We appreciate the comments of Drs. Fujiwara and Duclos-Vallée regarding our article, “Autoimmune acute liver failure: proposed clinical and histological criteria.”1 Dr. Fujiwara reports that approximately 50% of their patient population with acute liver failure (ALF) of unclear etiology was ultimately diagnosed with autoimmune ALF (AI-ALF) on the basis of liver histology and clinical parameters, similar to findings in our series (58%). The investigators advise caution in interpreting our work regarding the heterogeneity of histological findings in liver specimens from patients with ALF. Dr. Fujiwara presents data that demonstrate no difference between the time of onset of hepatitis to time of admission or liver biopsy between patients with autoimmune hepatitis presenting as acute-onset hepatitis, chronic hepatitis, or ALF, with a large degree of overlap, supporting the clinical heterogeneity of the disease.
Dr. Duclos-Vallée also raises concern about the fact that two-thirds of our liver specimens were sections from explants, whereas the remainder were transjugular needle biopsies. The lack of uniform biopsy technique, they suggest, may have influenced our results by increasing the probability of finding specific features of autoimmunity in the larger specimens obtained from an explant. We did not, however, find statistically significant differences in the prevalence of the four features of autoimmunity between specimens obtained from explanted livers and those obtained by transjugular biopsy.
Dr. Duclos-Vallée also requested further correlation between patients with centrilobular necrosis and their clinical phenotype and outcomes. Patients with central perivenulitis were characterized by a longer jaundice-to-encephalopathy interval, and a poorer prognosis (higher incidence of liver transplantation). These attributes can be ascribed to a more subacute liver injury in patients with AI-ALF compared to those with other indeterminate etiologies. Perhaps due to small numbers (13 of 72 patients; 18%), those patients with exclusive centrilobular necrosis were not clinically different than those without this feature.
Finally, Dr. Duclos-Vallée and colleagues raise concern about administering corticosteroids to patients with suspected AI-ALF, a major rationale for performing our study. We strongly agree with their contention that corticosteroid administration may introduce a significant risk of infection, and that no convincing evidence of efficacy exists.2 It should be noted, however, that no randomized, placebo-controlled studies have explored the efficacy of corticosteroids in patients with rigorously defined AI-ALF. In the absence of such information, we would reserve the administration of corticosteroids to patients with recent-onset AI-ALF and low-grade hepatic encephalopathy. Certainly, corticosteroids are unlikely to improve the transplant-free survival of a patient with AI-ALF late in the clinical course of the syndrome or with clinical attributes of poor outcome.