LIVER CIRRHOSIS

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LIVER CIRRHOSIS
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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
• Wilsons disease
• L1 Antitrypsin deficiency
• Cystic fibrosis
• Cryptogenic cirrhosis

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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

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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

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• LABORATORY TESTS
• - normal in patients with early compensated
  alcoholic cirrhosis
• - in advanced liver disease many abnormalities
  are present
• anemia (chronic GI blood lose, nutritional
  deficiencies, hipersplenism related to portal
  hypertension , hemolytic anemia- ZIEVES
  syndrome)
• platelets counts are often reduced early (PHT)
• total direct bilirubin- N/ elevated
• protrombin times prolonged
• ASTgtALT21ratio

• DIAGNOSIS
• Clinical features physical examination
  findings laboratory studies
• Liver biopsy,ultrasonography, UDE,CT ( dg. dif.
  Cancer)
• (abstinence maintained 6 months--gt residual,
  nonreversible disease)
• Patients who have had complications and who
  continue to drink have a lt50 5-year survival in
  contrast with those who remain abstinent
  --gtprognosis improved and LIVER TRANSPLANTATION -
  VIABLE OPTION

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TREATMENT

• Abstinence- cornerstone therapy
• Good nutrition and long term medical supervision
• Glucocorticoids are occasionally used(DFgt32)
• 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,B12SG10,Arginine,Aminohepa,Aspatofort

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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 --gt 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
  15aquires the infection vertically (at birth)
  and 25 may develop cirrhosis

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• 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

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CIRRHOSIS FROM AUTOIMMUNE HEPATITIS

• Positive autoimmune markers ANA,ASMA
• Active inflammation - elevated liver
  enzimes--gtimmunosuppresive 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

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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

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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

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PBC (primary biliary cirrhosis)

• CLINICAL FEATURES
• 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

• LABORATORY FINDINGS
• 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 middle-aged women
• AMA /- (10) --gt biopsy

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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)

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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

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PRIMARY SCLEROSING CHOLANGITIS

• CLINICAL FEATURES
• fatigue profound and nonspecific
• pruritus
• steatorrhea
• deficiencies of fat soluble vitamins
• metabolic bone disease
• LABORATORY FINDINGS
• abnormal liver enzymes (gt2 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

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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
  casesevolution 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

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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

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WILSONS 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
  (D-PENICILLAMINE/TRIENTINE/Zn)

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ALFA1-AT DEFICIENCY

• DEFINITION inherited disorder that causes
  abnormal folding of the alfa-1AT
  PROTEIN--gtfailure 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

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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

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TREATMENT FOR VARICEAL HEMORRHAGE 1. PRIMARY
PROPHYLAXIS2. 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 gt12 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)--gt stabilisation prior to
  endoscopic therapy
• esophageal varices extended into the proximal
  stomach - TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC
  SHUNT (angiographic guidance)

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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.

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MANAGEMENT OF RECURRENT VARICEAL HEMORRHAGE
RECURENT ACUTE BLEEDING ??ENDOSCOPIC THERAPY
/- PHARMACOLOGIC THERAPY?CONTROL OF BLEEDING ?

• ?
• COMPENSATED CIRRHOSIS (CHILDS CLASS A)
• ?
• SURGICAL SHUNT VS. TIPS
• ?
• LIVER TRANSPLANTATION

• ?
• DECOMPENSATED CIRRHOSIS ( CHILDS CLASS B,C)
• ?
• TRANSPLANT EVALUATION
• ?
• ENDOSCOPIC THERAPY OR BETA-BLOKERS
• ?
• TIPS
• ?
• LIVER TRANSPLANTATION

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ASCITES TREATMENT

• 1.Dietary sodium restriction-small amounts of
  ascites 6-8g/day ,lt2g/day ingtascites
• Fresh, frozen foods
• 2.Diuretic therapy-moderate amounts of
  ascitesSpironolactone100-200mg/day,4-600mg/dayFu
  rosemide40-80mg/day(peripheral edema)120-160mg/da
  y-necompliant patients.
• 3.Repeated large volume paracentesis,TIPS,liver
  transplantation(lt50 survive 2years after the
  onset of ascites).

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HEPATIC ENCEPHALOPATHY

• Ammonia levelsgt,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 antibioticsNeomicine/Metronidazole
  (renal failure,ototoxicity,peripheral
  neuropathy),RIFAXIMINE-NORMIX,NO side effects.
• 5. ZN supplementation

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SPONTANEOUS BACTERIAL PERITONITIS

• Neutrophil countgt250/mm3
• Occur in 30of patients with SBP and25 in
  hospital mortality rate
• Escherichiacoli/grambacteria(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

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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 HRSprogressive impairment in renal
  function and gtreduction in creatinine clearance
  within 1-2 weeks of presentation
• TYPE 2 HRS reduction in glomerular filtration
  rate with gtserum creatinine level(better outcome
  than type 1 HRS!)
• Dopamine,PG analogs
• Midodrine(alpha-agonist)
• Octreotide
• Albumine i.v.
• LIVER TRANSPLANTATION