Cirrosi Epatica
• Definizione
• Meccanismi della fibrogenesi epatica
• Fisiopatologia dell’ipertensione portale
• Complicanze maggiori della cirrosi
• Cenni di terapia delle complicanze
• Management della cirrosi
compensata/scompensata
CIRROSI
Alterazione dell’architettura del fegato caratterizzata da
noduli e formazione di tessuto collagene
CAUSE: Tutte le cause di danno epatico cronico
Progressione del danno epatico cronico
Causa
iniziale
Stadio
finale
Complicanze
●
anni
Cirrosi
-Fibrosi
-Distorsione dell’architettura
epatica
Portal
Vein
Hepatic Artery
Sinusoids
Bile Duct
Central
Veins
Normal
Cirrhosis
Changes of hepatic microcirculation in cirrhosis
Activation of HSC
LIVER CIRRHOSIS : from activation of HSC to
cirrhotic nodules
Fibrosi virale
Spazio
portale
1. – Necrosi a ponte porto-centrale
2. – Epatite da interfaccia e sviluppo di setti che circondano il
parechima
3. – Perdita di connessioni vascolari con il sistema portale
fibrosi biliare
Modello BDL
CBP
CB secondaria
CSP
Formazione di setti porto-portali
La vena centrolobulare è conservata
Spazio
portale
Centrolobular
fibrosis
portal tract
1. – Secondary to venous outflow problems (e.g. chronic heart
failure)
2. - Chronic ETOH consumption
3. – Development of central to central septa and “reversed
lobulation”
CONSEQUENCES OF DEVELOPING PROGRESSIVE
HEPATIC FIBROSIS
structural & functional
intrahepatic resistance
 splanchnic blood flow
(cirrhosis)
HCC
systemic
hyperdynamic circulation
portal hypertension
variceal bleeding
portosystemic collaterals
decrease central
volume
ascites
hepatic encephalopathy
hepatopulmonary syndrome
 cardiac output
cardiomyopathy
HRS
spontaneous
bacterial peritonitis
Ipertensione portale
• Condizione fisiopatologica causata dall’aumento
della pressione venosa nel distretto portale
• Principale conseguenza della cirrosi epatica e
principale meccanismo delle sue principali
complicanze cliniche
• Riconosce anche cause extraepatiche, in cui le
manifestazioni cliniche dominanti dipendono dalla
sede di origine della ipertensione portale
Anatomia e Fisiologia della
circolazione portale
Sistema venoso ad alta portata e bassa resistenza che drena il
sangue dagli organi addominali per convogliarlo al fegato; da
questo, attraverso i sinusoidi e le vene sovrepatiche, raggiunge la
vena cava inferiore e la circolazione sistemica
• Flusso epatico: 1.5 l/min
(80% venoso, portale)
• Pressione portale: 7 mmHg
(diretta o wedge)
• Pressione sovraepatiche/atrio dx: 3-5 mmHg
• Gradiente porto-epatico
(HVPG): ≤5
Classificazione e cause
• Cause Pre-epatiche
• Trombosi portale
• Trombosi splenica
• Cause Intraepatiche
• Presinusoidali
• Sinusoidali
• Postsinusoidali
• Cause post-epatiche
•
•
•
•
Membrana cavale
Pericardite costrittiva
Insufficienza tricuspidale
Grave scompenso cardiaco destro
Cause di ipertensione portale
intraepatica
• Pre-sinusoidali
• Schistosomiasi, sarcoidosi, tossici, fibrosi epatica
congenita, malattie mielo proliferative
• Sinusoidali o miste
• Cirrosi, epatite alcolica, iperplasia nodulare
rigenerativa
• Post-sinusoidali
• Malattia veno-occlusiva
• Sindrome di Budd-Chiari
PORTAL HYPERTENSION: pathophysiological sequelae
structural & functional
 splanchnic blood flow
intrahepatic resistance
(cirrhosis)
HCC
systemic
hyperdynamic circulation
portal hypertension
variceal bleeding
portosystemic collaterals
decrease central
volume
ascites
hepatic encephalopathy
hepatopulmonary syndrome
 cardiac output
cardiomyopathy
HRS
spontaneous
bacterial peritonitis
Conseguenze dell’ ipertensione
portale
• Splenomegalia ed ipersplenismo
• Circoli collaterali ed emorragie digestive
• Shunt porto-sistemici ed encefalopatia
porto-sistemica
• Vasodilatazione splancnica ed alterazioni
della emodinamica sistemica
Circoli collaterali
Ligamento falciforme
Gastro-esofagei
Parete addome e retro
peritoneo
Gastro-esofagei
Vene emorroidarie
Conseguenze degli shunts
portosistemici
• Riducono il flusso portale
• Aumentano insufficienza epatica
• NON riducono significativamente la pressione
portale
• Favoriscono la circolazione iperdinamica
• Favoriscono iperammoniemia
• Endotossinemia
• Encefalopatia porto sistemica
Complicanze maggiori della cirrosi
Complicanze maggiori della cirrosi
Natural History of Chronic Liver Disease
Development
of cirrhosis
Chronic
liver
disease
Compensated
cirrhosis
Decompensated
cirrhosis
Death
Development of
complications:
 Variceal
hemorrhage
 Ascites
 Encephalopathy
 HRS
Orthotopic
liver
transplant
(OLT)
Mortalità per complicanze di cirrosi
epatica - 384 Pts
35
follow-up: 5 anni
30
25
20
Complicanze
15
10
5
0
HCC
Ascit
Varix Bl Enceph/J >1 compl
Fattovich G et al, Gastroenterology
1997;112:463
Child-Turcotte-Pugh (CTP) Score
1
Encephalopathy
None
Points
2
Grade 1-2 Grade 3-4
(precipitant)
Ascites
3
(chronic)
None
Mild
Moderate
<2
2-3
>3
>3.5
2.8-3.5
<2.8
PT (seconds prolonged) <4
or INR
<1.7
4-6
1.7-2.3
>6
>2.3
Bilirubin (mg/dl)
Albumin (g/dl)
Child A: 5-6 pts
Child B: 7-9 pts
Child C: 10-15 pts
MINIMAL LISTING CRITERIA: CTP SCORE  7 POINTS
MELD (Model for End-Stage
Liver Disease)
 Predicts 3-month mortality among patients
with chronic liver disease on the liver waiting
list
 MELD = (0.957 x LN (creatinine) + 0.378 x LN
(bilirubin) + 1.12 x LN (INR) + 0.643) x 10
 Minimum score = 6 (risk of death on WL 20%)
 Maximum score = 40 (risk of death on WL
100%)
Diagnostica della cirrosi con
ipertensione portale
•
•
•
•
Clinico-semeiologica
Misurazione invasiva emodinamica portale
Eco-doppler
Endoscopia digestiva
Diagnosi clinico-semeiologica
•
•
•
•
•
•
•
Splenomegalia
Circoli collaterali superficiali
Gavoccioli emorroidari
Spider Naevi
Edema perimalleolare
Ascite
Asterixis
Semeiotica dell’ipertensione portale
Definition of ascites
• Uncomplicated
 Grade 1 (mild) detectable only by US
 Grade 2 (moderate) moderate symmetrical
abdominal distension
 Grade 3 (large) marked abdominal distension
• Refractory
Ascites that cannot be mobilized or early
recurrence of ascites not prevented by medical
therapy
 Diuretic-resistant
 Diuretic-intractable
Treatment of Ascites
• Bed rest unproven benefit
• Dietary sodium restriction to 5.2 g/d (90 mmol)
• Diuretics
 Anti-Mineralocorticoids Spironolactone, Canrenoate,
Canrenone
 Loop diuretics Furosemide, Torasemide, Ethacrynic
Acid
 Other potassium-sparing diuretics Amiloride,
Triamterene
Diagnostic Criteria of Refractory Ascites
• Treatment duration
Intensive diuretic therapy (spironolactone 400 mg/d + furosemide
160 mg/d) for at least 1 wk
Salt-restricted diet (< 90 mmol or 5.2 g of salt/d)
• Lack of response
Weight loss < 0.8 kg over 4 days
Urinary sodium output < sodium intake
• Early ascites recurrence
Grade 2 or 3 ascites within 4 wks of initial mobilization
• Diuretic-induced complications
Hepatic Encephalopathy, Renal Impairment, Hyponatremia,
Hypo/Hyperkalemia
PERITONITE BATTERICA SPONTANEA:
definizione ed epidemiologia
 Infezione del liquido ascitico
 PMN > 250/mm3 e colturale + su liquido ascitico
 Microbiologia:
G-: E. Coli, K. Pneumoniae (60%)
G+: Strepto (25%)
Anaerobi: rari
 Non evidente sorgente di infezione addominale
trattabile chirurgicamente
 10-25% dei cirrotici ospedalizzati con ascite
 Mortalità elevata (17-50%)
 Alto rischio di recurrence: 43-70% (6-12 mesi)
PERITONITE BATTERICA SPONTANEA:
forme cliniche
1. Classic
2. CNNA (culture negative neutrocytic ascites)
3. MNB (monomicrobial non-neutrocytic bacterascites)
 carcinosi peritoneale, pancreatite, peritonite TBC
Classica
CNNA
MNB
PMN
> 250
> 250
< 250
Colturale
+
-
+
PERITONITE BATTERICA SPONTANEA:
terapia e profilassi
 Cefotaxime: 2g/12 hrs per 5-10 gg
 Ciprofloxacina: 400 mg/12 hrs per 5 gg, poi orale
 Se non risposta: Stafilo?
 + Albumina: 1.5 g/kg alla diagnosi, 1 g/kg dopo 48
hrs (prevenire HRS!)
 Chinolonico long-term (Norfloxacina 400 mg/die)
soprattutto se proteine < 1 g/dl nel liquido ascitico
Definition of Hepatorenal Syndrome
(HRS)
•
Type I HRS
Rapid and progressive renal failure with a
doubling of serum creatinine to a level greater
than 2.5 mg/dl or a halving of the creatinine
clearance to less than 20 ml/min in less than 2
wks
•
Type II HRS
More chronic form with a slowly progressive
increase in serum creatinine level to greater
than 1.5 mg/dl or a creatinine clearance of less
than 40 ml/min
DIFFERENCES BETWEEN TYPE-1 AND TYPE-2 HRS
Onset
Renal failure
Consequence
Survival
Type-2
Type-1
Spontaneous
Precipitated
Moderate and steady
Severe and progressive
Refractory ascites
Terminal hepatorenal failure
Months
Days
Definition of Hepatorenal Syndrome:
Major Criteria
• Chronic or acute liver disease with liver failure
and portal hypertension
• Low glomerular filtration rate (serum creatinine
> 1.5 mg/dl or creatinine clearance < 40
ml/min)
• Absence of shock, excessive fluid loss,
ongoing bacterial infection and recent
treatment with nephrotoxic drugs
• No sustained improvement in renal function
following expansion with 1.5 l of isotonic saline
• Proteinuria < 0.5 g/dl
• No US evidence of renal tract disease
Definition of Hepatorenal Syndrome:
Minor Criteria
•
•
•
•
Urine volume < 500 ml/d
Urine sodium < 10 mmol/d
Urine osmolality < plasma osmolality
Urine red cell count < 50/high power
field
• Serum sodium < 130 mmol/l
The Pathophysiology of HRS
Diagnosi e classificazione
endoscopica
Varici esofagee
Varici fondo
Diagnosi e classificazione
endoscopica
Gastropatia ipertensiva
GAVE
Dilation and Rupture of Varices
Varix
P
Flow
Risk increases in portal
pressure and collateral blood
flow caused by:
• Meals
• Alcohol
• Exercise
• Increased intra-abdominal
pressure
Acute variceal bleeding
Sclerotherapy + Drugs vs Sclerotherapy alone
Mortality
PREVENZIONE RISANGUINAMENTO
(profilassi secondaria)
BB + nitrati
fallimento
fallimento
successo
continuare
LEV(+ BB)
Malattia epatica
avanzata
TIPS
OLT
successo
Malattia epatica
stabile
Continuare
+ follow up
TIPS
(DSSR)
D´Amico, 2004
HEPATIC ENCEPHALOPATHY – NOMENCLATURE
Hepatic Encephalopathy
Nomenclature
 Type A
Associated with Acute liver failure
 Type B
Associated with porto-systemic Bypass
without intrinsic hepatocellular disease
 Type C
Associated with Cirrhosis and portosystemic shunting
Ferenci et al., Hepatology 2002; 35:716
Encephalopathy of acute liver
failure (Type A)
 Rapid deterioration in the level of
consciousness
 Increased intracranial pressure (ICP)
 Reduced cerebral perfusion pressure
 Neuropathologically, there is brain edema
 Pathogenesis is multifactorial with
ammonia playing a major role
TYPE C HEPATIC ENCEPHALOPATHY IS THE ENCEPHALOPATHY OF CIRRHOSIS
Type C Hepatic
Encephalopathy is the
Encephalopathy of Cirrhosis
 Neuropsychiatric complication of
cirrhosis
 Results from spontaneous or surgical /
radiological portal-systemic shunt +
chronic liver failure
 Failure to metabolize neurotoxic
substances
 Alterations of astrocyte morphology and
function (Alzheimer type II astrocytosis)
CHARACTERISTICS OF TYPE A VS. TYPE C ENCEPHALOPATHY
Characteristics of Type A vs. Type C
Hepatic Encephalopathy
Type A
Type C
 Rapid onset
 Gradual onset
 Frequently fatal
 Rarely fatal
 Main cause:
cerebral edema
 Main cause:
shunting / toxin
 Precipitant
 Treatment: rarely
effective short of liver
transplant
 Treatment: usually
effective
PATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHY
Pathophysiology of Hepatic
Encephalopathy
Ammonia
Upregulation of astrocytic peripheral
benzodiazepine receptors (PBR)
Neurosteroid production
Modulation of GABAA receptor
Hepatic encephalopathy
PATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHY
Hepatic Encephalopathy
Pathogenesis
Toxins
NH3
Shunting
Failure to
metabolize
NH3
Bacterial action
Protein load
GABA-BD
receptors
Pathogenesis of Hepatic Encephalopathy:
role of GABA-BD receptors
HEPATIC ENCEPHALOPATHY IS A CLINICAL DIAGNOSIS
Hepatic Encephalopathy Is A
Clinical Diagnosis
 Clinical findings and history important
 Ammonia levels are unreliable
 Ammonia has poor correlation with
diagnosis
 Measurement of ammonia not
necessary
 Number connection test
 Slow dominant rhythm on EEG
STAGES OF HEPATIC ENCEPHALOPATHY
Stages of Hepatic Encephalopathy
Stage
Mental state
Neurologic signs
1
Mild confusion: limited attention
span, irritability, inverted sleep
pattern
Incoordination, tremor,
impaired handwriting
2
Drowsiness, personality changes,
intermittent disorientation
Asterixis, ataxia,
dysarthria
3
Somnolent, gross disorientation,
marked confusion, slurred speech
Hyperreflexia, muscle
rigidity, Babinski sign
4
Coma
No response to pain,
decerebrate posture
Poor Correlation of Ammonia Levels With
Presence or Severity of Encephalopathy
400
350
300
250
Venous
total
200
ammonia
mmol/L 150
100
50
0
Grade 0
Grade 1
Grade 2
Grade 3
Grade 4
Severity of Hepatic Encephalopathy
Ong et al., Am J Med 2003; 114:188
BLOOD AMMONIA LEVELS ONLY LEAD TO CONFUSION
“Blood ammonia levels cause as
much confusion in those
requesting the measurement as in
the patients in whom they are
being measured”
Adrian Reuben
Hepatology 2002;35:983
MINIMAL HEPATIC ENCEPHALOPATHY
Minimal Hepatic Encephalopathy
 Occurs in 30-70% of cirrhotic patients
without overt hepatic encephalopathy
 Detected by psychometric and neuropsychological testing
 May improve with lactulose or
synbiotics (probiotics and fermentable
fiber)
 Predicts overt encephalopathy
TREATMENT OF HEPATIC ENCEPHALOPATHY
Treatment of Hepatic
Encephalopathy
 Identify and treat precipitating factor
 Infection
 GI hemorrhage
 Prerenal azotemia
 Sedatives
 Constipation
 Lactulose (adjust to 2-3 bowel
movements/day)
 Protein restriction, short-term (if at all)
ACTIONS OF LACTULOSE
Actions of Lactulose
NH3
Decreased pH
NH4+
Lactic acid
NH3
Lactulos
e
Ureaseproducing
bacteria
Increase
cathartic effect
PROTEIN RESTRICTION IS NOT NECESSARY IN HEPATIC ENCEPHALOPATHY
Protein Restriction Is Not Necessary in
Hepatic Encephalopathy
4
Hypoproteic diet
Normoproteic diet
3
2
Hepatic
encephalopath
y stage
1
0
0
1
2
3
4
5
6
7
Day
Córdoba, J Hepatology 2004;
91:38
8
9 10 11 12 13 14
Treatment Recommendations - Cirrhosis
Decompensated
Compensated
Hepatoma Surveillance
U/S, AFP q 6 months
Variceal Bleed
SBP
Varices Surveillance
Ascites
Monitor Liver Function
PT, Alb, Bili q 3-6 months
HRS
Encephalopathy
(Garcia-Tsao G, 2003)
Management of cirrhosis

Maintain nutrition/reduce salt intake

Prevent bone loss

Prevent bleeding

Prevent encephalopathy

High index suspicion for sepsis

Close control diabetes

Management of complications

Early diagnosis and therapy of HCC

(Selected antiviral therapy)

Appropriate referral to transplant centres
Natural History of Cirrhosis in 2008:
Altered by What We Do
 More aggressive screening
 HCC identified earlier
 Ablative therapies for HCC (downstaging)
 Obliteration of varices/beta-blockade
 TIPSS
 Liver Transplantation
HEPATIC ENCEPHALOPATHY – TREATMENT SUMMARY
Hepatic Encephalopathy
Treatment: Summary
Increase ammonia
fixation in liver:
 Ornithine
aspartate
 Benzoate
Shunt
occlusion
or
reduction
Decrease
ammonia
production in gut:
 Lactulose
 Antibiotics
 Adjustment in
dietary protein
Liver Transplant
Indications
Contraindications
 Decompensated
 Extrahepatic
cirrhosis - all causes
malignancy
(hepatitis C most
common indication)  Active infection
 Intrahepatic
malignancy
 Active substance
abuse
 Acute liver failure
 Advanced
cardiopulmon-ary
disease
 Metabolic disease
Child score and survival in 424
patients
1.0
CPT - A
.8
.6
CPT - B
Cum Survival
.4
CPT - C
.2
0.0
0
200
400
OLT 1-yr
survival
Heumann et al
600
800
1000
1200
OLT 2-yr
survival
1400
1600
Days
MELD and Survival on Transplant Waiting
List
100
92.3%
90.7%
80
Probabilit
y of
survival
(%)
<15
15 - 20
66.0%
60
20 - 29
40
33.8%
30+
20
0
0
2
4
6
8
Months from listing
10
12
Organ Allocation for Liver
Transplant
 Fulminant hepatic failure has highest
priority
 MELD score determines priority in
cirrhosis
 Amongst patients with same blood type,
highest MELD score determines priority
 Waiting time used only to break ties with
identical MELD scores
 MELD scores are updated at regular
intervals
United Network for Organ Sharing (UNOS)
Regions
1
7
6
9
2
10
8
11
5
3
4
Liver Transplantation in the U.S.
 Current 1- and 3-year survival rates are 90%
and 80%, respectively
 During 2005, ~6,000 liver transplantations
were performed
 During 2005, ~17,000 patients were on the
waiting list and ~2,000 died on it or were
removed from it because they became too
sick for transplant
 Main problem is the shortage of donors
 Expansion of donor pool: marginal livers,
split-livers, live donors
NATURAL HISTORY OF CHRONIC LIVER DISEASE – SUMMARY
Natural History of Chronic Liver Disease
Development
of cirrhosis
Chronic
liver
disease
Compensated
cirrhosis
Decompensated
cirrhosis
Median
survival
~ 9 years
Median
survival
~ 1.6
years
Development
of
complications
 Variceal
:
hemorrhage
 Ascites
 Encephalopathy
 Jaundice
Death
Orthotopic
liver
transplant
(OLT)
MANAGEMENT OF COMPENSATED CIRRHOSIS – SUMMARY
Management of Compensated
Cirrhosis
Chronic
liver
disease
Compensated
cirrhosis
Decompensated
cirrhosis
Death
Diagnosis:
 Liver biopsy
 Clinical/LSS
Screen for varices (EGD):
 Large varices  beta-blockers
 Small varices  EGD in 1-2 yrs
 No varices  EGD in 2-3 yrs
Screen for HCC:
 Ultrasound and AFP q 6 mos
 Measures to stop alcohol use
 Hep A and B vaccination
Orthotopic
liver
transplant
(OLT)
MANAGEMENT OF ASCITES – SUMMARY
Management of Ascites
Chronic
liver
disease
Compensated
cirrhosis
Decompensated
cirrhosis
Death
Ascites
Diagnosis:
 Clinical
 US or CAT scan
Treatment:
 Spironolactone-based
 No NSAIDs
Early diagnosis of SBP:
 Paracentesis q admission
or with symptoms
 No aminoglycosides in
SBP
Orthotopic
liver
transplant
(OLT)
MANAGEMENT OF VARICEAL BLEEDING – SUMMARY
Management of Variceal Bleeding
Chronic
liver
disease
Compensated
cirrhosis
Decompensated
cirrhosis
Death
Variceal Bleed
Diagnosis / Treatment:
 Endoscopy within 12
hrs
Other Treatment:
 Prophylactic antibiotics
Prophylaxis of rebleed:
 Beta-blockers prior to d/c
or
 Serial ligation post d/c
Orthotopic
liver
transplant
(OLT)
MANAGEMENT OF HEPATIC ENCEPHALOPATHY - SUMMARY
Management of Encephalopathy
Chronic
liver
disease
Compensated
cirrhosis
Decompensated
cirrhosis
Death
Encephalopathy
Diagnosis
 Clinical
Treatment:
 D/C diuretics
 D/C sedatives
 Dx paracentesis
 No long-term
protein restriction
Orthotopic
liver
transplant
(OLT)
Cenni di terapia dell’ipertensione
portale
• Farmaci antifibrotici: una promessa ancora non
mantenuta
• L’unica terapia in grado di modificare la
progressione è, al momento, il trattamento del
fattore etiologico di base (es no Et-OH)
• Il target della terapia è quello di ridurre,
farmacologicamente o “chirurgicamente” il
gradiente venoso porto-epatico
• L’end-point clinico è la prevenzione primaria o
secondaria del sanguinamento da varici
Terapia dell’ipertensione portale
• Vasocostrittori arteriolari splancnici
• Beta bloccanti non selettivi
• Vasopressina ed analoghi
• Somatostatina ed analoghi
• Terapia Endoscopica
• Scleroterapia
• Legatura
• Terapia Chirurgica
• H shunt (mesocavale)
• Splenorenale distale
• TIPS
Mediatori vasoattivi nella ipertensione portale
VASODILATATORI
• Glucagone
• Prostaciclina
• Adenosina
• Fattore Natriuretico Atriale
• VIP
• Endotossine
• TNF
• NO
VASOCOSTRITTORI
• Norepinefrina
• Serotonina
• Endotelina
• Angiotensina II
• Vasopressina
Treatment of ascites:
Grade 1 Ascites
• No specific treatment, only reduction of
dietary sodium intake
Treatment of ascites:
Grade 2 Ascites
• Bed rest unproven benefit
• Dietary sodium restriction to 5.2 g/d (90 mmol)
• Diuretics
Anti-Mineralocorticoids Spironolactone, Canrenoate,
Canrenone
Loop diuretics Furosemide, Torasemide, Ethacrynic Acid
Other potassium-sparing diuretics Amiloride, Triamterene
Treatment of ascites:
use of Diuretics in Grade 2 Ascites
• Spironolactone: alone at first, 100-200 mg/d once
• Adequate response: weight loss = - 0.5 kg/d (1 kg/d if
peripheral edema)
• If not adequate response: stepwise increase
• If failure to spironolactone 200 mg/d after 2-3 wks:
+ Furosemide (20-40 mg/d)
• If failure: maximal doses of spironolactone 400 mg/d +
furosemide 160 mg/d
• Canrenoate, Amiloride (5-30 mg/d), or Torasemide
may be used alternatively
Treatment of ascites:
Complications of diuretic therapy
• Electrolyte imbalance (hyponatremia, hypo/hyperkalemia,
metabolic acidosis, metabolic hypochloremic alkalosis)
if hyperkalemia > 6 mmol/l: stop spironolactone
if hypokalemia < 3.5 mmol/l: stop furosemide
•
•
•
•
•
Renal impairment
Hepatic Encephalopathy
Gynecomastia
Testis hypotrophia
Muscle cramps (also related to effective hypovolemia):
may benefit from albumin, Zn sulfate
Treatment of ascites:
Contraindications of diuretic therapy
• Severe hyponatremia (< 120 mmol/l)
• Renal impairment (serum creatinine > 150
umol/l)
• Active bacterial infection
Treatment of ascites:
Grade 3 Ascites
• Paracentesis, followed by
• Sodium restriction
• Diuretic therapy
to reduce the risk of recurrence within 4 wks
(90% vs 20%)
Treatment of ascites:
use of Paracentesis in Grade 3 Ascites
• Effective and safe in single session
• All ascitic fluid may be removed, even though
in large amount
• Plasma volume expansion once paracentesis has
been completed
Plasma substitute if paracentesis < 5 l
Albumin if paracentesis > 5 l (6-8 g/l of ascites
removed)
Treatment of ascites:
Contraindications and complications of
paracentesis
• Severe coagulopathy or marked thrombocytopenia
(< 50.000/ml)
• Previous surgery or peritoneal adhesions (risk of
bowel perforations)
• Bleeding (may be fatal)
• Leakage of ascitic fluid
• Renal impairment
Treatment of ascites:
Refractory Ascites
• Repeated total paracentesis, followed by
• Sodium restriction
• Diuretic therapy (if tolerated; stop when
urine sodium output < 30 mmol/d)
• TIPS (if paracentesis are not tolerated any
more)
Treatment of dilutional hyponatremia
• No published controlled trials
• Water restriction is ineffective
• Plasma volume expansion with colloids
may have some benefit
• Vasopressin-2 receptor antagonists seem to
be promising
Therapy of Hepatorenal Syndrome:
present and future
•
•
•
•
Liver Transplantation
Vasopressin Analogues
α-Adrenergic Agonists
Molecular Adsorbent Recirculating System
Therapy of Hepatorenal Syndrome:
Vasopressin Analogues (Ornipressin, Terlipressin)
• Rationale: increase of splanchnic and
systemic vascular resistance, resulting in a
redistribution of the circulating blood
volume, via suppression of the RAA and
sympathetic activities
• Useful in combination with albumin and
low-dose dopamin
Therapy of Hepatorenal Syndrome:
α-Adrenergic Agonists (midodrine)
• Rationale: improvement of systemic
vasoconstriction and urinary sodium
excretion
• Effective in combination with plasma
volume expansion and octreotide (an
inhibitor of the release of endogenous
vasodilators)
HE:FATTORI PRECIPITANTI
•
•
•
•
•
•
•
•
•
ABUSO DI FARMACI (diuretici, sedativi, oppiati)
INFEZIONI INTERCORRENTI
ECCESSO DI ALCOL / PROTEINE
EMORRAGIA DIGESTIVA
INTERVENTI CHIRURGICI
COPROSTASI
IPERAZOTEMIA
ALCALOSI IPOKALIEMICA
HCC
HE: TERAPIA MEDICA
•
•
•
•
IDENTIFICARE FATTORE PRECIPITANTE
LIMITARE INTROITO PROTEICO
LATTULOSIO (attenzione meteorismo!)
ANTIBIOTICI TOPICI (Paromomicina,
Rifaximina)
• CLISTERINI MEDICATI sistematicamente!!!