Liver transplantation in patients with fulminant hepatitis

Initial recognition and management is key to prognosis

In patients with clinical or laboratory evidence of acute hepatitis, initial evaluation should begin with a thorough history to elucidate any potentially contributing factors followed by careful physical examination to identify subtle alterations in mentation and to rule out evidence of stigmata of chronic liver disease. Prothrombin time (PT) and INR should be monitored and if abnormal (PT prolongation of ≥ 4–6 seconds, INR ≥ 1.5) with the presence of encephalopathy, hospitalization is mandatory for frequent clinical and laboratory monitoring, preferably within an intensive care unit (ICU; see Chapters 26 and 77 ).

Prompt referral to a specialized liver unit and rapid medical intervention with specific therapies in certain etiologies can prevent progression and improve survival. Immediate contact with a transplant center should occur once altered mental status develops because clinical deterioration may be very rapid. Under ideal circumstances, transfer to a transplant center should occur when the patient has grade I or II hepatic encephalopathy (HE; Box 107.1 ) and is still clinically stable because within hours HE may progress, intracranial hypertension (ICH) may develop, and clinical instability may ensue, rendering the patient nontransferable because of a high risk of brain herniation.

Sedation should be avoided because it may mask the signs of worsening HE or cerebral edema. In patients who are severely agitated, short-acting benzodiazepines may be given with caution. Opioids must be avoided because they can decrease the seizure threshold. Antiemetics can also deteriorate mental status and should be avoided. Replacement therapy for thrombocytopenia and/or prolonged PT is recommended only in the setting of hemorrhage or before invasive procedures. Overall coagulation homeostasis, as measured by thromboelastography (TEG), is normal even in patients with a greatly elevated INR, making spontaneous bleeding uncommon. Additionally, serial evaluation of laboratory coagulation variables is critical for prognostic purposes, so administration of coagulation factors or plasma should be strictly limited. Nephrotoxic drugs and radiologic contrast agents should also be minimized because renal failure often complicates ALF and has a strong prognostic impact.

Efforts to determine the specific etiology of ALF should be initiated as early as possible to guide management decisions. Early initiation of specific etiologic therapy, when possible, can be lifesaving. The etiology of liver failure is recognized as one of the best prognostic indicators of ALF and plays an important role in the decision to proceed with LT. Early laboratory screening in these patients should focus on determining the severity of ALF and include routine chemistries, arterial blood gases (ABGs), complete blood count (CBC), and blood typing. Etiologic screening should include viral serologies, circulating acetaminophen (APAP) level, screens for other drugs and toxins, tests for Wilson disease, autoantibodies, and pregnancy tests for women ( Box 107.2 ). Considering the frequency of drug toxicity involved in ALF, a careful drug history should include all prescription and nonprescription drugs, herbs, and dietary supplements taken during the past year, duration involved, and recent quantity ingested. All nonessential medications should be discontinued. In patients with suspected or known APAP overdose, early (within 4 hours of ingestion) activated charcoal may be useful for intestinal decontamination. N -acetylcysteine (NAC) should also be given as soon as possible, although it may still be of value even 48 or more hours after ingestion. ^,