A patient with acute on chronic liver failure
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1 A patient with acute on chronic liver failure Dott.ssa Marta Cavallin Dept. of Medicine of University of Padova, Italy 6 th Post Meeting AISF Rome, 23 rd February 2013
2 Dott.ssa Marta Cavallin medico in formazione specialistica Dipartimento di Medicina dell Università di Padova Il sottoscritto dichiara di non aver avuto negli ultimi 12 mesi conflitto d interesse in relazione a questa presentazione e che la presentazione non contiene discussione di farmaci in studio o ad uso off-label
3 A 57 years old male was admitted to our Unit of Hepatic Emergencies and Liver Transplantation in Padova on the 4 th of July 2012.
4 Medical case-history (1) Diagnosis of alcoholic cirrhosis in Medical Division in Valdagno where he was admitted for acute bronchitis in July 2011 Ex heavy smoker (3 cigarette packages per day for 16 years) Obesity since youth got worse in Actually body weight=120 Kg. Diagnosis of diabetes mellitus in 2003, treated with insulin In 2008 Malaria contracted in Mozambico that was treated for one month (follow up reported negative) Bleeding gastric ulcer in 2003 Operation for bilateral cataracts in 2004 Allergy to graminaceous plants
5 Medical case-history (2) Travel in China one month before with the appearence of iperchromatic urine. When he came back to Italy he had cough, scleral jaundice, emesis, no fever antibiotic therapy for suspected pneumonia On the 25th of June 2012, because of the persistence of scleral and skin jaundice he went to the PS and he was recovered in General Medicine jaundice in hepatic alcoholic cirrhosis During the staying in this hospital he developed: ACLF: treatment with steroid therapy (Solumedrol 40 mg/die ev), furosemide ev and from 29/6 with acetilcistein ev (4 fl ev/die) An episode of supraventricular tachycardia that was treated with amiodarone (1 cp da 200 mg/die)
6 What about the etiology of the hepatic disease (1)? No familarity for hepatic diseases No consumption of mussels or raw fish in the last month No sexual intercourses at risk No work in fields No usage of FANS or other hepatotoxic drugs No usage of products of herbalist s shop Personal history of diabetes (2003) treated with insulin therapy Obesity (2003) Active potus: consumption of about 1500 cc of wine every day and 3 liquors per week until the recovery Mild subclinic hypothyroidism (TSH = pmol/l, ft4 = pmol/l, ft3 = 2.58 miu/l)
7 What about the etiology of the hepatic disease (2)? Negativity of IgM HAV Negativity of HbsAg, anti-hbs e anti-hbc Negativity of Ac anti-hcv Negativity of HEV Ag and Ac anti-hev Negativity of IgM EBV and CMV Negativity of IgM anti-leptospira Negativity of Ac anti-transglutaminasi Negativity of ANA, AMA, SMA, anti-lkm, anti-sla, ANCA Normal ceruloplasmin (0.28 g/l) and cupremia (19 µmol/l) Normal sideremia (21.7 µmol/l), reduction of transferrin (0.83 g/l), transferrin saturation index (>100%), hyperferritinemia (1348 µg/l). Negativity of HEF genotype
8 Medical Examination Alert, cooperative, oriented S/T/P Cutaneous and scleral jaundice Widespread ecchymosis on superior limbs PA=140/70 mmhg, HR=108 bpm ar, SatO2=98% in aa. Heart: arrhythmical tones, no cardiac murmurs Chest: MV present, no pathologic sounds Abdomen: globose, not aching. Moderate ascites. Epatomegaly and splenomegaly. Peristalsis present. AAII: light bilateral edemas Ex. neurologic: Mingazzini I e II negative, no deficit of cranial nerves. No flapping tremor.
9 Baseline clinical and laboratory features (1) DATA Hb (g/dl) (v.n ) 11.7 WBC (x 10 9 /l) (v.n ) Piastrine (x 10 9 /l) (v.n ) 26 PCR (mg/l) (v.n. 0-6) 36 Serum total bilirubin (µmol/l) (v.n ) (31 mg/dl) Serum direct bilirubin (µmol/l) (v.n ) (24.84 mg/dl) Serum creatinine (µmol/l) (v.n ) 142 (1.56 mg/dl) Serum Na (mmol/l) (v.n ) 131 Serum K (mmol/l) (v.n ) 3.4 INR 1.75 Albumin (g/l) (v.n ) 32 Total serum proteins (g/l) (v.n ) 54.2
10 Baseline clinical and laboratory features (2) DATA Ammonia (µmol/l) (v.n ) 80 AST (U/L) (v.n ) 76 ALT (U/L) (v.n ) 69 GGT (U/L) (v.n. 3-65) 103 ALP (U/L) (v.n ) 145 MELD score 30 MELD Na score 32 CTP class (score) C (13)
11 Diagnostic procedures Rx chest (10/07): ndp EGDS (6/07): blu F1 esophageal varices, cardia incontinence, congestive gastropathy TC abdomen with contrast medium (6/7): no focal hepatic lesions... open spleno-mesenteric-portal axis... Epatosplenomegaly... moderate ascites
12 What about the management of this patient? Liver failure Bacterial and/or fungal infections Renal Failure Cardiovascular problems Valuation for liver transplant
13 Management of liver failure According to Lille criteria steroid therapy was stopped. We started treatment with PENTOXYFILLINE (400 mg three times a day) and parenteral nutrition. This therapy was continued until the 9th of Agoust.
14 Management of infections (1) negativity of nasal, perianal, rectal tampons urine cultures blood cultures
15 Management of infections (2) It was prescribed antibiotic therapy with CEFTAZIDIME (1 g x 2/die) and TEICOPLANINA (initial dose of 600 mg and then 400 mg every 2 days) according to the results of urine culture modifing the doses according to renal clearence.
16 Management of infections (3)
17 Management of infections (4)
18 Management of infections (5) patient piretic (T=38 C) Antibiotic therapy was modified with the introduction of MEROPENEM (1 g x 3 /die) and DAPTOMICINA (500 mg/die). It was also started therapy for fungi with CASPOFUNGINA (50 mg/die).
19 Management of infections (6).following blood and urine cultures were negative.. so on the 14 th of August antibiotic therapy was stopped.
20 Management of renal failure (1) Trend of serum creatinine (µmol/l) during the stay in hospital
21 Management of renal failure (2) Trend of proteinuria of 24 h during the stay of hospital
22 Management of renal failure (3) Serial episodes of worsening of renal failure, which was still present at admission, that were treated with temporary withdrawal of diuretics, plasma volume expansion with albumin or saline.
23 Management of cardiovascular problems One episode of circulatory overloaded with initial signs of left cardiac failure that was treated with diuretics. Episodes of ventricular tachycardia with an arrhythmical ECG evocative for Brugada s syndrome that were treated with K and Mg addition (however they were already in range but at medium-low levels). Patient was still having amiodarone.
24 Perspective of liver transplantation (LT) There were 2 issues in the perspective of LT: 1) toxicological issue: not favourable opinion considering the insufficient willing for toxicological monitoring, the not proved withdrawal out of hospital and the negative familiar context. 2) cardiovascular issue: not favourable opinion because it needed further valuation considering the complex cardiologic problem (arrhytmy and cardiovascular risk factors) including coronarography. It was not possible to do coronarography because of the continuous instability of renal function.
25 Evolution of the clinical picture (1).on the 17 th of August general conditions were improved. The severity of liver failure was progressively reducing (total bilirubin=202 µmol/l (11.7 mg/dl), dir. = 143 µmol/l (8.3 mg/dl), INR = 1.49). Infections were solved. There was still renal failure (final serum creatinine=175 µmol/l or 1.9 mg/dl) and the ascites was moderate. Patient followed an oral nutritional management with still a partial parenteral support (1000 ml/day of Oliclinomel n 5 with the addition of insulin). Glycaemia was well controlled with insulin.
26 Evolution of the clinical picture (2) 1. On the 17th of August 2012 he was moved to the General Medicine at the Hospital of Valdagno (VI). 2. The final diagnosis was: Acute on chronic liver failure due to alcohol-related cirrhosis (with also evidence for a metabolic component and iron overload), actually with ascites and renal failure (functional component over an organic component), several episodes of ventricular tachycardia (suspected Brugada s syndrome), obesity, diabetes mellitus in patient, actually, non suitable to liver transplant.
27 Evolution of the clinical picture (3) 17th of August- 18th of September 2012: stay in General Medicine in Valdagno (VI) with an improvement of general conditions (when he was discharged: tot.bilirubin=2.1 mg/dl, serum creatinine=2.17 mg/dl) 27th of September-17th of October: new admission to the hospital of Valdagno because of worsening of renal failure (serum creatinine=5.21 mg/dl). He had FANS for shoulder pain!.he was treated with diuretics. At the moment of discharge: creatinine=2.34 mg/dl, total bilirubin=7.4 mg/dl, INR= th of November: admission to the hospital of Valdagno because of an increase of weight of 14 Kg, worsening of renal function (serum creatinine=3.7 mg/dl), encephalopathy...
28 Evolution of the clinical picture (4)..hepatorenal syndrome treated with albumin and terlipressin and diuretics without response... Patient died on the 18th of November 2012
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