MDC

10/07/2010

Revathi C Belur
 Case
CC: Right Flank, RUQ pain
HPI: 50 yo woman with a h/o ALL s/p stem cell
transplant in 2007, DM, RA, GERD, fatty liver
disease, and fibromyalgia presents to her
PCP with R flank, RUQ pain. Pt stated that
the pain began 4 nights ago following fever to
101.7, chills, sore throat, HA, and diarrhea in
the morning. She took 800mg ibuprofen at
that time w/o relief.
 PMHx

Pre B Cell ALL s/p stem cell transplant 2007

DM
RA
GERD
Fatty liver disease
Fibromyalgia
Carpal tunnel syndrome
 PSHx

Cholecystectomy 1984
C-section
tubal ligation
knee/ankle arthroscopic surgeries
 Home Medications

amitriptyline 25 mg QHS
aspirin 81 mg Daily
ergocalciferol
glipizide
ibuprofen 600 mg PO TID PRN
magnesium oxide 250 mg Daily
metformin 1,000 mg PO BID
mycophenolate mofetil 1,000 mg PO BID
 Home Medications
naproxen 500 mg PO BID
omeprazole 40 mg PO Daily
simvastatin 20 mg PO QHS
 History
• FamHx:
Mother and father - HL and HTN
Sister – CVA

• SocHx:
Denies tobacco, EtOH and illicits
Lives with her sister and 2 daughters
Disabled and no working
 Review of Systems
Daily HA, occasional electrical sensation
across her chest, muscle spasms of her
Feet. Denied CP, SOB, F/C, D/C,
heat/cold intolerance, bleeding disorder,
weight changes.
 General Medicine Consult
1.How should we approach abdominal
pain/flank pain in the outpatient setting
and what immediate work-up/exam
needs to be/can be done? 
2. When should we admit?
 Further care
She was sent to the ED to r/o pyelonephritis,
nephrolithiasis, or other intraabdominal
process. W/U at that time was notable for a
WBC to 14.6 and negative CXR and CT abd
and pelvis. She was given diazepam,
morphine, and ketorolac in the ED and
discharged. She presented again 2 days
later with the same complaints and was given
4mg IV morphine x4 with minimal relief of her
pain.
CT of abdomen, pelvis
 Imaging
• CT abdomen/pelvis
• Mild hyperdensity within the bilateral
collecting systems is likely the sequela
of recent IV contrast administration.
There is no evidence of renal calculi or
another acute intra-abdominal process.
 Imaging

• U/S Abdomen
Unremarkable ultrasound of the right
upper quadrant.
• CXR
No active cardiopulmonary disease.
 In ER
Repeat CT abd and pelvis and abd US
were negative. Her leukocytosis of 2
days ago had resolved. She denied
taking any Tylenol or Tylenol containing
narcotics. She vomited x1 after
receiving her last dose of morphine.
She denies trauma and post-prandial
variation. She stated that the pain was
unlike her fibromyalgia pain.
 Further w/u in ER
Hepatitis serologies checked: Hep A, Hep B,
Hep C negative.
UA with small blood.
 Physical Exam on Floor

Admitted for intractable right

flank/RUQ pain.
Vitals:
Temp: 98 deg Fahrenheit
BP:127/78 HR: 90 RR:18
 Physical Exam on Floor
General: awake, alert, NAD
HEENT: PERRL, MMM, OP clear
Neck: no LAD
Heart: RRR, S1 S2, no murmurs
Lungs: CTA-B
Abdomen: +NABS, nondistended, tenderness to
deep palpation in RUQ, no HSM
Pain with palpation of R CVA, no paraspinal
tenderness
Ext: no edema, cyanosis, or clubbing
 Labs
138 | 103 | 18
-------------------------<267
3.9 | 26 | 1.1

8.4>12.7/37.7<294
 Labs
PT 13.2
PTT 28.2
INR 0.95

Tbili 0.6
Dbili 0.1
Alk Phos 112
AST - 119 (29 ytd)
ALT - 155 (34 ytd)
albumin 3.3
 Labs

• lipase 17

• Hep A-C serology negative

• UA - small blood with 4 RBCs, trace

protein
 Differential Diagnoses of Right Flank Pain/
Right Flank pain
RUQ pain
Urolithiasis
Radicular/muscular
Pyelonephritis
Herpes Zoster
Renal Abscess
Renal Vein Thrombosis
Renal Infarction
Abdominal Aortic Aneurysm (AAA)
RUQ pain
Biliary: calculi, infection, inflammation, neoplasm
Hepatic: hepatitis, abscess, hepatic congestion, neoplasm, trauma.
Gastric: peptic ulcer disease (PUD), pyloric stenosis, neoplasm, alcoholic gastritis, hiatal hernia
Pancreatic: pancreatitis, neoplasm, stone in pancreatic duct or ampulla
Renal: calculi, infection, inflammation, neoplasm, rupture of kidney
Pulmonary: pneumonia, pulmonary infarction, right-sided pleurisy
Intestinal: retrocecal appendicitis, intestinal obstruction, high fecal impaction, diverticulitis
Cardiac: myocardial ischemia (particularly involving the inferior wall), pericarditis
Cutaneous: Herpes Zoster
Trauma
Fitz-Hugh-Curtis syndrome (perihepatitis)
 Differential Diagnoses of elevated
LFTs
Liver disease (e.g., viral hepatitis, cirrhosis, Reye’s syndrome)
Alcohol abuse
Drugs (e.g., acetaminophen, statins, NSAIDs, fenofibrates, antibiotics, anabolic steroids,
narcotics, heparin, labetalol, amiodarone, chlorpromazine, phenytoin
Hepatic congesions
Infectious mononucleosis, sepsis, CMV infection, HIV infection
Liver metastases
Autoimmune hepatitis
MI
Myocarditis
Severe muscle trauma
Dermatomyositis or polymyositis
Primary liver malignancy
Renal and Pulmonary infarction
Convulsions
Eclampsia
Dehydration (relative increase)
Chinese herbs
 Hospital Day 1
Since pt had RA and on cell cept,
Rheumatology was consulted.
Q uestions for Rheumatology consult”
1. Can RA, either directly or in relation to
treatment, lead to liver function
abnormalities?
2. How do you diagnose RA-related
(autoimmune?) hepatitis?
 Further development
Pt was noted to have erythematous rash
on right flank.
Labs continued to show elevated
transaminases and alk phos.
 Hospital Day 2
Liver enzymes continue to trend upwards.
Antimitochondrial antibody sent
Antismooth muscle antibody sent
CMV, HCV, EBV, HSV type 1, VZV PCR sent.

Pretransplant serologies 5/2007

+CMV
+VZV
+EBV
+HSV I/II
 Lab Results
Antimitochondrial antibody - Negative
Antismooth muscle antibody - Negative
CMV - None detected
HCV – None detected
EBV – None detected
HSV type 1 – None detected
VZV PCR - 6100
 Interpretation
Pt had disseminated VZV infection and
VZV hepatitis. Liver biopsy to confirm the
VZV hepatitis was deferred.
 Liver Consult
 
What are the causes of elevated LFTs in
a person on cellcept with RA?
 
How common is the liver infection caused
by non-hepatotropic virus?
 Heme Onc Consult
In a patient with stem cell transplant, on
immunosuppressant therapy, what are the
most common causes of elevated LFTs?
 
What would make you suspect GVHD versus
infectious hepatitis?
 
How would you treat GVHD?
 Transplant ID consult
How common is hepatitis in transplant
patients?
 
How common is hepatitis by non-
hepatotropic virus?
 
How is the diagnosis of VZV hepatitis
made?
 Evidence Based Medicine
There are many case reports, reporting the
infection of the liver by VZV in pts who are
immunosuppressed.
 EBM
• Case Reports
In a case report and review of literature review by Pishvaian
et al published in Digestive Diseases and Sciences in July
2006, reported a fatal case of VZV hepatitis.
Disseminated VZV and hepatitis
Pt’s herpes zoster vesicular rash was on the
same dermatome that corresponded to the
nerve distribution of liver also.
 VZV Hepatitis
• Varicella zoster virus (VZV), a member of the Herpesviridae family, also has
the potential to cause hepatitis. Primary varicella infection (chickenpox) is
most often seen in children, and it consists of a febrile illness associated with
vesicular rash. Hepatitis is uncommon in primary infection in
immunocompetent hosts although a mild derangement of liver enzyme tests is
sometimes present in children during chickenpox infection.
• Because of the high prevalence of varicella exposure in adult population, VZV
infection in adult transplant recipients is usually the result of the reactivation
of latent infection, and it usually presents as typical herpes zoster or shingles,
which are most often clinically evident as a vesicular rash in a dermatomal
distribution. Occasionally, a nondermatomal distribution of the rash is
observed; this may indicate generalized a high risk of associated visceral
involvement, including hepatitis. Distinguishing this presentation from
disseminated HSV may be clinically difficult, and scraping of a cutaneous
vesicle, followed by immunofluorescent examination to detect the presence of
antigens, is required to confirm the diagnosis. Liver involvement by VZV in
the absence of cutaneous disease is rare, but it has been occasionally described
as part of a generalized visceral VZV infection without rash.
 VZV Hepatitis
• Primary infection usually occurs in pediatric recipients although seronegative
adults are also at risk. Aggressive antiviral treatment with acyclovir may
prevent its dissemination and the associated visceral complications.
Vaccination has been recommended for nonimmune patients before
transplantation. Because this is a live attenuated varicella vaccine,
administration to SOT recipients is not recommended by the CDC. However,
this has been given to small numbers of patients usually as postexposure
prophylaxis with mixed results.
• Liver involvement by VZV is suggested by a typical varicella or zoster rash
that is accompanied with liver function abnormalities, fever, and abdominal
pain. In HSV hepatitis, elevated aminotransferases that are more than five
times the ULN are the predominant biochemical abnormality, but the bilirubin
may also be moderately increased to as much as three to four times the ULN.
Liver biopsy findings are similar to those seen in HSV hepatitis, with focal
coagulative necrosis and an inflammatory infiltrate. Viral inclusions may be
present, but their absence does not exclude the diagnosis.
Immunohistochemistry or in situ hybridization can help to distinguish between
HSV and VZV hepatitis.
 VZV in Transplant pts.
• That VZV infection tends to occur later in the post-
transplantation period than HSV, usually approximately 4
to 5 months after transplantation but most often within a
year of the procedure, is worth noting. Many of the reports
of liver involvement by VZV indicate that this occurs
relatively early in posttransplantation period, reflecting the
more intense state of immunosuppression at that time that
allows dissemination of the virus. Hepatic VZV, like other
visceral VZV infections, should be treated with high dose
IV acyclovir. Mortality from disseminated VZV infection
has been reduced with, but not eradicated by , acyclovir
treatment, thus highlighting the potentially serious nature
of hepatic involvement by VZV in this group of patients.
 VZV infection of allografts
• Herpes Simples and VZV viral hepatitis
• Herpes simplex (types I and II) virus and varicella-zoster virus (VZV)
have been identified as potential causes of liver allograft hepatitis.
Allograft involvement may occur as early as 3 days after transplant or
at any time thereafter. The clinical features include fever, vesicular
rashes, fatigue, and body pain, combined with serologic evidence of
hepatic injury. If HSV hepatitis is unrecognized, it can lead to
submassive or massive hepatic necrosis, hypotension, disseminated
intravascular coagulopathy, and metabolic acidosis quite rapidly.
Fulminant cases occur more often in patients who do not have
evidence of prior antibody-mediated immunity. Early recognition
using needle biopsy sampling is particularly crucial because effective
pharmacologic therapy is available.
 Management
Pt was started on IV acyclovir.

Pt was transferred to Hematology service.

Pt’s LFTs trended down and discharged

home.
 References
• Transplant Infections
By Raleigh A Bowden, Per Ljungman, David R Snydman
• Schiff's diseases of the liver, Volume 1
By Eugene R. Schiff, Michael F. Sorrell, Willis C. Maddrey
 Acknowledgement
Thanks to:
Dr. Zar
Dr. Tulley
Dr. Peace
Dr. Arami
Dr. Berkes
Dr. Reid
Dr. Zibelman
Team B