The prevalence and severity of autonomic dysfuncinduced and non-alcohol-induced liver disease, and tion appears to be related to the severity of liver diswhen present is an independent predictor of mortality. ease. 3 We postulated that patients awaiting liver trans-We postulated that patients who were awaiting liver plantation are likely to have a high prevalence of AN, transplantation are likely to have a high prevalence of and the presence of AN is associated with an increase autonomic neuropathy with an associated increase in in mortality. To test our hypothesis, we evaluated the mortality. To test our hypothesis, we evaluated the presprevalence of AN in a cohort of patients awaiting liver ence of autonomic neuropathy using a battery of tests transplantation and prospectively followed them to dein 33 patients awaiting liver transplantation and protermine their prognosis.
spectively followed them to determine their prognosis. Twenty-two of 33 (67%) patients with liver disease had PATIENTS AND METHODS evidence of autonomic neuropathy; of these, 12 (36%) had evidence of definite and 10 (31%) had early auto-All patients and volunteers gave informed consent, and nomic neuropathy. The prevalence of AN was similar in the study was approved by the Johns Hopkins Hospital Joint alcohol-induced and non-alcohol-induced liver disease. Committee for Clinical Investigation. Using Child-Pugh classification, 14.3% Child A, 31.3%
Thirty-four patients from the active waiting list for liver Child B, and 60% Child C had definite autonomic neuroptransplantation at the Johns Hopkins Hospital were screened athy. Six patients died during a median observation pefor AN. Patients on the waiting list were primarily UNOS riod of 10 months, and all had AN. Kaplan-Meier survival level II or III. Patients with fulminant hepatic failure, hepatic analysis showed a significantly higher mortality (P malignancy, hemochromatosis, atrial fibrillation, and Budd-ร
.05) in patients with AN. On the basis of this observa-Chiari syndrome were excluded. Patients with glucose intoltion, we suggest that consideration should be given for erance, diuretic therapy, and beta-blocker therapy were not early liver transplantation in patients with advanced excluded, but beta-blockers were held for 48 hours before liver disease and autonomic neuropathy. (HEPATOLOGY autonomic testing if the patient was clinically stable. All pa-1996;23:471-475.)
tients were abstinent from alcohol at the time of the study. Twenty-three men and 11 women were studied, with an age Chronic liver disease has been shown to be associated range of 20 to 63 years and 42 to 65 years, respectively. Seven patients had glucose intolerance, and four patients were tak-with autonomic neuropathy (AN) as well as hemodying beta-blockers. All patients had clinical evidence of cirrhonamic and circulatory disturbances. [1][2][3][4] This abnormalsis, and the liver disease was secondary to alcohol in 11, ity of the nervous system appears to be unrelated to hepatitis C in 9, primary biliary cirrhosis in 5, sclerosing the toxic effects of chronic alcohol use, because crosscholangitis in 2, autoimmune in 2, cryptogenic in 4, and sarsectional studies have shown an equal prevalence of coid in 1. Hepatic function was assessed by the Child-Pugh AN in alcohol-and non-alcohol-related liver disease. 1 classification, with 7 Child A, 16 Child B, and 11 Child C. 6
In a longitudinal study in patients with Child A liver Patients with Child A were listed for transplantation because disease, the 4-year mortality was found to be 30% in of recurrent variceal bleeding. In addition, 10 healthy volun- patients with autonomic neuropathy compared with 6% teers (controls) were studied to validate our testing methods. in patients without autonomic dysfunction; multiple Six female and 4 male controls were studied, with an age range of 36 to 48 years.
logistic regression analysis showed that the presence A history and a careful neurological examination was done of autonomic neuropathy and severity of liver disease in all patients and controls. Four standard cardiovascular were independent risk factors of mortality. 5 reflex tests were used, including blood pressure response to standing, heart rate variability (HRV) in response to the Valsalva maneuver, HRV in response to standing, and HRV in Abbreviations: AN, autonomic neuropathy; HRV, heart rate variability. response to deep breathing. The normal, borderline, and ab-From the 1 Departments of Medicine and 2 Anesthesiology and Critical Care normal values of these tests were those defined by Ewing Medicine, The