hsv infection is a well - known , chronic persistent viral infection of varying recurrence rate .
it has been reported that hsv can be the cause of esophagitis , as seen in immunodeficient patients under therapeutic immunosuppression [ 2 , 3 ] .
although the risk of a hsv infection appears to be correlated to a degree of depression of the cellular immune system , hsv infection is a rare condition after organ transplantation and consecutive immunosuppression therapy .
hsv manifestations after transplantation have been described ; however , usually a time delay between organ transplantation and hsv infection  corresponding with the time necessary for the achievement of full therapeutic immunosuppression  is seen .
the herpes virus group consists of the herpes zoster virus and the herpes simplex virus [ 1 , 4 ] , the former occurring much more often as a painful post - transplant infection [ 5 , 6 , 7 ] . infections or recurrences of hsv after transplantation are much more uncommon and comprise case reports describing esophagitis and nephritis [ 8 , 9 ] .
hsv manifestations as esophagitis are extremely rare ; they have been seen in singular cases after kidney [ 8 , 9 , 10 ] , liver , heart   and bone marrow transplant .
it was itoh et al . who investigated the relationship between histopathological features and hsv associated esophagitis after transplantation . reporting on 1,307 autopsies covering a 10-year period
, they detected a prevalence of 1.4% ( 14 out of 1,307 ) . a hsv related ulcer of the gastroesophageal junction after transplantation has not been reported so far .
we describe the very rare case of a seronegative herpes simplex induced ulcer occurring in the early postoperative phase after liver transplantation .
a 64-year - old man with a cryptogenic child pugh c liver cirrhosis suffered from hepatic encephalopathy , massive ascites , splenomegaly and consecutive thrombocytopenia and anemia .
on postoperative day 1 diffuse bleeding mandated relaparotomy , further complicated by systemic coagulopathy and transfusion requirements of 44 units of rpc , 118 units of ffp and 12 units of thrombocytes . a consecutive abdominal compartment syndrome and a hepatorenal syndrome necessitated haemodialysis for 5 days , during which programmed relaparotomies and abdominal washouts were performed . at day 10 ,
the patient reported dysphagia for liquids and solids without pain on swallowing , nausea and vomiting .
on esophagogastroduodenoscopy a huge ulcer situated at the gastroesophageal junction was discovered as well as moderate gastritis with normal duodenum mucosa ( fig .
the histopathological examination of biopsies taken from the border and center of the ulcer showed epithelial lesions rich in fibroblasts and capillaries which were highly suspicious of viral infection .
the picture was enlarged by megacaryocytes with large lobulated nuclei showing milk glass foggy karyoplasm .
on immunohistochemical analysis a distinct positive reaction for ntb - hsv antibodies was seen ( fig .
histopathological and immunohistochemical examinations showed a squamous cell epithelium with focal exasperated hsv loci without any sign of neoplasia .
immediate systemic antiviral therapy was started with acyclovir ( 15 mg / kg / day ) plus high - dose ppi ( esomeprazole ) ( 50 mg twice a day ) led to a complete remission of all clinical gastrointestinal symptoms within 48 h. the following course was uneventful ; repeated endoscopy seven days later revealed a complete remission of the previous ulcer of the gastroesophageal junction .
the patient was discharged in good health to the outpatient department with a good hepatorenal function .
a 64-year - old man with a cryptogenic child pugh c liver cirrhosis suffered from hepatic encephalopathy , massive ascites , splenomegaly and consecutive thrombocytopenia and anemia .
on postoperative day 1 diffuse bleeding mandated relaparotomy , further complicated by systemic coagulopathy and transfusion requirements of 44 units of rpc , 118 units of ffp and 12 units of thrombocytes . a consecutive abdominal compartment syndrome and a hepatorenal syndrome necessitated haemodialysis for 5 days , during which programmed relaparotomies and abdominal washouts were performed . at day 10 ,
the patient reported dysphagia for liquids and solids without pain on swallowing , nausea and vomiting .
on esophagogastroduodenoscopy a huge ulcer situated at the gastroesophageal junction was discovered as well as moderate gastritis with normal duodenum mucosa ( fig .
the histopathological examination of biopsies taken from the border and center of the ulcer showed epithelial lesions rich in fibroblasts and capillaries which were highly suspicious of viral infection .
the picture was enlarged by megacaryocytes with large lobulated nuclei showing milk glass foggy karyoplasm .
on immunohistochemical analysis a distinct positive reaction for ntb - hsv antibodies was seen ( fig .
histopathological and immunohistochemical examinations showed a squamous cell epithelium with focal exasperated hsv loci without any sign of neoplasia .
immediate systemic antiviral therapy was started with acyclovir ( 15 mg / kg / day ) plus high - dose ppi ( esomeprazole ) ( 50 mg twice a day ) led to a complete remission of all clinical gastrointestinal symptoms within 48 h. the following course was uneventful ; repeated endoscopy seven days later revealed a complete remission of the previous ulcer of the gastroesophageal junction .
the patient was discharged in good health to the outpatient department with a good hepatorenal function .
hsv infection is a common and life - long infection ; it may recur at any time as a reaction to different stimuli .
the possible association between hsv-1 infection and duodenal ulcer in immunocompromised patients has been described before . up to now , esophageal or esophagogastric ulcers following therapeutic immunosuppression have not yet been described . this is more than surprising , taking into account reports which describe hsv esophagitis after kidney transplantation , allogeneic liver transplantation , heart transplantation   and bone marrow transplantation .
report hsv hepatitis 4 years after transplantation , it could be speculated that ulceration would occur during the same period mentioned .
nevertheless , we report the case of a hsv ulcer of the gastroesophageal junction 17 days after allogeneic liver transplantation , which was diagnosed by endoscopy , histopathology and immunohistochemistry .
it is known that hsv infections can occur in immunocompromised patients and lead to concomitant seropositivity .
while in these patients preventive acyclovir medication may be applied , our patient had not been diagnosed with hsv infection before and was hsv - pcr negative .
antiviral medication was started in our patient from the date of confirmation of the hsv infection on . in general
it has been known that patients with combined hepatorenal dysfunctions have an increased risk for reactivation of hsv .
furthermore , cd4+/cd8 + depleted patients with liver cirrhosis have an increased risk for hsv recurrence [ 5 , 6 , 7 ] .
prophylactic antiviral medication can be chosen at least in patients at risk for cmv infection .
late infectious sequelae may thus be avoided , while costs and drug side effects may simultaneously increase . in our patient
we report the early postoperative reactivation of hsv , leading to ulcer in an uncommon place
. this might be due to a combination of hepatorhinorrhagia and massive transfusion which may have led to profound immunosuppression in our patient , although therapeutic immunosuppression was shown to be within therapeutic range .
the massive bleeding may have led to the depletion of cd4+/cd8 + cells in our patient , which further added to the immunocompromised state .
it can not be excluded that intraoperative hypotension and systemic catecholamine application added to a mucosal hypoperfusion state with impaired microcirculation , thus increasing the vulnerability of the gastroesophageal junction .
this may have led to a locally reduced immune surveillance in the gastrointestinal tract , which is regularly exposed to local microtraumata and infectious agents .
we could not identify any causative factor leading to the lesion in the esophagus  nor elsewhere in the gastrointestinal tract .
it is not known whether h2 blocking agents improve the healing in uncomplicated hsv ulcers .
we feel that especially patients on steroids need mucous protection , thus the drug doses of ppi were doubled with diagnosis of hsv ulcer . nevertheless , despite massive transfusion , immunocompromised situation and programmed relaparotomies , the patient recovered without sequelae , even in terms of immunocompetence .
the single ulcer found at the gastroesophageal junction was the only expression of hsv reactivation .
it was macroscopically impossible to deduce the hsv infection from the ulcer visualized on endoscopy .
astonishingly polymerase chain reaction revealed a negative serum anti - hsv titre pre- and postoperatively .
this case report demonstrates that even in the early postoperative phase after transplantation , hsv ulcer of the gastroesophageal junction can occur .
herpes ulcer , although very uncommon , must be added to the differential diagnosis in early postoperative ulcers of the gastroesophageal junction in immunocompromised patients .
fast diagnosis and targeted therapy may lead to a full and unproblematic recovery , as seen in this patient . as it may be difficult to confirm a hsv lesion by serum sample analysis alone
all authors certify that they have no commercial association that might pose a conflict of interest in connection with the submitted article , and disclose any financial and personal relationship with other people and organisations that could influence their work .
 herpes simplex infection is characterized by acute or subacute infection , often followed by a chronic carrier state . 
 consecutive recurrences may flare up if immunocompromise occurs . 
 herpes simplex associated esophagitis or duodenal ulcer have been reported in immunocompromised patients due to neoplasm , hiv / aids or therapeutically induced immune deficiency . here 
 we report the case of an hsv - dna seronegative patient who developed grade iii dysphagia 13 days after allogeneic liver transplantation . 
 endoscopy revealed an esophageal - gastric ulcer , and biopsy histopathology showed a distinct fibroplastic and capillary ulcer pattern highly suspicious for viral infection . 
 immunohistochemistry staining revealed a distinct nuclear positive anti - hsv reaction . 
 antiviral therapy with acyclovir and high - dose ppi led to a complete revision of clinical symptoms within 48 h. repeat control endoscopy after 7 days showed complete healing of the former ulcer site at the gastroesophageal junction . 
 although the incidence of post - transplantation herpes simplex induced gastroesophageal disease is low , the viral hsv ulcer may be included into a differential diagnosis if dysphagia occurs after transplantation even if hsv - dna pcr is negative . 
Introduction
Case Report
Patient History and Surgery
Histopathology
Discussion
Conflict of Interest