Case ReportAcute Liver Failure due to Disseminated VaricellaZoster Infection

Elizabeth Caitlin Brewer and Leigh Hunter

Methodist Hospitals of Dallas 1441 N Beckley Ave Dallas TX 75203 USA

Correspondence should be addressed to Elizabeth Caitlin Brewer drelizabethbrewergmailcom

Received 6 June 2018 Accepted 3 September 2018 Published 27 September 2018

Academic Editor Melanie Deutsch

Copyright copy 2018 Elizabeth Caitlin Brewer and Leigh Hunter This is an open access article distributed under the CreativeCommons Attribution License which permits unrestricted use distribution and reproduction in any medium provided theoriginal work is properly cited

Acute liver failure (ALF) can be due to numerous causes and result in fatality or necessitate liver transplantation if left untreatedPossible etiologies of ALF include ischemia venous obstruction medications toxins autoimmune hepatitis metabolic andinfectious causes including hepatitis A-E varicella-zoster virus (VZV) cytomegalovirus (CMV) herpes simplex virus (HSV)Epstein-Barr virus (EBV) and adenoviruswithVZVbeing themost rarely reported Pathognomonic skin lesions facilitate diagnosisof VZV hepatitis but definitive diagnosis is secured with liver biopsy tissue histopathology culture and specific VZV polymerasechain reaction (PCR) Antiviral treatment with intravenous acyclovir can be effective if initiated in a timely manner howevercomorbidities and complications frequently result in high mortality especially in immunocompromised hosts as exemplified inthis case presentation

1 Introduction

Varicella zoster virus can cause two clinical syndromes pri-mary (chickenpox) and secondary (herpes zoster) Primaryinfection presents mainly in children with a generalizedvesicular rashThe virus then establishes latency in the dorsalroot ganglia and can later reactivate as ldquoshinglesrdquo or herpeszoster a localized dermatomal vesicular eruption Cuta-neous and extracutaneous dissemination can occur mostcommonly in immunocompromised patients [1] Fulminanthepatic failure due to VZV hepatitis is even more rare anddeadly In review of the literature only 8 adult cases of acuteliver failure from VZV were found of which only 2 survived[2ndash9]

2 Case Presentation

A 66-year-old Caucasian woman with past medical historyof dermatomyositis dysphagia gastro-esophageal reflux andhypertension presented to the emergency department (ED)with several days of mid-epigastric constant moderateintensity nonradiating abdominal pain Additionally shereported 4-5 days of erythematous rash that began on her

face and chest that then spread to her arms and abdomen(Figures 1-2) She also reported white ldquospotsrdquo in her mouthAt that time CBC CRP ESR CK and UA were withinnormal limits Lipase was 675 UL and CMP was remarkablefor sodium 129 mEqL amino alanine transferase (ALT)158 UL and aspartate aminotransferase (AST) 111 ULthe rest of the CMP including alkaline phosphatase (ALP)was normal CXR was normal and abdominal radiographshowed evidence of constipation An abdominal ultrasoundwas ordered due to elevated lipase and LFTs and showedno evidence of gallbladder dysfunction or liver lesions Shewas diagnosed with pancreatitis thrush and folliculitis andwas discharged home with clear liquid diet orders andprescriptions for nystatin oral solution and oral doxycyclinefor possible secondary skin infection Two days later shereturned to the ED with persistent symptoms and decreasedurine output She reported nausea constipation and wors-ened dysphagia but denied vomiting weight change nightsweats fever chills chest pain cough and shortness ofbreath She also denied pertinent past surgeries familyhistory recent travel sexual activity drug use and alcoholand tobacco use She reported allergy to penicillin Hermedication list included prednisone mycophenolate mofetil

HindawiCase Reports in HepatologyVolume 2018 Article ID 1269340 5 pageshttpsdoiorg10115520181269340

2 Case Reports in Hepatology

Figure 1 Maculopapular rash

Figure 2 Crusted vesicle

(which she held since previous ED visit per doctor recom-mendations) trimethoprimsulfamethoxazole (TS) nystatinoral suspension carvedilol ranitidine estradiol calcium andvitamin D She was told by her dermatologist not to fill thedoxycycline prescription from the ED and increase the doseof TS

On physical examination the patient was alert andoriented with normal vital signsThe examwas significant fororal thrush but normal heart lung and abdominal examsSkin exam showed a diffuse maculopapular eruption witha few vesicles on face trunk and extremities Significantlaboratory data was as follows AST 1389 UL ALT 1570UL ALP 68 UL international normalized ratio (INR) 16and prothrombin time (PT) 18 seconds Complete abdominalultrasound demonstrated normal gallbladder without stonesno biliary ductal dilation no focal liver lesions and no ascitesor abnormal fluid collections The patientrsquos dermatologisthad performed skin biopsies 2 days prior to admissionthat showed multinucleated giant cells with viral inclusionssuggestive of some type of herpes virus infection (Figures3ndash5) The patient was initiated on intravenous (IV) acyclovirmicafungin vancomycin aztreonam and stress dose steroidsfor presumed disseminated herpes simplex with possiblesecondary bacterial infection and sepsis Over the subsequent48-72 hours AST and ALT increased to the 4000s INRincreased to 18 and PT to 206 Due to worsening acute liverfailure she was transferred to our facility for liver transplantevaluation

On arrival to our hospital her skin lesions were thoughtto be most consistent with VZV and skin biopsy cultures

Figure 3 Skin biopsy

Figure 4 Skin biopsy intact epidermis on one side and lesion onthe other

Figure 5 Skin biopsy viral cytoplasmic effect including multinu-cleated cells and marginalization of chromatin

from the outpatient dermatologist later confirmed VZVIV acyclovir and antibiotics for secondary bacterial sepsiswere continued As part of her liver transplant evaluationextensive serologic investigation ensued Acute hepatitis A-E serologies ANA IgG4 smooth muscle antibody (Ab)LKM-1 Ab ceruloplasmin a-1 antitrypsin mitochondrialM2 Ab AFP HIV HSV and EBV PCRs blood culturesgalactomannan and cryptococcal antigen were submittedand later found to be negative She was also found tobe pANCA MPO positive and PR3 negative Liver biopsywas performed which revealed multiple areas of necrotichepatocytes (up to 35 of liver parenchyma) (Figures 6-7) inzones 2 and 3 of the liver This was associated with some bile

Case Reports in Hepatology 3

Figure 6 Hepatocytes with frank necrosis

Figure 7 Larger foci of hepatocytes with frank necrosis

extravasation and acute inflammation No signs of bridgingor confluent necrosis were seen A trichrome stain outlinedregions of immature deposition of collagen near necroticareas This stain also showed increased perivenular fibrosisaround the central veins but no evidence of periportal fibro-sis The portal triads showed nominal chronic inflammationwith small lymphocytes rare large lymphocytes and a fewscattered neutrophils There was no bile duct injury paucityor vasculitisThe hepatocytes did not demonstrate significantsteatosis but there was bile stasis in a few canalicular spacesand hepatocytes Viral inclusions were not seen An ironstain showed no accumulation of hemosiderin within thehepatocytes PCR was negative for HSV EBV and CMVand positive for VZV The necrosis also abutted portal triadsseen in the specimens (Figure 8) A Periodic acid-Schiffstain with diastase did not show cytoplasmic globules BloodPCRs were positive with high levels of VZV and low levelsof CMV The CMV viremia was attributed to secondaryreactivation due to her severely immunosuppressed stateVZV immune globulin was considered as therapy but IVIGwas administered instead due to her severe coagulopathyand thrombocytopenia Outpatient skin biopsy cultures laterconfirmed VZV PCR was positive for VZV and negative forHSV

Her hospital stay was complicated by multidrug-resistantEnterobacter cloacae hospital acquired pneumonia and bac-teremia respiratory failure requiring prolonged intubationand multiple organ failure VZV PCR copies decreased withtreatment but her severity of illness and active infection

Figure 8 Areas of necrosis abutting portal triad with chronic min-imal inflammation no significant steatosis seen and no periportalfibrosis or vasculitis appreciated

prevented liver transplantation The patientrsquos code status waseventually changed to ldquodo not resuscitaterdquo and she expired

3 Discussion

Reactivation of VZV as ldquoshinglesrdquo is a common occurrencebut acute liver failure (ALF) due to VZV is exceedinglyrare with high mortality [2ndash9] The differential diagnosis ofALF includes multiple etiologies including ischemia venousobstruction medications toxins autoimmune hepatitis andmetabolic and infectious etiologies (predominantly virusesincluding hepatitis A-E VZV CMV HSV EBV and ade-novirus) with VZV being the one most rarely reportedBy imaging and history the patient was less likely tohave venous obstruction or ischemia from an unrecog-nized hypotensive event that triggered her hepatitis Shedenied exposure to toxins but had been on prophylactictrimethoprimsulfamethoxazole for long duration this was aconsideration for drug induced liver injury but was refutedby biopsy PCR and culture results There was no historyof ingestion of other toxins known to cause acute hepatitisbefore onset of illness Likewise the AST to ALT ratio wasnot in the classic pattern (21) for alcoholic hepatitis

In the setting of VZV hepatitis definitive diagnosis ismade by liver biopsy histopathology culture and VZV PCROf note some cases have been shown to be pANCA positiveas well Thus it is important to utilize physical examinationclues to prompt ordering of proper tests along with earlyempirical antiviral therapy

Disseminated varicella zoster is most common inimmunocompromised patients [1] Resultant fulminant liverfailure from VZV is even more rare and deadly In reviewof the literature only 8 adult cases of acute liver failurefrom this organism were found of which only 2 survivedThese cases are summarized in Tables 1 and 2 One casereport from France involved a 35-year-old woman fromthe Ivory Coast with past medical history (PMH) of HIVHBV and recent neurotoxoplasmosis [2] A second casereport from Spain was a 43-year-old male heart transplantrecipient 9 months prior to the time of ALF from a VZVepisode [3] In these cases IV acyclovir was the staple

4 Case Reports in Hepatology

Table 1 Case reports survivors [2 3]

Pt Info PMH Symptoms Treatment Diagnosis Liver Biopsy

35 yo African Ffrom Ivory Coast

HIV HBV and recentneurotoxoplasmosis Chest pain IV acyclovir

Vesicle swab VZV +by direct IF andculture liver bx

gt50 hepatic necrosis andinclusion bodies

43 yo M Sp heart transplant 9months earlier

NV epigastricpain

IV acyclovir VZVimmune globulinemergent livertransplant

Skin lesion biopsyHSV ndash VZV + liver

biopsy

Transjugular liver bx signsof herpetic hepatitis

histology of hepatectomyhepatic necrosis consistent

with VZV infection

Table 2 Case reports nonsurvivors [4ndash9]

Pt Info PMH Symptoms Treatment Diagnosis Liver Biopsy

49 yo M

ETOH and tobaccoabuse 15 days postradical dissection

neck andlaryngectomy for

SCC larynx

Abdominal painfever restlessness

ldquoIntensivesupportive carerdquo

Post mortem vialiver analysis

Post mortem liver VZVDNA + hepatic necrosis

with intranuclearinclusion bodies

47 yoJapanese M

MM sp chemosteroids 2 stem cell

transplantsmoderate GVHDand relapse of MMwith more chemo

and steroids

Generalized fatigue FFP plateletsRetrospective VZVPCR + blood andliver analysis

Autopsy + anti-VZVIgG stain of liver withhepatic necrosis seen

49 yo M

No PMH excepttreatment for

pharyngotonsillitis15 days prior withabx and prednisone

Acute retrosternalpain

IV acyclovir VZVimmune globulintotal hepatectomy

Skin cytology cwherpes family virus

amp immuno-cytochemistry

stain VZV + bloodVZV DNA +

Liver bx necrosis onlyPost mortem liver VZV

DNA +

15 yo M NoneFever abdominalpain myalgia skin

vesicles

IV acyclovir MARs Post mortem liveranalysis

Post mortem liveranalysis hepatic

necrosismultinucleation and

intranuclear inclusionsof Cowdry A bodiesliver VZV PCR +

26 yo CF

Diagnosed withMS 3 months priorand treated with

steroids

Abd pain andvomiting

PO acyclovir 997888rarrIV acyclovir

Blood and urineVZV PCR + postmortem liver

analysis

Post mortem liverhemorrhagic necrosis

and VZV PCR +

64 yo CF14 months post-op

esophago-gastrectomy ampsplenectomy

Fever malaise HA Vit KVZV titers D4 1-64997888rarr D7 1-256 liverautopsy analysis

Autopsy liverhemorrhagic necrosisand signs herpes familyvirus including CowdryA intranuclear bodiesEM intracellular virionsconsistent with herpes

family virus

of treatment [2 3] The heart transplant patient also wastreated with VZV immune globulin and emergent livertransplant [3] Other reported cases that did not surviveincluded a 49-year-old German man with PMH of alcoholand tobacco abuse 15 days post radical neck dissection and

laryngectomy for laryngeal squamous cell carcinoma whopresented for abdominal pain He received supportive careand was diagnosed post mortem [4] A Japanese 47-year-oldman with multiple myeloma status post chemotherapycorticosteroids 2 stem cell transplants moderate graft versus

Case Reports in Hepatology 5

host disease and relapse of the myeloma necessitatingadditional chemotherapy and corticosteroids presented withgeneralized fatigue He was treated with fresh frozen plasmaplatelet transfusions and was also diagnosed post mortem[5] Another case reported from Italy was a 49-year-oldman with no PMH except treatment for pharyngotonsillitiswith steroids and antibiotics 15 days before presentationwith retrosternal chest pain and truncal rash He wastreated with IV acyclovir VZV immune globulin and totalhepatectomy but was unable to receive a donor liver intime [6] The next case was of a 15-year-old Roman malewith no PMH who was treated with IV acyclovir MARS(molecular adsorbent re-circulating system) and bloodproduct transfusions Diagnosis was confirmed with apost mortem liver analysis [7] An additional case was of a26-year-old Czech female with diagnosis of multiple sclerosis3 months prior to admission followed by treatment withsteroids who presented with abdominal pain and vomitingand later developed a generalized rash She was originallytreated with oral acyclovir but because of progressiveworsening was changed to IV acyclovir Despite aggressivetreatment she also expired [8] The final reported caseinvolved a 64-year-old Caucasian woman in Vermont whowas 14 months post esophagogastrectomysplenectomy andcame to the hospital with headache malaise and feverShe was diagnosed post mortem with VZV by acute andconvalescent antibody titers and liver analysis She wastreated supportively with vitamin K but subsequently died aswell [9]

As shown early IV acyclovir is key to treatment of VZVacute liver failure Other considered therapies include VZVimmune globulin liver transplant IVIG and supportivecare [2ndash9] Since this cause of liver failure has such highmortality rates and early treatment is critical to survival VZVhepatitis should be considered in the differential diagnosis ofall patients with liver failure who present with a rash

Additional Points

Learning PointsTake-HomeMessages (1)VZV should be con-sidered as a cause of acute liver failure in the proper clinicalsetting (2) Diagnosis of VZV is dependent on liver biopsyhistopathology culture of tissue and PCR (3) Early antiviralmedication is essential to decrease morbidity and mortalityfrom disseminated VZV infection (4) Disseminated VZVwith ALF has a very high mortality rate

Consent

Informed consent was obtained

Conflicts of Interest

The authors declare that they have no conflicts of interest

References

[1] R J Whitley ldquoHerpesvirusesrdquo in Medical Microbiology SBaron Ed University of TexasMedical Branch Galveston Tex

USA 4th edition 1996 httpswwwncbinlmnihgovbooksNBK8157

[2] C Lechiche V Le Moing P Francois Perrigault and J ReynesldquoFulminant varicella hepatitis in a human immunodeficiencyvirus infected patient Case report and review of the literaturerdquoInfectious Diseases vol 38 no 10 pp 929ndash931 2006

[3] M Alvite-Canosa M J Paniagua-Martın J Quintela-FandinoA Otero and M G Crespo-Leiro ldquoFulminant Hepatic Failuredue to Varicella Zoster in a Heart Transplant Patient SuccessfulLiver Transplantrdquo The Journal of Heart and Lung Transplanta-tion vol 28 no 11 pp 1215-1216 2009

[4] U Drebber S F Preuss H U Kasper U Wieland andH P Dienes ldquoPostoperative fulminant varicella zoster virushepatitis with fatal outcome A case reportrdquo Zeitschrift furGastroenterologie vol 46 no 1 pp 45ndash47 2008

[5] H Saitoh N Takahashi H Nanjo Y Kawabata M Hirokawaand K Sawada ldquoVaricella-zoster virus-associated fulminanthepatitis following allogeneic hematopoietic stem cell trans-plantation for multiple myelomardquo Internal Medicine vol 52 no15 pp 1727ndash1730 2013

[6] U Maggi R Russo G Conte et al ldquoFulminant multiorganfailure due to varicella zoster virus and HHV6 in an immuno-competent adult patient and anhepatiardquo Transplantation Pro-ceedings vol 43 no 4 pp 1184ndash1186 2011

[7] S Natoli M Ciotti P Paba et al ldquoA novel mutation of varicella-zoster virus associated to fatal hepatitisrdquo Journal of ClinicalVirology vol 37 no 1 pp 72ndash74 2006

[8] S Plisek L Pliskova V Bostik et al ldquoFulminant hepatitis anddeath associated with disseminated varicella in an immuno-compromised adult from the Czech Republic caused by a wild-type clade 4 varicella-zoster virus strainrdquo Journal of ClinicalVirology vol 50 no 1 pp 72ndash75 2011

[9] J S Ross W L Fanning W Beautyman and J E CraigheadldquoFatal massive hepatic necrosis from varicella-zoster hepatitisrdquoThe American journal of gastroenterology US National Libraryof Medicine 2017

Case Reports in Hepatology 3

Figure 6 Hepatocytes with frank necrosis

Figure 7 Larger foci of hepatocytes with frank necrosis

extravasation and acute inflammation No signs of bridgingor confluent necrosis were seen A trichrome stain outlinedregions of immature deposition of collagen near necroticareas This stain also showed increased perivenular fibrosisaround the central veins but no evidence of periportal fibro-sis The portal triads showed nominal chronic inflammationwith small lymphocytes rare large lymphocytes and a fewscattered neutrophils There was no bile duct injury paucityor vasculitisThe hepatocytes did not demonstrate significantsteatosis but there was bile stasis in a few canalicular spacesand hepatocytes Viral inclusions were not seen An ironstain showed no accumulation of hemosiderin within thehepatocytes PCR was negative for HSV EBV and CMVand positive for VZV The necrosis also abutted portal triadsseen in the specimens (Figure 8) A Periodic acid-Schiffstain with diastase did not show cytoplasmic globules BloodPCRs were positive with high levels of VZV and low levelsof CMV The CMV viremia was attributed to secondaryreactivation due to her severely immunosuppressed stateVZV immune globulin was considered as therapy but IVIGwas administered instead due to her severe coagulopathyand thrombocytopenia Outpatient skin biopsy cultures laterconfirmed VZV PCR was positive for VZV and negative forHSV

Her hospital stay was complicated by multidrug-resistantEnterobacter cloacae hospital acquired pneumonia and bac-teremia respiratory failure requiring prolonged intubationand multiple organ failure VZV PCR copies decreased withtreatment but her severity of illness and active infection

Figure 8 Areas of necrosis abutting portal triad with chronic min-imal inflammation no significant steatosis seen and no periportalfibrosis or vasculitis appreciated

prevented liver transplantation The patientrsquos code status waseventually changed to ldquodo not resuscitaterdquo and she expired

3 Discussion

Reactivation of VZV as ldquoshinglesrdquo is a common occurrencebut acute liver failure (ALF) due to VZV is exceedinglyrare with high mortality [2ndash9] The differential diagnosis ofALF includes multiple etiologies including ischemia venousobstruction medications toxins autoimmune hepatitis andmetabolic and infectious etiologies (predominantly virusesincluding hepatitis A-E VZV CMV HSV EBV and ade-novirus) with VZV being the one most rarely reportedBy imaging and history the patient was less likely tohave venous obstruction or ischemia from an unrecog-nized hypotensive event that triggered her hepatitis Shedenied exposure to toxins but had been on prophylactictrimethoprimsulfamethoxazole for long duration this was aconsideration for drug induced liver injury but was refutedby biopsy PCR and culture results There was no historyof ingestion of other toxins known to cause acute hepatitisbefore onset of illness Likewise the AST to ALT ratio wasnot in the classic pattern (21) for alcoholic hepatitis

In the setting of VZV hepatitis definitive diagnosis ismade by liver biopsy histopathology culture and VZV PCROf note some cases have been shown to be pANCA positiveas well Thus it is important to utilize physical examinationclues to prompt ordering of proper tests along with earlyempirical antiviral therapy

Disseminated varicella zoster is most common inimmunocompromised patients [1] Resultant fulminant liverfailure from VZV is even more rare and deadly In reviewof the literature only 8 adult cases of acute liver failurefrom this organism were found of which only 2 survivedThese cases are summarized in Tables 1 and 2 One casereport from France involved a 35-year-old woman fromthe Ivory Coast with past medical history (PMH) of HIVHBV and recent neurotoxoplasmosis [2] A second casereport from Spain was a 43-year-old male heart transplantrecipient 9 months prior to the time of ALF from a VZVepisode [3] In these cases IV acyclovir was the staple

4 Case Reports in Hepatology

Table 1 Case reports survivors [2 3]

Pt Info PMH Symptoms Treatment Diagnosis Liver Biopsy

35 yo African Ffrom Ivory Coast

HIV HBV and recentneurotoxoplasmosis Chest pain IV acyclovir

Vesicle swab VZV +by direct IF andculture liver bx

gt50 hepatic necrosis andinclusion bodies

43 yo M Sp heart transplant 9months earlier

NV epigastricpain

IV acyclovir VZVimmune globulinemergent livertransplant

Skin lesion biopsyHSV ndash VZV + liver

biopsy

Transjugular liver bx signsof herpetic hepatitis

histology of hepatectomyhepatic necrosis consistent

with VZV infection

Table 2 Case reports nonsurvivors [4ndash9]

Pt Info PMH Symptoms Treatment Diagnosis Liver Biopsy

49 yo M

ETOH and tobaccoabuse 15 days postradical dissection

neck andlaryngectomy for

SCC larynx

Abdominal painfever restlessness

ldquoIntensivesupportive carerdquo

Post mortem vialiver analysis

Post mortem liver VZVDNA + hepatic necrosis

with intranuclearinclusion bodies

47 yoJapanese M

MM sp chemosteroids 2 stem cell

transplantsmoderate GVHDand relapse of MMwith more chemo

and steroids

Generalized fatigue FFP plateletsRetrospective VZVPCR + blood andliver analysis

Autopsy + anti-VZVIgG stain of liver withhepatic necrosis seen

49 yo M

No PMH excepttreatment for

pharyngotonsillitis15 days prior withabx and prednisone

Acute retrosternalpain

IV acyclovir VZVimmune globulintotal hepatectomy

Skin cytology cwherpes family virus

amp immuno-cytochemistry

stain VZV + bloodVZV DNA +

Liver bx necrosis onlyPost mortem liver VZV

DNA +

15 yo M NoneFever abdominalpain myalgia skin

vesicles

IV acyclovir MARs Post mortem liveranalysis

Post mortem liveranalysis hepatic

necrosismultinucleation and

intranuclear inclusionsof Cowdry A bodiesliver VZV PCR +

26 yo CF

Diagnosed withMS 3 months priorand treated with

steroids

Abd pain andvomiting

PO acyclovir 997888rarrIV acyclovir

Blood and urineVZV PCR + postmortem liver

analysis

Post mortem liverhemorrhagic necrosis

and VZV PCR +

64 yo CF14 months post-op

esophago-gastrectomy ampsplenectomy

Fever malaise HA Vit KVZV titers D4 1-64997888rarr D7 1-256 liverautopsy analysis

Autopsy liverhemorrhagic necrosisand signs herpes familyvirus including CowdryA intranuclear bodiesEM intracellular virionsconsistent with herpes

family virus

of treatment [2 3] The heart transplant patient also wastreated with VZV immune globulin and emergent livertransplant [3] Other reported cases that did not surviveincluded a 49-year-old German man with PMH of alcoholand tobacco abuse 15 days post radical neck dissection and

laryngectomy for laryngeal squamous cell carcinoma whopresented for abdominal pain He received supportive careand was diagnosed post mortem [4] A Japanese 47-year-oldman with multiple myeloma status post chemotherapycorticosteroids 2 stem cell transplants moderate graft versus

Case Reports in Hepatology 5

host disease and relapse of the myeloma necessitatingadditional chemotherapy and corticosteroids presented withgeneralized fatigue He was treated with fresh frozen plasmaplatelet transfusions and was also diagnosed post mortem[5] Another case reported from Italy was a 49-year-oldman with no PMH except treatment for pharyngotonsillitiswith steroids and antibiotics 15 days before presentationwith retrosternal chest pain and truncal rash He wastreated with IV acyclovir VZV immune globulin and totalhepatectomy but was unable to receive a donor liver intime [6] The next case was of a 15-year-old Roman malewith no PMH who was treated with IV acyclovir MARS(molecular adsorbent re-circulating system) and bloodproduct transfusions Diagnosis was confirmed with apost mortem liver analysis [7] An additional case was of a26-year-old Czech female with diagnosis of multiple sclerosis3 months prior to admission followed by treatment withsteroids who presented with abdominal pain and vomitingand later developed a generalized rash She was originallytreated with oral acyclovir but because of progressiveworsening was changed to IV acyclovir Despite aggressivetreatment she also expired [8] The final reported caseinvolved a 64-year-old Caucasian woman in Vermont whowas 14 months post esophagogastrectomysplenectomy andcame to the hospital with headache malaise and feverShe was diagnosed post mortem with VZV by acute andconvalescent antibody titers and liver analysis She wastreated supportively with vitamin K but subsequently died aswell [9]

As shown early IV acyclovir is key to treatment of VZVacute liver failure Other considered therapies include VZVimmune globulin liver transplant IVIG and supportivecare [2ndash9] Since this cause of liver failure has such highmortality rates and early treatment is critical to survival VZVhepatitis should be considered in the differential diagnosis ofall patients with liver failure who present with a rash

Additional Points

Learning PointsTake-HomeMessages (1)VZV should be con-sidered as a cause of acute liver failure in the proper clinicalsetting (2) Diagnosis of VZV is dependent on liver biopsyhistopathology culture of tissue and PCR (3) Early antiviralmedication is essential to decrease morbidity and mortalityfrom disseminated VZV infection (4) Disseminated VZVwith ALF has a very high mortality rate

Consent

Informed consent was obtained

Conflicts of Interest

The authors declare that they have no conflicts of interest

References

[1] R J Whitley ldquoHerpesvirusesrdquo in Medical Microbiology SBaron Ed University of TexasMedical Branch Galveston Tex

USA 4th edition 1996 httpswwwncbinlmnihgovbooksNBK8157

[2] C Lechiche V Le Moing P Francois Perrigault and J ReynesldquoFulminant varicella hepatitis in a human immunodeficiencyvirus infected patient Case report and review of the literaturerdquoInfectious Diseases vol 38 no 10 pp 929ndash931 2006

[3] M Alvite-Canosa M J Paniagua-Martın J Quintela-FandinoA Otero and M G Crespo-Leiro ldquoFulminant Hepatic Failuredue to Varicella Zoster in a Heart Transplant Patient SuccessfulLiver Transplantrdquo The Journal of Heart and Lung Transplanta-tion vol 28 no 11 pp 1215-1216 2009

[4] U Drebber S F Preuss H U Kasper U Wieland andH P Dienes ldquoPostoperative fulminant varicella zoster virushepatitis with fatal outcome A case reportrdquo Zeitschrift furGastroenterologie vol 46 no 1 pp 45ndash47 2008

[5] H Saitoh N Takahashi H Nanjo Y Kawabata M Hirokawaand K Sawada ldquoVaricella-zoster virus-associated fulminanthepatitis following allogeneic hematopoietic stem cell trans-plantation for multiple myelomardquo Internal Medicine vol 52 no15 pp 1727ndash1730 2013

[6] U Maggi R Russo G Conte et al ldquoFulminant multiorganfailure due to varicella zoster virus and HHV6 in an immuno-competent adult patient and anhepatiardquo Transplantation Pro-ceedings vol 43 no 4 pp 1184ndash1186 2011

[7] S Natoli M Ciotti P Paba et al ldquoA novel mutation of varicella-zoster virus associated to fatal hepatitisrdquo Journal of ClinicalVirology vol 37 no 1 pp 72ndash74 2006

[8] S Plisek L Pliskova V Bostik et al ldquoFulminant hepatitis anddeath associated with disseminated varicella in an immuno-compromised adult from the Czech Republic caused by a wild-type clade 4 varicella-zoster virus strainrdquo Journal of ClinicalVirology vol 50 no 1 pp 72ndash75 2011

[9] J S Ross W L Fanning W Beautyman and J E CraigheadldquoFatal massive hepatic necrosis from varicella-zoster hepatitisrdquoThe American journal of gastroenterology US National Libraryof Medicine 2017

4 Case Reports in Hepatology

Table 1 Case reports survivors [2 3]

Pt Info PMH Symptoms Treatment Diagnosis Liver Biopsy

35 yo African Ffrom Ivory Coast

HIV HBV and recentneurotoxoplasmosis Chest pain IV acyclovir

Vesicle swab VZV +by direct IF andculture liver bx

gt50 hepatic necrosis andinclusion bodies

43 yo M Sp heart transplant 9months earlier

NV epigastricpain

IV acyclovir VZVimmune globulinemergent livertransplant

Skin lesion biopsyHSV ndash VZV + liver

biopsy

Transjugular liver bx signsof herpetic hepatitis

histology of hepatectomyhepatic necrosis consistent

with VZV infection

Table 2 Case reports nonsurvivors [4ndash9]

Pt Info PMH Symptoms Treatment Diagnosis Liver Biopsy

49 yo M

ETOH and tobaccoabuse 15 days postradical dissection

neck andlaryngectomy for

SCC larynx

Abdominal painfever restlessness

ldquoIntensivesupportive carerdquo

Post mortem vialiver analysis

Post mortem liver VZVDNA + hepatic necrosis

with intranuclearinclusion bodies

47 yoJapanese M

MM sp chemosteroids 2 stem cell

transplantsmoderate GVHDand relapse of MMwith more chemo

and steroids

Generalized fatigue FFP plateletsRetrospective VZVPCR + blood andliver analysis

Autopsy + anti-VZVIgG stain of liver withhepatic necrosis seen

49 yo M

No PMH excepttreatment for

pharyngotonsillitis15 days prior withabx and prednisone

Acute retrosternalpain

IV acyclovir VZVimmune globulintotal hepatectomy

Skin cytology cwherpes family virus

amp immuno-cytochemistry

stain VZV + bloodVZV DNA +

Liver bx necrosis onlyPost mortem liver VZV

DNA +

15 yo M NoneFever abdominalpain myalgia skin

vesicles

IV acyclovir MARs Post mortem liveranalysis

Post mortem liveranalysis hepatic

necrosismultinucleation and

intranuclear inclusionsof Cowdry A bodiesliver VZV PCR +

26 yo CF

Diagnosed withMS 3 months priorand treated with

steroids

Abd pain andvomiting

PO acyclovir 997888rarrIV acyclovir

Blood and urineVZV PCR + postmortem liver

analysis

Post mortem liverhemorrhagic necrosis

and VZV PCR +

64 yo CF14 months post-op

esophago-gastrectomy ampsplenectomy

Fever malaise HA Vit KVZV titers D4 1-64997888rarr D7 1-256 liverautopsy analysis

Autopsy liverhemorrhagic necrosisand signs herpes familyvirus including CowdryA intranuclear bodiesEM intracellular virionsconsistent with herpes

family virus

of treatment [2 3] The heart transplant patient also wastreated with VZV immune globulin and emergent livertransplant [3] Other reported cases that did not surviveincluded a 49-year-old German man with PMH of alcoholand tobacco abuse 15 days post radical neck dissection and

laryngectomy for laryngeal squamous cell carcinoma whopresented for abdominal pain He received supportive careand was diagnosed post mortem [4] A Japanese 47-year-oldman with multiple myeloma status post chemotherapycorticosteroids 2 stem cell transplants moderate graft versus

Case Reports in Hepatology 5

host disease and relapse of the myeloma necessitatingadditional chemotherapy and corticosteroids presented withgeneralized fatigue He was treated with fresh frozen plasmaplatelet transfusions and was also diagnosed post mortem[5] Another case reported from Italy was a 49-year-oldman with no PMH except treatment for pharyngotonsillitiswith steroids and antibiotics 15 days before presentationwith retrosternal chest pain and truncal rash He wastreated with IV acyclovir VZV immune globulin and totalhepatectomy but was unable to receive a donor liver intime [6] The next case was of a 15-year-old Roman malewith no PMH who was treated with IV acyclovir MARS(molecular adsorbent re-circulating system) and bloodproduct transfusions Diagnosis was confirmed with apost mortem liver analysis [7] An additional case was of a26-year-old Czech female with diagnosis of multiple sclerosis3 months prior to admission followed by treatment withsteroids who presented with abdominal pain and vomitingand later developed a generalized rash She was originallytreated with oral acyclovir but because of progressiveworsening was changed to IV acyclovir Despite aggressivetreatment she also expired [8] The final reported caseinvolved a 64-year-old Caucasian woman in Vermont whowas 14 months post esophagogastrectomysplenectomy andcame to the hospital with headache malaise and feverShe was diagnosed post mortem with VZV by acute andconvalescent antibody titers and liver analysis She wastreated supportively with vitamin K but subsequently died aswell [9]

As shown early IV acyclovir is key to treatment of VZVacute liver failure Other considered therapies include VZVimmune globulin liver transplant IVIG and supportivecare [2ndash9] Since this cause of liver failure has such highmortality rates and early treatment is critical to survival VZVhepatitis should be considered in the differential diagnosis ofall patients with liver failure who present with a rash

Additional Points

Learning PointsTake-HomeMessages (1)VZV should be con-sidered as a cause of acute liver failure in the proper clinicalsetting (2) Diagnosis of VZV is dependent on liver biopsyhistopathology culture of tissue and PCR (3) Early antiviralmedication is essential to decrease morbidity and mortalityfrom disseminated VZV infection (4) Disseminated VZVwith ALF has a very high mortality rate

Consent

Informed consent was obtained

Conflicts of Interest

The authors declare that they have no conflicts of interest

References

[1] R J Whitley ldquoHerpesvirusesrdquo in Medical Microbiology SBaron Ed University of TexasMedical Branch Galveston Tex

USA 4th edition 1996 httpswwwncbinlmnihgovbooksNBK8157

[2] C Lechiche V Le Moing P Francois Perrigault and J ReynesldquoFulminant varicella hepatitis in a human immunodeficiencyvirus infected patient Case report and review of the literaturerdquoInfectious Diseases vol 38 no 10 pp 929ndash931 2006

[3] M Alvite-Canosa M J Paniagua-Martın J Quintela-FandinoA Otero and M G Crespo-Leiro ldquoFulminant Hepatic Failuredue to Varicella Zoster in a Heart Transplant Patient SuccessfulLiver Transplantrdquo The Journal of Heart and Lung Transplanta-tion vol 28 no 11 pp 1215-1216 2009

[4] U Drebber S F Preuss H U Kasper U Wieland andH P Dienes ldquoPostoperative fulminant varicella zoster virushepatitis with fatal outcome A case reportrdquo Zeitschrift furGastroenterologie vol 46 no 1 pp 45ndash47 2008

[5] H Saitoh N Takahashi H Nanjo Y Kawabata M Hirokawaand K Sawada ldquoVaricella-zoster virus-associated fulminanthepatitis following allogeneic hematopoietic stem cell trans-plantation for multiple myelomardquo Internal Medicine vol 52 no15 pp 1727ndash1730 2013

[6] U Maggi R Russo G Conte et al ldquoFulminant multiorganfailure due to varicella zoster virus and HHV6 in an immuno-competent adult patient and anhepatiardquo Transplantation Pro-ceedings vol 43 no 4 pp 1184ndash1186 2011

[7] S Natoli M Ciotti P Paba et al ldquoA novel mutation of varicella-zoster virus associated to fatal hepatitisrdquo Journal of ClinicalVirology vol 37 no 1 pp 72ndash74 2006

[8] S Plisek L Pliskova V Bostik et al ldquoFulminant hepatitis anddeath associated with disseminated varicella in an immuno-compromised adult from the Czech Republic caused by a wild-type clade 4 varicella-zoster virus strainrdquo Journal of ClinicalVirology vol 50 no 1 pp 72ndash75 2011

[9] J S Ross W L Fanning W Beautyman and J E CraigheadldquoFatal massive hepatic necrosis from varicella-zoster hepatitisrdquoThe American journal of gastroenterology US National Libraryof Medicine 2017

Case Reports in Hepatology 5

host disease and relapse of the myeloma necessitatingadditional chemotherapy and corticosteroids presented withgeneralized fatigue He was treated with fresh frozen plasmaplatelet transfusions and was also diagnosed post mortem[5] Another case reported from Italy was a 49-year-oldman with no PMH except treatment for pharyngotonsillitiswith steroids and antibiotics 15 days before presentationwith retrosternal chest pain and truncal rash He wastreated with IV acyclovir VZV immune globulin and totalhepatectomy but was unable to receive a donor liver intime [6] The next case was of a 15-year-old Roman malewith no PMH who was treated with IV acyclovir MARS(molecular adsorbent re-circulating system) and bloodproduct transfusions Diagnosis was confirmed with apost mortem liver analysis [7] An additional case was of a26-year-old Czech female with diagnosis of multiple sclerosis3 months prior to admission followed by treatment withsteroids who presented with abdominal pain and vomitingand later developed a generalized rash She was originallytreated with oral acyclovir but because of progressiveworsening was changed to IV acyclovir Despite aggressivetreatment she also expired [8] The final reported caseinvolved a 64-year-old Caucasian woman in Vermont whowas 14 months post esophagogastrectomysplenectomy andcame to the hospital with headache malaise and feverShe was diagnosed post mortem with VZV by acute andconvalescent antibody titers and liver analysis She wastreated supportively with vitamin K but subsequently died aswell [9]

As shown early IV acyclovir is key to treatment of VZVacute liver failure Other considered therapies include VZVimmune globulin liver transplant IVIG and supportivecare [2ndash9] Since this cause of liver failure has such highmortality rates and early treatment is critical to survival VZVhepatitis should be considered in the differential diagnosis ofall patients with liver failure who present with a rash

Additional Points

Learning PointsTake-HomeMessages (1)VZV should be con-sidered as a cause of acute liver failure in the proper clinicalsetting (2) Diagnosis of VZV is dependent on liver biopsyhistopathology culture of tissue and PCR (3) Early antiviralmedication is essential to decrease morbidity and mortalityfrom disseminated VZV infection (4) Disseminated VZVwith ALF has a very high mortality rate

Consent

Informed consent was obtained

Conflicts of Interest

The authors declare that they have no conflicts of interest

References

[1] R J Whitley ldquoHerpesvirusesrdquo in Medical Microbiology SBaron Ed University of TexasMedical Branch Galveston Tex

USA 4th edition 1996 httpswwwncbinlmnihgovbooksNBK8157

[2] C Lechiche V Le Moing P Francois Perrigault and J ReynesldquoFulminant varicella hepatitis in a human immunodeficiencyvirus infected patient Case report and review of the literaturerdquoInfectious Diseases vol 38 no 10 pp 929ndash931 2006

[3] M Alvite-Canosa M J Paniagua-Martın J Quintela-FandinoA Otero and M G Crespo-Leiro ldquoFulminant Hepatic Failuredue to Varicella Zoster in a Heart Transplant Patient SuccessfulLiver Transplantrdquo The Journal of Heart and Lung Transplanta-tion vol 28 no 11 pp 1215-1216 2009

[4] U Drebber S F Preuss H U Kasper U Wieland andH P Dienes ldquoPostoperative fulminant varicella zoster virushepatitis with fatal outcome A case reportrdquo Zeitschrift furGastroenterologie vol 46 no 1 pp 45ndash47 2008

[5] H Saitoh N Takahashi H Nanjo Y Kawabata M Hirokawaand K Sawada ldquoVaricella-zoster virus-associated fulminanthepatitis following allogeneic hematopoietic stem cell trans-plantation for multiple myelomardquo Internal Medicine vol 52 no15 pp 1727ndash1730 2013

[6] U Maggi R Russo G Conte et al ldquoFulminant multiorganfailure due to varicella zoster virus and HHV6 in an immuno-competent adult patient and anhepatiardquo Transplantation Pro-ceedings vol 43 no 4 pp 1184ndash1186 2011

[7] S Natoli M Ciotti P Paba et al ldquoA novel mutation of varicella-zoster virus associated to fatal hepatitisrdquo Journal of ClinicalVirology vol 37 no 1 pp 72ndash74 2006

[8] S Plisek L Pliskova V Bostik et al ldquoFulminant hepatitis anddeath associated with disseminated varicella in an immuno-compromised adult from the Czech Republic caused by a wild-type clade 4 varicella-zoster virus strainrdquo Journal of ClinicalVirology vol 50 no 1 pp 72ndash75 2011

[9] J S Ross W L Fanning W Beautyman and J E CraigheadldquoFatal massive hepatic necrosis from varicella-zoster hepatitisrdquoThe American journal of gastroenterology US National Libraryof Medicine 2017

Stem Cells International

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

MEDIATORSINFLAMMATION

of

EndocrinologyInternational Journal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Disease Markers

Hindawiwwwhindawicom Volume 2018

BioMed Research International

OncologyJournal of

Hindawiwwwhindawicom Volume 2013

Hindawiwwwhindawicom Volume 2018

Oxidative Medicine and Cellular Longevity

Hindawiwwwhindawicom Volume 2018

PPAR Research

Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Immunology ResearchHindawiwwwhindawicom Volume 2018

Journal of

ObesityJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Computational and Mathematical Methods in Medicine

Hindawiwwwhindawicom Volume 2018

Behavioural Neurology

OphthalmologyJournal of

Hindawiwwwhindawicom Volume 2018

Diabetes ResearchJournal of

Hindawiwwwhindawicom Volume 2018

Hindawiwwwhindawicom Volume 2018

Research and TreatmentAIDS

Hindawiwwwhindawicom Volume 2018

Gastroenterology Research and Practice

Hindawiwwwhindawicom Volume 2018

Parkinsonrsquos Disease

Evidence-Based Complementary andAlternative Medicine

Volume 2018Hindawiwwwhindawicom

Submit your manuscripts atwwwhindawicom