Relentless: The Concurrent Alcohol Abuse, Liver Disease Epidemics in the US

Here was another one. A young hospitalist at Massachusetts General Hospital in Boston during the early-to-mid 2000s, Eugene Lambert, MD, frequently saw patients admitted like this one right now: early 20s, and already with a history of substance abuse. Sometimes the patients were recovering from an overdose, or excessive drinking. Other times they were fighting, and losing, to a chronic sickness derived from their addiction.

This case—the one Lambert recalls clearly about 20 years later—was particularly grim: a young man with a history of heroin use, and prosthetic valve infective endocarditis to show for it.

Lambert saw a young man actively trying to kill himself, in a particularly miserable way, with his injection drug use. And he couldn’t help but to ask the patient why—why would he keep using heroin, even after a valve replacement? Why would he continue to put his life at risk?

“He looked at me, and I can never forget his face,” Lambert told HCPLive. “He said, ‘Do you think this is what I want? Do you think I am constantly making this decision to hurt myself?’”

Lambert earnestly did not know the answer to that question. He felt embarrassment over his lack of understanding to what his patients were experiencing from substance use disorder; in his role as a hospitalist, his interactions were fast-paced, high-stakes, and sometimes lacking context of the whole patient.

By the mid-2010s, Lambert was experiencing feelings of burnout and moral distress. Similar to so many of his peers, he was in some ways overwhelmed by the opioid epidemic—a 30-year-old crisis at the time that introduced concurrent struggles to curb heroin, stimulant and fentanyl product use. By 2021, nearly 1 in 5 adults aged ≥18 years old in his home state of Massachusetts were estimated to have a substance use disorder.¹

He sought to educate himself on treating his patients’ addictions like the diseases they were. Eventually, he took on a fellowship in addiction medicine, and in the 5 years since Lambert has been focusing a majority of his clinical practice in treating severe substance use disorders among inpatients. As the current medical director of addiction counseling services at Mass General, Lambert has found a way to mentally and practically overcome the overwhelming sense of frustration that the addiction epidemic has had on him and his peers.

And it’s also given him perspective on a similar health crisis on the rise—one with complicated consequences throughout numerous fields of care: the rapid increase of alcohol abuse and concurrent liver disease in the US.

“I don’t know if we, as a society, can create a healthcare system that’s going to address what I consider an emerging health crisis,” Lambert said. “What I see in the hospital, what we see in terms of the data…it’s very concerning, but it’s nothing we didn’t see coming.”

Relentless: The Concurrent Alcohol Abuse, Liver Disease Epidemics in the US

Opening the Floodgates

The United States’ alcohol abuse crisis has been in the making for at least 5 years. A cross-sectional analysis of data from the Centers for Disease Control and Prevention (CDC) published earlier this year suggested that annual alcohol-related mortality rates shifted from a stable trend from 1999 – 2007, to an annual increase of 3.0% from 2007 – 2018 (95% CI, 2.6 – 3.5). Then from 2018 – 2020, alcohol-related mortality rates increased by 14.1% each year (95% CI, 8.2 – 20.3).²

Interestingly, the most common causes of alcohol-related death were liver disease and mental/behavior disorders. The rate of women dying annually from alcohol-associated disease was also significantly greater than that of men during that time period, a trend which investigators noted correlates with global-specific data showing a closing sex gap in harmful alcohol consumption rates.

Other assessment into specific diseases like alcohol-associated hepatitis show a similar spike in the last 5 years—and heightened impact on groups including women. A cohort analysis from the Mayo Clinic this year showed the incidence of alcohol-associated hepatitis increased more than 7-fold among US women from 2000 – 2018. What’s more, individuals living on a lower income constituted nearly three-fourths (73.3%) of all alcohol-associated hepatitis cases between 2015 – 2019. Even among men, the rate of disease nearly doubled between 2000 – 2004 and 2015 – 2018.³

What’s to blame? Each of these investigative teams—as well as Lambert and multiple hepatology and psychiatry experts that have spoken to HCPLive—point to a myriad of potential sociocultural, economic, behavioral, and psychiatric factors driving alcohol abuse to new heights. But the timing of these trends and others point to the COVID-19 pandemic as a focal point in the crisis.

It is no great secret that excessive drinking increased significantly during the earliest waves of COVID-19, beginning in 2020. Per data from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the United States purchased more than 40.8 million gallons worth of ethanol—constituting liquor, beer and wine—in July 2020 alone. The total was 17.2% greater than the average total across the previous 3 July’s since 2017.⁴

Months prior to and following that July additionally showed spikes in overall alcohol purchasing and consumption, as the impacts of stressors related to the pandemic—and public health measures to mitigate the virus, including stay-at-home mandates and public business limitations—drove many people to unhealthy habits including increased drinking.

“Maybe it was the stress, the isolation, uncertainties during COVID-19—human beings have different ways they cope with problems,” Suthat Liangpunsakul, MD, MPH, professor of medicine at Indiana University School of Medicine, told HCPLive.

Liangpunsakul and colleagues published cross-sectional analyses of National Inpatient Sample (NIS) data earlier this year showing that alcohol-associated hepatitis hospitalizations actually increased by about 16% in the US from 2019 to 2020—despite national hospitalizations overall decreasing by 9% during the isolating first year of the pandemic. The average annual growth of hospitalizations due to alcohol-associated hepatitis shifted from 5.5% during 2015 – 2019, to 15.6% in 2019 – 2020.⁵

In Liangpunsakul’s experience, it is not only alcohol-associated hepatitis, but cirrhosis and other liver diseases impacted by alcohol consumption that have been exponentially increasing in prevalence in his patients—to the extent that it is among the most prevalent factors in necessary liver transplants. Even more concerning is that he is not observing this trend among the aging US population; more and more patients in their 20s and 30s are presenting with liver disease due to excessive alcohol use.

“Not only is the disease burden increasing, but the target population that we see nowadays is much younger,” Liangpunsakul said. “The reason why we see these trends is because the patients that consume alcohol in an excessive amount are (often) at a much younger age.”

However, the relationship between alcohol use and alcohol-associated liver disease is not a 1:1 relationship; an individual who drinks excessively is predispositioned, not predetermined, to develop concurrent liver disease. They progress first to alcohol-induced fatty liver, Liangpunsakul explained, which is asymptomatic and is therefore generally not identified through screening.

Alcohol-associated hepatitis and/or cirrhosis is generally when scarring and other clearer signs and symptoms persist. But by then, patients are often so burdened by alcohol use disorder and severe liver disease that treatment outcomes are less optimal. As such, investigators like Liangpunsakul have staked interest in identifying clearer biomarkers of disease risk that may inform timelier interventions, including genetic risk factors.

“There are actually several papers already that show that there are certain genes that, if you have them and drink alcohol very heavily, that will predispose you to have more advanced liver disease,” he explained.

A major hurdle to this research development is the challenge to establish better real-world representation in clinical assessments; racial and ethnic subgroups like Black men carry a 60% greater risk of liver and intrahepatic bile duct cancer and mortality due to disease than non-Hispanic White men. Black women—already included in the observed spike in alcohol-associated liver disease among women overall—currently carry a 30% increased risk of liver-related cancer and death versus White women.6 Despite these and similar disparities in disease prevalence and mortality, biomarker research lacks adequate patient diversity.

“If you look at the makeup of (research) patient populations, they’re mostly Caucasian,” Liangpunsakul said. “One of the (high-risk) genes is more prevalent in the Hispanic population, but we don’t have data for large Hispanic populations.”

Other subpopulations, including American Indian and Alaskan Native individuals, have been historically burdened with high rates of excessive alcohol use and related liver disease, Liangpunsakul said. The access to equitable data has been more difficult to accrue for such groups than Black and Hispanic populations.

Regardless of the alcohol-associated disease’s origin, or an individuals’ circumstantial or genetic tendency to develop the disease, the issue remains in detecting it quickly and intervening effectively.

A Slowly Burning Disease

Is there such thing as “mild” alcohol-associated liver disease? Of course. But for hepatologists like Nancy S. Reau, MD, the proof is few and far between. Reau, the Richard B. Capps Chair of Hepatology at RUSH Medical College, told HCPLive most of her patients are admitted presenting with ascites, jaundice, or other concerning symptoms that are visibly clear indicators of poor health to the patient and their loved ones.

“If you’re an individual with alcohol-related liver disease, that’s scary,” Reau said. “You turn bright yellow, you throw up blood, you have a belly full of fluids, so much so that you look pregnant. These are frightening things to the patient.”

These are not cases that an addiction specialist nor primary care physician are casually referring to Reau and colleagues—these are already emergent cases.

“If you have problematic drinking, but you don’t seem to have symptomatic liver disease, you’re probably not going to make it to a liver specialist,” Reau said. “So, most of our patients are experiencing significant liver dysfunction.”

At the point when hepatologists have an opportunity to treat alcohol-associated liver disease, the condition is often more severe, and the hurdles to recovery are far greater.

Reau said organizational guidelines consistently outline the need for staging or assessment in persons with alcohol use disorder—individuals with pattern of alcohol use and a family history of alcohol-associated liver disease should receive some noninvasive method of testing for simple steatosis at the least.

“In everyone with alcohol use disorder, it’s implied that they’re having some form of alcohol impacting their life, and they should be talking to addiction management to help become more safe or quit drinking,” Reau said. “But as a subspecialist, we would love to see these individuals that have been identified as high risk for progression at a time when our interventions are going to be more effective because they are not as sick.”

Direct pharmacotherapy options for alcohol-associated liver disease are limited, and often patients are prescribed therapies relevant to their condition’s effects: corticosteroids for the reduction of liver inflammation, for example. Liver failure remains the lone solution in instances of progression to liver failure, of course. So for Reau, she sees opportunities for improved care, screening and preventive strategies to come from stakeholders other than herself. In that case, the onus may be on the addiction medicine team to initiate the care process.

“The toolkit is going to depend on the patient’s presentation,” Reau said. “If their problem is predominantly addiction, and their liver is relatively well preserved, they need addiction management or a program that helps with alcohol use disorder.”

Just as liver specialists are limited in their treatment capability for later-stage, severe disease, patients are limited in their ability to treat alcohol use disorder once they’ve been admitted for care. Reau recalled hospitalized patients joining Alcoholics Anonymous virtual meetings from a tablet in their room, or struggling to undergo rehabilitation while practically disabled by their liver disease. Others may progress through their hospital stay with a false sense of security over their use disorder because while they receive care, they are completely cut off from alcohol until they are discharged.

Plain and simple, drinking drives the disease—and so it’s the drinking that must be treated first.

“If you have high blood pressure, but you’re unwilling to make dietary changes or take a blood pressure medication, you’re going to be at risk for stroke and heart attack,” Reau said. “Alcohol use disorder is not that different.”

Treating the Person

Lambert also compared alcohol use disorder to hypertension, and a handful of other chronic diseases impacted by behavioral decisions. Only his reasoning is that these are diseases that affect individuals—and so care must be catered to the individual. Why, and how, have they developed a drinking problem? What underlying factors drove their use disorder? What does the tailored model of care look like?

The effect of COVID-19 on alcohol use disorder and, therefore eventually, alcohol-associated liver disease, was multifactorial. But it boiled down to 3 major impacts: exposure to a traumatic event that which may trigger a relapse or increase in alcohol use, disruption to their abstinence support systems, and creation of uncertainty over what they may experience in the future.

“These are people reaching out to what I say is their only known ability to control the anxiety and uncertainty in their lives—and unfortunately, it led to a number of increased healthcare utilizations: emergency department visits, hospitalizations, to transplant waitlists,” Lambert said.

The challenges to resolve this epidemic are staggering. Lambert discussed at length the limitations of the US healthcare system as they relate to curbing alcohol use disorder—let alone alcohol-associated liver disease: misaligned patient care; inadequate mental health services; limited staffing to treat growing substance use disorders; and an ever-increasing rate of individuals drinking excessively.

“When you look at the population studies, they say nearly 29 million adults (in the US) have an alcohol use disorder,” Lambert said. “Less than 3% actually seek treatment, and of those who do, less than 1% actually get an FDA-approved medication.”

“The numbers, in terms of what we need to do to shift this momentum and change the dynamics of this emerging public health crisis, I don’t think this is a built-enough infrastructure,” Lambert said.

One advantage stakeholders have—as is often the case when a public health emergency grows out of control—is the awareness such a glaring issue brings to the general population. Reau said patients experiencing the first concerning signs of liver dysfunction present rather “scared” to her practice, and are more than willing to address their alcohol use disorder—a subject once too stigmatized to acknowledge by individuals. It’s critical clinicians use that moment of intervention to establish a long-term commitment to treating the chronic diseases of both liver dysfunction and addiction.

Reau emphasized a message and care strategy that “divorces the guilt and self-deprecating behavior” from the disease itself, and allows both the patient and caregiver to approach it with a more clinical mindset.

“I think the models are probably going to come best from addiction medicine,” Reau said. “I think there is less stigma now with alcohol use disorder than there used to be. And there are a lot more preventative and integrative programs, and awareness around anxiety and depression—which are often driving problematic behaviors like alcohol use disorder.”

Especially in the strife for positive long-term outcomes—which in many cases, may mean a successful liver transplant and sustained abstinence from drinking—Liangpunsakul envisions a collaborative care team between specialists to ensure a patient remains sober and with a healthy liver post-operation.

“The relapse to alcohol there is more psychological,” he explained. “It’s not something that as a hepatologist we deal with often, which is why I think it needs to be multidisciplinary to make sure the patient maintains sobriety after a transplant.”

An addiction medicine specialist himself, Lambert added that it’s also on hepatologists and direct interventionists to continue developing trust and understanding with the individual patient—hear their perspective on what drives their addiction and how they want to be helped overcome it, just as he did with that impactful patient decades ago.

“That’s where we as clinicians struggle,” Lambert said. “We don’t know how to process that—we can’t just give them a drug to get better. No, it’s actually listening, talking and building relationships, and allowing this aspect of trust to be developed between you and a patient who has an issue with alcohol.”

After Lambert shifted his career into addiction medicine, he went back into his discharge files. He found one describing a patient with alcohol use disorder; the summary simply read, “Patient was not encouraged to drink anymore.” He reflects on how his own team at Mass General has made strides in the wake of this years-long crisis; discharge forms are now filled with addiction medicine referrals, prescriptions, recommendations to outpatient community care centers.

The difference in incremental efforts to see and hear the entire patient—to address the addiction as much as they do the liver—are enough to encourage hope against the current odds.

“I’m impressed with the changes we’ve made over the last decade,” Lambert said, “but we need to be moving with a certain degree of urgency.”

References

1. ^{Substance Abuse and Mental Health Services Administration (SAMHSA). 2021 NSDUH: Model-Based Estimated Prevalence For States. Data table. Published March 8, 2023. https://www.samhsa.gov/data/report/2021-nsduh-state-prevalence-estimates}
2. ^{Karaye IM, Maleki N, Hassan N, Yunusa I. Trends in Alcohol-Related Deaths by Sex in the US, 1999-2020. JAMA Netw Open. 2023;6(7):e2326346. doi:10.1001/jamanetworkopen.2023.26346}
3. ^{Kunzmann K. Alcohol-Associated Hepatitis Rapidly Increasing in the US. HCPLive. Published July 18, 2023. https://www.hcplive.com/view/alcohol-associated-hepatitis-rapidly-increasing-us}
4. ^{NIAAA. Surveillance Report COVID-19: Alcohol Sales During the COVID-19 Pandemic. Data table. Published September 22, 2021. https://www.niaaa.nih.gov/publications/surveillance-reports/alcohol-sales-during-covid-19-pandemic#fig10}
5. ^{Kunzmann K. Alcohol-Associated Hepatitis Hospitalizations Increased During COVID-19. HCPLive.Published August 10, 2023. https://www.hcplive.com/view/alcohol-associated-hepatitis-hospitalizations-increased-covid-19}
6. ^{US Department of Health and Human Services Office of Minority Health. Chronic Liver Disease and African Americans. Infographic. Publication date unavailable. https://minorityhealth.hhs.gov/chronic-liver-disease-and-african-americans#:~:text=In%202020%2C%20chronic%20liver%20disease,ages%2045%2D64%20years%20old.&text=African%20American%2Fblack%20men%20are,to%20non%2DHispanic%20white%20men.}