We present a case of initially unexplained fever in a living right liver lobe transplant donor that turned out to be due to primary cytomegalovirus infection.

Key words : Cytomegalovirus, Living, Liver trans-plantation

Introduction

Fever is common after hepatic lobectomy; affecting about 90% of patients undergoing lobectomy to manage hepatic neoplasm or after trauma.¹ Infectious complications can explain only about half of these febrile complications; the other half remain unexplained and resolve spontaneously.¹ In recently published systemic literature review of donor morbidity after a right lobectomy for living-donor liver transplant;² unexplained fever was only rarely reported in such donors. Liver lobe donors are usually healthy, so the incidence of fever after liver lobectomy for other reasons, such as malignancy, may be higher. We report a case of fever caused by primary cytomegalovirus (CMV) infection after a right hepatic lobectomy for a living-donor liver transplant.

Case Report

A 27-year-old otherwise healthy man underwent a right living-donor hepatectomy for his father on October 13, 2014. His recovery was uneventful until postoperative day number 6, when he developed fever (38.2°C), malaise, and anorexia. Other vital signs were within their respective normal ranges and his physical examination was normal including his incision. Laboratory studies showed white blood cell count of 5080 /μL with normal differential cell count, hemoglobin concentration of 11.6 g/dL, and a platelet count 97 000 /μL, alanine aminotransferase of 90 U/L, aspartate aminotransferase of 60 U/L, and normal bilirubin and alkaline phosphatase concentrations. All his other laboratory work was normal before donation.

Blood cultures were negative and computerized abdominal tomography showed expected post-operative findings, including some air and tissue stranding in the subcutaneous tissue and no sign of bile leak or abdominal fluid collection. Chest roentgenography showed right pleural effusion. Doppler ultrasound of his arms and legs ruled out deep venous thrombosis. Fevers persisted, so the abdominal wound was explored in the operating suite. It revealed healthy granulation tissue without purulence and tissue cultures were negative. Right thoracentesis showed transudative fluid. Throm-bocytopenia persisted and on postoperative day 15, his blood absolute neutrophil count was 920 K/μL. He did not receive blood products during or after surgery that would suggest transfusion-associated infection. Cytomegalovirus deoxyribonucleic acid (DNA) detection in blood performed by polymerase chain reaction (PCR) was 8989 copies/mL of whole blood (linear range of this assay 313 copies/mL to 1 million copies/mL). No specific antiviral therapy was recommended, and he gradually felt better and his fever went down during the next 4 weeks. Repeat testing for CMV DNA by PCR on postoperative day 33 was undetectable. His CMV immunoglobulin G was negative 1, 8, and 21 days before donation.

Discussion

Seroprevalence of CMV infection varies worldwide; with 40% to 100% of adults becoming infected by the fourth decade of life.³ Primary infection in immunocompetent adults is usually subclinical; with only 10% developing a mononucleosislike illness characterized by fever, malaise, mild leucopenia, lymphocytosis, thrombocytopenia, and abnormalities of liver function tests. Illness is self-limited, with complete recovery expected in days to weeks. Tissue invasive CMV infection is rare in immunocompetent adults.⁴

A systematic review of the literature of 12 studies including 409 adult-to-adult donors of a right lobe revealed donor morbidity ranging from 0% to 67%.2 The most commonly reported postoperative events were bile leak, prolonged ileus, and minor wound problems. Mean hospital stay was 10 days, and 97% returned to work within 2 months. Primary CMV was not a reported postoperative event.

Our patient developed primary CMV syndrome 6 days postoperatively. Family members who visited postoperatively including his 1-year-old son did not have similar symptoms. None of his health care providers had similar symptoms. It is, therefore, unclear how he acquired CMV infection, but the above data suggest he acquired it shortly after donation. Epidemiologic data point to his 1-year-old son as the source of infection.⁵ This cannot be confirmed; however, it is plausible.

Primary CMV infection is frequently asymptomatic in immunocompetent individuals. We hypothesize that the surgical stress decreased this patient’s ability to handle the infection, resulting in a febrile illness with associated laboratory abnormalities. Perhaps the patient was tested for CMV, because he was admitted in a transplant unit where CMV infection is a familiar issue, but also because he had clinical and laboratory findings consistent with acute CMV infection, and because a search for an alternate cause for postoperative fever was unrevealing.

Serum CMV IgM and CMV IgG were not tested after recovery, as this was not needed clinically to manage this patient. Cytomegalovirus IgM is frequently false-positive; therefore, one should not rely upon those results to confirm the diagnosis of acute CMV infection. Natural history is for CMV IgM to be transiently positive during the early phase of illness, then turn negative after recovery, and for CMV IgG to turn positive during the later phase of illness, then remain positive for the rest of the patient’s life. Our patient was CMV IgG negative before the onset of illness and was well at the time of donation, so there was no clinical indication to test for CMV IgM. Delayed sample preparation has been associated with false-positive CMV PCR because of leucocyte lysis.⁶ There was no delay in the sample preparation in this case, and his viral load of 8989 copies/mL is moderately high, because the lower limit of detection of this assay is 313 copies/mL. Therefore, a false-positive test is not likely. All this points to a diagnosis of acute CMV infection.

Clinical take-home message of this case is to consider primary CMV syndrome in liver lobe donors with compatible clinical and laboratory findings, particularly when other, more common, causes of postoperative fever have been excluded. We do not recommend CMV serology before any liver surgery; however, we do recommend CMV IgG in transplant donor candidates before liver lobectomy, because CMV donor and recipient IgG serologies have important implications for management and prognosis of the recipient. We do not recommend CMV PCR testing in all cases of unexplained fever; only in cases with clinical and laboratory findings consistent with acute CMV infection.

References:

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