|Year : 2017 | Volume
| Issue : 3 | Page : 163-165
Fulminant hepatic failure secondary to herpes simplex virus type 2 infection in a renal allograft recipient
Amaravadi Ayyappa, Manisha Sahay, Kiranmai Ismail, P Sharmas Vali
Department of Nephrology, Osmania Medical College, Hyderabad, Telangana, India
|Date of Web Publication||20-Dec-2017|
Dr. Manisha Sahay
Department of Nephrology, Osmania General Hospital, Afzalgunj, Hyderabad - 500 012, Telangana
Source of Support: None, Conflict of Interest: None
Herpes simplex virus is a relatively less reported cause of hepatitis post transplant. Patient presented post transplant with fever, jaundice and rash. He was evaluated for causes of hepatitis. He was found to be HSV positive and was treated with Acyclovir. He developed fulminant hepatic failure. Hepatitis is an uncommon manifestation of HSV and should be considered in all post transplant patients with jaundice.
Keywords: Fulminant hepatitis, herpes simplex virus, renal transplantation
|How to cite this article:|
Ayyappa A, Sahay M, Ismail K, Vali P S. Fulminant hepatic failure secondary to herpes simplex virus type 2 infection in a renal allograft recipient. Indian J Transplant 2017;11:163-5
|How to cite this URL:|
Ayyappa A, Sahay M, Ismail K, Vali P S. Fulminant hepatic failure secondary to herpes simplex virus type 2 infection in a renal allograft recipient. Indian J Transplant [serial online] 2017 [cited 2021 Apr 15];11:163-5. Available from: https://www.ijtonline.in/text.asp?2017/11/3/163/221193
| Introduction|| |
Herpes simplex virus Type 1 (HSV-1), also known as human herpesvirus 1, an alphavirus, often infects individuals early in life, leading to seroprevalence of 50%–80% among adults. HSV-2 spreads through sexual contact.
Viral hepatitis is an infrequent manifestation of herpes simplex virus (HSV). Both HSV-1 and HSV-2 can cause fulminant hepatitis, mainly in immunocompromised patients, and prognosis is generally poor. HSV-induced hepatitis accounts for only 1% of all the acute liver failure cases and only 2% of all viral cases of acute liver failure.,
There are two types of HSV, HSV-1 and HSV-2. More commonly HSV-1 causes infections around the mouth and HSV-2 causes infections of the genital region. Infection is acquired by the direct contact with the body fluids or lesions of the infected individual. After recovery from infection, viruses are transmitted along the sensory nerves to the cell bodies where they reside for longtime. Disease may recur when the patient's immune function is compromised.
Both HSV-1 and HSV-2 can cause fulminant hepatic failure that is seen mainly in immunocompromised patients. Symptoms may include fever, flu-like symptoms, abdominal pain, icterus, and vesicular skin lesions.
Prognosis for fulminant HSV-induced hepatitis is generally poor. Diagnosis can be established either by viral culture or by DNA polymerase chain reaction (PCR) from the specimens – fluid from vesicles or blood.
The following case report describes a renal allograft recipient with fulminant HSV-2 hepatitis.
| Case Report|| |
A 30-year-old male with end-stage renal disease secondary to chronic interstitial nephritis, with native kidney disease being reflux nephropathy was on maintenance hemodialysis twice a week for 8 months. He was vaccinated for hepatitis B. His pretransplant cytomegalovirus (CMV) was negative. He underwent live-related renal allograft transplantation in June 2010 with mother as the donor. Posttransplant, he was kept on triple immunosuppression – tacrolimus, mycophenolate mofetil, and prednisone. Induction therapy was not given. He had immediate good graft function posttransplant and was discharged in 2 weeks' time.
He had acute cellular rejection (peak creatinine 2.4 mg/dl) 10 months posttransplant; he was treated with pulse steroids. He recovered and his serum creatinine decreased to 1.4 mg/dl. The patient developed new onset diabetes after transplantation 1 year post transplant and was on treatment with insulin Mixtard (30/70) since then. The patient had a second episode of graft dysfunction (with peak creatinine of 2.2 mg/dl) 3 years posttransplant; he was biopsied and was found to have mild acute tubular necrosis. The patient was managed conservatively and serum creatinine decreased to 1.6 mg/dl. The patient had a history of herpes zoster, 2 years posttransplant, and improved after treatment with acyclovir.
During the current admission, 7 years post transplantation he presented to the outpatient department with complaints of fever with chills, abdominal pain, and jaundice. The patient has been started on broad-spectrum empiric antibiotics and appropriate investigations sent. Two days after admission, the patient developed vesicular rash over the face and right forearm and lesions progressed to involve the right hand and right leg sparing the trunk and other areas of the body.
On examination, the patient had temperature of 38°C, jaundice, and right upper quadrant tenderness. Initial investigations revealed hemoglobin of 10.2 g/dl, leukocyte count of 8200 cells/mm 3, platelet count of 1.2 lakhs/mm 3, blood urea of 60 mg/dl, and serum creatinine of 2 mg/dl; liver function tests (LFTs) revealed serum bilirubin – 16 mg/dl; direct bilirubin – 9.0 mg/dl, aspartate aminotransferase (AST) – 1100 IU/ml, alanine aminotransferase (ALT) – 2200 IU/ml, and alkaline phosphatase – 500 IU/ml; prothrombin time/international normalized ratio (PT/INR) – 1; and serum albumin was low (2.2 g/dl), PT/INR – 1. Urine and blood cultures were sterile, fasting lipid profile was normal, and serum ferritin was normal. Follow-up complete blood picture 2 days later revealed pancytopenia with Hb of 8.2 g/dl, white blood cell of 2,200 cells/mm 3, and platelet count of 12,000 cells/mm 3.
Serological tests for viral hepatitis include hepatitis B (anti-HBV antibody and HBsAg – negative); hepatitis C (anti-HCV antibody – negative); hepatitis A (anti-HAV antibody test – negative); and hepatitis E (anti-HEV antibody – negative). Malaria, dengue serology, and IgM antileptospiral antibody tests were negative. Anti-HSV-1 IgM antibody was negative; however, anti-HSV-2 IgM antibody was positive; ultrasonography abdomen showed mild hepatomegaly. The liver architecture was normal.
After 5 days of admission, the patient had persistent fever, despite empiric antibiotics, and the patient developed bleeding manifestations in the form of bleeding from the injection sites, petechiae and purpura. Repeat blood cultures were sent. The patient continued to have persistent fever, urine and blood cultures, however, remained negative, and serum transaminases continued to increase. Laboratory investigations revealed LFTs, serum bilirubin – 8.5 mg/dl, AST – 2109 IU/L, ALT – 3198 IU/L, PT/INR – 2.6, and serum albumin – 2.2 g/dl.
Other investigations including HCV RNA PCR, HSV-1 DNA PCR, CMV DNA PCR, and parvovirus B19 DNA PCR were negative. However, HSV-2 DNA PCR was positive.
The patient was started on intravenous (IV) acyclovir at a dose of 10 mg/kg body weight every 8th hourly, but this could not prevent progressive liver failure. Liver biopsy was considered but could not done in view of persistent severe coagulopathy. Later, the patient developed abdominal distension, which was gradually progressive in nature to massive ascites, associated with mild pedal edema.
Follow-up ultrasound was done in view of ascites and it revealed hepatomegaly with irregular surface and ascites; Doppler splenoportal axis was suggestive of portal hypertension; FibroScan – 40.4 KPa; and upper gastrointestinal endoscopy showed Grade 2 esophageal varices.
The patient continued to develop rapidly progressive liver failure despite specific treatment with acyclovir, and approximately 10th day after admission, the patient developed hepatic encephalopathy, which progressed from Grade 1 to Grade 3, with serum ammonia − 110 μM (10–55). The patient was registered under high priority for liver transplantation. However, the patient condition deteriorated and the patient expired about 2 weeks after admission despite our efforts.
| Discussion|| |
Here, we report a case of fulminant hepatic failure due to disseminated HSV-2.
Fulminant hepatitis due to HSV may be caused by both HSV-1 and HSV-2. The fulminant hepatitis cases reported previously almost exclusively occurred in immunocompromised patients or in pregnant woman in the third trimester and rarely seen in immunocompetent individuals. HSV hepatitis presents with nonspecific flu-like symptoms including fever, myalgia, and abdominal pain, and only 30%–50% of patients show characteristic herpetic mucocutaneous lesions.,,, Laboratory investigations often show leukopenia, thrombocytopenia, and coagulopathy.,,
Fulminant hepatitis due to HSV in renal transplant individuals almost always had a fatal outcome.,,,,, However, as in immunocompetent individuals, milder episodes of HSV hepatitis can also occur in immunocompromised individuals.
Although severe hepatitis has a treatable cause, it has very poor prognosis. This may be due to delay in diagnosis, particularly in patients where the typical herpetic mucocutaneous lesions are absent, and even in patients with typical mucocutaneous lesions, the possibility of HSV hepatitis is rarely considered.
Treatment options include IV acyclovir with or without foscarnet. The extent of the disease at the initiation of therapy is an important factor predicting the responsiveness to medical treatment, and with early initiation of treatment, outcomes may be improved.,,, In view of this, many recommend empirical treatment with acyclovir in patients' acute hepatitis of unknown origin. At an advanced stage, liver transplantation may improve the prognosis.
Diagnosis can be established with serological tests (IgM anti-HSV antibodies), HSV DNA PCR, and/or viral cultures. The gold standard for the diagnosis of HSV hepatitis is liver biopsy with culture and immunohistochemical staining. However, liver biopsy is not always possible due to coagulopathy. The pathognomonic finding for HSV hepatitis on liver biopsy specimen is the presence of Cowdry type A inclusions surrounded by clear halo.,
Taking these into considerations, HSV should be considered in the differential diagnosis in all transplant patients presenting with fever, abdominal pain, jaundice, and elevated transaminases with or without the typical herpetic mucocutaneous lesions.
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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