**2.1.3 Multiorgan failure**

The severity of multiorgan failure at the time of OLT is also a predictor of post-transplant survival. Decreased renal function is associated with worse spontaneous survival in non-APAP-induced liver injury. In a multivariate analysis of UNOS data (1988–2003), four risk factors predicting post-transplant survival were identified: pretransplant use of life support, recipient age >50 years, recipient body mass index ≥30 kg/m2, and serum creatinine >2 mg/dL. If an individual had all of these risk factors, the 5-year post-transplant survival was only 44–47%. Whereas, if none of these features were present, the 5-year post-transplant survival was 82–83% (Barshes et al., 2006).

#### **2.1.4 Hepatic encephalopathy**

Mortality rates correlate with the severity of hepatic encephalopathy (HE), reported at 30% for grade 2, 45-50% for grade 3 and 80-90% for grade 4 HE (Daas et al., 1995; Hoofnagle et al., 1995). A multicenter US series, in which 39% participants had APAP hepatotoxicity, showed a 52% 3-week transplant-free survival in patients with grade 1-2 encephalopathy, but only 33% with grade 3-4 HE survived without transplant (Ostopowicz et al., 2002). Conversely, 85% of patients with non-APAP ALF without HE experienced spontaneous recovery (Elinav et al., 2005). Paradoxically, those with more rapid development of HE (i.e., APAP-induced) appear to have a better outcome than those with a longer interval between the development of symptoms and HE (i.e., DILI) (Bernuau et al., 1986a; O'Grady et al., 1989; O'Grady et al., 1993). A distinctive feature ALF-induced HE is the development of cerebral edema, the complete pathophysiology of which remains poorly understood. Cerebral edema develops in nearly 80% of patients who progress to grade 4 HE, leading to intracranial hypertension with subsequent ischemic brain damage or brainstem herniation, accounting for up to 50% of ALF mortality (Clemmensen et al., 1999; Jalan et al., 2003). Intracranial pressure (ICP) monitoring is more often utilized in patients who are deemed candidates for OLT, and ICP may be more aggressively managed in these cases. ICP monitors may also be of significant value during the transplant operation, when fluctuations in ICP are common (Philips et al., 1998). ICP monitoring is associated with up to a 10% risk of intracranial hemorrhage, and it has not been shown to change 30 day post-OLT survival (Gasco et al., 2010). Thus, the indication and timing of use of ICP monitoring devices remain controversial (Vaquero et al., 2005). Intracranial hypertension may persist during the first 10-12 hours following liver transplantation, thus ICP monitoring, if utilized, should continue during and after surgery (Bismuth et al., 1995; Jalan et al., 2003).

#### **2.1.5 Infection**

ALF-induced hemodynamic changes can be difficult to distinguish from infection and sepsis and are complicated by the fact that ALF patients may not develop leukocytosis or fever. Bacterial infection is the cause of death in up to 37%, with the most common sites of infection being pulmonary (47%), blood (26%), and urine (23%) (Bernal et al., 2003). Fungal infections, especially Candida sp., are seen in up to 32%, occur later in the course of disease, particularly after use of antibiotics or in the setting of renal dysfunction, and are often associated with bacterial infection (Rolando et al., 1991; Vaquero et al., 2003). Active infection is a contraindication to OLT. The empiric use of antibiotics is controversial. Prophylactic antibiotics decrease the number of infections, but do not change overall outcome (Rolando et al., 1990; Rolando et al., 1996; Stravitz et al., 2007). Some centers administer anti-infectives (antibacterial and antifungal) to patients who have significant isolates on surveillance cultures, have progression to Stage 3-4 HE, have refractory hypotension, or have clinical evidence of systemic inflammatory response syndrome (Stravitz et al., 2007). Periodic surveillance cultures and frequent chest radiographs can help detect bacterial and fungal infections early.

#### **2.1.6 Psychosocial predictors**

The burden of medical follow-up after OLT can be substantial, and quality of life can be significantly affected. Therefore, the decision to offer OLT to an individual patient also needs to consider more controversial issues such as psychosocial factors (i.e., adequacy of social support and substance and/or alcohol abuse), and adequacy of medical insurance coverage. For example, in one study, four patients (12%) died in the post-transplant followup period from deliberate self-harm (Bernal et al., 1998).
