# Presentation: 499467

## Acute Liver Failure in the USA: Results of the US ALF Study Group

**William M. Lee, MD**
**Meredith Mosle Distinguished Professor in Liver Disease**
**University of Texas Southwestern Medical Center Dallas, TX**
**www3.utsouthwestern.edu/liver**

## Slide 2

## Acute Liver Failure (ALF): Definition

**Altered mentation**
**Coagulopathy (INR **_**>**_**1.5)**
**Acute illness (< 26 wks)**
**No cirrhosis**
**Variety of etiologies**

## Acute Liver Failure (ALF) Background

**Orphan disease: ca. 2,000 cases/yr**
**No one center can study the condition**
**No viable treatment for all patients**
**High mortality/morbidity**
**Transplantation has helped--how much?**

## Acute Liver Failure Study GroupA consortium to study a rare disease

**14 academic med centers initially in 1998, now 25**
**Also 23 pediatric sites, since 2000**
**Detailed prospective data and serum samples**
**N-acetylcysteine trial for non-ACM ALF**
**Numerous ancillary studies in progress**

**Funded by NIH R03, FDA Orphan Grant, NIH R01 (‘00-’05)**

## Case Report Form

**Case Report Form**

## ALF etiologies: prior US studies (%)

- <date/time>

**ALF etiologies: prior US studies (%)**

**** ‘Infectious and serum hepatitis’***

**Medicine 1969;48:151-72, Dig Dis Sci 1991;36:1223-8, Mayo Clin Proc 1985;60:289-92, Liver Transpl Surg 1999;5:29-34, and Liver Transpl 2000;6:163-9.**

## Slide 8

## Comparison Between Retrospective Study (1994-96; n = 295) and Current Study (1998-2001; n = 308)

**   **

**+ NS**

## Comparison of Different ALF Etiology Groups

**Comparison of Different ALF Etiology Groups**
**Variable****	****       Acetaminophen   Drug Induced  Indeterminate   All Others     p**
**	****              ****(n = 120)             (n = 40)****	****          (n = 53)         (n = 95)****      ****value**
**Sex (%F)****	****     79   ****	****                 73                      60****	****         72            ****NS**
**Age (yrs)****	****     36                      41                      38                    43****	****         ****0.02**
**Jaundice (days)****	****       1****	****	****  12****	****              12****	****           4        ****<0.001****  **
**Coma III/IV (%)         50                      43                      47                    47            ****NS**
**ALT****	****                4310                    574                    947               1060****	****      ****<0.001**
**Bilirubin****	****    4.3****	****              20.2                   24.5                12.6        ****<0.001**
**Tx (%)                         6                      53                      51                   36****        ****<0.001**
**Spont surv (%)        68                      25                      17                    33        ****<0.001**
**Overall surv (%)      73                      70                      64                    61****	****           ****NS**

## ALF etiologies outside the US (%)

- <date/time>

**ALF etiologies outside the US (%)**

## Presentations of acetaminophen poisoningAccidental vs. suicidal cases

**Suicidal: single time point ingestion with suicidal intent**
**Accidental: multiple time points, cause for pain, suicidal intent denied**

## Acetaminophen Toxicity in an Urban County Hospital

- <date/time>

**Acetaminophen Toxicity in an Urban County Hospital**

- 		 	  **Accidental****	****	****Suicidal         p-value**
**	****	****	****      ****(n=21)****	****	****  (n=50)**
**Present >24h          64%****	****	****     14%   ****	****    0.001**
**EtOH****	****abuse****	****	****63%****	****	****      25%****	****    0.009**
**ACM level mg/L****	****  7****	****	****     126 ****	****  <0.001**
**ALT (IU/L)             7430             ****	****    1501****	****    0.001**
**ALT ≥1000 IU/L****	****62%****	****	****     20%****	****  <0.002**
**Rec’d NAC****	****	****76%****	****	****     80%****	****     0.76**
**Hepatic coma         33%****	****    ****	****       6%****	****  <0.001**
**Death****	****	****	****19%****	****	****       2%****	****     0.04**

**The Parkland Study: Schiødt et al., NEJM 1997;337:1112-7**
**All patients admitted with *****potential *****ACM injury**

## Acetaminophen Toxicity Leading to ALF

- <date/time>

**Acetaminophen Toxicity Leading to ALF**

**Female 79%, median age 36 (19-63)**
**Alcohol use: 57%; alcohol abuse: 19%**
**Narcotic combinations: 38%**
**Dose ≥ 4 gm/day: 69%; ≥ 10 gm/day: 32%**
**ACM level detectable: 82%; > 50 mg/L: 42%**
**ALT > 7,000 IU/L: 51%; ALT > 3,500 IU/L: 92%**
**Cr ≥ 2.0 52%; pH ≤ 7.3  17%**

**Results in 108 patients, 12 deleted**

## Suicidal vs. Accidental ACM ALF Cases

- 			  **Accidental****	****Suicidal      p-value**
**	****	****	****      ****(n=59)****	****	****  (n=44)**
**Age****	****	****	****39****	****	****     33   ****	****    0.011**
**Tot ACM (g)****	****20****	****	****     29   ****	****      NS**
**Antidepress’t****	****36%****	****	****     34%****	****      NS**
**EtOH****	****	****	****55%****	****	****     61%****	****      NS**
**Double use****	****24%****	****	****      5%****	****    0.02**
**Narcotic/acet****	****54%****	****	****     14%          0.001**
**ALT (IU/L)         3,616****	****             5,929****	****  <0.001**
**Creatinine****	****	****2.5****	****	****     1.3****	****    0.008**
**Survival****	****	****71%****	****	****     75%****	****       NS**

## Slide 16

## Outcomes for Acute Liver Failure patients 

- <date/time>

**Acetamin.: 30**
**Indetermin: 20**
**Drug-induced: 9**
**Shock liver: 7**
**Hepatitis B: 4**
**Malignancy: 4**
**Pregnancy:  3**
**Autoimm. hep.: 3**
**Wilson: 2**
**Hepatitis A: 2**
**Budd-Chiari: 1**
**Others: 2**

**Outcomes for Acute Liver Failure patients**** **

## Summary: Acetaminophen-related ALFConstitutes 1/3 of all US ALF deaths

**The most common cause for  ALF and a (?growing) problem in US (~150-800/year in US)**
**Alcohol relationship less apparent**
**Accidental and suicidal cases similar clinically**
**Relatively low mortality cf. other ALF causes**
**Role of anti-depressants 35%, narcotics 38% and repeated daily dosing needs further attention**
**Pediatric cases also of concern (~20%)**