CIRRHOSIS &

LIVER CA
Dr. Samuel Halim SpPD
Kuliah Blok Hepato-bilier
FK UNTAR 2013

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 .

NORMAL

Micronodular Cirrhosis

Macronodular Cirrhosis

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

This end stage of CLD is

characterised by :
Bridging Fibrous Septa
Parenchymal nodules
Disruption of the architecture of the
entire liver

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

Etiology

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

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

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,anorexia & malaise.
Or they may present with more
specific complication of CLD
ascites,upper GI bleed etc

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

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

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

Palmar erythema

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

Alcoholic Cirrhosis

S.Bilirubin normal / elevated

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

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.

Cirrhosis d/t Chr.Hepatitis

B&C
Specific Treatment :
HBV : Lamivudine, Adefovir,
Entecavir, Tenofovir
HCV: Pegylated Interferon, Ribavirin

Investigations

Complete Hemogram

Peripheral Smear

Platelet Count

PT INR

LFT S. Bilirubin, S. Albumin, S. Globulin, SGPT, SGOT,

ALP

Hepatitis Profile

Alpha Fetoprotein - optional

Investigations

Blood sugar

Ureum, Creatinine

Sodium, Potassium

Ascitic fluid examination

X-Ray chest

USG / CT Abdomen

Confirmation by Liver Biopsy

Fibro Scan

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

Complications of
Cirrhosis

Coagulopathy : Factor deficiency

Fibrinolysis
Thrombocytopenia
Bone Disease : Osteopenia/Osteoporosis/
Osteomalacia
Haematological abn : Anaemia
Hemolysis
Thrombocytopenia
Neutropenia

Collaterals

Portal Hypertension

1.
2.

Elevation of hepatic venous pressure gradient to > 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.

Portal Hypertension

Portal HTN directly responsible for 2

complications variceal
haemorrhage and ascites
Also hypersplenism,
congestive gastropathy,
renal failure and
hepatic encephaopathy

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

Variceal Bleed

Diagnosis : identified by endoscopy

Pt with a gradient of >12 mm Hg are at a
greater risk for variceal bleed.

Precipitating Factors Alcohol, Aspirin, Analgesics

(NSAIDs), Adrenal Corticosteroids

Assessment Drop in systolic BP > 10 mmHg, rise in

pulse > 15 beats / minute on sitting up 10 to 20%

Supine Hypotension - > 20%

Systolic BP < 100 mmHg / Baseline Tachycardia >

25%

RESUSCITATION

Stabilize BP 2 large bore IV line

Isotonic saline / Ringer Lactate / fresh blood /

packed RBC transfusion Maintain 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 < 50,000

Airway protection endotracheal intubation

to prevent aspiration

RESUSCITATION

Nasal Gastric Aspiration

OCTREOTIDE Infusion 50 to 100 gm bolus
25 to 50 gm / 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 )

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.
Lactulose
Antibiotics

prophylaxis

Beta blockers propranolol resting

heart rate to be reduced by 25 %.
Repeated variceal band ligation until
varices are obliterated.

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

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

Mechanism of
Ascites

Ascites

Diagnostic paracentesis
SAAG :
>1.1g/dL portal hypertension
<1.1g/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 >250 /cu.mm - SBP

Ascites - Treatment

Small amounts of ascites dietary sodium

restriction ( <2g/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

Ascites - treatment
Refractory ascites Large volume
paracentesis
TIPS
Liver
Transplantation
Prognosis pts of cirrhosis with ascitespoor
<50 % of pts survive 2 yrs after the
onset of ascites.

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 > 2 organisms are identified secondary
bacterial peritonitis d/t perforated viscus to be
considered
Ascitic fluid PMN > 250/cu.mm

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 weeklyadministration of antibiotic as
prophylactic measure

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 <10 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

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

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

Hepatic
Encephalopathy
Mechanism

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

GRADING OF HEPATIC
ENCEPHALOPATHY

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

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

HCC

CHILD PUGH Scoring

Clinical and biochemical Points scored for increasing
measurements
abnormality
1
2
3
Albumin (g/dl)
Bilirubin (mg/dl)

> 3.5
1 to 2

2.8 to 3.5
2 to 3

< 2.8
>3

<4

4 to 10

> 10

PT (secs prolonged)*
Or
INR*

1 to 4
< 1.7

4 to 6
1.7 to 2.3

>6
> 2.3

Ascites

Absent

Slight

Moderat

For cholestatic
diseases : bilirubin
(mg/dl)

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

THANK YOU
Ready for some Quiz ???

Quiz
1.

2.

3.

4.

Bagaimana cara kerja Lactulose sehingga

bermanfaat pada perdarahan varises
esofagus dan ensefalopati hepatik?
Berapa cm diameter abses hati utk indikasi
aspirasi abses?
Terapi nutrisi untuk ensefalopati hepatik?
Bagaimana mekanisme kerjanya?
Jelaskan scr skematik indikasi pengobatan
antivirus pada Hep B kronik

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