Vaccines, immunotherapy and STI

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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
• 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
• 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
Differential Diagnosis
Drug-induced liver injury
Immune reconstitution syndrome
Other infections
– Fungal
– Parasitic
– Viral
• Hepatitis B
Drug-induced liver injury
• Possible causes:
– ARVs, particularly EFV
– Antituberculous therapy, either INH or
• However, now ~4-5 months into ATT
– Fluconazole can occasionally cause liver
• 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
• Kaposi’s sarcoma
– No evidence of cutaneous disease or other
sites of visceral involvement
• Lymphoma
– No adenopathy
– No paraneoplastic phenomenon, such as
• Hepatocellular carcinoma
• Metastatic carcinoma
– No known primary site
Immune reconstitution Syndrome
• TB
– No evidence of TB IRIS elsewhere
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?
– 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 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
• 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
– Review adherence
• Fibrosing cholestatic hepatitis
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,
• Check HBV DNA
• Hold antituberculous therapy, fluconazole,
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