Background and Aims: Acute liver failure (ALF), characterized by sudden onset of coagulopathy (international normalized ratio [INR] ≥ 1.5) and encephalopathy, may occur during pregnancy either as a pregnancy-associated etiology or an unrelated and coincidental liver injury. The U.S. Acute Liver Failure Study Group, comprised of 33 tertiary care liver centers, has enrolled consecutive patients with ALF or acute liver injury (ALI; INR ≥ 2.0 with no encephalopathy), over two decades. Approach and Results: Etiologies, clinical features, and outcomes of 70 of 3,155 patients (2.2%) who developed ALF or ALI during pregnancy were reviewed to determine how many were pregnancy associated (pregnancy-associated liver disease; PAALD) and how many were attributed to other etiologies. Thirty-five of the 70 were considered PAALD, of whom nearly half were attributed to hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and half to acute fatty liver of pregnancy (AFLP), although, in some instances, the distinction was unclear. Virtually all with PAALD had been delivered before hepatology referral, mostly by cesarean section. Acetaminophen toxicity accounted for 21 (60% of the remaining cases), with the remainder resulting from a variety of other causes, but not including viral hepatitis A through E. Although recovery with delivery or supportive measures was possible in most cases, 11 of 70 (16%) required liver transplantation and 8 (11%) died. Swansea criteria to diagnose AFLP were met by all patients with PAALD and also by virtually all women with other forms of ALF. Conclusions: Only half of those with ALF during pregnancy appeared to have HELLP or AFLP. Morbidity and mortality for mother and fetus are strongly associated with etiology of liver failure.
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