|Year : 2021 | Volume
| Issue : 3 | Page : 240-242
Herpes simplex virus-2 related fulminant hepatic failure in liver transplant recipient
Sunil Raviraj Kothakota, Madhu Sasidharan, Harish Kareem, Ajith Kumar Nair
Department of Gastroenterology, KIMS Hospital, Thiruvananthapuram, Kerala, India
|Date of Submission||21-May-2021|
|Date of Decision||07-Aug-2021|
|Date of Acceptance||07-Aug-2021|
|Date of Web Publication||28-Dec-2021|
Dr. Sunil Raviraj Kothakota
Department of Gastroenterology, KIMS Hospital, Anayara, Thiruvananthapuram - 695 029, Kerala
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kothakota SR, Sasidharan M, Kareem H, Nair AK. Herpes simplex virus-2 related fulminant hepatic failure in liver transplant recipient. J Med Evid 2021;2:240-2
|How to cite this URL:|
Kothakota SR, Sasidharan M, Kareem H, Nair AK. Herpes simplex virus-2 related fulminant hepatic failure in liver transplant recipient. J Med Evid [serial online] 2021 [cited 2022 Aug 10];2:240-2. Available from: http://www.journaljme.org/text.asp?2021/2/3/240/333955
| Introduction|| |
Infections continued to be one of the common morbidities in transplant recipient patients despite improvement in management. Bacterial agents are a common source of infection followed by viral pathogens. Among viral infections, the most common agent is cytomegalovirus (CMV), whereas herpes simplex virus (HSV) infection is rare., Cutaneous involvement is most common with HSV infection due to mucocutaneous shedding of virus, however, disseminated infection causes significant morbidity in either hematopoietic stem cell or solid organ transplant recipients due to exposure to immunosuppressive medication in post-transplant period., Herein, we report a case of end-stage liver disease who underwent a deceased donor liver transplant (DDLT) and developed fatal fulminant hepatic failure during the immediate post-operative period due to HSV-2 infection.
| Case Report|| |
A 50-year-old male with cryptogenic decompensated cirrhosis with portal hypertension, underwent DDLT-surgery after thorough workup. Recurrent hepatic encephalopathy and refractory ascites were his co-morbidities. At the time of transplant surgery, he was in Child-Turcotte-Pugh Stage C and his model for end-stage liver disease-sodium (MELD-Na) score was 37. He had hepatic hydrothorax for which ultrasound-guided pleurocentesis immediately before the transplant procedure. Intraoperative course was uneventful and the presence of normal anatomy led to the completion of biliary and vascular reconstruction without any difficulty. During the post-operative period, he recovered well, extubated after 24 h and started on oral feeds. He was given antibiotics, anti-fungal along with immunosuppressive medication (prednisolone, tacrolimus and mycophenolate mofetil) as per our hospital protocol. The recipient was also started on oral valganciclovir (900 mg OD) from day-2 onwards for prophylaxis of CMV infection as the IgG serology was positive in recipient. Donor serology for CMV was negative, but his anti-HSV IgG was found positive during pretransplant workup. During the initial 4 days, all parameters (clinical, haematological and biochemical) improved well and ultrasound doppler at frequent intervals assured functioning of graft. On post-operative day-5, rise in liver enzymes (aspartate transferase, alanine transferase) was noted along with hyperbilirubinemia, thrombocytopenia and derangement of coagulation parameters [Table 1]. A cycle of steroids was given in view of biochemical acute cellular rejection on the same day. Workup for infectious causes was done. Herpes virus serology (anti-HSV-2 IgM) and qualitative real-time polymerase chain reaction (RT-PCR) assay for HSV-2 were found to be positive. Markers for cytomegalovirus (both serology and viral PCR), hepatitis B virus, hepatitis A and E virus infections and other bacterial and fungal infections were negative. Oral valganciclovir was continued and intravenous acyclovir (500 mg TID) was added on day-6. Simultaneously liver biopsy was performed. Histopathological examination showed perivenular and periportal necrotic inflammation along with few areas of hepatocanalicular cholestasis [Figure 1]a and intracellular inclusions in the periphery of necrosis [Figure 1]b. His clinical condition worsened rapidly after the initial spike in liver enzymes. He developed hepatic encephalopathy, acute respiratory distress syndrome, acute kidney injury along with further worsening of liver function and coagulation parameters [Table 1]. He needed mechanical ventilation and ionotropic support. As there was no response to conventional measures, plasma exchange was also given. However, despite all measures, his clinical profile was not improved and subsequently on post-operative day-8 he succumbed to the disease.
|Table 1: Haematological and biochemical parameters of recipient during posttransplant period|
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|Figure 1: Liver histopathology (H and E) showing neutrophilic inflammation with areas of confluent necrosis (a) and inclusion bodies (arrows) in peripheral region of necrosis (b)|
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| Discussion|| |
HSV is an enveloped virus with a double-stranded DNA genome. Both HSV-1 and HSV-2 have 50% homology in genome sequence, however, HSV-1 is more prevalent than HSV-2 in the general population (27%–60% vs. 0.8%–21%). Because of tropism for oral (HSV-1) and genital (HSV-2), epithelium mucocutaneous manifestations are most common. However, in immunosuppressed individuals, disseminated infection can occur which manifests as diffuse cutaneous lesions, meningitis or fulminant hepatitis. HSV accounts for <1% of all causes of acute liver failure and 2% of all viral aetiologies. In patients underwent solid organ transplant, reactivation of latent infection is the common source of HSV manifestations, however, it can also transmit through a donor. In our case, the source of infection could be the graft as recipient's HSV serology before the transplant was negative and the donor's status was positive. HSV prophylaxis (acyclovir 400–800 mg BD or valacyclovir 500 mg BD or famciclovir 500 mg BD for 1 month) during post-transplant period is recommended if either donor's or recipient's HSV IgG was found positive during the pre-transplant workup. If recipient qualifies the criteria for both CMV and HSV prophylaxis as in our case, oral valganciclovir (900 mg once daily) is enough to prevent both infections.
Diagnosing HSV-related hepatitis at an early stage is difficult and mortality associated with acute liver failure is very high, hence a high index of suspicion and early antiviral therapy is imperative. Acute rejection, other viral hepatitis (acute HBV or CMV hepatitis) and ischemia-reperfusion injury are the common differentials which need to be ruled out. In most of the active cases of HSV-related hepatitis, viremia may present, hence virologic tests in serum can diagnose the disease with accuracy, however, molecular assay (i.e. PCR) is preferable to serology. Classical PCR may take a long time, but RT-PCR can give results within 3 h. Liver histology is an important diagnostic tool. As in our case, extensive necrotic inflammation and inclusion bodies on histopathology are the clues for HSV infection. Immunostaining for HSV can confirm the diagnosis which was not done in our subject. Intravenous acyclovir 10 mg/kg at an 8-hour interval is the definitive treatment for active HSV infection which was administered to our patient. Mortality in liver transplant recipients with HSV hepatitis was reported as 38% with treatment and 100% without treatment. Apart from anti-viral agents in treating disseminated HSV infection, plasma exchange also has a potential role, which was tried in our patient. However, despite all measures, we could not save our patient. HSV hepatitis should be considered an infectious disease emergency and empirical therapy should be considered for suspected cases, particularly in countries such as India where the prevalence of latent HSV infection is high. The early diagnosis and treatment of HSV hepatitis in liver transplant recipients can decrease the mortality.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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