through the concentration of the chemical in individuals’ blood in people 20 and older from the years 2017-2020, the most recent years for which information is available, finding that some 7% of the population had detectable PCE.

They then examined which individuals with PCE in their blood had significant liver fibrosis and found that people exposed to PCE were three times more likely to have significant liver fibrosis than those without exposure.

These results held steady independent of factors such as age, sex, race, ethnicity and education level.

The study did show that those most at risk of PCE exposure were from higher-income households. “People with higher incomes may be more likely to use dry cleaning services, which could increase their exposure to PCE,” said Lee. “However, people who work in dry cleaning facilities may also face elevated risk due to prolonged, direct exposure to PCE at work.”

The researchers also found that for every one nanogram per milliliter increase in PCE concentration in the blood (one nanogram is one-billionth of a gram), the individual’s odds of having significant liver fibrosis increased five-fold.

Of particular note, alcohol use and fat buildup in the liver linked with obesity and other health factors did not appear to play a role in significant liver fibrosis when PCE was present. “Patients will ask, how can I have liver disease if I don’t drink and I don’t have any of the health conditions typically associated with liver disease, and the answer may be PCE exposure,” said Lee.

Future research needed

Lee would like to see future research in the field of environmental toxins and how they affect liver disease. “No doubt there are other toxins in our environment besides PCE that are dangerous to the liver,” he said.

He also thinks the study may lead to improved outcomes for patients. “We hope our research will help both the public and physicians understand the connection between PCE exposure and significant liver fibrosis,” he said. “If more people with PCE exposure are screened for liver fibrosis, the disease can be caught earlier and patients may have a better chance of recovering their liver function,” said Lee.

MASLD occurs when fat builds up in the liver and is associated with one or more of five conditions: obesity, Type 2 diabetes, high blood pressure, high blood sugar and low HDL cholesterol, known as “good” cholesterol. These conditions are characterized as cardiometabolic risk factors because they affect the heart or metabolism.  

MASLD can lead to serious illness, such as advanced liver, heart and kidney disease, but little research has been done to examine if certain cardiometabolic risk factors for those with MASLD are more associated with death than others.  

The deadliest cardiometabolic risk factors  

Now, a new study from Keck Medicine of USC published in Clinical Gastroenterology and Hepatology reveals that three of the cardiometabolic risk factors carry the greatest risk of death for those with MASLD: high blood pressure, pre-diabetes or Type 2 diabetes, and low HDL, which raise the risk of death by 40%, 25% and 15%, respectively.  

These results were independent of how many or which combination of cardiometabolic risk factors patients had, and held steady despite individuals’ gender, sex, race or ethnicity.  

“MASLD is a complicated disease, and this study sheds new light on where doctors may want to focus their efforts when treating patients,” said Norah A. Terrault, MD, a hepatologist with Keck Medicine and a senior author of the study. “Knowing which aspects of MASLD might lead to poorer outcomes can help us offer patients the best possible care.”  

Researchers were especially surprised to discover that high blood pressure was associated with a higher chance of death than diabetes, said Matthew Dukewich, MD, PharmD, MS, a USC transplant hepatology fellow and lead author of the study. “Until now, it was commonly thought that diabetes was the most pressing health problem for MASLD patients, which is a key insight.” 

The study also found that obesity, the most common cardiometabolic risk factor of MASLD,  can substantially raise the risk of mortality depending on a patient’s body mass index (BMI), which is a formula used to estimate body fat percentage based on an individual’s height and weight. The higher a patient’s BMI, the higher the association with death. 

Additionally, the study adds to the growing body of research that patients with more cardiometabolic risk factors have poorer outcomes. The study found that the risk of death in MASLD patients increased by 15% for each additional cardiometabolic risk factor present. 

How the study was conducted  

Researchers used data from the National Health and Nutrition Examination Survey (NHANES), which collected health information about children and adults in the United States from 1988-2018, the most current year for which data was available for their study. Out of 134,515 participants 20 years or older, some 21,000 patients qualified as having MASLD.  

The study authors tracked all-cause mortality rates by individual cardiometabolic risk factors to reach their conclusions.  

Looking ahead, the study authors hope to conduct further studies examining patients’ genetic background, dietary habits and alcohol use in relation to MASLD outcomes to provide more comprehensive risk profiles. “The more we can understand about the drivers of the disease, the more we can identify those most in need of interventions and prioritize our resources for enhanced outcomes,” said Terrault.  

Liyun Yuan, MD, a transplant hepatologist with Keck Medicine, is also a study author. 

The answer may lie in three common underlying medical conditions, according to a new study published in Clinical Gastroenterology and Hepatology from Keck Medicine of USC. The research found that heavy drinkers with either diabetes, high blood pressure or a high waist circumference are as much as 2.4 times more likely to develop advanced liver disease.  

“The results identify a very high-risk segment of the population prone to liver disease and suggest that preexisting health issues may have a large impact on how alcohol affects the liver,” said Brian P. Lee, MD, MAS, a hepatologist and liver transplant specialist with Keck Medicine and principal investigator of the study. 

Diabetes, high blood pressure and a high waist circumference (35 inches for women; 40 inches for men), which is associated with obesity, belong to a cluster of five health conditions that influence an individual’s risk for heart attack and stroke known as cardiometabolic risk factors.  

Cardiometabolic risk factors have been linked to the buildup of fat in the liver (also known as metabolic dysfunction-associated steatotic liver disease), which can lead to fibrosis, or scarring of the liver. These risk factors affect more than one in three Americans, and cardiometabolic health has been worsening among the population, especially among those under 35, according to Lee.  

Alcohol also causes fat buildup in the liver, and alcohol consumption has been on the rise since the COVID-19 pandemic, said Lee. Due to the prevalence of both cardiometabolic risk factors and drinking in the United States, Lee and his fellow researchers undertook the study to investigate which cardiometabolic risk factors predisposed the liver to damage from alcohol. 

They analyzed data from the National Health and Nutrition Examination Survey, a large national survey of more than 40,000 participants, looking at the intersection of heavy drinking, individual cardiometabolic risk factors and the incidences of significant liver fibrosis. Significant liver fibrosis refers to liver scarring that can lead to liver failure.  

For the study, heavy drinking was characterized as 1.5 drinks a day for women (20 grams) and two drinks a day for men (30 grams). 

Researchers discovered that heavy drinkers with either diabetes or a high waist circumference were 2.4 times more likely to develop advanced liver disease and those with high blood pressure 1.8 times more likely. They found that the other two cardiometabolic risk factors — high triglycerides (elevated levels of a type of fat in the blood) and low HDL (high-density lipoprotein or “good” cholesterol) had less significant correlations to liver disease.  

While the study did not analyze why these three cardiometabolic risk factors are more dangerous for the liver, Lee speculates that these conditions share a common pathway to fat buildup in the liver that when combined with extra fat deposits in the liver from excessive alcohol, can cause significant damage.  

Lee emphasizes that the study does not imply it is safe for those without these three cardiometabolic risks to consume large amounts of alcohol. “We know that alcohol is toxic to the liver and all heavy drinkers are at risk for advanced liver disease,” he said.  

Lee hopes that the study results will encourage people to consider their individual health and risk profile when making decisions about alcohol consumption. He would also like to see practitioners offer more personalized health screenings and interventions for those who drink with cardiometabolic risk factors so that liver damage among this high-risk group can be caught early and treated.  

Norah Terrault, MD, a Keck Medicine gastroenterologist and division chief of gastroenterology and liver diseases at the Keck School of Medicine, was also a study author.  

From pre-pandemic (2018) to the height of the pandemic (2020), heavy alcohol use among Americans rose by 20%, and any alcohol use rose by 4%. In 2022, the increases were sustained.  

The rise in drinking was seen across all age groups, genders, race, ethnicities and regions of the country, except for Native Americans and Asian Americans. Adults ages 40-49 had the highest increase in heavy alcohol use.  

“These numbers reflect an alarming public health issue that could result in severe health consequences for far too many people,” said Brian P. Lee, MD, MAS, a hepatologist and liver transplant specialist with Keck Medicine of USC and principal investigator of the study. “Our results suggest men and women under 50 are at special risk.” 

Excessive alcohol use is a leading preventable cause of illness and death in the United States, according to the Centers for Disease Control and Prevention. Half of all liver-related deaths are caused by alcohol, and alcohol-related cirrhosis is now the leading cause of liver transplants, according to Lee.  

To reach their conclusions, researchers studied data from the National Health Interview Survey, one of the largest and most comprehensive health surveys in the country. The survey collected alcohol use information as well as demographic and socioeconomic data for more than 24,000 adults age 18 or older. They compared 2018 with 2020 alcohol use numbers, then 2018 with 2022. 

While the U.S. Department of Health and Human Services announced the official end of the pandemic in May 2023, the study defined the year 2022 as post-pandemic, as behaviors were beginning to return to normal.  

Adults were characterized as having any alcohol use or heavy alcohol use within one year of the survey, and researchers calculated the rate of both measures of alcohol use. Heavy drinking was defined as greater than or equal to five drinks a day or 15 drinks a week for men, and greater than or equal to four drinks a day or eight drinks a week for women.  

The study did not analyze why there was an increase in alcohol consumption between 2018 to 2022, but Lee hypothesizes that pandemic stress may have caused drinking to become more normalized. He further speculates that the effects of the pandemic, including disruptions to school and work, may have driven the increases in alcohol use in adults ages 40-49. 

Lee hopes the study will bring more awareness to the issue. “We encourage health care providers to offer more screenings for harmful drinking as well as interventions for at-risk populations,” he said. 

Divya Ayyala-Somayajula, MD, from Thomas Jefferson University in Philadelphia, was lead author of the study. 

Jennifer Dodge, MPH, an associate professor of research medicine and population and public health science at the Keck School of Medicine of USC, Adam Leventhal, PhD, professor of population and public health sciences at the Keck School and director of the USC Institute for Addiction Science, and Norah Terrault, MD, a Keck Medicine gastroenterologist and division chief of gastroenterology and liver diseases at the Keck School, were also study authors.  

A new study from Keck Medicine of USC published in The American Journal of Gastroenterology finds that transgender adults have double the prevalence of cirrhosis compared to cisgender adults (people whose gender identity matches the sex they were assigned at birth), suggesting a need for more supportive, preventive care. 

“Our study reveals that cirrhosis disproportionately affects transgender individuals and highlights a pressing health issue that needs addressing,” said Brian P. Lee, MD, MAS, a hepatologist and liver transplant specialist with Keck Medicine and principal investigator of the study.   

Lee and his colleagues launched the study to provide scientifically backed liver health guidance for physicians so they could offer transgender patients a higher level of care. 

Besides discovering that transgender cirrhosis rates are double that of the cisgender population, the study authors also learned that the majority of transgender adults with cirrhosis (60%) have a diagnosis of anxiety and/or depression, compared to 40% of the cisgender patients with cirrhosis.  

They also found that alcohol was the leading cause of cirrhosis in the transgender group, accounting for some 60% of cases while the percentage of cisgender adults with alcohol-associated cirrhosis was approximately 50%. 

In other findings, transgender patients with cirrhosis also tended to be younger (a larger portion were 44 or younger), had higher rates of viral hepatitis and were five times more likely to have HIV/AIDS than their cisgender counterparts.  

Possible reasons behind the disparity  

Lee hypothesizes that the increased rates of depression and anxiety may be driving higher rates of alcohol use among transgender patients, which in turn, may result in greater cases of cirrhosis.  

The increased rate of HIV/AIDS among transgender patients may also be a factor in that both conditions are known to be associated with liver disease progression, according to Lee.  

Lack of access to quality health care could also play a role, hypothesizes Jeffrey Kahn, MD, a hepatologist and liver transplant physician with Keck Medicine and co-author of the study.  

Researchers also studied the five-year outcomes among all transgender and cisgender patients with cirrhosis. Interestingly, despite the differences in the two groups, the number of possible negative outcomes of cirrhosis — liver failure, liver transplant and liver cancer, as well as death, by any cause — was the same.  

“This finding suggests that the transgender community is underserved in the initial stages of liver disease, but individuals are able to secure the care they need once cirrhosis is diagnosed,” said Kahn. “Early prevention is key because if liver disease is caught in time, there is less of a chance it will progress to cirrhosis.”  

To reach their conclusions, study authors culled data from a large national database, Optum Clinformatics® Data Mart Database (Optum), that contained medical claims for more than 60 million patients covered by commercial insurance or Medicare between the years of 2007-2022. They first identified all transgender and cisgender adults, and then compared the incidences of cirrhosis among each group as well as causes of the disease. Additionally, researchers tracked depression and anxiety in patients. 

Lee and Kahn hope the study will spur more research and motivate health care practitioners to provide transgender patients with extra support, including liver screenings and access to mental health resources. “This population requires specific attention from clinicians and researchers alike,” said Lee.  

Keck Medicine efforts to support transgender patient wellness  

Keck Medicine launched the USC Gender-Affirming Care Program to provide tailored, supportive health care to the transgender population. The program provides a full range of expert, compassionate health care services for the transgender, non-binary and gender-diverse community, including everything from routine health care, such as preventive cancer screenings, yearly checkups and flu shots, to gender-affirming hormone therapy and surgery.  

The program is comprised of physicians from several disciplines, including family medicine, plastic surgery, gynecology, urology and otolaryngology. Specialists in voice, occupational and physical therapy are also available to patients.  

Additionally, Keck Medicine hospitals have been awarded the ‘LGBTQ+ Healthcare Equality Leader’ designation in the Human Rights Campaign Foundation’s 2024 Healthcare Equality Index (HEI) for seven times in recent years. HEI is the leading national benchmarking survey of health care facility policies and practices dedicated to the equitable treatment and inclusion of LGBTQ+ patients, visitors and employees. 

What explains the different outcomes?  

The answer may lie in a condition known as metabolic syndrome, a cluster of conditions that together raise the risk of coronary heart disease, diabetes, stroke and other serious health problems. This syndrome, characterized by symptoms such as abdominal fat, high blood pressure, high cholesterol and high blood sugar, affects more than one in three Americans.  

A new study from Keck Medicine of USC published in the Annals of Internal Medicine shows that heavy alcohol use may be dramatically more damaging to the liver for people with metabolic syndrome.  

“Our research suggests that metabolic syndrome and alcohol interact in such a way that they multiply the effect of alcohol on the liver, more than doubling the risk of advanced liver disease among heavy drinkers,” said Brian P. Lee, MD, MAS, a hepatologist and liver transplant specialist with Keck Medicine who is the lead author on the study. “Drinking is harmful to the liver, but especially so for this segment of the population.”  

In the study, heavy alcohol use was defined as two drinks (a total of 12 fluid ounces) a day for women and three drinks (a total of 18 fluid ounces) per day for men.  

Lee and his colleagues were motivated to research a connection between advanced liver disease, alcohol use and metabolic syndrome after noticing that between 2009-2018, deaths from alcohol-associated liver disease surged in the United States by more than 30% while alcohol use, including heavy drinking, remained stable or declined.  

During the last 20 years, the number of Americans with metabolic syndrome increased significantly. Previous research has shown that metabolic syndrome can cause liver abnormalities.  

“We therefore hypothesized that metabolic syndrome could be an important contributor to this unexplained surge in advanced liver disease,” said Lee.  

For the study, Lee and his fellow researchers used data from the National Health and Nutrition Examination Survey, which assesses the health and nutritional status of adults and children in the United States, pulling together samples representing the U.S. population 20 years or older between 1999 and 2018. 

While the data revealed a slight increase in advanced liver disease with heavy alcohol use without metabolic syndrome, the greatest increase in advanced liver disease was found in those with combined heavy alcohol use and metabolic syndrome. 

Lee believes that the increased risk of liver damage from drinking is a result of an increase in the amount of fat in the liver. A healthy liver contains less than five percent fat; any more than that can lead to inflammation and cirrhosis (scarring) of the liver, liver cancer and liver failure.  

“Both metabolic syndrome and drinking increase liver fat, and we think that the combination of the two accelerates the accumulation of fat in the liver and fuels inflammation, resulting in a greater chance of liver disease,” said Lee.  

He hopes the study will encourage physicians who screen and diagnose patients with metabolic syndrome to also ask about alcohol use and look for liver disease.  

“Our study indicates that these conditions may often coexist, and it is in patients’ best interest to address both issues,” he said. “It’s also important for people with metabolic syndrome to realize they may be at an increased likelihood of advanced liver disease, and to monitor their drinking accordingly,” he added.  

The other authors of the study are Jennifer Dodge, MPH, assistant professor of research medicine and population and public health sciences with the Keck School of Medicine of USC;  Wendy Mack, PhD, professor of population and public health sciences with the Keck School of Medicine; Adam Leventhal, PhD, professor of population and public health sciences with the Keck School of Medicine and director of the USC Institute for Addiction Science and Norah Terrault, MD, MPH, a Keck Medicine gastroenterologist and division chief of gastroenterology and liver diseases with the Keck School of Medicine.