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SIROSIS HEPATIS

Sigit Widyatmoko

Fakultas Kedokteran UMS

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Normal Liver

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Introduction

Cirrhosis is common end result of many chronicliver disorders.

Diffuse scarring of liver follows hepatocellularnecrosis of hepatitis.

Inflammation healing with fibrosis -Regeneration of remaining hepatocytes formregenerating nodules.

Loss of normal architecture & function.

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Introduction

Irreversible chronic injury of the hepatic

parenchyma, include extensive fibrosis in

association with the formation of regenerative

nodules

Result from hepatocyte necrosis, collapse of

supporting reticulin network, with subsequent

connective tissue deposition, distortion of thevascular bed, and nodular regeneration of

remaining liver parenchyma.

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Clinical features of cirrhosis derive from themorphologic alterations and often reflect the

severity of hepatic damage rather than the etiology

of the underlying liver disease

Classification:

Alcoholic

Cryptogenic and post hepatitis

Biliary

Cardiac

Metabolic, inherited, and drug related

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Definition:

1. Diffuse disorder of liver characterised by;

2. Complete loss of normal architecture,

3. Replaced by extensive fibrosis with,

4. Regeneratingparenchymalnodules.

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Classification

Morphologic classification: less useful Micronodular cirrhosis: uniform nodules < 3 mm

Macronodular cirrhosis: nodular variation > 3 mm

Mixed cirrhosis

Etiologic classification: preferred

The most useful clinically

The two most common cause of cirrhosis: alcohol useand viral hepatitis

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Pembagian lain:

Sirosis kompensata

Sirosis dekompensata: ikterus, perdarahan varises,

asites, ensefalopati hepatikum, karsinoma hepatikum

Perubahan kompensata menjadi dekompensata:

5-7% pertahun

Survival menurun jauh: Sirosis kompensata: 12 tahun

Sirosis dekompensata: 2 tahun

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Epidemiologi

Prevalensi di Indonesia antara 3,6-8,4% pada pasienbangsal Jawa dan Sumatera atau rata-rata 47,4%

dari seluruh pasien penyakit hati yang dirawat

Pria : wanita 2,1 : 1

Usia rata-rata= 44 tahun

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Normal LiverHistology

CV

PT

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Cirrhosis

Fibrosis

Regenerating Nodule

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Etiology of Cirrhosis

Alcoholic liver disease 60-70%

Viral hepatitis 10%

Biliary disease 5-10%

Primary hemochromatosis 5%

Cryptogenic cirrhosis 10-15%

Wilsons, 1AT def rare

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Alcoholic Liver Injury:

Ethyl alcohol : Common cause ofacute/Chronic liver disease

Alcoholic Liver disease - Patterns Fatty change,

Acute hepatitis (Mallory Hyalin)

Chronic hepatitis with Portal fibrosis

Cirrhosis, Chronic Liver failure

All reversible except cirrhosis stage.

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Alcoholic Liver Injury

May be clinically silent, and many cases (10-40%)are discovered incidentally at laparotomy

Occuring usually > 10 years of excessive alcohol

use Increased peripheral release of fatty acids.

Inflammation, Portal bridging fibrosis

Stimulates collagen synthesis fibrosis. Micronodular cirrhosis.

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Alcoholic Liver Damage

Mallorys hyalin: eosinophilic fibrillar material seen in

ballooned hepatocytes

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Alcoholic Fatty Liver

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Cirrhosis in Alcoholism
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Alcoholic Cirrhosis

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Cirrhosis

Nodules of fatty and

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Nodules of fatty and

regenerating liver cells

separated by scars

(cirrhosis)
http://web.med.unsw.edu.au/pathmus/_vti_bin/shtml.dll/f1338012.htm/map

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Pathogenesis:

Hepatocyte injury leading to necrosis. Alcohol, virus, drugs, toxins, genetic etc..

Chronic inflammation - (hepatitis).

Bridging fibrosis. Regeneration of remaining hepatocytes

Proliferate as round nodules.

Loss of vascular arrangement results inregenerating hepatocytes ineffective.

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Cirrhosis Features:

Liver Failure

Parenchymal regeneration

Portal obstruction, Porta systemic shunts Portal hypertension, Splenomegaly

Jaundice, Coagulopathy, hypoproteinemia,

toxemia, Encephalopathy,

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Micronodular cirrhosis

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Micronodular cirrhosis:

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Macronodular Cirrhosis

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Clinical Features

Hepatocellular failure.

Malnutrition, low albumin & clotting factors,bleeding.

Hepatic encephalopathy.

Portal hypertension.

Ascites, Porta systemic shunts, varices,

splenomegaly.

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Bleeding in Liver disease:

vitamin K in livergamma-carboxyglutamic acid for coagulationfactors II, VII, IX, and X.

Liver disease factor VII is the first to goso the defect will appear initially in theextrinsic pathway, i.e., abnormal PT. When

severe it affects both pathways.

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Cirrhosis

Clinical

Features

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Gynaecomastia in cirrhosis

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Porta-systemic anastomosis:

Prominent abdominal veins.

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MRI Cirrhosis

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Complications:

Congestive splenomegaly.

Bleeding varices.

Hepatocellular failure. Hepatic encephalitis / hepatic coma.

Hepatocellular carcinoma.

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Impaired Metabolic and EndocrineFunctions

Hyperglycemia - portal to systemic shunting,

which decreases the efficiency of

postprandial glucose extraction from portal

blood by hepatocytes. mesa@food

Hypoglycemia - hepatocyte destruction and

impaired glycogenolysis and

gluconeogenesis

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Impaired protein synthesis1

Albumin low oncotic pressure

Angiotensinogen low blood pressure

Insulin-like growth factor 1, thyroid hormonebinding proteins poor growth and metabolism

Impaired protein processing

Oxidative deamination, transamination, ureacycle buildup of toxic biological compoundssuch as ammonia

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Disruptions in the entero-hepatic circulation

of bile

Cholestasis impairs dietary absorption of lipids

and fat-soluble vitamins A, D, E, K

Inhibited excretion of bilirubin jaundice, buildup

of bile acids pruritus

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Decreased synthesis of sex hormone binding

globulin, decreased hepatic clearance of

unbound sex hormones, increased peripheral

aromatization of androgens to estrogens feminization (testicular atrophy, gynecomastia,

loss of male-distribution body hair), pituitary

and gonadal suppression1

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Hematologic Derangements

Thrombocytopenia impaired liver

production of thrombopoietin, increased

destruction due to hypersplenism from

splenic vein engorgement

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Gastrointestinal Varices

Varices are a direct consequence of portalhypertension, and patients are at risk with portalpressures greater than 10 mmHg

Esophageal varices are present in 30% of patientswith compensated cirrhosis and 60% of patients withdecompensated cirrhosis11

Each episode of bleeding carries a 20% mortality

rate12

Untreated patients have a 70% rebleeding riskwithin one year13

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Varicose veins in the esophagus
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All patients should undergo screening upper

endoscopy when cirrhosis is first diagnosed.

Those without varices should undergo repeat

endoscopy every 3 years if liver function isstable, or once a year if there are any signs

of deterioration. Screening endoscopy can

be stopped once patients are on beta

blockers.

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Primary Prophylaxis No definitive data to support treatment of small varices

Medium to large varices should be treated withnonselective beta blockers, which can reduce portal

pressure by an average of 15 20%, and can decreaseoverall upper gastrointestinal bleeding by 40%;Endoscopic band ligation is recommended for thoseunable to tolerate beta blockers

The dose of beta blocker should be titrated up to producea 25% reduction in the patients baseline heart rate, or until

a resting heart rate of 5560 beats per minute is reached

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Acute variceal bleed - high risk of death

within weeks from uncontrolled bleeding,

early rebleeding, infection, or renal failure

Treatment should be initiated immediately withresuscitation, prophylactic antibiotics,

vasoactive drugs (eg, octreotide for 48 hours

5 days), and endoscopic therapy

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Ascites Pathogenesis :

sinusoidal portal hypertension increasedhepatic lymph production collection of lymph

fluid in the peritoneal cavity when drainage

mechanisms are overwhelmed

Aliran darah melalui v porta sirkulasi

spanknik dan sistemik vasodilatasi ret Na dan

air + aktivasi SSP ( aliran darah ginjal dan LFG )

air mengumpul

Any patient with new onset ascites should have a

diagnostic paracentesis for cell count with diff,

protein, albumin

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SAAG (serum albumin ascites albumin) >

1.1g/dL is consistent with portal hypertension orhipoalbuminemia (nonperitoneal

SAAG < 1,1 : penyakit peritoneum atau eksudat

4 tingkatan asites:

Hanya dapat dideteksi dengan px seksama

Deteksi lebih mudah dengan jumlah sedikit

Tampak jelas tetapi tidak terasa keras

Asites mulai terasa keras Komplikasi asites terdapat pada 10% pasien CH

Survival pasien menurun: 50% dalam 5 th

A it i Ci h i

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Ascites in Cirrhosis

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Ascites

ascites accumulation of fluid in the abdominal cavity

A it i Ci h i

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Ascites in Cirrhosis

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Ascites

Treatment

Dietary sodium restriction 1-2g/day (effective in 20% ofpatients)

No need for fluid restriction

Diuretic therapy with spironolactone plus furosemide inratio of 100mg to 40mg, max 400mg/160mg21, 22

Note: loop diuretics may worsen hyponatremia and causehepatic encephalopathy by increasing renal ammonia

production In patients with poor response, check 24 hour urine

sodium for compliance (should be less than prescribeddaily sodium limit)

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Spontaneous Bacterial Peritonitis

Cairan dalam perut merupakan tempat ideal

pertumbuhan kuman

Mekanisme: pertumbuhan bakteri dan

tranlokasi melalui dinding usus yangpermeabilitasnya

SBP occurs in up to 30% of patients with

ascites

Diagnosis - > 250 PMNs per mm3 of fluid

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Bakteri utama gram negatif, tetapi juga

ditemukan Stafilokokus aureus

Klinis: demam, menggigil, nyeri abdomen, diare,

asites memburuk

SBP is associated with the development of

hepatorenal syndrome in about 30% of patients.The risk can be decreased by intravenous

albumin infusion at a dose of 1.5mg/kg at the

time of SBP diagnosis and 1.0mg/kg after 48

hours.

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Spontaneous Bacterial Peritonitis

Upper GI bleed carries a high risk of SBP,

even in patients who do not have ascites, and

prophylactic antibiotics are warranted x 7

days

Norfloxacin 400mg PO BID

Ofloxacin 400mg IV daily

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Hepatic Encephalopathy

Pathogenesis unclear, ammonia hypothesis states

that ammonia is directly neurotoxic, but there is no

correlation between severity of encephalopathy and

ammonia level

Wide range of clinical manifestations, from reversal

of sleep-wake cycle, mood disturbance,

psychomotor impairment, visual impairment, to

decreased attention

May see characteristic hand flap (asterixis)

h i f i

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BRAIN

LIVER

Toxic N2 metabolites

From Intestines

Porta systemic

shunts

Pathogenesis of HepaticEncephalopathy

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Faktor Pencetus

Peningkatan amniogenesis: perdarahansaluran cerna, sembelit, dehidrasi, infeksi,asupan protein meningkat

Penurunan fungsi hepatoselular: dehidrasi,hipotensi, sepsis, hipoksia, anemia,karsinoma

Peningkatan pintas portokaval: trombosisvena porta, pintasan pintasan transjugularintrahepatik portosistemik

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Pemakaian obat psikoaktif: golonganbenzodiazepin, etanol, antimual,antihistamin

Faktor pencetus lain: pemberian produkdarah yang disimpan

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Hepatic Encephalopathy

Treatment

Look for triggers: gastrointestinal bleeding, hypovolemia,hypoglycemia, hypokalemic metabolic alkalosis, infection,constipation, hypoxia, sedatives

Non-absorbable disaccharides (lactulose, starting at 30gBID, titrated to 2-3 loose BMs daily) to increase ammoniaclearance

Non-absorbable antibiotics (neomycin, rifaximin) todecrease intestinal ammonia production

Probiotic: improves hepatic encephalopaty by decreaseammonia concentration

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L-ornithine-L-aspartate: decreased ammoniaconcentration dose dependent

Consider liver transplantation, encephalopathy mostlyreversible, but minimal symptoms may persist after

transplantation

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Hepatorenal Syndrome

Pathogenesis renal vasoconstriction from lowrenal perfusion

Type 1 rapidly progressive, doubling of serumcreatinine to > 2.5mg/dL in < 2 weeks; frequently

develops from Type 2 after a precipitating eventsuch as infection, GI bleed, surgery, acutehepatitis. Without treatment, type 1 HRS has amedian survival of 2 weeks

Type 2 - moderate and steady decline in renalfunction with creatinine >1.5mg/dL, dominantfeature is refractory ascites. Median survival is 6months

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Hepatorenal Syndrome

Diagnosis

Rule out other causes of renal failure

Urine studies consistent with prerenal etiology

(low FENa and FEUrea)

No improvement in renal function after empiric

fluid challenge of at least 1.5 L

Proteinuria < 500mg/day

Renal ultrasound without evidence of obstructive

uropathy or parenchymal disease

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Hepatocellular Carcinoma

Annual incidence 1.4% in patients withcompensated cirrhosis and 4% in patientswith decompensated cirrhosis

Screening should be done with AFP andultrasound every 6 months

Patients with HCC amenable to liver

transplant are exempt from MELD calculationand have priority on the transplant list

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Hepatitis dapat terjadi kanker hati dengan atau

tanpa sirosis terlebih dahulu

Hepatoma lebih banyak ditemukan pada

hepatitis C

Sirosis hepatoma: 2-4% pertahun tergantung

penyebabnya

Pada hepatitis B: HBeAg (+) paling berisiko

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Hepatocellular Carcinoma

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