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Alan Bonder, MD, and Juan Pablo Arab, MD on Alcohol-Related Liver Disease: Part 1
In the first of 2 podcasts, Drs Alan Bonder and Juan Pablo Arab discuss the prevalence of alcohol-related liver disease and how the population of patients has changed over time.
Alan Bonder, MD, is assistant professor of medicine at Harvard University Medical School and medical director of liver transplantation at Beth Israel Deaconess Medical Center in Boston, Massachusetts. Juan Pablo Arab, MD, is associate professor of Medicine in the Division of Gastroenterology and the Department of Epidemiology and Biostatistics at the Schulich School of Medicine of Western University in London, Ontario, Canada.
TRANSCRIPT:
Welcome everyone to another session of the Gastroenterology Learning Network. I am Alan Bonder, one of the main editors for the hepatology section and I have the pleasure to have Dr Juan Pablo Arab, who is a world expert in acute alcoholic liver disease. He is an associate professor of medicine. He is originally from Chile, he just moved to Canada. Juan Pablo, thank you so much for joining us. It's a pleasure to have you here and hopefully have a really good discussion and answer some questions that we have in the hepatology world.
Dr Arab
Thank you very much, Alan, for inviting me and thank you everyone that is listening today.
Dr Bonder
To start, Juan Pablo, I think we've seen this new trend in alcoholic liver disease. I think what we've seen in the clinics or in the hospitals, in the transplant world, is we've seen a change in our patient population from alcoholic liver disease. Can you comment a little bit what's going on? What are we facing on the day-to-day? What do you think we are doing on a day-to-day in the hepatology world?
Dr Arab
This is true, indeed, 43% of the global population consume alcohol and then between 5 and 6% of them will have an alcohol use disorder, which is basically not only consuming alcohol, but having mental issues with the alcohol consumption, social issues, and that can lead to alcohol-related liver disease. 90% of the people that consume alcohol heavily will develop hepatic steatosis; of those, between 20% and 40% will develop a more advanced form of the disease with fibrosis, which is the scarring of the liver. And of those, between 10 to 20% will develop cirrhosis, which is the advanced scarring of the liver, including all the complications such as liver cancer.
At any point of the disease patients can also develop what we call alcohol-associated hepatitis, which is inflammatory form, with very high mortality, up to 50% at 3 months. Alcohol-related liver disease has been very frequent in the past. It was probably kind of a neglected disease due to the stigma, but now we are realizing that these numbers are not only not improving, indeed these are worsening.
In the past we used to see mainly people in their 60s, drinking heavily every day — what we call chronic alcohol consumption—but now most of the patients are younger patients, in their 30s or 40s. We are seeing a special increase in females over males and also in ethnic minorities, such as Hispanics or Latinos, which have a higher risk of developing complications of the alcohol use. What it is clear is that alcohol-related liver disease is increasing, especially in the most severe forms, including alcohol-associated hepatitis. Indeed 77.4% of the population that is hospitalized for alcohol-associated hepatitis are young or females. So between 17 years old and 35 years old. We need to take this into account when we are interviewing patients in our liver clinics, for example, for elevated liver function tests or when we found steatosis, which is fatty liver, in an ultrasound. Sometimes we think about NAFLD, which is nonalcoholic fatty liver disease, but we shouldn't forget that alcohol-related liver disease is very prevalent.
Dr Bonder
So I think you bring a good point Juan Pablo and I think number 1 is we can divide our conversation. So what are we doing as an outpatient, or what are we doing as an inpatient? The main question is right now as hepatologist, we do feel, I would say, uncomfortable using all the medications to basically cut the cravings for alcohol consumption. Is there anything you want to discuss? For example, here in Boston, I would say most of us will not be comfortable prescribing a acamprosate or naltrexone. Is there any comment from your end to see, should we hepatologists be more comfortable prescribing this medications in our day-to-day clinics?
Dr Arab
Yeah. Every time that I, especially when I talk to my fellows, say when you have a patient with ALD, you need to take into account that. Before the liver is damaged, the brain is already damaged, and what the alcohol does in the brain is the same that cigarettes or marijuana does in the brain. It's basically it's pushing the reward cycle and it's pushing the same button all over again. The first sign of alcohol use disorder is loss of control. So when the patient tells you that they were planning to drink one can of beer and then they ended up drinking the full six pack of beer, then you need to think that that patient is having loss of control and having an alcohol use disorder. And then when they have seeking behavior, to try to find alcohol or failing to comply with social, work activities, family activities, all those are criteria of alcohol use disorder.
I think we are failing in treating these patients in a holistic way. We are treating the liver disease and we are good at that, but we are neglecting the psychiatric comorbidity, which is the alcohol use disorder. The problem is it's not realistic to expect that every patient will see an addiction specialist or an addiction psychiatrist. And the other thing that I also tell my fellows is the bond that you develop with your patients is strong. They will trust you. Sometimes many of these patients, you met them in the inpatient with variceal bleeding or an acute alcohol-associated hepatitis, they were very sick and they trust you. So you need to use that to leverage the trust in helping them to deal with the alcohol use disorder. There is a study from the VA [Veterans Affairs System] that show that from all VA patients with cirrhosis due to alcohol, only 1.4% of them are receiving treatment for alcohol use disorder. That’s bad!
This is not only for the hepatologist. There is one study in the UK showing how many times general practitioners or family doctors ask the patient in the last 5 years about alcohol consumption, it’s between 3 and 10%. So most of the patients are never asked about alcohol consumption. I think we are failing. And then from a hepatology perspective, we are not being trained to treat these patients. So we don't feel comfortable treating them. Indeed, we did a survey from the alcohol-related liver disease special interest group at the AASLD and we found that most of the hepatologists are not prescribing AUD medication, because they don't know how to use them and they don't feel comfortable. So we need to train them.
So couple of tips or clinical pearls. So number 1) is: the old one is disulfiram, but usually we are not going to use it, because it's contraindicated in cirrhosis. Probably you have also had couple of patients that were prescribed disulfiram, they were cirrhotics and they develop acute liver failure.
So tip number 1 is, don't use the disulfiram in patients with advanced liver disease. Then the other options, FDA-approved, we have 2. One is naltrexone, and the other one is acamprosate. Naltrexone is good, it's especially useful in patient that has opioid use disorder comorbidity. It's very useful for reducing cravings, achieving abstinence, but also to maintaining abstinence. And you have 2 ways to administer this. One is 50 milligrams oral daily and the other one is you can use it also 380 milligrams intramuscular once a month and you need to monitor. The only thing is to be careful with naltrexone in patient with advanced liver disease; for example, I don't use it in patients Child C, only Child A or low Child B. The other FDA-approved is acamprosate. This is also first line for the American Psychiatric Association, is not as good in achieving abstinence, but it's very good at maintaining abstinence.
The only problem is the dosing, because it's 3 times per day. So it's very difficult for the patients to be compliant with taking a medication 3 times per day and it is 666 milligrams. I don't know why this weird dosage, but that's a dosage for acamprosate. Easy to remember. Main issue with acamprosate is very often produces diarrhea, but most importantly it is metabolized and excreted by the kidney. So don't use it in patient with kidney dysfunction I will say less than 30 ml per minute. So those are the main two drugs that we have. Also, you can use topiramate; baclofen has a trial in Lancet in 2007, that show very good benefits. In my own experience, sometimes for patients, it's difficult to tolerate baclofen, because of fatigue or dizziness, sleepiness or dry mouth and they tend to stop the medication, but it's also useful.
And the one that I'm using every time more is gabapentin. It's a second line drug, but it's very useful when you have concurrent chronic pain for example. It's very safe to use. Usually the dose goes from 300 to 600 milligrams also 3 times per day. But usually I start 300 in the morning, 600 at night, so the patient doesn't feel sleepy during the day and you get the benefit of the medication and then you try to uptitrate it, it is very good also for cravings. So helping the patient to achieve abstinence.
And just one more comment— this is the pharmacological treatment, but to be honest, even more than the pharmacological treatment, the most effective interventions are on the side of behavioral therapy. This is basically cognitive behavioral therapy or motivation enhancement therapy.
For example, telling the patient, "So you have this gastrointestinal bleeding and you know that alcohol is producing that bleeding, you were very sick and you say that you don't want to die, but on the other hand you want to keep drinking. So how that makes you feel?" So basically showing that he's being ambivalent regarding something that he know that he needs to do, but the alcohol use is always not allowing him to do it.
And the other thing that we can do without being addiction specialists, is brief interventions. So we need to identify in which part of the cycle the patient is. So when they are in a precontemplative stage, probably they are not going to make any change, but you should ask, "You know that these elevation of your liver function tests are likely secondary to alcohol, how do you feel about that? Did you ever think about quit drinking or have someone ever tell you that you should stop drinking or that some of your problem may be related to alcohol?" So you are triggering the patient to get into and start thinking about quitting alcohol, making plans, making an action and then maintaining abstinence.
Dr Bonder
This is great information from Juan Pablo. I think the thing as you mentioned is, I think we lack or we are actually not doing a really good job about treating the alcoholic liver disorders in our liver clinics.
References:
https://pubmed.ncbi.nlm.nih.gov/36577100/
