Outcomes following liver transplantation for seronegative acute liver failure: Experience during a 12-year period with more than 100 patients

Abstract

Seronegative hepatitis is a common cause of acute liver failure (ALF) requiring liver transplantation. The primary aim of this study was to examine outcomes following transplantation in this group and to identify factors associated with early (<2 months) mortality. Patients studied were 110 consecutive cases of seronegative ALF transplanted at the Queen Elizabeth Hospital, Birmingham, between January 1992 and January 2004. Univariate analysis of 44 pretransplantation recipient, donor, and operative variables was performed initially to identify factors associated with early posttransplantation mortality. Variables identified as significant or approaching significance were analyzed using stepwise multiple logistic regression analysis. Survival following transplantation for seronegative hepatitis was 83%, 81%, and 73% at 2, 12, and 60 months, respectively. The majority (71%) of deaths occurred within the 1st 2 months and sepsis / multiorgan dysfunction was the most common cause of early death. Univariate analysis revealed 9 variables predicting early death. Subsequent multivariate analysis identified high donor body mass index (BMI; a possible surrogate marker for hepatic steatosis) as the most important predictor of early death (P ‫؍‬ .009; odds ratio, 1.2; 95% confidence interval, 1.0-1.3). Recipient age >50 (P ‫؍‬ .015; odds ratio, 4.2; 95% confidence interval, 1.3-14.1) and nonCaucasian recipient ethnicity (P ‫؍‬ .015; odds ratio, 4.9; 95% confidence interval, 1.2-19.2) were other variables associated with early death on multivariate analysis. This study specifically examined factors that determine the early outcome of transplanted seronegative ALF patients. In conclusion, we found that donor and recipient factors identify patients who have a high chance of early death after transplantation. (Liver Transpl 2005;11:27-34.) S eronegative (also known as non-A, non-B or non-A, non-B, non-C or non-A-E, or non-A-E) acute liver failure refers to an idiopathic hepatitis resulting in acute liver failure (ALF). Well recognized causes of ALF are excluded and serological markers for hepatitis A and B serology are negative. Seronegative ALF is an important cause of liver transplantation for ALF. In the United Kingdom, seronegative ALF is the most common indication for liver transplantation in ALF, due to a steady decline in the number of patients transplanted following paracetamol (acetaminophen) overdoses. 1 Despite the frequency of liver transplantation for seronegative ALF, the etiology of this condition remains unknown. A viral etiology has been assumed, however the discoveries of the hepatitis C and E viruses and the more recent discoveries of the hepatitis G and transfusion transmitted viruses have failed to account for the majority of patients with "non-A non-B" ALF. 2 -5 Other viruses (e.g., cytomegalovirus, herpes simplex virus, Epstein-Barr virus, parvovirus B19) are rare causes of ALF and are unlikely to be implicated in the majority of seronegative ALF cases.Although the etiology of seronegative ALF remains obs...

Diagnostic value and utility of the simplified International Autoimmune Hepatitis Group (IAIHG) criteria in acute and chronic liver disease†

“…17,18 Nonetheless, the presence of autoantibodies in patients with FHF remains of clinical interest, because many of these patients demonstrate features associated with autoimmunity such as female sex and the presence of human leukocyte antigen DR3 allotype. 19,20 Although there is indeed some overlap between our FHF cohort and that evaluated by Bernal et al, this equated to only nine cases or 13% of the total (W. Bernal, personal communication). Importantly, in our series, the simplified IAIHG criteria appear less sensitive than the "gold standard" of the 1999 criteria, in ascribing an overall (probable or definite) diagnosis of AIH (24% versus 40%).…”

Role of Liver Transplantation in Acute Liver Failure

“…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.…”

“…Graft steatosis, reduced graft size, and ABO-incompatible grafts have all been shown in multivariate analyses to lead to decreased patient and graft survival (Bernal et al, 1998;Bismuth et al, 1995). On multivariate analysis of data from the United Kingdom, the strongest predictor of early mortality in seronegative ALF was higher donor body mass index (BMI), which may be a marker for donor graft steatosis (Wigg et al, 2005). This group found an odds ratio (OR) of 1.2 for every unit increase in donor BMI relative to a normal donor (BMI 25 kg/m2).…”

“…Nearly one third of post-OLT deaths in this setting are from bacterial or fungal infections (Barshes et al, 2006). The majority of these deaths occur within the first 2-3 months following the transplantation, usually due to neurologic complications or sepsis (Bismuth et al, 1995;DeVictor et al, 1992;Hoofnagle et al, 1995;W Lee, 2003;O'Grady et al, 1988;Russo et al, 2004;Wigg et al, 2005). In the largest Canadian study (60 patients transplanted between 1994-2007); the wait-list mortality rate was 6% with mean waiting time of 2.7 days.…”

Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure

“…2 However, even in those patients that fulfill the required transplantation criteria, 3 more than 20% will die in 1 year after LT, and half of the patients will succumb in the next 10 years. 4 In this sense, interventions intended to restrict organ damage may stop or prevent the progression to liver failure, allowing the recovery of organ function, which may ultimately reduce the necessity of liver transplants.…”