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PROPRANOLOL AND SALT AND WATERHOMOEOSTASIS IN CHRONIC LIVER DISEASE

SIR,-Dr Hayes and colleagues (Nov 10, p 1064) report thatpatients with chronic liver disease treated with propranolol showeda fall in total body water (TBW) at 6 months, and did not show therise iri total body exchangeable sodium (TBES) that occurred inplacebo-treated patients. In this study of sixteen patients (eightpropranolol-treated, eight placebo-treated) statistical analysis byStudent’s t test (paired and direct computation) does not appear tobe valid. The variables TBW and TBES do not conform to thenormal distribution hypothesis in such a small number of patients.A more appropriate method would have been to calculate for eachparameter in each group the differences between basal and 6-monthvalues and basal and 12-month values and to compare thedifferences with those in the other group by a non-parametric test(for example, the Mann-Whitney U test). Using the raw data inHayes’ table t we found no significant difference between thegroups in TBW at 6 months (U = 11) or 12 months (U = 10) or TBESat 6 months (U = 17) or 12 months (U=9). However, significantdifferences were present at 12 months in the patients’ weight (U = 5,p=0-05) and skinfold thickness (U=5, p<005). We think thatsome of the reported changes in water and salt metabolism and theconclusions of this study must be interpreted cautiously.

Department of Metabolism and Endocrinology,H&ocirc;pital Saint-Louis,75475 Paris, France

E. ABADIEP. LOMBRAIL

** This letter has been shown to Dr Hayes and his colleagues,whose reply follows.-ED L.

SIR,-The reduction in total body water (TBW) and TBW/kgafter 6 months of propranolol therapy given in our table n remainssignificant (p<0-05) when a non-parametric test (Wilcoxonmatched-pairs test) is used. Although interpretation of these datashould ideally be against the placebo-treated patients the largescatter of results in these controls (fig 3A) reduces the statisticalsignificance. We wished to draw attention to the consistent changesin the propranolol-treated patients, which did not seem to occur inthe placebo group.The small sample number in the total body exchangeable sodium

data after 12 months does not allow analysis by the Wilcoxon’matched pairs test, and we agree with Abadie and Lombrail that theincrease of 215&plusmn;197 mmol in placebo-treated patients comparedwith - 3&plusmn;378 mmol in the propranolol group is not significant onthe Mann-Whitney test. Abadie and Lombrail ask us to calculatedifferences between basal and 6 month values; this is incorporatedas table 11 in our paper.

Department of Medicine,Ninewells Hospitaland Medical School,

Dundee DD1 9SY

P. C. HAYESW. W. STEWARTI. A. D. BOUCHIER

C-REACTIVE PROTEIN AS EARLY PREDICTOR OFLIVER VIABILITY AFTER TRANSPLANTATION

SIR,-Orthotopic transplantation of the liver is increasinglyconsidered a valuable therapeutic option for patients with

appropriate indications.1-3 Although ischaemic liver necrosis is arecognised cause of early perioperative graft failure,2-4 traditionalliver-function tests do not directly discriminate an injured but viableliver from an irreversibly compromised organ. Classical indicatorsof hepatic synthetic function, such as the prothrombin time andserum albumin concentration, are directly altered by the extensivehaemotherapy used during the transplant operation. Markers ofliver necrosis, such as serum transaminase levels, are initially raisedin all transplant patients and fall to normal only after 48-72 h inuncomplicated cases.2,3 Nevertheless, early recognition of graftfailure in the immediate perioperative period might afford valuabletime to locate a replacement donor organ. In contrast to the usualindicators of liver function, C-reactive protein (CRP) is an earlyacute phase reactant which is produced by the liver but is generallyabsent in normal human sera when assayed by conventional

POSTOPERATIVE SERUM CRP TITRE IN FIVE PATIENTS AFTER LIVER

TRANSPLANTATION

*Patients 1-4 survived at least 1 month postoperatively; patient 5 died after 3 days (graftfailure).

methods. Therefore, CRP should be a sensitive indicator of hepaticsynthetic function independent of transfused blood products.We studied serum CRP levels retrospectively in multiple

perioperative serum samples from five patients who underwentliver transplantation at the Yale-New Haven Hospital (table). Fourof these patients (cases 1-4) demonstrated significant increases inserum CRP titres within 3-6 h of discharge from the operatingroom. These patients survived the transplant procedure and arealive at the time of this report. In case 5, serum samples wereconsistently negative for CRP postoperatively: this patient died72 h after surgery, and necropsy disclosed massive necrosis of the

transplanted liver.These limited data strongly suggest that the assay of CRP has an

early, predictive value for graft function and survival after livertransplantation. It is possible that the timing and/or magnitude ofthe increase in CRP may be related to the extent of liver injuryincurred during organ procurement and transplantation, therebyfurther enhancing the value of this test. We are studying other acutephase reactants to identify useful indicators of graft integrity afterliver transplantation.

Department of Laboratory Medicine,Yale Medical School,New Haven, Connecticut 06504, USA

S. R. MCCORMICKA. BAUMGARTEN

1. Editorial Liver grafting (transplantation overview). Transplantation 1983, 35: 109.2. Starzl TE, Iwatsuki S, Van Thiel DH, et al. Evolution of liver transplantation

Hepatology 1982; 2: 614-36.3. Van Thiel DH, Schade RR, Starzl TE, et al. Liver transplantation in adults Hepatology

1982, 2: 637.4 Wall WJ, Calne RY, Herbertson BM, et al Simple hypothermic preservation for

transporting human livers long distances for transplantation. Transplantation 1977;23: 210-16.

5 Morley JJ, Kushner I. Serum C-reactive protein levels in disease. In: Kushner I,Volanakis JE, Gewurz H, eds. C-reactive protein and the plasma protein response totissue injury. Ann NY Acad Sci 1982, 389: 406-18

DETECTION OF Fc-RECEPTOR-BLOCKINGANTIBODIES IN ANTI-Rh(D) HYPERIMMUNE

GAMMAGLOBULIN

SIR,-Rh(D) sensitisation of a non-immunised Rh(D)-negativepregnant woman can be prevented by a single intramuscularinjection of anti-D IgG when the pregnancy is completed. Thepreparations injected contain IgG from hyperimmunised donorsand have high-titre anti-D activity. In an unpublished lecture givenin Hungary in 1983, M. Kerenyi reported a procedure in whichanti-D IgG was given to pregnant women who were already Rh(D)sensitised. IgG blocked the progress of the immunisation in 88% of67 cases and the prospects for the endangered fetus were muchimproved. This result remained unexplained but we wondered ifimmunisation could be blocked by some factor other than the anti-Dactivity in the IgG preparations used.Enhancement of Fc-receptor-blocking antibodies during

pregnancy and in kidney transplantation has been reported2,3 andnon-specific Fc-receptor blockade is also attainable by bloodtransfusion. Might anti-D IgG preparations also contain Fc-

receptor-blocking antibodies?