Function of partial liver allografts after heterotopic transplantation

LETTERS TO THE EDITOR

246 TABLE I Serological markers of hepatitis B during interferon treatment Interferon treatment

H Bs-titer immuno-diffusion

H Be-Ag

Anti-HBe

Before During (month 1) During (month 2) During (month 3) During (month 4) After (month 3) After (month 6) After (month 12) After (month 16) After (month 18) After (month 24) After (month 36)

I/32 1/16 1/16 1/16 1/8 1/8 I/8 1/16 1/8 1/16 1/8 1/4

pos. pos. pos. pos. pos. pos. neg. neg. neg. neg. neg. neg.

neg. neg. neg. neg. neg. pos. pos. pos. pos. pos. pos. pos.

(IU/ml)

HBV-DNA (pg/ml)

HBV PCR a

325 225 192 188 147 normal normal normal normal normal normal normal

1000 400 80 40 0 0 0 0 3 0 0 0

ND ND ND ++++ ++++ ++++ ND +++ ND + + + + + +

ALAT

Anti-HBs Test A

Test B

0 0 ND 0 0 0 0 ND ND ND ND ND

ND 21 17 ND ND 7 5 6 ND I neg. neg.

" Results by visual evaluation of the spot colour intensity: + + + + = very strongly positive, + + + =strongly positivie, + + =positive, - = negative. N D = n o t done.

end of the treatment, indicating that they were only temporarily induced. These findings could be interpreted as the beginning of an immune response potentially capable of completely eliminating HBV and that this response was abrogated after the (too early?) end of the treatment. The prospective use of these tests should have lead us to continue interferon for a longer period and/or with a higher dosage until the possible complete HBV elimination. Thus interferon-or treatment induced a substantial inhibition of HBV replication and seroconversion from HBe to anti-HBe. This was to the benefit of the patient whose liver enzyme values returned to normal and who

experienced a considerable improvement in quality of life. Liver histology was not repeated. We conclude that a battery of sensitive serological tests would permit a better and more individual adaptation of the dose and the duration of interferon-or treatment in chronic active hepatitis B. The case presented took part in the Swiss multicenter study for the treatment of chronic hepatitis B run by the Swiss Association for the Study of the Liver.

References

for the detection of serum hepatitis B virus DNA using the polymerase chain reaction technique. J Clin Microbiol 1989; 27(9): 1930-3. 4 Tiollais P, Charnay P, Vyas GN. Biology of hepatitis B virus. Science 1981; 213: 406-I I. 5 Guo K J, Bowden DS. Digoxigenin-labeled probes for the detection of hepatitis B virus DNA in serum. J Clin Microbiol 1991; 29: 506-9. 6 Carman WF, Dourakis S, Karayiannis P, Crossey M, Drobner R, Thomas HC. Incidence of hepatitis B viraemia, detected using the polymerase chain reaction, after successful therapy of hepatitis B virus carriers with interferon-alpha. J Med Virol 1991; 34:114-8.

1 Lavanchy D, Peitrequin R, Vu DH, Frei PC. Measurement of antiHBs production after vaccination: comparison of results obtained by two different immunoassays. In: Coursaget P, Tong M J, eds. Progress in Hepatitis B Immunization. John Libbey/INSERM, 1990; 194: 73-7. 2 Seibl R, Holtke H J, Ruger R, et al. Non-radioactive labeling and detection of nucleic acids. III. Applications of the digoxigenin system. Biol Chem Hoppe Seyler 1990; 371: 939-51. 3 Kaneko S, Feinstone SM, Miller RH. Rapid and sensitive method

D..Lavanchya, C. Mayerat a, P.C. FreP and A.L. Blum b °Division of Immunology and Allergy and bDivision of Gastroenterology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland

HEPAT 01169

Function of partial liver allografts after heterotopic transplantation In the field of liver transplantation both heterotopic grafting and the regular use of clearance studies in the follow-up of patients are far from commonplace. We routinely performed indocyanine green (ICG) and anti-

pyrine (AP) elimination tests in 10 patients who received heterotopic partial liver allografts because of end-stage chronic liver disease (1). Four of these patients had chronic hepatitis-B virus infections, two with f-virus

247

LETTERS T O T H E E D I T O R TABLE 1 Fractional clearance of indocyanine green and antipyrine before and after heterotopic partial liver transplantation Patient

HBV

Week Pre-ICG

3

13

26-39

52

1 2 3 4 5 6 7 8 9 10

+ + + +

2.1 4.2 2.5 2.5 4.5 3.0 0.7 7.1 3.4

21.3 15.6 16.4 13.7 15.2 15.7 17.9 20.3 18.5 -

17.3 8.3 14.0 13.1 15.7 13.7

11.5 10.7 16.8 20.9 21.5 14.3 13.2 8.0 11.4

20.2 7.8 16.7 15.8 16.2 14.8 I 1.6 12.8 I 1.0 10.8

18.1 9.8

Pre-AP 3.8 0.7 1.2 1.7 2.3 1.4 1,7 1,8

3 6.5 7.6 9.5 28.3 7.3 9.9 -

13

26-39

6.8 5.9

5.0 7.4

16.1 8.3 6.1 5.4 4.6 -

14.6 7.1 5.8 9.5 4.0 3.4 4.0

52 5.0 5.6 7.0 14.3 6.4 5.5 7.8 3.9 4.4 5.9

H B V = reinfection of the graft with hepatitis-B virus yes (+) or no (-). ICG =fractional clearance of indocyanine green in %/min (normal values > 12.4%/rain). A P = fractional clearance of antipyrine in %/h (normal values >4.4%/h). Note: Patients 4 and 7 were treated with antiepileptic drugs.

superinfection. Reinfection of the graft occurred in all 4 with viral replication in the graft at 1-3 weeks and the first signs of structural liver damage at 6 months on routine biopsies. Serum concentrations of bilirubin, albumin and clotting factors, however, remained normal during the first year of follow-up. All patients were followed for at least 1 year after transplantation. Tests were performed before and at 3, 13, 26-39 and 52 weeks after transplantation. Of the 50 planned tests, 5 ICG and 10 AP test were not done for various reasons. ICG (2) and AP (3) elimination rates were measured as described by others. Fractional clearances were calculated by linear regression analysis of log-transformed concentrations against time. Normal values are > 12.4%/ rain for ICG and >4.4%/h for AP. Repeated testing of one normal subject gave variation coefficients of 13% at an ICG fractional clearance of 17%/min and 19% at an AP fractional clearance of 10%/h. The results for preoperative measurements all were markedly subnormal (ICG 0.7-7.1%/min, AP 0.73.8%/h) and rose to normal levels at 3 weeks after transplantation (15.2-21.3%/min and 6.5-28.3%/h, respectively). In the patients with recurrent viral hepatitis a decline was found (10.8-12.8%/min and 3.9-7.8%/h,

respectively at 52 weeks). In the other 6 patients none of the 17 AP tests were abnormal, but 4 out of a total of 17 ICG tests at 13 weeks and later gave subnormal results. Three abnormal ICG tests were found in one single patient (Table 1), possibly as a result of the portal hypertension and portosystemic shunting that persisted in this patient until 6 months after transplantation. The low ICG fractional clearance in Patient 1 at 26 weeks may well be a spurious result. In the 6 patients without viral reinfection there were no significant differences between the measurements at different times after transplantation, indicating a stable liver function during 1 year follow-up. We conclude that in patients with end-stage chronic liver disease, heterotopic liver transplantation effectively restores hepatic function as measured by ICG and AP elimination tests. Clearance tests may be useful in the follow-up of patients after liver transplantation, since they appear to detect deterioration of liver function before bilirubin rises or albumin and clotting factors decline.

References

2 Caesar J, Shaldon S, Chiandussi L, Guevara L, Sherlock S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 1961; 21: 34-57. 3 Van Boxtel C J, Wilson JT, Lindgren S, Sj6qvist F. Comparison of the half-life of antipyrine in plasma, whole blood and saliva of man. Eur J Clin Pharmacol 1976; 9: 327-32.

1 Terpstra OT, Schalm SW, Weimar W, et al. Auxiliary partial liver transplantation for end-stage chronic liver disease. N Engl J Med 1988; 319: 1507-11.

S. de Rave a, H.J. Metselaa#, O.T. Terpstra b and S.W. Schalm ~ Departments of alnternal Medicine and bSurgery, University Hospital Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands