Cirrhosis Hepatis With

Complication

Siti Nurdjanah
 Introduction
Cirrhosis represents a late stage of
progressive hepatic fibrosis
characterized by distortion of the
hepatic architecture and the
formation of regenerative nodules.
 The Actiology of LC
1. Viral hepatitis types B + Delta; C
2. Alcohol
3. Metabolic, e.g. haemochromatosis,
Wilsons diseases Alpha1 Anti trypsin
deficiency; NAS, Intestinal bypass
4. Prolonged cholestasis, intra and extra
hepatic
5. Hepatic venous ouobstruction e.g. veno
occlusive disease, contrictive pericatditis;
Budd-chiari Syndrome
6. Autoimmune hepatitis
7. Toxin and therapeutic agents
8. Indian chilhood cirrhosis
 Comparison of the hepatitis viruses
Hepatiti
Hepatiti Hepatitis Hepatitis Hepatiti
sC
s A virus B virus D virus s E virus
virus
Virus class Picorna- Hepadna- Flavivirus Deltavirus Calcivirus
virus virus
Genome RNA DNA RNA RNA RNA

Route of Faecal- Bodily Bodily Bodily Faecal-

transmission oral fluids fluids fluids oral
Incubation 1550 28160 15150 Variable 1545
(days)
Chronicity No Yes Yes Yes No

1. Purcell R, et al. Proc Natl Acad Sci 1994; 91: 2401

2. Ryder S & Beckingham I. BMJ 2001; 322: 151
3. WHO. Hepatitis C Fact Sheet no. 164. 2000
Model of Natural History of
Chronic Hepatitis B
Chronic hepatitis
Inactive disease
Cirrhosis
Reactivation

Hepatocellular Decompensated
carcinoma cirrhosis

Death
 Natural History of HBV Infection

Early > 95% Immune

Adulthood
Childhood Tolerance

< 5%

HBeAg- HBeAg+
Chronic Cirrhosis Chronic
Hepatitis B Hepatitis B

Inactive
Carrier
Courtesy of W. Ray Kim, MD.
Chen DS, et al. J Gastroenterol Hep. 1993;8:470-475.
Seeff L, et al. N Engl J Med. 1987;316:965-970.
 Natural History of HBV Infection

Early > 95% Immune

Adulthood
Childhood Tolerance

< 5%

HBeAg- HBeAg+
Chronic HCC Chronic
Hepatitis B Hepatitis B

Inactive
Carrier
Courtesy of W. Ray Kim, MD.
Chen DS, et al. J Gastroenterol Hep. 1993;8:470-475.
Seeff L, et al. N Engl J Med. 1987;316:965-970.
 Phases of Chronic HBV
Infection
Immune Immune Low Replicative Reactivation
Tolerance Clearance Phase Phase
HBeAg+ HBeAg-/anti-HBe+ (precore/core promoter variants)
< >< >
> 2000 IU/mL
HBV DNA < 2000 IU/mL
2 x 108 -
2 x 1011 IU/mL 200,000 - 2 x 109 IU/mL

ALT

Normal/mild Moderate/severe CH Normal/mild CH Moderate/severe CH

CH
Cirrhosis Inactive cirrhosis Cirrhosis

HBeAg+ Inactive-carrier state HBeAg-

chronic hepatitis chronic hepatitis
Slide courtesy of A. S. F. Lok, MD.
 Clinical Profiles of Chronic
HBV Infection
Immune HBeAg+ CHB Inactive HBeAg- CHB
Tolerant HBsAg (Precore
Carrier Mutant)
HBsAg + + + +
HBeAg + +
Anti-HBe + +
ALT Normal Normal
> 20,000 > 20,000
< 200 IU/mL > 2000 IU/mL
IU/mL IU/mL
HBV DNA (< 103 (> 104
(> 105 (> 105
copies/mL) copies/mL*)
copies/mL) copies/mL)
*Expert opinions vary as to this value.
Histology Normal/mild Active Normal Active

Lai CL, et al. Lancet. 2003:362:2089. Lok AS, et al. Gastroenterology. 2001:120:1828.
 Risk Factors for Progression of Liver
Disease (Cirrhosis, Liver Failure, HCC)
HBV genotype High geographic endemicity

HBeAg positivity Older age

Presence of hepatic Male sex

inflammation/ Immune status: HIV or organ
fibrosis/cirrhosis transplant
Severity at presentation
Alcohol abuse
Sustained activity of liver
Smoking
disease
Elevated ALT
Positive family history for liver
Elevated HBV DNA
cancer*

HBV/HCV and HBV/HDV Aflatoxin exposure*

coinfection
Liver iron
Liver fat *HCC only
Fattovich G et al. Gastroenterology. 2004;127:S35-S50.
Yang HI, et al. N Engl J Med. 2002;347:168-174.
Tang B, et al. J Med Virol. 2004;72:35-40.
 HCV viral structure

RNA genome

Nucleocapsid
(core) protein

Envelope
 Disease progression in hepatitis C:
person-to-person variability
(Slow)

30 years after infection

Female sex, young age
Rate of disease progression

Decompensation
(~20%)

HCC
Normal Acute Chronic Chronic Cirrhosis (14% per
liver infection infection hepatitis (20%) year)
(80%)

Infection Stable Slowly progressive

resolves hepatitis (~75%)
spontaneously (80%)
(20%)
(Fast)

20 years after infection

Alcohol use, co-infection with HIV or hepatitis B virus

HCC = hepatocellular carcinoma Lauer G & Walker B. N Engl J Med 2001; 345: 41
 Cirrhotic individuals at risk of
serious morbidity and mortality
Cirrhosis
1.5%/yr 1.1%/yr 0.4%/yr 2.5%/yr

Variceal Hepatic Ascites

HCC bleeding encephalopathy

86%/yr 40%/yr 68%/yr 11%/yr

Death

Buti M, et al. J Hepatol 2000; 33: 651

 Factors accelerating
progression of chronic hepatitis C
Previous and concurrent alcohol
consumption1
Older age at time of infection (>40 years)1
Male gender1
Other comorbidities:
HIVHCV co-infection2
HIVHBV co-infection3
obesity

1. Poynard T, et al. Lancet 1997; 349: 825

2. Di Martino V, et al. Hepatology 2001; 34: 1193
3. Lana R, et al. Med Clin. (Barc). 2001; 117: 607
 Clinical Manifestations
They may have stigmata of chronic
liver disease discovered on routine
physical examination
They may have undergone laboratory
or radiologic testing or an unrelated
surgical procedure that incidentally
uncovered the presence of cirrhosis.
 Physical findings
Spider angiomata
Are vascular lesions consisting of a central
arteriole surrounded by many smaller vessels.
Palmar erythema
An exaggrearation of the normal speckled
mottling of the palm, caused by altered sex
hormone metabolism
Nail changes
Muehrckes nails are paired horizontal white
bands separated by normal color, caused by
hypoalbuminemia.
 Gynecomastia
Gynecomastia is defined histologically
as a benign proliferation of the
glandular tissue of the male breast and
caused by increased production of
androstenedione from the adrenals,
enhanced aromatization of
androstenedione to estrone to estradiol.
 Testicular atrophy
Hypogononadism is manifested by
impotence, infertility loss of sexual
drive, and testicular atrophy.
Hepatomegaly
The cirrhotic liver may be enlarged,
normal sized, or small when palpable,
the cirrhotic liver has a firm and nodular
consistency.
Ascites
Ascites is the accumulation of fluid in
the peritoneal cavity.
 Caput medusa
Blood from the portal venous system may be
from the portal venous system may be
shunted through the periumbilical veins into th
e umbilical vein and ultimately to the
abdominal wall veins.
Fetor hepaticus
A sweet pungent smell to the breath of a
cirrhostic patient my occasionally be
encountered caused by increased
concentrations of dimethylsulphide.
Constitutional symptoms weakness, fatigue,
anorexia, and weight loss.
 Laboratory findings
Amino transferases Aspartate
aminotransferase (AST and alaine
aminotransferase (ALT) : moderately
elevated . AST : more often elevated than
ALT, normal aminotransferases do not
preclude a diagnosis of cirrhosis.
Alkaline phosphatase ALP elevated 2
3 times the upper normal limit.
Gamma-glutamyl transpeptidase
Gamma-glutamyl transpeptidase (GGT)
levels correlate with ALP in lever disease.
 Bilirubin Bil : Normal in compensated
cirrhosis, rise as the cirrhosis progresses.
Albumin Albumin is synthesized
exclusively in the liver. Albumin levels fall.
Prothrombin time increases as the
ability of a cirrhotic liver to synthesize
clotting factors diminishes.
Globulins Globulins tend to be
increased in patients with cirrhosis.
Serum sodium hyponatremia
 Hematologic abnormalities
Anemia
Thrombocytopenia
Leukopenia and neutropenia
Coagulation defects
 Radiographic findings
Not adequately sensitive or specific
 Ultrasonography
Non invasive
Tolerated
Available
Provides
Valuable information
 Computed tomography
Tomography is not routinely used
Magnetic resonance imaging
The role of MRI in the diagnosis of
cirrhosis is unclear
 Complication of LC
Portal Hypertension
Ascites
Esophageal varices
Spontaneous bacterial peritonitis
Hepatorenal bacterial peritonitis
Hepato-renal syndrome
Gepatic encephalopathy
 Ascites
Portal hypertension
Renal retention of sodium
Splanchnic arterial vasodilation
Systemic vascular changes
Increased splanhnic and hepatic
lymphformation
ASCITES
 Secondary effects
A pleural effusion 5 10% 85%
it is right sided (defects in the
diaphragma)
Oedema
 Mangement of ASCITES
Bed rest 70 90 mmol sodium diet
Spironolactone 100 200 mg daily
It tense ascites paracentesis
After 4 days consider adding furosemide
40 mg daily
Check serum electrolytes
Continue to monitor weight, increase diuretics
as necessary
Stop diuretics if pre-coma, hypokalemia,
azotemia or alkalosis
Spontaneous Bacteriil peritonitis
Infection of ascitic fluid
spontaneous/follow a previous
paracentesis
 Spontaneous Bacterial Peritonitis
Suspect grade B and C cirrhosis with
ascites
Clinical feature may be absend and WBC-N
Ascitic protein < 1 g/dl
Monomicrobial and gram-neg.
Start AB if ascites > 250 mm polymorphs
50% die
69% recur in year
 The pathogenesis of SBP
RE function GI haemorrhage

Bacteralmia

Enteric bacterial Invasive procedures,

translocation catheters

Bacterascites

Poor Ascites fluid Good

Opsonic activity

SBP Resolution
 SBP
Ascites polymorh > 250 cells/mm3
and positive cultur monomicrobial
Therapy of SBP :
Cefotoxine 2 gr/12 h during 5 days.
Amixycillin or clavulamic acid i.v.
followed by oral therapy
 Hepatic Encephalopathy
A reversible neuropsychiatric state that
complicates liver disease
Aetiological factors.
Diuresis
Haemorrhage
Paracentesis
Diarrhoea & voviting
Sedatives
Infections
Constipation
Alcaholic surgery
Diarrhoea & vomiting
 Therapy :
Identification and treatment of the
precipitating cause
Intervention to reduce production
and absorrption of gut-derived
ammonia and other toxins
Give agents to modity
neurotransmitter balance diurectly
biomocriptine, fluororenil) or
indirectly (BCAA)
 Hepato Renal syndrome
Development of Renal failure in the
absence of any identifiable renal
pathology in severe liver disease
patients
Gambar : Anatomi Sistem Portal
 No Varices
HVPG normal/-10 mmHg

Small varices No hemorrhage

HVPG >10 mmHg
Varices development rate 8% per year

Medium/large varices No hemorrhage

Hyperdynamic circulation
Progression from small to large 8% per year

Variceal hemorrhage
Pressure > variceal wall tension (>10-12 mmHg)
Esophageal hemorrhage 5%-15% yearly
Gastric hemorrhage: bleeding in patients with gastric varices
Is reported in approximately 25% in 2 years (higher for fundal varices)

Recurrent hemorrhage
Persistence of portal pressure and variceal status

Figure : Natural History Varises Esofagus Pada Pasien Sirosis

(World Gastroenterology Organisation, 2007)
 Development of varices
High portal vein pressure : I IVPG >10 mmHg in patients
who have no varices at initial endoscopic screening

Progression from small to large varices

Decompensated ciirhosis (Child-Pugh B/C)
Alcoholic cirrhosis
Presence of red wale marks at baseline endoscopy
(longitutinal dilated venules resembling whip marks on the variceal surface

Initial varices bleeding episode

Poor liver function
Continuing alcohol somsumption
Ascites
Acid reflux

Variceal hemorrhage
Size of varices highes risk of first hemorrhage (15% per year)
in patients with large varices)
Decompensated cirrhosis (Child-Pugh B/C)
Endoscopic presence of Red wale marks

Figure : Faktor Risiko Terbentuknya Varices dan Perdarahan (Dite et al, 2008)