Have you wondered what the role of antibiotics is in alcoholic hepatitis?
Hi I am Dr K from iMedicalSchool and even if you haven’t, stick around and I will
guarantee you will learn something.
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Alcoholic hepatitis is an inflammation of the liver caused by excessive and typically
long term alcohol use.
In severe cases it can require hospitalization and even lead to severe organ damage and death.
Currently, avoiding alcohol is the only intervention that improves long term survival.
To determine the severity of alcoholic hepatitis we calculate the Maddrey Discriminant Function.
You take the patient’s prothrombin time minus the normal prothrombin time.
Multiply this by 4.6 and add the total bilirubin in mg per deciliter to find the patient’s
maddrey discriminant function.
This formula can be found on MDcalc and I included a link in the description of the
video.
A maddrey discriminant function score of greater than 32 indicates severe alcoholic hepatitis.
Previous studies have shown some survival benefit in using steroids, like prednisolone,
in acute severe alcoholic hepatitis.
This is why we use steroids to this day in the management of severe alcoholic hepatitis.
The reason we use prednisolone, as the steroid of choice, is that prednisone is a prodrug
that needs to be converted to prednisolone by the liver.
Prior studies have shown a lower level of steroid in the blood when prednisone is used
versus prednisolone in alcoholic hepatitis, likely as a result of liver inflammation leading
to poor liver function.
Unfortunately more recent data has placed the benefit of steroids in improving long
term survival into doubt.
The STOPAH trial also known as the Steroids or Pentoxifylline for alcoholic hepatitis
trial looked at the benefit of steroids for alcoholic hepatitis.
It was a multicenter randomized trial of over 1000 patients.
Pentoxyfilline did not improve survival in patients with alcoholic hepatitis.
When comparing patients who received prednisolone versus those that did not, a trend toward
reduced 28-day mortality in the steroid group was seen but did not reach statistical significance.
In addition the survival benefit was no longer seen at 90 days.
Interestingly the rate of infection in the steroid group was twice as high as the placebo
group but mortality rates remained the same.
Though the standard of care is to still use steroids, we do calculate a Lillie score to
see if an individual has responded to steroids and whether continuation would be beneficial
versus those who do not have improvement and where continuing steroids would have no benefit
do to the lack of benefit in their predicted survival.
A Lilie score greater than 0.45 indicates a poor long term survival.
In addition it indicates a lack of response to steroids and the steroids should be discontinued
to prevent potential complications like infection.
The Lillie score is typically calculated at day 7 of admission but recent data has shown
that calculating it at day 4 can help identify steroid non-responders earlier.
Another topic of controversy is the use of antibiotics in alcoholic hepatitis.
When a patient presents with alcoholic hepatitis they commonly present with jaundice, fever,
abdominal pain, weakness, and confusion..
They may have a leukocytosis or elevated white blood cell count.
When someone has an elevated white blood cell count we should think of infection.
In alcoholic hepatitis, liver injury can also lead to the elevation in white blood cells.
As a result, it is not uncommon for patients with alcoholic hepatitis to be placed on antibiotics
due to concern that there may be an underlying infection.
Now, animal models have shown that antibiotics can help alcohol induced liver injury, but
does this translate to humans?
Do antibiotics help in alcoholic hepatitis?
Well those are the questions the JAMA article titled “Effect of Prophylactic Antibiotics
on Mortality in Severe Alcoholic Related Hepatitis” aims to answer.
This article reviews the AntibioCor trial.
This is a two group randomized placebo controlled trial conducted at 25 centers across France
and Belgium.
Patients were 18 to 75 years old and were eligible if they were heavy drinkers who were
clinically diagnosed with alcoholic hepatitis, and had a Maddrey score of 32 or higher.
All the patients received 40 mg per day of prednisolone for 30 days.
The participants were randomized to either amoxicillin-clavulanate 1 g/125 mg three times
daily or to placebo for 30 days.
The main outcome of the study was to evaluate 60 day all cause mortality . The result of
this study showed that those who received antibiotics did not have a significant difference
in 60 day all cause mortality compared to those who received placebo.
What is interesting is that there was a significant difference in the rates of infection between
the two groups.
In the antibiotic group infections were seen in 17.3% versus 41.5% in those receiving placebo;
however, the difference in rates of infection did not translate to a difference in 60 day
all cause mortality.
In addition the 7 day lillie score and the MELD score at 60 days were also not different
between these two groups.
As a result, we now know that prophylactic antibiotics do not improve survival in severe
alcoholic hepatitis even though it does decrease the rate of infection.
It is important to understand there are limitations to this study.
First the population studied were from centers in France and Belgium.
Extrapolating this information to the United States or other countries based on cultural
and ethnic differences would be premature.
Second, typically we assess a patient with the Lillie score 7 days after being on prednisolone
to determine if the steroids should be continued.
In this study instructions were not provided whether to discontinue steroids or not, so
this could confound the results.
Despite these limitations I think this study highlights three important points.
First alcohol cessation is still the most important factor in improving long term survival
for severe alcoholic hepatitis.
Resources should be focused on providing support and counseling patients on how to abstain
from alcohol and addressing underlying mental illness that can contribute to addiction.
Second, antibiotics should not be considered a mainstay of treatment and should be weaned
off if no active infection has been identified.
Third, despite this information we should still treat with antibiotics when there is
concern for infection as alcoholic hepatitis does increase the chance of infections and
we know that infections in this population contributes to a higher chance of morbidity
and mortality.
If you have questions place them down below and if you learned something please like,
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This is Dr. K and I will see you next time.