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Fatal cirrhosis decompensation due to brucellosis:
therapeutic issues.
Maria Kosmidou,1 Leonidas Christou1 Markos Marangos,2
Georgios Panos,2 Epameinondas V Tsianos1
1:
Department of Internal Medicine, Medical School, University of Ioannina,
Greece
2: Department of Infectious Diseases, Medical School, University of Patras,
Greece
• Brucellosis: prevalent zoonotic disease worldwide, still
endemic in Greece and the Balkans
• Known opportunistic infection in patients with hematologic
or chronic rheumatologic diseases
• Affinity for reticuloendothelial system (RES) which includes
the liver and peritoneal phagocytic system
• Liver involvement mild typically in brucellosis, sometimes
induces benign granulomas, rare chronic hepatosuppurative
disease, known predisposition to spontaneous bacterial
peritonitis (SBP in patients with underlying liver disease
• Need for combined, protracted antibiotic treatment with
potentially hepatotoxic agents
The new global map of human brucellosis
Pappas G, et al, Lancet Infect Dis 2006
Hepatic involvement in brucellosis
Liver biopsy. Arrows indicate 2 epithelioid
granulomas
within the parenchyma (hematoxylin-eosin,
200).
Liver biopsy. Note dense lymphocytic
infiltrates in the
portal areas (hematoxylin-eosin, 200).
Akritidis N, et al, Clin Gastroenterol Hepatol 2007
Three cases of cirrhosis decompensation in the course of
brucellosis (direct, due to the infection, or indirect, due to
antibiotics’ adverse effects)
Not all cirrhotics are decompensated during the course of
brucellosis (numerous cases, even with HCC, successfully
treated)- this case series presents mechanisms of
decompensation
• Case 1: 47-year male, alcoholic cirrhosis, compensated for >6
months, also IDDM
• Evening fever, abdominal dilatation
• US: Ascites, splenomegaly, no portal thrombosis
• Peritoneal fluid cultures: Brucella melitensis (recalled
consumption of unpasteurised dairy products)
• Treatment:? (history of tetracycline intolerance)
• TMP-SMX + CIPRO: initial response, relapse on day 12substitute TMP-SMX with DOX (salvage)- remission- outpatientday 40 encephalopathy-death
• Encephalopathy induced either by antibiotic hepatotoxicity or
by disease relapse (no autopsy)
Case 2: 50-year male, alcoholic cirrhosis with no complication
history, shepherd
Mild fever and abdominal distention
Blood cultures: Brucella melitensis
Aggressive treatment: DOX +RIF 600+ CIPRO- symptom
remission on day 5- progressive increase in LFTs/INR- lowering
RIF to 300
Day 41: encephalopathy, bilirubin total 16mg/dl, further INR
increase- stop antibiotics
Referral for transplant- transplant performed/ perioperative
fatal event
Encephalopathy induced potentially by antibiotic
hepatotoxicity
Case 3: 46-year male, novel diagnosis of alcoholic
cirrhosis
Persistent low fever, trip to Spain and consumption of
unpasteurised dairy products 2months ago
Blood cultures: Brucella melitensis
Treatment: DOX + CIPRO- day 4 massive increase in
LFTs and DIC- death on day 33 post encephalopathy and
spontaneous intracranial hemorrhage
DIC induced potentially by infection (known
complication of brucellosis)
No currently acceptable regimen can be used safely:
• Potential hepatotoxicity of DOX/RIF
• Potential for hepatorenal syndrome By AMGs
DOX+ STR or GENT Not safe,
DOX + RIF Not safe
What to do?
Awareness for a potentially fatal opportunistic
infection
Enhancement of patient health literacy in order to
prevent exposure and infection