Physicians should avoid routinely testing patients with acute liver failure for Wilson’s disease unless there is “high clinical suspicion” for the disorder, according to a new guideline from the American Gastroenterological Association Institute.
Wilson’s disease so rarely accompanies acute liver failure that a positive test will have low predictive value, Steven L. Flamm, MD , of Northwestern University, Chicago, and his associates wrote in the February issue of Gastroenterology ( doi: 10.1053/j.gastro.2016.12.026 ). Diagnosing Wilson’s disease also is unlikely to change treatment “because liver transplantation is the ultimate outcome,” they emphasize.
This is 1 of 11 recommendations in the guideline, which attempts to reconcile “many areas of controversy” in diagnosing, predicting outcomes, and managing acute liver failure (ALF), the authors write. Given the relative lack of randomized controlled trials, they make only one strong recommendation – to use N-acetyl cysteine in patients with acetaminophen-associated ALF. This guidance is based on three trials that yielded a “marginally significant mortality benefit with N-acetyl cysteine in conjunction with relatively minor toxicity,” they state.
The guideline grades seven recommendations as “conditional” based on “very-low” quality evidence. These include the statement on Wilson’s disease testing, plus suggestions to test and treat patients with ALF for herpes simplex virus (HSV) infection, to test pregnant patients for hepatitis E virus infection, and to perform autoantibody testing for autoimmune hepatitis. Case series report only about a 1% prevalence of HSV infection in ALF, and there is little information on diagnostic accuracy or treatment in this setting, the guidelines state. Although acyclovir is relatively safe and inexpensive, data on efficacy is limited to “a suggestion on a case-report level that patients with acute hepatitis secondary to HSV do better with treatment than without.”
The guideline also conditionally recommends against routine testing for varicella zoster virus infection and routine liver biopsy in ALF. The authors note only about 10 case reports of varicella zoster–associated ALF and few data on how liver biopsy results in ALF alter treatment plan, outcome, or the choice to seek liver transplantation. The experts do recommend prognostic scoring with Model for End-Stage Liver Disease , which pooled analyses have found to be more sensitive than King’s College Criteria , they wrote.
The guideline conditionally recommends against empirically treating elevated intracranial pressure in ALF, on the basis of five randomized trials that found no overall mortality benefit of moderate hypothermia, hypertonic saline, L-ornithine, L-aspartate, intravenous mannitol, or hyperventilation.
The experts cite insufficient evidence to recommend using N-acetyl cysteine in patients whose ALF is not associated with acetaminophen exposure. Likewise, they find inadequate data to make any recommendation about using extracorporeal liver support systems outside of the setting of clinical trials. Although such systems can “potentially” buy time for patients to either spontaneously recover without transplant or survive longer on the transplantation list, three systematic reviews found “no clear effect on mortality,” and randomized trials reported either null results or a “marginally significant survival benefit” in the face of steep costs and potentially significant toxicities, the authors emphasize.
None of the experts had relevant financial disclosures.