A Case of Pediatric Alcohol-Associated Hepatitis Evaluated for Liver Transplant Listing : JPGN Reports

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Case Report: Hepatology

A Case of Pediatric Alcohol-Associated Hepatitis Evaluated for Liver Transplant Listing

Schenker, Rachel B. MD*; Dybbro, Eric MD; Kim, Brian MD; Patel, Shreena MD*; Yanni, George MD*

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JPGN Reports 4(2):p e311, May 2023. | DOI: 10.1097/PG9.0000000000000311
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Abstract

INTRODUCTION

Alcohol-associated hepatitis (AH) refers to liver injury from alcoholic intake that usually occurs after prolonged alcohol abuse (1). Frequent, heavy alcohol consumption causes hepatic inflammation, fibrosis, and cirrhosis. Some patients develop severe AH, which carries high short-term mortality and is the second most common reason for adult liver transplants (LTs) (2). Severe AH involves acute onset jaundice, elevated aspartate aminotransferase, aspartate aminotransferase/alanine transferase>2, international normalized ratio (INR), and bilirubin >5 mg/dL (1).

It takes an average of 20 years of alcohol usage to develop AH and the mean age of presentation is 53 years (2). AH has been reported after excessive drinking for 3 months and in individuals as young as 20 years, but never in teenagers (3). We report one of the first cases of a teenager with severe AH evaluated for LT listing.

CASE REPORT

Our patient was a 15-year-old male with generalized anxiety disorder (GAD), depression, class 3 obesity, and type 2 diabetes mellitus who presented with epistaxis and 1 month of jaundice after 3 years of alcohol abuse. Patient’s alcohol intake began as occasional beers at age 12 years, progressed to daily beers at 13 years, and deteriorated to daily vodka pints at 14 years after his father’s death. Table 1 contains medical and family history. The admission examination was notable for normal mental status, jaundice, scleral icterus, and hepatomegaly. Table 2 shows labs on presentation. Work-up for infectious, autoimmune, and genetic/metabolic causes of liver injury was unrevealing. Abdominal ultrasound demonstrated marked hepatomegaly, mild splenomegaly, and diffusely abnormal vascular flow. Given the patient’s alcohol-use history, elevated serum ethanol, and typical clinical presentation, he was diagnosed with acute liver failure from severe AH. Initial management included nothing by mouth, intravenous (IV) fluids, broad-spectrum antibiotics until 48 hours of negative blood cultures, frequent neurologic checks, treating agitation and hallucinations from alcohol withdrawal (AW) with IV lorazepam 4 mg every 4 hours for 2 days (and then tapering off), and 3 days subcutaneous vitamin K 10 mg. We also consulted adult hepatology, given the rarity of pediatric severe AH, who recommended daily steroids based on an initial Model For End Stage Liver Disease of 40 and Maddrey Discrimination Function (DF) of 286. As the patient was nothing by mouth, we gave IV methylprednisolone 40 mg daily. No insulin was required for hyperglycemia. The patient was urgently evaluated for LT on day 3 of admission, which involved extensive discussion with the LT team (pediatric hepatologists, social workers, and surgeons), adult hepatologists, psychiatry, and psychology. The patient was recommended for LT followed by alcohol rehabilitation, but was ultimately not listed as insurance required 6-month abstinence.

TABLE 1. - Patient’s lab values at presentation, 5 days after presentation, and 4 months after presentation
Lab Normal values Value at presentation Value at 5 days after presentation Value at 4 months after presentation
WBC (k/µL) 3.84–9.84 39 34 7.34
Hgb (g/dL) 11–14.5 10.7 8.9 9.8
Plt (k/µL) 9.6–11.8 346 344 210
Na (mmol/L) 135–145 138 137 140
K (mmol/L) 3.6–5 3.8 3.8 4.3
Cl (mmol/L) 98–107 105 108 110
CO2 (mmol/L) 22–30 20 16 19
BUN (mg/dL) 4–21 12 22 16
Creatinine (mg/dL) 0.7–1.5 0.76 0.85 0.77
Glucose (mg/dL) 60–115 159 127 132
HgbA1c (%) 3–6 5.6
Alk Phos (U/L) 30–250 262 255 97
AST (units/liter) 15–46 296 175 38
ALT (units/liter) <42 45 51 24
GGT (units/liter) 15–85 476 461 107
Albumin (g/dL) 3.2–4.5 1.8 3 4.2
Total bilirubin (mg/dL) 0.1–1.3 26.1 39.26 0.97
Ammonia (µMOL/L) 10–50 86 Not available Not available
INR <4 9.26 2.5 1.5
PT (sec) 8.8–12.5 72.2 25.8 16.9
Serum ethanol level (mg/dL) <10 218 <10
Urine toxicology screen Negative Negative
Acetaminophen 10–29 <2
Blood culture No growth No growth
A1AT level (mg/dL) 76–190 281
Ceruloplasmin (mg/dL) 24–71 40
Copper (mcg/dL) 75–187 133
Smooth muscle antibody (U) <20 <20
ANA IFA Negative Negative
CMV IgM (U/mL) <0.6 <0.6
EBV IgM Negative Negative
HepatitisA IgM Non-reactive Non-reactive
HepatitisB sAg Negative Negative
HepatitisC Ab Negative Negative
HIV Ab Non-reactive Non-reactive
RPR Non-reactive Non-reactive
ANA = Antinuclear antibodies; ALT = alanine transferase; AST = aspartate aminotransferase; BUN = Blood Urea Nitrogen; CMV = Cytomegalovirus; EBV = Epstein-Barr virus; GGT = Gamma-Glutamyl Transpeptidase; HIV = Human immunodeficiency virus; Hgb = Hemoglobin; Plt = Platelets; PT = Prothrombin time; RPR = Rapid plasma reagin; WBC = White Blood Cell Count.

TABLE 2. - Medical and family history
Medical history
Diagnosis Age of diagnosis Treatment at presentation
Generalized anxiety disorder Since at least age 9 years Therapy
Depression Since at least age 9 years Therapy
Type 2 diabetes mellitus Diagnosed at age 12 years based on HgbA1C of 7.4. Prescribed metformin 1000 mg BID, but stopped taking at least 1 year before presentation.
Class 3 obesity BMI>41 since at least age 12 years when patient was first seen at our hospital Given diet and exercise recommendations by endocrinology, but did not follow.
Family history
Family member Diagnosis
Dad Substance use disorder
Chronic pancreatitis
Type 2 diabetes mellitus
Died from complications of COVID-19
Mom Type 2 diabetes mellitus
No known family history of liver disease in the extended family.

While the patient’s severe AH persisted, his INR decreased to 2.5 after day 5 of admission, so insurance was not appealed. Bilirubin rose and steroids were discontinued due to suspicion of ineffectiveness and concern for exacerbating underlying metabolic syndrome. After 3 weeks of hospitalization, INR stabilized at 2. The patient was eventually discharged with close LT follow-up and routine serum ethanol and liver function checks. Four months postdischarge, he was sober in alcohol rehabilitation. As Table 2 shows, his liver function normalized.

DISCUSSION

Despite our patient’s severe presentation, he recovered without LT. Pediatric AH is challenging due to the inexperience of pediatric providers with extensive alcohol abuse and the inability to accurately extrapolate adult prognosticators. We discuss five considerations for pediatric AH management: (1) alcohol withdrawal, (2) steroid utilization, (3) mental health support, (4) LT listing, and (5) adult hepatology collaboration.

Alcohol Withdrawal

Hospitalized adolescents with heavy, prolonged alcohol usage require observation for AW using a validated assessment (4). AW can cause seizures, hallucinations, hypertension, and death. Benzodiazepines are the first-line treatment for AW despite making it difficult to assess encephalopathy. Lorazepam, a short-acting benzodiazepine, is recommended for liver dysfunction (5).

Steroid Utilization

Steroids improve 28-day survival in adults with severe AH but increase the risk of gastrointestinal bleeding and infections (6,7). The American Association for the Study of Liver Diseases has a pathway that uses DF (which involves PT and bilirubin) to determine who is a candidate for steroids and the Lille Model (LM) (which uses age, creatinine, albumin, PT, admission bilirubin, and bilirubin on day 7 of steroids) to assess steroid effectiveness after 7 days (6–8). While DF and LM utilize adult data, in the absence of pediatric studies, we gave our patient steroids for elevated DF. As LM heavily weighs age, it will usually recommend continuing steroids in pediatrics, which may not make sense. We left the American Association for the Study of Liver Diseases pathway as we felt steroids were not helping and could increase the risk of decompensation from comorbidities.

Mental Health Support

Depression, GAD, bipolar disorder, and conduct disorder are frequently comorbid with the alcohol-use disorder in adolescents (9). As underlying psychiatric disorders may be masked by alcohol before admission and benzodiazepines during AW treatment, providing interventions and pharmacologic options to aid with sobriety is essential.

LT Listing

AH is a leading cause of LT in adults (8). In individuals who abstain from alcohol after LT, prognosis is excellent. Historically, LT centers required 6-months of alcohol abstinence before LT listing to ensure patients remained sober and allow for liver recovery. This 6-month sobriety period, which United Network for Organ Sharing does not require, is now controversial as LTs can improve survival in individuals unresponsive to medical therapies (8). Our adult hepatology colleagues have a list of requirements patients with AH must meet to be considered for LT (presented in Table 3). While our patient did not satisfy all requirements, we still recommended LT given his severe presentation and, ultimately, the fact he was a child. He was not listed as insurance required 6-months sobriety before authorization and, as his liver recovered, appeal was not needed. Adult hepatologists frequently appeal LT denials, though are often unsuccessful.

TABLE 3. - Adult hepatology requirements before recommendation for liver transplant in alcohol-associated hepatitis
Adult hepatology requirements Did our patient meet the requirement?
The patient should be medically suitable to undergo organ liver transplant. Yes
The patient must have been functional in employment, family, social, and/or community activities with no evidence of impairment due to alcohol. No – patient ran away from home several weeks before admission and was not regularly attending school.
The patient must have adequate social support and a proven plan of care as determined by the medical social worker. Yes – patient’s mother felt to be adequate social support.
There should be no alcohol-related convictions within the past two years. Yes – no alcohol-related convictions.
There should be no evidence that the patient had any prior knowledge of organ damage due to alcohol, including, but not exclusive to, liver disease, pancreatitis, and heart disease. Yes – no prior known history of organ damage.
There should be no unmanageable underlying psychiatric disease as determined by a psychiatrist. Yes - patient had depression and GAD but felt to be manageable by psychiatry and psychology.
The patient or their primary support person named in the plan of care must sign the Abdominal Transplant Center – Liver Transplant Candidacy Agreement agreeing to participate in a substance abuse rehabilitation program that must be acceptable to the transplant team. Yes – patient willing to go to rehabilitation.
Pa Patient or their primary support person agrees to random alcohol and/or drug testing. Yes – patient willing to do random alcohol and/or drug testing.
Th There should be no evidence of poly-substance abuse. Yes – patient previously tried marijuana but was not using it before admission.

Adult Hepatology Collaboration

Adult hepatologists provided us with a more thorough understanding of severe AH throughout the hospitalization.

CONCLUSION

While severe pediatric AH is previously unheard of because parental supervision, minimal access, and limited finances reduce minor alcohol consumption, binge drinking in adolescents increased during COVID-19 (10). It is possible we may see more severe pediatric AH. We hope our experience aids pediatric AH care while we await further research.

ACKNOWLEDGMENT

The patient provided assent and his mother provided consent for the publication of this case report.

REFERENCES

1. Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med. 2009;360:2758–2769.
2. Hosseini N, Shor J, Szabo G. Alcoholic hepatitis: a review. Alcohol Alcohol. 2019;54:408–416.
3. Doycheva I, Watt KD, Rifai G, et al. Increasing burden of chronic liver disease among adolescents and young adults in the USA: a silent epidemic. Dig Dis Sci. 2017;62:1373–1380.
4. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management. J Addict Med. 2020;14(3S Suppl 1):1–72.
5. Sachdeva A, Choudhary M, Chandra M. Alcohol withdrawal syndrome: benzodiazepines and beyond. J Clin Diagn Res. 2015;9:VE01–VE07.
6. Mathurin P, O’Grady J, Carithers RL, et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut. 2011;60:255–260.
7. Louvet A, Naveau S, Abdelnour M, et al. The Lille model: a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology. 2007;45:1348–1354.
8. Crabb DW, Im GY, Szabo G, et al. Diagnosis and treatment of alcohol-associated liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2020;71:306–333.
9. Deas D, Brown ES. Adolescent substance abuse and psychiatric comorbidities. J Clin Psychiatry. 2006;67:e02.
10. Leventhal AM, Cho J, Ray LA, et al. Alcohol use trajectories among U.S. adults during the first 42 weeks of the COVID-19 pandemic. Alcohol Clin Exp Res. 2022;46:1062–1072.
Keywords:

alcoholic hepatitis; alcohol-associated hepatitis; pediatrics; liver transplant; obesity; depression; anxiety; adolescent; alcohol abuse; COVID; teenager

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.