SIGNIFICANCE OF SEROCONVERSION IN HBV AND HCV POSITIVE
PATIENTS ON HEMODIALYSIS FOR POTENTIAL KIDNEY
TRANSPLANTATION
Gašparovic Vladimir1, Pehar Mario2, Ostojic Rajko3, Grahovac Blazenka4, Gjurašin Mirko1
1 Division of Emergency and Intensive Care Medicine and Centre for Hemodialysis,
Department of Medicine, Zagreb, Croatia
2 Centre for Hemodialysis, Sesvete, Croatia
3 Division of Gastroenterology, Department of Medicine, Zagreb, Croatia
4 Department of Transfusion Medicine, Zagreb, Croatia
SAZETAK
Kronično zatajenje bubrega rezultira u nizu specifičnih problema tih bolesnika. Nedostatak
eritropoetina, renalna anemija te posljedične transfuzije rezultirale su povećanom učestalošću
pozitivnih virusnih markera u krvi kod tih bolesnika. Pozitivna antigenemija u kroničnih
bubrežnih bolesnika uobičajeno prolazi bez značajne pridružene hepatalne lezije. Uspješna
transplantacija bubrega ima, međutim za posljedicu pogoršanje jetrenog statusa, s razvojem
teških lezija sve do smrtnog ishoda. U ovom radu prikazuju se rezultati serokonverzije
pozitivne antigenemije bolesnika na hemodijalizi, kako bi po uspješnom odstranjenju
virusnog markera bili uključeni na listu čekanja za transplantaciju bubrega. Očekujemo da će
odstranjenje pozitivnog virusnog markera iz krvi bolesnika na hemodijalizi rezultirati boljim
preživljavanjem bolesnika , bez pridruženog oštećenja jetre.
SUMMARY
Chronic end-stage renal failure results in various specific problems in these patients. The lack
of erythropoietin and need for blood transfusion in hemodialysis units has brought up
considerably higher incidence of positive virus markers than would be expected in the given
geographic area .. Positive virus marker in patients on hemodialysis commonly has no major
clinical implications. In these patients the course of hepatitis does not involve important
clinical
exacerbation.
However,
successful
kidney
transplantation,
despite
immunosuppression with the aim of keeping the graft, can result in significant deterioration
of liver function.. Patients in whom seroconversion was successful were reincluded in the
waiting list for renal transplantation. We expect better results and better patients survival rate,
without associated hepatic lesion.
INTRODUCTION
Patients with chronic end-stage renal failure survive due to intermittent hemodialysis
performed most commonly three times a week. These procedures of extracorporeal
circulation correct high azotemia end eliminate hyperkalemia as a risk factor for malignant
heart rhythm disturbances. Renal anemia due to the lack of erythropoietin has previously
resulted in blood transfusions and unfortunate transmission of B and C virus markers to
hemodialysis units (1). According to the statistics, the incidence of positive virus marker in
our country is high (2). Recently there have been attempts of seroconversion in positive
antigenemia, with the aim to eliminate the virus from the blood of patients with hepatitis and
normal kidneys (3). For patients with chronic end-stage renal failure this is of special
importance, because it allows their inclusion in the waiting list for kidney transplantation and
enhances the quality of life after successful renal transplantion.
PATIENTS AND METHODS
In the group of patients with chronic renal failure on hemodialysis, virus markers for B and C
hepatitis were determined (HBsAg, HbeAg, anti-HBc, anti-HBs, anti-Hbe, anti-HCV and
HBV RNA, HCV RNA). Determinations were done at three-month periods. In positive
patients, virus replication was determined using the PCR technique. According to protocol,
in addition to other biochemical parameters, bilirubin, alkaline phosphatase, AST, ALT and
GGT were determined in all patients six months before (-6), three months before (-3), and at
the institution of interferon-alpha treatment. Subsequently, virus markers including tests for
virus replication were determined at three-month periods. Liver function tests, bilirubin,
alkaline phosphatase, transaminases and GGT were determined at three months (+3, +6, +9,
+12). All side effects of interferon-alpha treatment were recorded in the protocol. Patients
with positive HCV marker received three times 3,000 units of interferon-alpha s.c. upon
completed hemodialysis, and those with positive HBV antigen received three times 5,000
units of interferon-alpha s.c. after hemodialysis. The obtained results are summarized in the
table and statistically processed.
RESULTS
In the group of 16 patients there were 11 males and five females. Average age was 44.7 years.
All patients were dialyzed three times a week. Three patients with positive HBV hepatitis
were submitted to kidney transplantation without previous attempt of seroconversion with
interferon. They died in the period from two years and nine months to eight years and three
months later, with severe hepatic lesion (Table 1). Levels of transaminases, AP, GGT,
bilirubin and the results of seroconversion are shown on Table 2. These are interim results
because the study is still going on.
DISCUSSION
Chronic end-stage renal failure results in various specific problems in these patients. The lack
of erythropoietin and need for blood transfusion in hemodialysis units has brought up
considerably higher incidence of positive virus markers than would be expected in the given
geographic area (4). Timely vaccination against B virus can only partially solve the problem
of B hepatitis spreading in this group of patients, while the problem of C hepatitis remains
completely unsolved (5). Positive virus marker in patients on hemodialysis commonly has no
major clinical implications. Transaminase levels are mainly normal or moderately elevated,
and bilirubinemia is uncommon. In these patients the course of hepatitis does not involve
important clinical exacerbation. However, successful kidney transplantation, despite
immunosuppression with the aim of keeping the graft, can result in significant deterioration
of liver function. This was the case with our three patients who died later because of hepatic
failure after successful renal transplantation (6).
On the other hand, virus positive patients on hemodialysis are a permanent potential source
of infection for their healthy sexual partners, as well as for hemodialysis staff. Viremia in
hemodialysis personnel as a rule results in turbulent clinical picture of B or C hepatitis,
implying permanent consequences - high incidence of cirrhosis in C hepatitis, possibility of
malignant alteration etc. Each year about 3-5% of patients with positive C marker get
hepatocellular carcinoma (7). All this points to the importance of seroconversion in HBV and
HCV positive patients on hemodialysis. Our patients with positive virus marker on
hemodialysis were treated with interferon-alpha. The clearance of virus marker with
interferon-alpha is effected via cellular immune response. HBV clearance from blood with
interferon is the consequence of the induction of interleukin 12 receptor expression and
inflammatory response, and increased expression of MHL callus I antigen. The action of
interferon-alpha in HCV infection is less clear, but it acts as a direct antiviral substance,
decreasing the HCV titre in peripheral blood (in addition to stimulation of host immune
response) (8). Our results indicate that seroconversion in cases of C antigenemia was more
successful, i.e. in 54.5% (six out of 11 patients). In five patients seroconversion did not ensue
neither after 16 weeks. With regard to various side effects, predominantly flu like syndrome
and loss of appetite, the treatment with interferon-alpha has been transiently discontinued
before the definitive conclusion about the unsuccessfulness of the treatment. When a number
of patients became seronegative, those seropositive showed an additional compliance and
willingness to continue with the treatment.
It is important to note that in repeated checking of C antigenemia, only a part of the patients
are still being followed-up, the percentage of virus replication, remained still negative.
Attempts of seroconversion in patients with HBV antigenemia were not successful, despite a
higher dose of interferon (3x5,000 units s.c.). It is known that this seroconversion is difficult
even in population with healthy kidneys. One of the problems observed in patients with
chronic renal failure on hemodialysis, who were treated with interferon-alpha, was the
inhibition of control samples by the patient sera. At this moment it is difficult to offer a
definite explanation. However, it is possible that the sera of patients with chronic renal
failure might contain “like” substances which may give false positive or false negative
findings (9). Patients in whom seroconversion was successful were reincluded in the waiting
list for renal transplantation. We expect better results and better patients survival rate, without
associated hepatic lesion.
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