1. Fatal cirrhosis decompensation due to brucellosis: therapeutic issues. Maria Kosmidou, 1 Leonidas Christou 1 Markos Marangos, 2 Georgios Panos, 2 Epameinondas V Tsianos 1 1 : Department of Internal Medicine, Medical School, University of Ioannina, Greece 2 : Department of Infectious Diseases, Medical School, University of Patras, Greece

2. 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

3. The new global map of human brucellosis Pappas G, et al, Lancet Infect Dis 2006

4. 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). Hepatic involvement in brucellosis Akritidis N, et al, Clin Gastroenterol Hepatol 2007

5. 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

6. 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 12- substitute TMP-SMX with DOX (salvage)- remission- outpatient- day 40 encephalopathy-death Encephalopathy induced either by antibiotic hepatotoxicity or by disease relapse (no autopsy)

7. 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

8. 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)

9. 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