Regarding diarrhea in liver transplant recipients: Etiology and management.

Abstract

In the August 2005 edition of your journal, the etiology and management of diarrhea after liver transplantation (LT) was discussed in an extensive review by Ginsburg and Thuluvath.1 Diarrhea occurred in about 10% of adult patients following LT.2 The authors reported post-transplant episodes of acute diarrhea to be frequently related to immunosuppressive medications such as mycophenolate mofetil, tacrolimus and sirolimus, and infectious agents with Clostridium difficile (CD) being the most relevant one. Overall, CD was causative in about one third of all cases.1 Second in line for infectious reasons were Cytomegalovirus associated infections (15%-40%). A variety of other viruses also rarely were responsible for episodes of diarrhea after LT.1 Rotavirus (RV), a member of the family Reoviridae, was also mentioned.3 Rotavirus is the most common cause of viral enteritis in infants and young children,3-5 with an estimated 9 million annual cases of severe diarrhea globally, causing approximately 87,0000 deaths worldwide in 1985.5 Rotavirus infections are commonly transmitted fecal-orally and often require hospital admission because of excessive fluid losses in children up to 5 years.3-5 In immunocompromised or elderly patients an even more severe course of the disease has been reported.3, 4 Only symptomatic treatment is currently recommended for RV infection, as treatment with various antiviral agents or immunoglobulins has shown disappointing results.4 We would like to report our institutional findings on RV-related enteritis following LT during a ten-years period between 1994 and 2004. We investigated infectious causes of enteritis in 305 adult and 39 pediatric liver transplant recipients. Testing for Rotavirus, using an immunochromatografic- or enzyme-linked - immunosorbent-assay, was routinely performed in all pediatric organ recipients and from 2003 also in all adult liver recipients who presented with diarrhea. We found a much higher incidence of Rotavirus-associated enteritis compared to the numbers reported in the literature (1.3-2.6%).4 Out of 344 liver recipients, RV-associated diarrhea was diagnosed in 16 patients (4.7%), all of them presenting with prolonged diarrhea and significant fluid loss. The median onset of RV enteritis was 117 (11-2159) days post transplant. While RV caused enteritis in three adult LT recipients, pediatric liver recipients were found to be at a much higher risk. Thirteen out of the 39 children, i.e. 33.3%, had RV-infection. Two children presented with several episodes of RV associated diarrhea. Within the same 344 patients, 22 (6.4%), including two multivisceral transplant recipients, had CD infection. Six liver recipients (1 adult and 5 pediatrics) had both RV and CD infections with simultaneous isolation of both pathogens. All developed secondary infection including infected ascites (n=1), pneumonia (n=1) and multiorgan failure with death (n=1 pediatric). Clostridium difficile colitis was diagnosed in ten children (28.2%). Therefore, Rotavirus was the most common pathogen causing post-transplant diarrhea in our pediatric liver population, while in the adult population, Clostridium difficile was the most common enteric infection. None of our patients with RV or CD enterocolitis required surgical intervention, however, all patients were severely ill with significant fluid and electrolyte losses, requiring intensive care and prolonged fluid resuscitation. As previously reported, during RV enteritis a rise in tacrolimus trough levels was also observed in our patients,4 and reduction of immunosuppression was carried out in all our patients. We feel it is important to consider Rotavirus as a possible cause of diarrhea also in adults. Even co-infection might be observed. In conclusion, liver recipients with diarrhea should undergo stool testing for RV and CD.4 In order to avoid nosocomial outbreaks, pediatric and adult liver recipients should be kept separated. In our series infection was the most common cause of diarrhea with CD and RV being by far the most common pathogens. Once available, pre-transplant vaccination against RV might be considered for adult solid organ recipients.4 I. Stelzmueller MD*, M. Biebl MD*, I. Graziadei MD , S. Wiesmayr MD , R. Margreiter MD, PhD*, H. Bonatti MD*, * Department of General, Thorax and Transplant Surgery, Innsbruck Medical University, Department of Gastroenterology and Hepatology, Innsbruck Medical University, Department of Paediatrics, Innsbruck Medical University.