We present a 24-year-old man who developed primary cytomegalovirus peritonitis without gut perforation, but with concomitant colitis 6 weeks after liver transplant from a deceased donor for end-stage liver disease because of primary sclerosing cholangitis. The patient was treated only medically, with no need for surgery, and is well at 12 months. This case represents the need for suspicious for cytomegalovirus peritonitis in the appropriate setting in post liver transplant even in the absence of perforation.
Key words : Cytomegalovirus, Peritonitis, Liver transplantation, Iran
Cytomegalovirus (CMV) is a common complication in the first 6 months after solid-organ transplant including the liver.1 Posttransplant disease may occur without specific organ involvement, which is referred to as CMV syndrome, and may involve specific organs. The colon is the most commonly affected organ; however, other organs including the liver, the retina, and the lung also may be involved.
Peritonitis with CMV is a rare complication of this infection. Most cases have been reported in patients with acquired immunodeficiency syndrome asso-ciated with perforation of the colon owing to colitis in pre-HAART era.2 Here, we a present a case of viral peritonitis after a liver transplant without bowel perforation.
A 24-year-old man who underwent a transplant for end-stage liver disease, caused by primary sclerosing cholangitis (PSC), presented to clinic with a spiking fever of 1 week’s duration. He was diagnosed as having PSC 7 years earlier associated with ulcerative colitis. His last colonoscopy was done 3 months before transplant, and it showed patchy moderate inflammation throughout the length of colon confirmed by biopsy with no evidence of dysplasia. In pretransplant work-ups, tuberculin skin test was less than 5 mm after 72 hours, but CMV antibody IgG was positive.
He underwent a liver transplant with Roux-en-Y anastomosis from a deceased donor on December 25, 2013. The CMV status of donor was not known. Immunosuppression induction was with 1 gram methylprednisolone for 3 days. He had an uncomplicated postoperative course and was discharged on day 10 after transplant on tacrolimus 2 mg twice daily, mycophenolate mofetil 1 gram twice daily, prednisolone 20 mg once daily, cotrimoxazole 80/400 mg at bedtime, mesalazine 3 grams per day, with calcium and vitamin D supplements. Upon discharge from the hospital, his serum concentration for the pp65 CMV antigenemia, as well for CMV PCR, was negative. The explanted liver had no evidence of cholangiocarcinoma.
He was well for the next 6 weeks, when he noticed feverishness, nonproductive cough, and sneezing followed by headache, nausea, vomiting abdominal pain, and diarrhea, which was watery 4 to 5 times per day without visible blood.
He was admitted in our center again on of February 12, 2014. On admission, he was afebrile with stable vital signs, but he had herpetic lesions on lips. An abdominal examination showed shifting dullness, bulging flanks, and mild generalized tenderness. Bowel sounds were normal. His course in the hospital was without fever.
Abdominal sonography revealed ascites, few small lymph nodes in para-aortic region measuring at most 4 mm in diameter, an enlarged spleen, and a normal transplanted liver. An abdominal computer tomography scan was unremarkable except for presence of ascites and splenomegaly. Specifically, there was no evidence of perforation of hollow viscus or intra-abdominal collection.
Laboratory data and serial abdominal fluid analysis are shown in Tables 1 and 2. Abdominal fluid staining with a Gram stain and an acid-fast stain was negative. Serial liver enzymes and urinalysis were normal. Blood culture and ascetic fluid culture for microorganisms including aerobic, anaerobic, mycobacteria, and fungi were negative.
With the impression of peritonitis and herpes labialis, acyclovir, imipenem, vancomycin, and metronidazole were started intravenously. No change in diarrhea, abdominal pain, and ascites was noticed after 3 days of treatment.
On day 3 of the admission, a colonoscopy was done for the patient, which showed patchy inflammation of the whole length of colon with more severe involvement on right side of the colon, and normal appearing terminal ileum. Biopsy confirmed CMV colitis on cecal and sigmoid but not on rectal biopsies.
Three days after admission, the results of CMV PCR of first abdominal fluid were reported positive at 500 copy/mL, while serum PCR for CMV, as well as PP65 antigenemia, were negative. Polymerase chain reaction of abdominal fluid for Candida also was negative.
At this time, intravenous ganciclovir was started and acyclovir discontinued. After 1 week’s treatment with ganciclovir, diarrhea and abdominal pain stopped. A physical examination at this time was normal with no shifting dullness. An abdominal sonography showed only minimal fluid. The patient was discharged on valganciclovir for another 6 weeks. The patient is now well with no recurrence of ascites or fever, and with completely normal paraclinical data including abdominal sonography after 1 year follow-up.
Cytomegalovirus disease after solid-organ trans-plant, either in the form of primary infection in recipients with negative serology for CMV or reactivation in CMV-positive recipients, is one of the most common infections in the first 6 months after transplant.1 The disease may present with nonspecific signs and symptoms such as fever, malaise, body pain, leukopenia, or it may present with signs and symptoms of organs involved such as colon, liver, lung, or retina.3
Cytomegalovirus peritonitis is considered a rare manifestation of CMV disease. This rare manifestation was initially reported in patients with acquired immunodeficiency syndrome in the pre-HAART era. Most reported cases had associated colon perforation because of CMV colitis,4,5 but cases of primary peritonitis without gut perforation have been reported.2
Although CMV peritonitis also has been reported after solid-organ transplant, it is rare and mostly associated with gut perforation. In a series of CMV infections after solid-organ transplanted patients from Spain, 2 cases of peritonitis were reported but both had intestinal perforation.6 Another series of 3 patients with CMV-associated peritonitis were reported after renal transplant, but all had sigmoid perforation documented on laparotomy.7 There is one report of CMV peritonitis without gut perforation after renal transplant in a patient who was previously on peritoneal dialysis.8 In that case, induction of immunosuppressive treatment was performed with the anti–CD-52 antibody alem-tuzumab combined with methylprednisolone. The patient presented 1 month after transplant with severe abdominal pain. The authors’ explanation for this presentation was intense immunosuppression in the setting of positive CMV status of the recipient.
The present case is probably the second case of CMV peritonitis without gut perforation after a solid-organ transplant and the first such case after liver transplant. In this case, the CMV infection was the result of reactivation, as the patient had positive serology for CMV infection before transplant. The use of immunosuppressive drugs including mycophenolate mofetil may have contributed to reactivation of CMV. Because of new-onset ascites in the setting of colitis, our initial impression was gut perforation with secondary peritonitis. We started antibiotics to cover this possibility from beginning, but the absence of clinical signs of peritonitis, lymphocyte dominancy of cell count in serial ascetic fluid analysis, negative cultures, and negative CT scan of the abdomen excluded this possibility. There was also no response to antibiotics.
The other consideration was tuberculosis. Although our patient had negative preoperative evaluation for tuberculosis, reactivation of latent tuberculosis in the form of extrapulmonary tuberculosis in peritoneum was still a possibility.9 However, we could not detect tuberculosis in the ascitic fluid in PCR, culture, and acid-fast stain. Further, concentrations of adenosine deaminase were not raised. This test is considered a marker of peritoneal tuberculosis with acceptable sensitivity and specificity.10
The detection of CMV in PCR of the ascetic fluid and good response to ganciclovir with rapid resolution of ascites all favored the diagnosis of CMV peritonitis without perforation in this case of CMV colitis after liver transplant. One might consider negative blood PCR and PP65 antigenemia against the diagnosis of CMV disease in this patient, but these laboratory tests in the setting of local manifestations of CMV infection might be negative, especially in CMV-positive recipients, and the negative results should not deviate attention from this infection.11
In CMV syndrome, many centers continue treatment, either with ganciclovir or valganciclovir for 6 weeks, with 3 negative blood PCRs, and then continue therapy with reduced dosage for at least 3 months to avoid recurrence.12 For local manifes-tations, like CMV colitis, there is much less agreement between centers.13
We treated our patient with ganciclovir 10 mg/-kg/day during the first week, and continuing with valganciclovir 900 mg twice daily for the next 2 weeks, and then valganciclovir 900 mg daily for another 3 weeks. Our plan was to continue antiviral medications further for 3 months to avoid recurrence, but the patient could not afford this therapy because of his economic situation. Despite this, there was no recurrence of disease in any form in 12 months’ follow up. This may raise concern about the duration of treatment and rational for prophylaxis of CMV infection after treatment of CMV local disease.
The pathogenesis of CMV peritonitis in this setting is not clear. It could be because of translocation of virus from inflamed large bowel secondary to superimposed CMV colitis on preexisting ulcerative colitis. Other explanations, such as viremia with superimposed infection of the ascites fluid, seem less likely, as our patient did not have ascites before presentation at the hospital.
An argument could be raised as to why our patient did not receive prophylactic treatment for CMV because his CMV serology was positive before transplant. In our center, our current protocol in adults with positive serology for CMV is to monitor them with weekly assays for pp65 antigen and CMV quantitative PCR and start treatment accordingly. We found this protocol more cost effective in our setting, with more than 90% of adult recipients being serologically positive for CMV.
In conclusion, this case report represents the need for suspicion of CMV in the appropriate setting in postliver transplant. Even in the absence of perforation, CMV could present with peritonitis. After exclusion of other common causes of peritonitis after a liver transplant, CMV should be considered.
Volume : 15
Issue : 1
Pages : 106 - 109
DOI : 10.6002/ect.2014.0213
From the 1Health Policy Research Center; the 2Gastroenterohepatology
Research Center; and the 3Shiraz Transplant Research Center, Shiraz
University of Medical Sciences, Shiraz, Iran
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Kamran B. Lankarani, Health Policy Research Center, Shiraz University of Medical Sciences, Zand Blvd. postal code 71348, Shiraz, Iran
Phone: +987 13 230 9615
Fax: +987 13 230 9615
Table 1. Laboratory Data During Hospitalization
Table 2. Abdominal Fluid Analysis During Hospitalization