LIVER CIRRHOSIS
DEFINITION:
pathological condition with the development of fibrosis to the
point that there is architectural distorsion with formation of regenerative nodules
CAUSES:
• Alcoholism
• Chronic viral hepatitis (Hepatitis
B, Hepatitis C)
• Autoimmune hepatitis
• Nonalcoholic steatohepatitis
• Billiary cirrhosis
• Primary billiary cirrhosis
• Primary sclerosing cholangitis
• Autoimmune cholangiopathy
•
•
•
•
•
•
•
Cardiac cirrhosis
Metabolic liver disease:
Hemocromatosis
Wilson’s disease
L1 Antitrypsin deficiency
Cystic fibrosis
Cryptogenic cirrhosis
ALCOHOLIC CIRRHOSIS
•14 milion adults in US -alcohol abuse or dependence
•10th most common cause of death in adults
• alcoholic cirrhosis accounts 40% of deaths due to
cirrhosis
CLINICAL FEATURES
•
•
•
•
•
•
•
•
•
•
•
•
NON SPECIFIC SYMPTOMS:
vague right upper quadrant pain
fever
nausea and vomiting
diarrhea
anorexia
malaise
LATER , SPECIFIC COMPLICATIONS:
ascites
edema
bleeding (UDH)
jaundice/encephalopathy
• incidentally at the time of
autopsy or elective surgery
PHYSICAL EXAMINATION
• liver and spleen enlarged with
the liver edge firm and nodular
• scleral icterus
• palmar erythema
• spider angiomas
• parothid gland enlargement
• digital clubbing
• muscle wasting
• edema and ascites
• decreased body hair,
gynecomastia
• testicular atrophy
• menstrual irregularities/
amenorrheic women
These changes are often reversible
following cessation of alcohol
-
LABORATORY TESTS
DIAGNOSIS
normal in patients with early
compensated alcoholic
cirrhosis
• Clinical features + physical
examination findings +
laboratory studies
• Liver biopsy,ultrasonography,
UDE,CT ( dg. dif. Cancer)
(abstinence maintained 6 months-> residual, nonreversible
disease)
- in advanced liver disease many
abnormalities are present:
• anemia (chronic GI blood lose,
nutritional deficiencies,
hipersplenism related to portal
hypertension , hemolytic
anemia- ZIEVE’S syndrome)
• platelets counts are often
reduced early (PHT)
• total direct bilirubin- N/
elevated
• protrombin times prolonged
• AST>ALT2:1ratio
Patients
who
have
had
complications
and who
continue to drink have a <50%
5-year survival in contrast with
those who remain abstinent ->prognosis improved and LIVER
TRANSPLANTATION - VIABLE
OPTION
TREATMENT
•
•
•
•
Abstinence- cornerstone therapy
Good nutrition and long term medical supervision
Glucocorticoids are occasionally used(DF>32)
Oral PENTOXIFYLINE decrease tumour necrosis factor
alpha (TNF-alpha) and other proinflamatory cytokines
• Parenterally adm. of inhibitors of TNF-alpha
(INFLIXIMAB/ ETANERCEPT)
• Medication that reduce craving for alcohol
ACAMPROSATE CALCIUM
• Vit.B1,B6,B12+SG10%,Arginine,Aminohepa,Aspat
ofort
CIRRHOSIS DUE TO CHRONIC VIRAL
HEPATITIS B OR C
• patients exposed to the hepatitis C (HCV) - 80% develop chronic hepatitis C
and ,of those,-20-30% will develop cirrhosis over 20-30 years
•world wide , 170 million individuals have hepatitis C
•progression of liver disease due to chronic HC is characterized by :
•portal- based fibrosis with brindging fibrosis and nodularity developing -->
cirrhosis
•inflammatory infiltrate in portal areas
•lobular hepato-cellular injury and inflammation
•HCV genotype 3, steatosis is often present
•Hepatitis B exposure : 5% develop chronic hepatitis B, 20% will go to
develop cirrhosis
•in US 1,25 million carriers of HB; Asia, Africa 15%aquires the infection
vertically (at birth) and 25% may develop cirrhosis
CLINICAL FEATURES
• fatigue
• malaise
• right upper quadrant pain
LABORATORY EVALUATION
• HCV-RNA,genotype
• AgHBS
• anti HBS
• HBe Ag
• anti HBe
• HBV-DNA levels
TREATMENT IN HEPATITIS B
•
•
•
•
LAMIVUDINE100mg/day
ADEFOVIR
ENTECAVIR 0.5mg/day
TENOFOVIR
INTERFERON ALFA should not
be used in decompensated
cirrhotics
with EV,ascites,jaundice
CIRRHOSIS FROM AUTOIMMUNE
HEPATITIS
•Positive autoimmune markers ANA,ASMA
•Active inflammation - elevated liver enzimes->immunosuppresive therapy
•Obesity in western countries - patients with
nonalcoholic fatty liver disease
•Management of complications of cirrhosis due to AIH
or NASH is similar to that for other forms of cirrhosis
BILLIARY CIRRHOSIS
Cholestatic liver disease result from necroinflammatory lesions :
•congenital
•metabolic processes
•external bile duct compresion
2 broad categories reflect the anatomic sites of abnormal bile
retention :
•intrahepatic -- different approach
•extrahepatic--surgical/endoscopic biliary tract decompression
PBC (primary biliary cirrhosis)
100-200 / million(female preponderence / median age - 50
years )-at the time of diagnosis
Cause: unknown
It is characterized by portal inflammation and necrosis of
cholangiocytes in small and medium size bile ducts
Lab findings: elevated bilirubine level
progressive liver failure
LIVER TRANSPLANTATION- treatment of choice for patients
with decompensated cirrhosis
URSODEOXYCHOLIC ACID (UDCA)
AMA - 90% patients with PBC - useful markers for PBC
PBC (primary biliary cirrhosis)
CLINICAL FEATURES
LABORATORY FINDINGS :
•
•
•
fatigue
pruritus 50% - bothersome in the
evening; prior to jaundice
(severe disease and poor
prognosis)
•
•
•
PHYSICAL EXAMINATION
• JAUNDICE
• hepatomegaly
• splenomegaly
• ascites
• edema
• hiperpigmentation-trunk,arms
• xantelasma (xanthomata)
• bonepain :
osteopenia/osteoporosis
• scratching lesions
augmentation of GGT, ALP, ALT,
AST, IgM
hiperbilirubinemia
trmobocytopenia , leucopenia,
anemia -- PHT, hipersplenism
LIVER BIOPSY - 10% AIH,
“overlap” syndrome
DIAGNOSIS
Patients with chronic colestatic liver
enzyme abnormalities in middleaged women
AMA +/- (10%) --> biopsy
TREATMENT
• UDCA (early initiated 13-15 mg/kg/day) improve
bichemical and histological features; it does not reverse
and cure the disease; side effects: diarrhea, headache
• LIVER TRANSPLANTATION –decompensated disease
• Antihistamines
• Narcotic receptor antagonist (naltrexone)
• Rifampin
• Cholestyramine-bile salt sequestering agent
• Plasmapheresis intractable pruritus
• Bisphosphonate should be instituted when bone disease is
identified (bone density testing)
PRIMARY SCLEROSING
CHOLANGITIS
Definition: chronic cholestatic syndrome –
diffuse inflamation, fibrosis involving the
entire biliary treeobliteration of both intra
and extrahepatic biliary tree, leading to
biliary cirrhosis / portal hipertension/ liver
failure
Cause: unknown
•bile duct proliferation, ductopenia,
pericholangitis
•liver biopsy : periductal fibrosis
PRIMARY SCLEROSING CHOLANGITIS
CLINICAL FEATURES :
• fatigue profound and nonspecific
• pruritus
• steatorrhea
• deficiencies of fat – soluble vitamins
• metabolic bone disease
LABORATORY FINDINGS:
• abnormal liver enzymes (>2 ALP and ↑ AST,ALT)
• albumin levels ↓
• TP↑
• overlap syndrome between PSC and AIH
• autoantibodies + in overlap syndrome , - in PSC alone (only);
P-ANCA is + in 65% of those with PSC; in PSC50% patients
have UCcolonoscopy
PRIMARY SCLEROSING CHOLANGITIS
DIAGNOSIS
• colangiographic imaging-multifocal stricturing and beading
• MRCP-initial evaluation
• ERCP-whether or not a dominant stricture is present
The strictures are typically short with intervening segments of normal or
slightly dilated bile ducts diffusely distributed beaded appearance
Gallbladder, cystic duct involved in 15% of cases;evolution gradually to
biliary cirrhosis decompensation with ascites , esophageal variceal
hemorrhage , encephalopathy
TREATMENT
•
•
•
•
nonspecific
high-dose (20mg/kg/day) UDCA
endoscopic dilatation of strictures
LIVER TRASPLANTATION (LT) ; Cholangiocarcinoma relative CI for LT
HEMOCHROMATOSIS
DEFINITION: inherited disorder of iron metabolism that
results in a progressive increase in hepatic iron deposition
whitch , over time, can lead to a portal-based fibrosis
progressing to cirrhosis / liver failure/ hepatocellular
cancer
Serum iron studies :
• elevated transferin saturation
• ↑ feritine level
• HFE mutation analysis
TREATMENT is straight forward with regular
therapeutic phlebotomy
WILSON’S DISEASE
DEFINITION: inherited disorder of cooper homeostasis with
failure to excrete excess amounts of cooper , leading to
accumulation in the liver.
1/30000 individuals; affects adolescents and young adults
DIAGNOSIS:
• ceruloplasmin levels
• 24-hours urine cooper levels
• liver biopsy
PHYSICAL EXAMINATION - KAYSER-FLEICHER corneal ring
TREATMENT : cooper chelating medication (DPENICILLAMINE/TRIENTINE/Zn)
ALFA1-AT DEFICIENCY
DEFINITION: inherited disorder that causes
abnormal folding of the alfa-1AT PROTEIN->failure of secretion of that protein from the liver
22 genotype / 10-20% - chronic liver disease
DIAGNOSIS:
• determining of alfa1 AT levels/ genotype
• liver biopsy : PAS+ ; diastase- resistant globules
TREATMENT: LT is curative
COMPLICATIONS OF CIRRHOSIS
• Portal hypertension:
-GE varices
-portal hypertensive gastropathy
-splenomegaly, hypersplenism
-ascites
-SBP
• Hepatorenal syndrome I,II
• Hepatic encephalopaty
• Hepatopulmonary
syndrome
• Portopulmonary
hypertension
• Malnutrition
• Bone disease:
-osteopenia
-osteoporosis
-osteomalacia
• Hematologic abnorm.:
-anemia
-hemolysis
-neutropenia
-trombocytopenia
- coagulopathy
TREATMENT FOR VARICEAL HEMORRHAGE :
1. PRIMARY PROPHYLAXIS
2. PREVENTION OF RECURRENT BLEEDING
1. PRIMARY PROPHYLAXIS
- screening by endoscopy of all patients with cirrhosis
-non-selective betabloblokers or variceal band ligation / sclerotherapy
((PROPRANOLOL, NADOLOL)
-hepatic vein pressure >12 mmHg
ACUTE BLEEDING :
•
•
•
•
•
fluid and blood product replacement
prevention of subsequent bleeding with EVL
vasoconstrictive agenta : SOMATOSTATIN , OCTREOTIDE 50-100 ug/h by
continuous infusion (VASOPRESIN -in the past)
BALLON TAMPONADE (Sengstaken-Blakemore tube / Minnesota tube)-->
stabilisation prior to endoscopic therapy
esophageal varices extended into the proximal stomach - TRANSJUGULAR
INTRAHEPATIC PORTOSYSTEMIC SHUNT (angiographic guidance)
2. PREVENTION OF RECURRENT BLEEDING
• repeated VBL until varices are obliterated
• betablockade- recurrent VBL
• portosystemic shunt surgery , TIPS for patients
with good hepatic synthetic function who
could benefit by having portal decompressive
surgery.
MANAGEMENT OF RECURRENT VARICEAL
HEMORRHAGE
RECURENT ACUTE BLEEDING 
ENDOSCOPIC THERAPY +/- PHARMACOLOGIC THERAPY
CONTROL OF BLEEDING 
↓
COMPENSATED CIRRHOSIS
(CHILD’S CLASS A)
↓
SURGICAL SHUNT VS. TIPS
↓
LIVER TRANSPLANTATION
↓
DECOMPENSATED CIRRHOSIS (
CHILD’S CLASS B,C)
↓
TRANSPLANT EVALUATION
↓
ENDOSCOPIC THERAPY OR BETABLOKERS
↓
TIPS
↓
LIVER TRANSPLANTATION
ASCITES TREATMENT
• 1.Dietary sodium restriction-small amounts of ascites
6-8g/day ,<2g/day in>ascites
• Fresh, frozen foods
• 2.Diuretic therapy-moderate amounts of
ascites:Spironolactone100-200mg/day,4600mg/day+Furosemide40-80mg/day(peripheral
edema);120-160mg/day-necompliant patients.
• 3.Repeated large volume paracentesis,TIPS,liver
transplantation(<50% survive 2years after the onset
of ascites).
HEPATIC ENCEPHALOPATHY
• Ammonia levels>,mercaptans
• 1.Hydration and correction of electrolyte imbalance
• 2.Replacing animal-based protein with vegetable-based
protein
• 3.Lactulose-elimination of nitrogenous products(2-3soft
stools/day)
• 4. Nonabsorbed antibiotics:Neomicine/Metronidazole(renal
failure,ototoxicity,peripheral neuropathy),RIFAXIMINENORMIX,NO side effects.
• 5. ZN supplementation
SPONTANEOUS BACTERIAL
PERITONITIS
• Neutrophil count>250/mm3
• Occur in 30%of patients with SBP and25% in hospital
mortality rate
• Escherichiacoli/gram+bacteria(Streptococcus
viridans,Staphilococcus aureus,Enterococcus
• Second –generation cephalosporin-CEFOTAXIM
4g/day
• In those with UDB,the frecquency of SBP is
increased and prophylaxis against it is recommended
HEPATO-RENAL SYNDROME
• Functional renal failure without renal pathology that occurs in 10% of
patients with advanced cirrhosis or acute liver failure
• Step-wise progressive increase in creatinine in those with large amount of
ascites
• TYPE 1 HRS:progressive impairment in renal function and >reduction in
creatinine clearance within 1-2 weeks of presentation
• TYPE 2 HRS: reduction in glomerular filtration rate with >serum creatinine
level(better outcome than type 1 HRS!)
• Dopamine,PG analogs
• Midodrine(alpha-agonist)
• Octreotide
• Albumine i.v.
• LIVER TRANSPLANTATION