**2.1.2 Clinical and laboratory criteria**

252 Liver Transplantation – Basic Issues

et al., 2009). Thus, it is important to identify and delist patients who are too ill to benefit

It is crucial that reliable predictive models of survival and the need for OLT be developed. Successfully predicting outcome would allow more judicious use of scarce organs and spare those who will ultimately recover the need for lifelong immunosuppression. There are at present no standardized criteria to predict who should be listed for OLT. Several prognostic models have been developed to help identify appropriate patients for transplantation. Unfortunately, these prognostic models have limitations, and their predictive accuracy

Many factors may help determine which ALF patients are more likely to die; however, they are generally unreliable in predicting who will ultimately survive or require transplantation.

The etiology of ALF is one of the most important predictors of spontaneous outcome (Ostapowicz et al., 2002). The lowest mortality is seen with ALF secondary to acetaminophen (N-acetyl-p-aminophenol; APAP) toxicity (~30%), hepatitis A virus infection (~50%), shock liver, and pregnancy-related ALF (Larson et al., 2005; Ostapowicz et al., 2002; Schiodt et al., 2003). In contrast, the non-transplant mortality for the remainder of causes, including ALF secondary to drug-induced liver injury, remains abysmal (80% to 100%) (O'Grady et al., 1988; Ostapowicz et al., 2002). Therefore, understanding which causes of ALF predominate in a particular region can help lead to the early evaluation and listing of

ALF secondary to drug-induced liver injury (DILI) predominates in Europe and North America, with a high prevalence of APAP-induced ALF in the US and United Kingdom (Hoofnagle et al., 1995; Larson et al., 2005; Ostapowicz et al., 2002; Schiodt et al., 1999; Williams, 1996). Viral hepatitis predominates in developing countries. The US ALF study group looked at 1198 patients with ALF over an 11 year period and a total of 133 (11.1%) subjects were deemed by expert opinion to have DILI ALF. Transplant-free (3-week) survival was poor (27.1%), but with successful transplantation in 42.1%, overall survival was 66.2%. Transplant-free survival in DILI ALF is determined by the degree of liver dysfunction, specifically baseline levels of bilirubin, prothrombin time/international normalized ratio (PT/INR), and Model for End-Stage Liver Disease (MELD) scores (Reuben

In the United Kingdom, the number of patients with APAP ALF has declined due to legislative changes in drug packaging, leading to an increase in the relative number of cryptogenic or seronegative cases (16% of all ALF). The majority (88%) of these latter ALF patients met King's College transplant criteria (see below), reflecting the low likelihood of spontaneous recovery (Wigg et al., 2005). A recent study from the UK suggested that OLT is a more favorable approach to managing patients with non-APAP induced ALF compared to patients with APAP induced ALF. This was predominantly due to the frequent psychosocial

contraindications in patients with APAP induced ALF (Simpson et al., 2009).

from OLT.

varies (Blei, 2005; Anand et al., 1997).

**2.1 Predictors of prognosis** 

these latter cases for OLT.

**2.1.1 Etiology** 

et al., 2010).

The clinical criteria most commonly used to exclude a patient from OLT vary by transplant center but may include age older than 70 years, the presence of certain malignancies outside of the liver, severe cardiac, lung, or multiple organ failure, severe infection, uncontrolled septic shock and brain death (Table 1) (Samuel & Bismuth, 2001). Patients with grade 3-4 encephalopathy and fixed pupils, cerebral perfusion pressure <40 mmHg, sustained elevation in intracranial pressure >50 mmHg, or seizures are at high risk for postoperative neurologic complications or brain death. They are usually not deemed candidates for OLT (Bismuth et al., 1995). As long as the pupils remain active and the patient does not have posturing movements, liver transplantation can still be considered (Daas et al., 1995). The degree of serum aminotransferase elevation and the rate of its recovery do not predict prognosis. In fact, improvement of aminotransferase levels in conjunction with worsening bilirubin, hepatic encephalopathy, and coagulopathy (INR) signals complete liver failure and is a particularly ominous sign.

#### **Common Exclusion Criteria**

Age >70 years old (relative) Certain malignancies outside of the liver Severe cardiac, lung, or multiple organ failure Severe infection Uncontrolled septic shock Brain death **UNOS Status 1a Listing Criteria for ALF**  Age ≥ 18 years Life expectancy without a liver transplant of <7 days Onset of encephalopathy within 8 weeks of the first symptoms of liver disease Absence of pre-existing liver disease (except for the diagnosis of fulminant Wilson's disease) Residence in the intensive care unit At least one of the following: ventilator dependence, renal replacement therapy, or INR

>2.0

Table 1. Exclusion and Listing Criteria for Transplantation for Acute Liver Failure. INRinternational normalized ratio
