CIRRHOSIS OF LIVER

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CIRRHOSIS OF LIVER

• Dr.Vemuri Chaitanya

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Cirrhosis

• Chronic generalized liver disease
• A condition that is defined histopathologically
  and has a variety of clinical manifestations and
  complications, some of which can be life
  threatening.
• Pathologic features development of fibrosis to
  the point that there is architectural distortion
  with formation of regenerative nodules (
  micronodular / macronodular )
• This results in decrease in hepatocellular mass,
  thus function .

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NORMAL
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Micronodular Cirrhosis
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Macronodular Cirrhosis
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Epidemiology

• 40 cases asymptomatic
• It is the 12th leading cause of death in United
  States.
• Approximately 30,000 to 50,000 deaths per year
• Additional 10,000 deaths due to liver cancer
  secondary to cirrhosis

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This end stage of CLD is characterised by

• Bridging Fibrous Septa
• Parenchymal nodules
• Disruption of the architecture of the entire
  liver

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pathogenesis

• Hepatocellular death
• Regeneration
• Progressive fibrosis
• The induction of fibrosis occurs with activation
  of hepatic stellate cells, resulting in formation
  of increased amounts of collagen other
  components of extracellular matrix.
• Stimuli 1.Chr.inflammation cytokines like
  TNF,
• Lymphotoxin, IL-1
• 2.Cytokine production by
  injured Kupffer cells,
• endothelial cells,
  hepatocytes, bile duct epithelial cells
• 3.Disruption of ECM
• 4.Direct stimulation of
  stellate cells by toxins

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Etiology

• Alcoholism
• Chronic Viral Hepatitis Hepatitis B
• Hepatitis C
• Autoimmune Hepatitis
• Nonalcoholic steatohepatitis
• Biliary Cirrhosis Primary biliary cirrhosis
• Primary sclerosing
  cholangitis
• Autoimmune
  cholangiopathy

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Etiology

• Cardiac Cirrhosis
• Budd Chiari Syndrome
• Inherited metabolic liver disease
• Hemochromatosis
• Wilsons Disease
• Alpha 1 Antitrypsin deficiency
• Cystic Fibrosis
• Cryptogenic Cirrhosis
• Others Galactosemia , Tyrosinemia,
• Drug induced alpha methyldopa
• Syphilis

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Clinical Features

• Asymptomatic for long periods.
• Onset of symptoms insidious , less often
  abrupt.
• Non specific symptoms vague right upper
  quadrant pain, fever, nausea, vomiting,diarrhea,an
  orexia malaise.
• Or they may present with more specific
  complication of CLD ascites,upper GI bleed etc

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Signs

• Loss of hair ( alopecia )
• Icterus
• Pallor
• KF Ring
• Parotid enlargement
• Fetor hepaticus
• Loss of axillary pubic hair
• Spider nevi
• Gynecomastia
• Atrophy of breasts in females
• Wasting of muscles

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Signs

• Glossitis, cheilitis
• Palmar erythema
• Clubbing
• Leuconychia
• Dupuytrens contracture
• Ascites
• In 70 cases liver is enlarged, firm if not hard
  and nodular
• Splenomegaly
• Caput medusae

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Signs

• Bleeding tendencies deficiency of clotting
  factors check PT /INR
• Fever
• Hyperpigmentation
• Hyperdynamic circulatory state
• Edema
• Hernia
• Testicular atrophy
• Delirium
• Constructional apraxia
• Flapping tremors
• Inversion of sleep rhythm

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Palmar erythema
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Alcoholic Cirrhosis

• Accurate history regarding amount duration of
  alcohol consumption is required.
• Lab tests
• Completely normal in early compensated alcoholic
  cirrhosis
• Hb Anemia ( chr.GI loss, nutritional def,
• hypersplenism )
• Platelet count reduced early in disease,
• portal htn with
  hypersplenism

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Alcoholic Cirrhosis

• S.Bilirubin normal / elevated
• PT often prolonged
• S. Transaminases elevated
• AST / ALT gt 2/1
• Liver biopsy
• Treatment
• Abstinence is the cornerstone of therapy.
• Treatment of any complications
• Glucocorticoids if DF gt 32
• Oral Pentoxiphylline

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Cirrhosis d/t Chr.Hepatitis B C

• Of patients exposed to HCV, approximately 80
  develop Chronic hepatitis and of those, about 20
  30 will develop cirrhosis over 20-30 yrs.
• Here , liver is small shrunken with a
  characteristic features of mixed micro and macro
  nodular cirrhosis seen on biopsy.
• Of patients exposed to HBV, about 5 develop
  chronic hepatitis about 20 of those patients
  go on to develop cirrhosis.
• Liver is small shrunken and has mixed micro
  macronodular cirrhotic pattern.
• Invg Routine investigations HCV RNA, HBsAg,
  anti HBs, HBeAg, anti HBe, HEV DNA.

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Cirrhosis d/t Chr.Hepatitis B C

• Specific Treatment
• HBV Lamivudine, Adefovir, Entecavir, Tenofovir
• HCV Pegylated Interferon, Ribavirin

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Primary Biliary Cirrhosis

• Female preponderance
• Median age of around 50 yrs
• Etiology unknown
• Portal inflammation necrosis of cholangiocytes
  in small and medium sized bile ducts.
• Antimitochondrial antibodies in 90 of pts
• Pathology earliest lesion- Chronic
  Nonsuppurative Destructive Cholangitis

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Primary Biliary Cirrhosis

• Fatigue
• Pruritis
• On ex hepatomegaly
• splenomegaly
• ascites
• edema
• Unique to PBC Hyperpigmentation,Xanthelasma,Xant
  homata

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Primary Biliary Cirrhosis

• LAB
• Elevated GGT, ALP with mild elevations of AST
  ALT
• Hyperbilirubinemia
• Thrombocytopenia, leukopenia, anemia
• TREATMENT
• UDCA _at_ 13 15 mg/Kg per day
• Liver Transplantation
• Cholestyramine
• Bisphosphonates osteopenia/osteoporosis

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Primary Sclerosing Cholangitis

• Etiology unknown
• Diffuse inflammation fibrosis of entire biliary
  tree chronic cholestasis obliteration of
  intra extrahepatic biliary tree biliary
  cirrhosis portal htn liver failure
• Cli fea fatigue, pruritis, steatorrhea, fat sol
  vitamin deficiencies
• Lab 2 fold rise in ALP, elevated
  aminotransferases, p-ANCA ( 65)
• Diagnosis MRCP , Cholangiogram
• Treatment No proven treatment.
• High dose 20 mg/kg/day
  UDCA.
• Endoscopic dilatation of
  dominant strictures
• Liver Transplantation

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Cardiac Cirrhosis

• Pts with long standing right sided CHF may
  develop chronic liver disease cardiac Cirrhosis
• Cli fea symptoms of Rt.Heart.Failure
  Hepatomegaly
• Lab ALP raised,
• AST gt ALT normal / raised
• Diagnosis cardiac case with elevated ALP
  enlarged liver

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Cirrhosis other causes

• Hemochromatosis
• Wilsons Disease
• Alpha1 Antitrypsin Deficiency
• Cystic Fibrosis

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Investigations

• Complete Hemogram
• Peripheral Smear
• Platelet Count
• PT INR
• LFT S. Bilirubin, S. Albumin, S. Globulin,
  SGPT, SGOT, ALP
• Hepatitis Profile
• Alpha Fetoprotein

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Investigations

• Blood sugar
• Urea, Creatinine
• Sodium, Potassium
• Ascitic fluid examination
• X-Ray chest
• USG / CT Abdomen
• Confirmation by Liver Biopsy

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Complications of Cirrhosis

• Portal HTN Gastroesophageal Varices
• Portal hypertensive
  Gastropathy
• Splenomegaly,
  Hypersplenism
• Ascites SBP
• Hepatorenal Syndrome Type 1 2
• Hepatic Encephalopathy
• Hepatopulmonary Syndrome
• Portopulmonary Hypertension
• Malnutrition

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Complications of Cirrhosis

• Coagulopathy Factor deficiency
• Fibrinolysis
• Thrombocytopenia
• Bone Disease Osteopenia/Osteoporosis/
  Osteomalacia
• Haematological abn Anaemia
• Hemolysis
• 
  Thrombocytopenia
• Neutropenia

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Portal Hypertension

• Prehepatic Portal Vein thrombosis
• Splenic Veinf Thrombosis
• Massive Splenomegaly
• Hepatic Presinusoidal Schistosomiasis
• 
  Cong.hepatic fibrosis
• Sinusoidal Cirrhosis
• Alcoholic
  hepatitis
• Postsinusoidal Veno-occlusive
  Disease

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• Posthepatic Budd Chiari syndrome
• Inferior vena caval webs
• Cardiac Causes
• Restrictive
  Cardiomyopathy
• Constrictive Pericarditis
• Severe CHF

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Portal Hypertension

• Elevation of hepatic venous pressure gradient to
  gt 5mm Hg.
• It is caused by combination of 2 simultaneously
  occuring hemodynamic processes
• Increased intrahepatic resistance to passage of
  blood flow through liver
• Increased splanchnic blood flow secondary to
  vasodilation.
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  

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Portal Hypertension

• Portal HTN directly responsible for 2
  complications variceal haemorrhage and ascites
• Also hypersplenism,
• congestive gastropathy,
• renal failure and
• hepatic encephaopathy

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CLINICAL FEATURES

• Splenomegaly Hypersplenism Thrombocytopenia,
  Neutropenia, Anemia
• Dilated Abdominal Veins, Caput Medusae, Ascitis.
• Oesophageal varices

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Variceal Bleed

• Approx 5 15 of cirrhotics per year develop
  varices and it is estimated that majority of
  patients with cirrhosis will develop varices over
  their lifetime
• 1/3rd of patients with varices develop bleeding.
• Factors predicting variceal bleed
• Severity of cirrhosis ( Childs Class )
• Ht of wedged hepatic vein pressure
• Size and location of varix
• Endoscopic stigmata red wale sign, hematocystic
  spots, diffuse erythema, bluish color, cherry red
  spot white nipple spot
• Tense ascites

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Variceal Bleed

• Diagnosis identified by endoscopy
• Pt with a gradient of gt12 mm Hg are at a
  greater risk for variceal bleed.
• Precipitating Factors Alcohol, Aspirin,
  Analgesics (NSAIDs), Adrenal Corticosteroids
• Assessment Drop in systolic BP gt 10 mmHg, rise
  in pulse gt 15 beats / minute on sitting up 10
  to 20
• Supine Hypotension - gt 20
• Systolic BP lt 100 mmHg / Baseline Tachycardia gt
  25

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RESUSCITATION

• Stabilize BP 2 large bore IV line
• Isotonic saline / Ringer Lactate / fresh blood /
  packed RBC transfusion Maintain ½ hour pulse,
  BP, respiration chart (In emergency situation
  O-ve blood)
• MEASURE URINE OUTPUT
• Correction of coagulopathy FFP, parenteral Vit
  K 10 mg
• Platelet transfusion if count lt 50,000
• Airway protection endotracheal intubation to
  prevent aspiration

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RESUSCITATION

• Nasal Gastric Aspiration
• OCTREOTIDE Infusion 50 to 100 µgm bolus
• 25 to 50 µgm / hour infusion
• VASOPRESSIN 0.3 unit / minute IV gradually
  increased to 0.9 units/minute Side-effects
  Myocardial ischemia, infarction, arrhythmia,
  cardiac arrest, mesenteric ischemia
• ( now not preferred )

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Resuscitation

• Endoscopic Therapy Variceal band ligation
• Variceal
  sclerotherapy
• Balloon tamponade ( Sengstaken-Blakemore tube or
  Minnesota tube ) in pts who cannot get
  endoscopic therapy or those who need
  stabilization prior to endoscopic therapy
• TIPS When esophageal varices extend into
  proximal stomach
• In Pts eho fail endoscopic /
  medical treatment
• and also poor subjects for surgery.

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prophylaxis

• Beta blockers propranolol resting heart rate
  to be reduced by 25 .
• Repeated variceal band ligation until varices are
  obliterated.

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Splenomegaly Hypersplenism

• Congestive splenomegaly is common in pts with
  portal htn.
• Clinical features include enlarged spleen,
  thrombocytopenia, leukopenia
• Some significant left sided/ left upper
  quadrant abdominal pain
• No specific treatment
• Splenectomy
• Hypersplenism with development of
  thrombocytopenia first indicator of portal
  hypertension

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Ascites

• Accumulation of fluid within the peritoneal
  cavity
• M.C cause cirrhosis with portal hypertension
• Clinical features increase in abdominal girth
• peripheral edema
• dyspnea if
  massive
• bulging flanks
• shifting dullness
• fluid thrill
• Hepatic hydrothorax more common on rt.side
• 
  implicates rent in diaphragm with
• free flow
  of ascitic fluid into thoracic cavity

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Ascites

• Diagnostic paracentesis
• SAAG
• gt1.1g/dL portal hypertension
• lt1.1g/Dl neoplasm,Tb, pancreatitis,
• Ascitic fluid proteins low high chance of
  developing SBP
• Ascitic fluid high RBCs traumatic tap, HCC,
  ruptured omental varix
• Ascitic fluid PMN gt250 /cu.mm - SBP

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Ascites - Treatment

• Small amounts of ascites dietary sodium
  restriction ( lt2g/day )
• Moderate diuretic is essential
• Spiranolactone 100-200
  mg/day OD
• Furosemide 40-80 mg/day
• - if peripheral edema
• Pt is compliant but ascitic fluid , then
• Spiranolactone 400 -600 mg/day
• Furosemide 120-160 mg/day
• If ascites still , then it is REFRACTORY ASCITES

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Ascites - treatment

• Refractory ascites Large volume paracentesis
• TIPS
• Liver
  Transplantation
• Prognosis pts of cirrhosis with ascites- poor
• lt50 of pts survive 2 yrs after the onset of
  ascites.

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Spontaneous Bacterial Peritonitis

• Spontaneous infection of ascitic fluid without
  any intraabdominal source.
• Bacterial translocation gut flora transversing
  the intestine into mesenteric lymph nodes,
  leading to bacteremia and seeding of ascitic
  fluid
• MC E.coli
• Others Step.viridans, Staph.aureus
• If gt 2 organisms are identified secondary
  bacterial peritonitis d/t perforated viscus to be
  considered
• Ascitic fluid PMN gt 250/cu.mm

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SBP

• Pt can present with altered sensorium, elevated
  WBC, abdominal pain/discomfort
• Treatment cephalosporins
• In pts with an episode(s) of SBP and recovered ,
  once weekly- administration of antibiotic as
  prophylactic measure

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Hepatorenal Syndrome

• Functional renal failure without renal pathology
• 10 of pts with cirrhosis / advanced liver
  failure
• Diagnosis presence of large amount of ascites
• progressive rise in
  creatinine
• urinary sodium lt10 mEq
• Type 1 HRS progressive impairment of renal
  function significant reduction in creatinine
  clearance within 1- 2 wks . BAD PROGNOSIS
• Type 2 HRS reduction in GFR, with rise in
  S.Creat
• BETTER PROGNOSIS

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Hepatorenal Syndrome

• Seen in refractory ascites
• Exclude causes of ARF
• Treatment
• Midodrine, an alpha agonist along with Octerotide
  and IV Albumin
• Liver transplantation

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HEPATIC ENCEPHALOPATHY

• Precipitating factors
• GI Bleeding
• Excess protein intake
• Electrolyte abnormalities, Ascitic Aspiration
• Uremia
• Dehydration, Constipation
• Alcohol
• Viral infections, SBP
• Anaesthetic agents, Surgery, Narcotics,
  Tranquilisers
• Hepatic toxins, Portosystemic shunts - TIPS

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HEPATIC ENCEPHALOPATHY

• TreatmentCORRECT/ AVOID PRECIPITATING FACTORS
• Dietary protein restriction-30 - 40 gm protein /
  day
• Non absorbable disaccharide LACTULOSE 15 to
  45 ml BID / QID
• Lactulose enema
• Neomycin 1 gm 6th hrly
• Metronidazole 250 mg 8th hrly
• Bowel wash / Lactobacillus

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GRADING OF HEPATIC ENCEPHALOPATHY

• 0 Normal
• 1 Inverted sleep rhythm, restless
• 2 Lethargy, slow response
• 3 Drowsy, arousable but confused
• 4 - Coma

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HEPATOPULMONARY SYNDROME

• Clubbing, cyanosis, spider nevi, orthodeoxia
• Hypoxia in standing position-ORTHODEOXIA
• Hypoxia is due to intrapulmonary shunting through
  direct arteriovenous communications
• Intra Pulmonary Vascular dilatation in the
  absence of intrinsic cardio pulmonary disease
• Resistant hypoxaemia (PaO2 lt 9.3 kPa or 70 mmHg),
  intrapulmonary vascular dilatation and chronic
  liver disease with portal hypertension
• Treatment liver transplantation

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Portopulmonary Hypertension

• Similar to 'primary pulmonary hypertension
• defined as pulmonary hypertension with increased
  pulmonary vascular resistance and a normal
  pulmonary artery wedge pressure in a patient with
  portal hypertension
• caused by vasoconstriction and obliteration of
  the pulmonary arterial system and leads to
  breathlessness and fatigue.

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MALIGNANT TRANSFORMATION

• Rapid, unexplained weight loss
• Unexplained fever
• Pain in the right Hypochondrium
• Rapid enlargement of liver / one of the nodules
• Hepatic Rub / Hepatic Bruit
• Hemorrhagic ascitic fluid
• Malignant cells in cytology of Ascitic fluid
• Confirmation by USG / CT / AFP / Biopsy

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HCC
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CHILD PUGH Scoring
Clinical and biochemical measurements Points scored for increasing abnormality Points scored for increasing abnormality Points scored for increasing abnormality
Clinical and biochemical measurements 1 2 3
Albumin (g/dl) gt 3.5 2.8 to 3.5 lt 2.8
Bilirubin (mg/dl) 1 to 2 2 to 3 gt 3
For cholestatic diseases bilirubin (mg/dl) lt 4 4 to 10 gt 10
PT (secs prolonged) Or INR 1 to 4 4 to 6 gt 6
PT (secs prolonged) Or INR lt 1.7 1.7 to 2.3 gt 2.3
Ascites Absent Slight Moderate
Encephalopathy (grade) None 1 2 3 4
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CHILD -PUGH SCORING SYSTEM

• Class A 5 to 6 points
• Class B 7 to 9 points
• Class C 10 to 15 points
• B C Potential candidates for Hepatic
  transplantation

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THANK YOU