Alcoholic Liver Disease: Clinician Collaboration Needed to Encourage Abstinence

Alcoholic liver disease is one of the most common forms of liver disease in the world and, in 2012, approximately 3.3 million global deaths were attributed to alcohol consumption. Alcohol-related health disorders are often determined by the amount and duration of alcohol consumption. To date, the most effective way to prevent alcohol-related health disorders and alcoholic liver disease is abstinence, according to experts.

“Treatment for alcoholic liver disease is really founded on alcohol abstinence first, and supportive care for the complications,” Helen S. Te, MD, FAASLD, FAST, AGAF, associate professor of medicine, and medical director of the adult liver transplantation center for liver diseases, The University of Chicago, told Healio Gastroenterology. “Alcohol abstinence provides the best chance at improving outcome, above any other interventions.”

Lorenzo Leggio, MD, PhD, MSc, clinical investigator and chief of the section on clinical psychoneuroendocrinology and neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, agreed that abstinence is needed to prevent further liver damage in ALD.

“Long-term abstinence is preferable and recommended,” Leggio said. “A brief intervention may be an opening to starting a discussion with a patient and helping them to realize that they need to reduce drinking. On top of brief intervention, you can also add an adjunct treatment,” a number of which are approved in the U.S. and in Europe for alcoholic disorders.

Ashwani K. Singal, MD, MS, FACG, assistant professor at the University of Alabama at Birmingham, told Healio Gastroenterology abstinence is most important and certain medications used with behavioral or motivational therapy for abstinence have shown success, but there is a high chance for relapse.

“Abstinence or cessation of alcohol use is the single most important effective intervention for ALD. These approaches are effective to achieve abstinence in 50% to 70% of cases. However, the efficacy is short lasting and the relapse rates of alcohol use can be as high as 50% after discontinuation of respective treatment,” Singal said.

Clinician Collaboration

Although a hepatologist or liver specialist can recommend abstinence and assist with medical complications from ALD, they are not experts in alcoholism or alcohol addiction; therefore, an addiction specialist and other specialists should be considered when a patient is diagnosed with ALD. However, integrating a hepatologist, addiction specialist, psychologist and other specialists into a personalized health program for a patient with ALD can be a difficult task.

“This is still a challenge and it’s no one’s fault,” Leggio said. “Not everybody can be an expert at everything. However, we need to become more and more aware of ALD and understand we all need to work together to help a patient stop drinking.”

Multiple specialists are needed for this patient population due to their varying levels of expertise, according to Leggio.

“Hepatologists are needed for their expertise in liver damage, addiction psychiatrists or specialists are needed for their expertise in addiction, psychologists are needed for their expertise in behavior and can contribute to behavior treatments,” adding that social workers could be helpful as well.

Singal said a psychologist can have a vital role in managing a patient with ALD, but this collaboration is lacking at many liver centers.

“Psychologists can play an important role in the management of these patients and we know this historically from alcoholics deriving benefit in controlling this behavior by enrolling in the alcohol rehabilitation programs and attending the Alcoholic Anonymous meetings. However, most liver centers — including those with special expertise on alcoholic liver disease — do not work in tandem with psychologists to manage these patients,” Singal said. “Clearly this is an unmet need and area of future research to examine potential barriers to this collaborative approach in the management of patients with alcoholic liver disease.”

According to Te, a psychologist will not always be available to a patient with ALD.

“The hepatologist’s role is mostly to manage the medical complications, but the management of the addiction lies mostly in the hands of a psychologist and/or psychiatrist. Yes, they should work together, but there are not too many psychologists and/or psychiatrists who are interested or trained in the management of alcohol addiction,” Te said.

A nutritionist may also play a role in patient care “because people with alcoholic use disorder often have malnutrition,” Leggio said. “They play an important role because if people abstain from alcohol, there is a change in their calorie intake and it is important to ensure these patients have a proper balance of carbohydrates and fat.”

Te agreed a nutritionist is most important when the liver is recovering and a person is abstaining from alcohol.

“The nutritional support is important, particularly for those who have more advanced liver disease where it is a critical component of the foundation for recovery of the liver, once alcohol abstinence is established.”

Singal said that a patient who is now malnourished due to reduced alcohol intake during abstinence would benefit most from a nutritionist.

“Patients with alcoholic liver disease and alcoholic hepatitis are often malnourished. ... Extremely malnourished patients — due to severely reduced oral intake — can benefit from a nutritionist and enteral nutrition supplementation,” adding that taking a daily caloric count of patients admitted with ALD can help identify who can really benefit from this supplementation.

Natural History, Risk Factors

ALD is a progressive disease that if left untreated can develop into more severe forms of disease, such as alcoholic hepatitis and alcoholic cirrhosis. ALD alone is responsible for approximately 48% of deaths from cirrhosis. Although the degree at which people develop severe ALD varies, it begins with steatosis from drinking and can actually rid itself within a few weeks of abstinence, according to Leggio.

“Hepatic steatosis is the most prevalent form of ALD in the U.S. and worldwide because it is the first stage in ALD from a natural history perspective,” Leggio said. “Everyone who drinks excessively (90%) will have a fatty liver at some point. When this persists, some experience additional progression to liver fibrosis (20% to 40%) then to alcoholic hepatitis and alcoholic cirrhosis.”

According to Leggio, between 8% and 20% of patients with ALD develop alcoholic cirrhosis.

“These patients can then also develop hepatocellular carcinoma (2% to 10%), due to the fact cirrhosis is a risk factor for HCC,” adding that this is more common in patients with both ALD and HCV.

Singal said the prevalence of alcoholic cirrhosis and alcoholic hepatitis has remained constant over the last decade and there is still an “unmet need” to examine the true prevalence of early ALD in patients with a history of excessive and harmful alcohol use.

Despite the relatively constant rate of alcoholic liver disease in the U.S., the Institute for Health Metrics and Evaluation reports an increase in heavy and binge alcohol drinking at the county level between 2005 and 2012, Te said.

“This has been attributed to increasing alcohol use in women,” Te explained. “In addition, hospitalizations for alcohol-related complications are increasing. These parameters support an increasing trend for ALD in the future.”

However, clinicians need to keep in mind that every patient is different and not every person who drinks will develop alcohol use disorder or even ALD.

“This is a very complex situation. ... We know that in addition to the amount of alcohol you drink, the longer you drink has an impact as well, but some people develop liver disease and some do not. We can’t explain it,” Leggio said.

There are also many other factors that determine why a person does or does not develop ALD. These include, but are not limited to, sex, race, nutrition, genetics and cultural factors.

In a study by Valentina Medici, MD, associate professor of internal medicine at UC Davis Health System, Sacramento, Calif., and colleagues, people of certain ethnic origins, mainly Hispanic people, had an increased risk for ALD compared with non-Hispanic whites.

“This study shows that Hispanics not only have a higher risk for ALD, but also for obesity and other metabolic disorders. These are all overlapping problems,” Leggio said.

Te also said Hispanics and blacks are more likely to have ALD and associated mortality compared with non-Hispanic whites. “The answer to why is probably multifactorial — genetics and environment play a role, including socioeconomic status,” Te said.

There have not been many reports on ethnic predispositions to ALD, Singal said. However, reports of the role of genetics in predisposing a person to ALD have been abundant. Further, the most consistent data show the PNPLA3 gene to have the most effect on a person’s risk for ALD.

“Patients with heterozygous and homozygous compared to wild type for this gene are more likely to develop alcoholic liver disease and develop more advanced and progressive liver disease such as cirrhosis and liver cancer,” Singal said.

Leggio echoed Singal’s sentiments and said for this specific variation, people have an increased risk for advanced liver cirrhosis and fibrosis.

“The hope is you can use these genetic biomarkers to identify those at higher risk to see if you can develop a new medication. We are far from there, but it is promising,” Leggio said.

Recent data presented at the International Liver Congress in Barcelona by Stephen Atkinson, MBBS, MA, MRCP, clinical research fellow in the department of internal medicine at Imperial College London, U.K., showed variants in the PNPLA3 and SLC38A4 genes increase the risk for alcoholic hepatitis. In the study, researchers compared genetic differences of patients with severe alcoholic hepatitis (n = 860) with patients with alcohol dependence without alcoholic hepatitis (controls; n = 1,191) to conclude which variants are risk factors for the disease.

“This may be a step forward in allowing us to work toward building an idea of which patients who drink in excess are at increased risk for developing severe forms of alcoholic hepatitis,” Atkinson said at the congress.

Current Therapies for Abstinence

The most common medications to encourage abstinence are disulfiram, baclofen, acamprosate, gabapentin and naltrexone, according to Singal.

“Of the drugs, baclofen in the most effective and safest option that has been tested in many randomized controlled patients, including patients with decompensated alcoholic cirrhosis and alcoholic hepatitis,” Singal said.

However, recent data presented at Digestive Disease Week showed baclofen failed to best placebo in controlling metrics of alcohol use in a cohort of veterans with hepatitis C virus infection. In the study, 88 patients were treated with 10 mg of baclofen three times daily for 12 weeks, and 92 patients were treated on the same schedule with placebo. Results indicated that 7.6% of 79 patients in the study drug group and 10.1% of 80 patients in the placebo group reached abstinence. Alcohol use decreased among both patient groups. However, baclofen did not exhibit a greater effect vs. placebo.

“It is possible that higher dose baclofen may prove effective, but at this time, clinicians are encouraged to use other medications to reduce alcohol use in patients with chronic liver disease,” Peter Hauser, MD, of the VA Long Beach Healthcare System and the University of California, Irvine, said at DDW.

Other treatment options for more severe ALD include liver transplantation. ALD has been the leading indication for liver transplant in Europe and the U.S., with 7.5% of all transplants going to patients with ALD.

“In patients with end-stage liver disease and cirrhosis, liver transplantation is definitive therapy. Most centers in the world require minimum 6 months of abstinence from alcohol consumption before considering these patients for liver transplant,” Singal said.

Leggio said brief interventions, such as conversations during a clinician visit, with a patient may be effective in assisting them to become abstinent.

“They require a short amount of time, but they are important because they can increase motivation to change their behavior.” These can also be done in a primary care physician setting, Leggio said.

Looking to the Future

Although there are treatment options for abstinence and ALD, barriers still exist.

A recent study presented at the International Liver Congress by Richard Aspinall, MD, consultant hepatologist, Portsmouth Hospitals NHS Trust, U.K., showed universal screening for alcohol may be able to identify individuals at greatest risk for alcohol-related harm and, in turn, reduce the risk for more severe liver damage in the future.

In the study, 53,165 individuals admitted to the acute medical unit of a major acute hospital were systematically screened for alcohol. Those at increasing risk for alcohol harm were referred for brief intervention or assessment by an alcohol specialist nurse service at a local acute medical center. Of these, 2.3% were considered at increasing risk for alcohol harm (n = 1,122) and 4% were at high risk for alcohol harm (n = 1,921). High risk patients had more hospital admissions in the past 3 years (4.74%) compared with the low risk (3%) and increasing risk (2.92%) for alcohol harm groups (P < .001). The high risk patients also had more visits to the ED (7.68%) compared with the lower risk (2.65%) and increasing risk groups (3.81%; P < .001 for both).

“Screening for alcohol misuse certainly can be a good start and I think it is a realistic goal,” Te said in reference to the study by Aspinall and colleagues. “But whether it will really reduce the risk of more severe liver damage in a significant number of patients remains to be seen.”

Te said many patients with ALD are advised to quit drinking, yet they continue to drink excessively and endure recurrent hospitalizations for alcohol-related complications.

“Without the linkage to care to effect cessation of alcohol use in susceptible individuals, screening alone would not necessarily translate to changes in clinical outcomes,” Te said.

Singal said the universal screening suggested by Aspinall and colleagues may help identify ALD at an earlier stage.

“Screening for alcohol use should be performed by every clinician at every face-to-face encounter, including emergency department visits, hospital admissions and clinic visits, with an aim to identify high-risk individuals,” Singal said.

Feasibility of universal screening presents a big challenge, according to Leggio.

“Screening is definitely something that is beneficial, especially universal screening, but it takes time and when there is limited time for doctors to see patients, this could be challenging. Implementing this on a larger scale could really be beneficial because the sooner you identify alcohol use disorder, the better.”

Even after identifying these patients, there is still a stigma associated with alcohol use disorder and this may play a role in whether or not a clinician can treat them.

“Alcohol and drugs are those agents where you are still in a level of denial because there is a stigma in society associated with alcohol and drugs, meaning that if you drink or do drugs you are a bad person or not normal,” Leggio said. “This becomes a big problem because patients will have a harder time admitting they have a problem,” adding that the stigma exists for mental health disorders in general, not just for alcohol use disorder.

Te said that patients may not be completely honest about the amount of alcohol they drink and how often.

“Many alcoholics are not forthcoming with their drinking habits, and they tend to minimize the amounts or duration of use,” Te said. “They also tend to minimize the impact of their drinking habits on their work and professional lives.”

Until these barriers are overcome, ALD will continue to be a major cause of mortality and morbidity worldwide.

“Alcohol is responsible for a significant amount of liver disorders. The problem becomes even more important in this day because as we know there are exciting innovations in the world of HCV treatments,” Leggio said. “This means we expect and hope that HCV is going to be less and less a cause of advanced liver disease because we can treat it. As a consequence, alcohol is going to be an even more important etiology to address. The field of hepatology will need to pay even more attention to alcohol as one of the etiologies for liver disorders.”– by Melinda Stevens

• References:
• Aspinall R, et al. Abstract #THU-312. Presented at: International Liver Congress; April 13-17, 2016; Barcelona, Spain.
• Atkinson S, et al. Abstract #GS03. Presented at: International Liver Congress; April 13-17, 2016; Barcelona, Spain.
• Hauser P, et al. Abstract #654. Presented at: Digestive Disease Week; May 21-24, 2016; San Diego, Calif.
• Levy R, et al. Alcohol Clin Exp Res. 2015;doi:10.1111/acer.12660.
• Liangpunsakul S, et al. Gastroenterology. 2016;doi:10.1053/j.gastro.2016.02.043.
• Moreno C, et al. Gastroenterology. 2016;doi:10.1053/j.gastro.2015.12.038.

• For more information:
• Lorenzo Leggio, MD, PhD, MSc, can be reached at National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse, 10 Center Dr., Room 1-5429 Bethesda, MD, 20892-1108; email: lorenzo.leggio@nih.gov.
• Ashwani K. Singal, MD, MS, FACG, can be reached at The University of Alabama at Birmingham, 1808 7th Ave. South, BDB 351, Birmingham, AL, 35294; email: ashwanisingal.com@gmail.com.
• Helen S. Te, MD, FAASLD, FAST, AGAF, can be reached at The University of Chicago, 5841 S. Maryland Ave., MC 7120, Chicago, IL, 60637; email: hte@medicine.bsd.uchicago.edu.

Disclosures: Lorenzo reports no relevant financial disclosures. Singal reports serving on the consultant/advisory board for Gilead Sciences, Intercept Pharmaceuticals, Recordati and Synagewa Pharmaceuticals; and has received funding from American College of Gastroenterology, Gilead Sciences, Intercept Pharmaceuticals, the National Institutes of Health, Synagewa Pharmaceuticals and a Comprehensive Transplant Institute Cooper Award from the University of Alabama. Te reports serving on the advisory board for Bristol-Myers Squibb, Intercept Pharmaceuticals and Gilead Sciences, and receiving research support from AbbVie, Conatus and Gilead Sciences.