A potential prognostic indicator of fultninant hepatic failure : A valuable adjunct in preliver transplant assesstnent ?

B YACYSHYN, CM CHEUNG, DG MALKIN, SC PAPPAS. A potential prognostic indicator of fulminant hepatic failure: A valuable adjunct in preliver transplant assessment? Can J Gastroenterol 1994;8(5):308-312. The use of thyroid function tests as a method of monitoring patients with fulminant hepatic failure has been previously proposed. The use of these indices in two cases with fulminant hepatic failure are described. Both patients had simultaneous ingestion of hepatotoxic mushroom (amanita virosa). Their parallel clinical courses and recovery without liver transplantation is described, outlining the potential long term cost-savings achievable by such tests in the selection of patients for liver transplantation and the need for further study of these indices for this application.

T HE USE OF THYROID FUNCTION testing as a monitor of severe illness has been proposed in many dive rse disease states (1).The measurement of the reverse triiodothyronine (rT3) level has been shown to correlate with a poor prognos is (2).Although the measurement of thyro id function has been evaluated in cirrhos is and employed in the evaluation of liver transplantation candidates, the simultaneous evaluation of two patients (husband and wife) fro m the identical onset to the resolution of fulmi na nt hepatic fa ilure (FHF) using thyroid indices has not been reported (3 ).In these patients, the leve ls of r T 3 and triiodothyronine (T3), and rT3:T 3 ra tios have been reported to parallel closely their clinical course (2).These indices may prov ide an adjunct to current methods of assessing patients before liver transplantation and should be conside red.

CASE ONE
A 42-year-old Caucas ian female was admitted to hospital with ac ute abdominal pain, diarrhea and encephalopathy.No pertinent previous medica l history was obtained from relatives; however, the patient and her husband    1 ).Diagnostic paracentesis revealed a leukocyte is of greater than 600 leukocytes/ml ascitic fluid .The patient was then started on intravenous antibiotics (ampicillin and gentamicin) and continued to recover.Identification of amanita virosa as the ingested mushroom was made by the patient after recovery, and confirmed by a mycologist after examining the area from which the mu hrooms were picked.

DISCUSSION
The need for objective biochemical indices to monitor patients with FHF before liver transplantation has been more pressing due to health care budgetary pressures ( 4 ).The long term expense in the care of liver transplant patients is not trivial, and the decision to perform a transplant therefore has long term considerations and should be buttressed by laboratory and clinical data best able to identify those patients in whom transplantation is necessary, although supportive care to allow native liver regeneration is the preferable management when possible.
O'Grady et al (5) reviewed 588 patients with acute hepatic failure using unvaried and multivarient analysis.They identified several criteria to determine prognosis of FHF to assist in detennining when liver transplantation is indicated (5).These parameters include blood pH, serum bilirubin, prothrombin time, serum creatinine, age and degree of encephalopathy among others.
Hepatotoxin ingestion resulting in Fl-IF is frequently managed by liver transplantation.Of these, certain poisonous mushrooms have long been known to contain hepatotoxins, and identification of their pecific toxins have provided models of hepatotoxicity (6,7).The ingestion of amanita virosa by these patients inadvertently provided an opportunity to evaluate serial thyroid function testing in two patients with acute FHF.
A direct primary action of toxic mushroom ingestion on the thyroid gland is not described.The liver has been identified as an important regulator of thyroid hormone homeostasis (8-12).Identification of specific patterns of thyroid hormone abnormalities has been described for different hepatic diseases.For instance, serum T3 has been proposed as an index of the severity of alcoholic liver disease ( 13)  However, degradation of rT3 and T3 is catalyzed by the enzyme iodothyronine 5'-deiodinase located primarily in liver and kidney (14).Severe forms of hepatic disease with a deficiency of this enzyme result in a reduction in plasma T3 levels and an increase in rT3 levels in association with a normal TSH level.This pattern of thyroid indices is known as the 'low T3 syndrome' and is prognostically useful in alcoholic liver disease and in assessing potential liver transplant recipients (3,13-15).Furthermore, replacement thyroid hormone therapy has not been shown to benefit euthyroid-sick patients (16).
The prognostic use of rT3 in patients with hepatocellular disease has been described with one study attributing an 11-fold increased risk of death to an rT3 value greater than 0.590 ng/mL which is equal to 0.761 nmol/L (3).As shown in case 1, the elevation of rT3 corresponded to clinical deterioration with development of spontaneous bacterial peritonitis on day 10 with this measurement decreasing progressively with clinical improvement (Table 1).This correlation of rT3:T3 to hepatocellular damage corresponds with the aspartate aminotransferase levels of each patient (Figures 1,2).Similarly, the more serious clinical course was experienced by case 1 who consistently had a higher rT3:T3 ratio than case 2 (Table 1).
The depressed thyroid hormone level associated with poor prognosis in evere liver disease was at first shown in our patients, but returned to normal as both patients returned to euthyroid cirrhosis: Relation to hepatocellular damage and normalization on improvement in liver dysfunction.Am J Gastroenterol 1983;78:750-5.1,2) (13).Furthermore, a good relationship was shown between rT3:T3 and prothrombin time (Figures 3,4).This finding is consistent with that from a group at Oxford -identification of prothrombin time as a progno tic factor in FIIF (5).With acute forms of hepatitis, an increase in serum thyroxine and thyroxine-binding globulin has been shown.These increases have been postulated to be secondary to increased thyroxine-binding globulin in regenerating hepatocytes, the release of thyroxine-binding globulin by damaged hepatocytes or decreased thyroxinebinding globulin clearance (17)(18)(19).
As these two patients illustrate, the level of rT3 and T3, and the rT3:T3 ratio correlate well with the clinical status of Fl IF due to hepatotoxic mushroom ingestion.These patients exhibit a high rT3:T3 ratio, reflecting the clinical course of Fl IF.Overall, this pattern is consistent with the low T3 syndrome; however, the low TSH found in case 2 is likely due to the severe physiological stress of FHF.The use of thyroid indices as adjunctive indicators of hepatic function in Fl-IF allowed for prediction of clinical deterioration before the development of spontaneous bacterial peritonitis in one patient, and subsequently paralleled their eventual complete recovery.Such mea urements are useful in the assessment of hepatic disease in view of the liver's key role in thyroid hormone metabolism and homeostasis.Such information should be studied in other etiologies of Fl IF and may be of valuable assistance in treating a patient in whom the need for liver transplantation is borderline.failure.Gastroenterology l 989;97:439-45.
Thyroid indices in fulminant hepatic failure