Transcript Vaccines, immunotherapy and STI

Case Summary
• 29 yo M with HIV (CD4 25, VL 48,000), TB (lung, bone
marrow), HBeAg negative chronic HBV infection,
schistosomiasis and cryptococcal meningitis presenting
with jaundice about 3 months after starting
AZT/3TC/EFV.
• Exam notable for icterus, hepatosplenomegaly and no
signs of chronic liver disease.
• He has elevated total bilirubin (conjugated and
unconjugated) and ALT and evidence of hepatic
synthetic dysfunction. CXR: improving infiltrates on TB
therapy.
• A liver biopsy done just after starting ARVs, but before
the development of jaundice, showed mild inflammatory
changes and steatosis, but no evidence of granuloma or
malignancy.
Differential Diagnosis
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Drug-induced liver injury
Malignancy
Immune reconstitution syndrome
Other infections
– Fungal
– Parasitic
– Viral
• Hepatitis B
Drug-induced liver injury
• Possible causes:
– ARVs, particularly EFV
– Antituberculous therapy, either INH or
rifampicin
• However, now ~4-5 months into ATT
– Fluconazole can occasionally cause liver
injury.
• Was he on this drug at the time of the jaundice?
– Bactrim.
• Was he on this drug at the time of the jaundice?
– ? Any use of traditional medicines or alcohol
Malignancy
• Kaposi’s sarcoma
– No evidence of cutaneous disease or other
sites of visceral involvement
• Lymphoma
– No adenopathy
– No paraneoplastic phenomenon, such as
hypercalcemia
• Hepatocellular carcinoma
• Metastatic carcinoma
– No known primary site
Immune reconstitution Syndrome
• TB
– No evidence of TB IRIS elsewhere
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Not told that he is having any fevers, chills, sweats
No significant adenopathy on exam or CXR
Pulmonary infiltrates are improving
Pancytopenia—evidence of myelophthsis on
peripheral smear?
• HBV
– Will come back to this possibility
• Other: MAC, cryptococcus
Other infections
• Schistosomiasis
– Detected on rectal biopsy (not told why it was done)
– S. mansoni and japonicum are the usual causes of liver disease
• S. mansoni present in Africa
– Adult worms live in the mesenteric vessels of the colon in
permanent copulation
– Eggs travel hematogenously to the liver and other sites
– In the liver, eggs lodge in the presinusoidal spaces of the portal
vein and elicit a granulomatous fibrosing reaction
– Secondary portal hypertension ensues, leading to splenomegaly,
ascites, varices
– One would not expect rapidly deteriorating liver function tests or
hepatic dysfunction in chronic schistosomiasis
– Patient did not have symptoms of acute schistosomiasis
(Katayama fever) or signs of chronic portal hypertension
– No evidence of granulomas or fibrosis on recent liver bx
Other infections
• CMV
– CMV can cause acute hepatitis
– May be associated with a mononucleosis-like
syndrome, with atypical lymphocytosis
– CMV IgM positive, but this can be unreliable unless
done in an experienced lab
– CMV antigenemia or PCR is usually more reliable
– Would check CMV IgG
• Cryptococcus
– Look for evidence of recurrent cryptococcus in the
CNS or blood
• Bacterial infections: Syphilis, Bartonella (peliosis
hepatis), Salmonella, Listeria
Viral hepatitis
• HAV
• HCV
• HDV
• CMV
• EBV
• HSV
HBV
• HBeAg negative
– May be due to long-standing infection,
development of pre-core mutant
– May be more aggressive
– Check HBV DNA
HBV Flare
• HBV Resistance
– 25%/year of 3TC monotherapy
– Has only been on 3TC for 3-4 months
• Discontinuation of 3TC
– Patient had been receiving DOT in
hospital
– Review adherence
• Fibrosing cholestatic hepatitis
• HBV IRIS
What would I do? (1)
• Check abdominal U/S:
– ? Adenopathy, obstruction
• Monitor PT, platelets, albumin closely
• Give oral vitamin K
• Check serologies for HAV, HDV, HCV, EBV,
CMV IgG and PCR, RPR
• Check HBV DNA
• Hold antituberculous therapy, fluconazole,
bactrim
What would I do? (2)
• Liver biopsy
– If presence of eosinophils, suggests druginduced liver injury
– Stain for HBV. Look for inflammation to suggest
HBV flare
– Look for fibrosing cholestatic hepatitis
• If liver biopsy shows HBV is the main
problem, then would add tenofovir, would
not add steroids