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CIRRHOSIS OF LIVER

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CIRRHOSIS OF LIVER Dr.Vemuri Chaitanya Portal Hypertension Portal HTN directly responsible for 2 complications variceal haemorrhage and ascites Also hypersplenism ... – PowerPoint PPT presentation

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Title: CIRRHOSIS OF LIVER


1
CIRRHOSIS OF LIVER
  • Dr.Vemuri Chaitanya

2
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 .

3
NORMAL
4
Micronodular Cirrhosis
5
Macronodular Cirrhosis
6
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

7
This end stage of CLD is characterised by
  • Bridging Fibrous Septa
  • Parenchymal nodules
  • Disruption of the architecture of the entire
    liver

8
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

9
Etiology
  • Alcoholism
  • Chronic Viral Hepatitis Hepatitis B
  • Hepatitis C
  • Autoimmune Hepatitis
  • Nonalcoholic steatohepatitis
  • Biliary Cirrhosis Primary biliary cirrhosis
  • Primary sclerosing
    cholangitis
  • Autoimmune
    cholangiopathy

10
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

11
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

12
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

13
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

14
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

15
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16
Palmar erythema
17
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

18
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

19
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.

20
Cirrhosis d/t Chr.Hepatitis B C
  • Specific Treatment
  • HBV Lamivudine, Adefovir, Entecavir, Tenofovir
  • HCV Pegylated Interferon, Ribavirin

21
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

22
Primary Biliary Cirrhosis
  • Fatigue
  • Pruritis
  • On ex hepatomegaly
  • splenomegaly
  • ascites
  • edema
  • Unique to PBC Hyperpigmentation,Xanthelasma,Xant
    homata

23
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

24
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

25
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

26
Cirrhosis other causes
  • Hemochromatosis
  • Wilsons Disease
  • Alpha1 Antitrypsin Deficiency
  • Cystic Fibrosis

27
Investigations
  • Complete Hemogram
  • Peripheral Smear
  • Platelet Count
  • PT INR
  • LFT S. Bilirubin, S. Albumin, S. Globulin,
    SGPT, SGOT, ALP
  • Hepatitis Profile
  • Alpha Fetoprotein

28
Investigations
  • Blood sugar
  • Urea, Creatinine
  • Sodium, Potassium
  • Ascitic fluid examination
  • X-Ray chest
  • USG / CT Abdomen
  • Confirmation by Liver Biopsy

29
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

30
Complications of Cirrhosis
  • Coagulopathy Factor deficiency
  • Fibrinolysis
  • Thrombocytopenia
  • Bone Disease Osteopenia/Osteoporosis/
    Osteomalacia
  • Haematological abn Anaemia
  • Hemolysis

  • Thrombocytopenia
  • Neutropenia

31
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

32
  • Posthepatic Budd Chiari syndrome
  • Inferior vena caval webs
  • Cardiac Causes
  • Restrictive
    Cardiomyopathy
  • Constrictive Pericarditis
  • Severe CHF

33
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.




















34
Portal Hypertension
  • Portal HTN directly responsible for 2
    complications variceal haemorrhage and ascites
  • Also hypersplenism,
  • congestive gastropathy,
  • renal failure and
  • hepatic encephaopathy

35
CLINICAL FEATURES
  • Splenomegaly Hypersplenism Thrombocytopenia,
    Neutropenia, Anemia
  • Dilated Abdominal Veins, Caput Medusae, Ascitis.
  • Oesophageal varices

36
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

37
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

38
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

39
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 )

40
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.

41
prophylaxis
  • Beta blockers propranolol resting heart rate
    to be reduced by 25 .
  • Repeated variceal band ligation until varices are
    obliterated.

42
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

43
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

44
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

45
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

46
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.

47
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

48
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

49
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

50
Hepatorenal Syndrome
  • Seen in refractory ascites
  • Exclude causes of ARF
  • Treatment
  • Midodrine, an alpha agonist along with Octerotide
    and IV Albumin
  • Liver transplantation

51
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

52
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

53
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54
GRADING OF HEPATIC ENCEPHALOPATHY
  • 0 Normal
  • 1 Inverted sleep rhythm, restless
  • 2 Lethargy, slow response
  • 3 Drowsy, arousable but confused
  • 4 - Coma

55
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

56
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.

57
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

58
HCC
59
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
60
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

61
THANK YOU
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