CMV hepatitis after liver transplantation: incidence, clinical course, and long-term follow-up.
Cytomegalovirus (CMV) hepatitis is described as the most frequent manifestation of CMV tissue invasive disease after liver transplantation. Its correlation with HLA-matching, hepatic artery thrombosis, and chronic rejection is still controversial. Risk factors, incidence, clinical course, and complications of CMV hepatitis were retrospectively analyzed in a 12-year series of 1,146 consecutive liver transplantations in 1,054 patients. All patients received only low-dose acyclovir but no gancyclovir prophylaxis. CMV infection was diagnosed by viral culture, pp65 antigenemia, or by polymerase chain reaction (PCR). CMV hepatitis was proven by liver biopsy. Treatment of CMV disease consisted of intravenous ganciclovir for a minimum of 14 days. Long-term follow-up of patients included monthly routine laboratory values and routine liver biopsies 1, 3 and 5 years after transplantation. CMV hepatitis was a rare event after liver transplantation, with a total incidence of 2.1% (24 cases). It was significantly more frequent in CMV seronegative (5.2%) than in seropositive recipients (0.7%). The leading indication in patients with CMV hepatitis was HCV cirrhosis (n = 8). The maximum number of pp65 positive white blood cells was 82 +/- 23 per 10,000 cells. Most courses manifested as isolated hepatitis; only 2 patients had disseminated disease. Nine of 24 patients had received OKT3 monoclonal antibodies because of steroid-resistant rejection before CMV hepatitis. In seronegative patients with CMV hepatitis, 71% revealed 1 or 2 HLA DR matches, in contrast to 32% in patients without CMV hepatitis. One-, 3-, and 5-year graft survival was 78%, 65%, and 59% in patients with CMV hepatitis compared with 88%, 81%, and 79% in patients without. Chronic rejection was observed in one patient, but already before onset of CMV hepatitis. Beneath D+R-constellation and OKT3 treatment as risk factors, HLA DR-matched grafts and HCV seem to favor manifestation of CMV hepatitis after liver transplantation. Long-term complications of CMV hepatitis were not observed, and especially no correlation with chronic rejection was found.
Seehofer
Daniel
D
Department of General, Visceral, and Transplant Surgery, Charité Campus Virchow, Humboldt University of Berlin, Berlin, Germany. daniel.seehofer@charite.de
Rayes
Nada
N
Tullius
Stefan G
SG
Schmidt
Christian A
CA
Neumann
Ulf P
UP
Radke
Cornelia
C
Settmacher
Utz
U
Müller
Andrea R
AR
Steinmüller
Thomas
T
Neuhaus
Peter
P
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002908:Chronic Disease; D003586:Cytomegalovirus Infections / Q000453:epidemiology*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D006525:Hepatitis, Viral, Human / Q000453:epidemiology*; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D018579:Patient Selection; D011183:Postoperative Complications / Q000453:epidemiology; D012189:Retrospective Studies; D013997:Time Factors
D007166:Immunosuppressive Agents