CIRRHOSIS

I. DEFINITION = HISTOLOGICAL

 Irreversible process affecting the entire liver

 Characterized by 3 main lesions:

o Micro (<3mm) or macro (>3mm) regeneration nodules

o Surrounded by annular cicatricial fibrosis

o Transformation of normal hepatic lobular architecture (cells and vessels)

Cirrhosis may be evoked on the basis of a number of arguments:

 Clinical

 Biological

 Radiology

 A biopsy is not always necessary

o Insidious installation over several years

o Final stage of many liver diseases

II. CONSEQUENCES

 Decreased number of hepatocytes:

o Decrease in functional hepatocyte mass with risk of hepatocellular deficiency:

 Reduced synthesis functions

 Reduced purification functions

 Reduced biliary functions

 Disturbances of intrahepatic circulation:

o Through fibrosis-induced architectural changes with risk of PH:

 Congestive splenomegaly (hypersplenism)

 Development of bypass routes: Porto-cava anastomoses

 Varicose veins and the risk of digestive hemorrhage

 Precancerous state: risk of HCC

III. EPIDEMIOLOGY

 In Morocco: post-viral cirrhosis (B and C) +++

 In Europe:
 o Post-alcoholic cirrhosis +++ (50 to 75% of cases)

o Then post-viral cirrhosis C

 Age: any age, depending on etiology

 Sex: no gender predominance

IV. CLINICAL MANIFESTATIONS

 Compensated cirrhosis

 Decompensated cirrhosis

A. CIRCUMSTANCES OF DISCOVERY

1. Incidentally: compensated cirrhosis:

o Clinical examination or surgery

o Liver test abnormalities

o Ultrasound abnormalities

o Positive viral serological markers/blood donation

o Esophageal and/or gastric varices during FOGD

2. When monitoring chronic liver disease

3. Complications: decompensated cirrhosis:

o Digestive hemorrhage

o Hepatic encephalopathy

o Ascites, oedemato-ascitic syndrome, etc.

B. PHYSICAL SIGNS +++

1. Liver:

o Size:

 Normal

 Hepatomegaly

 Atrophic liver

 Atropho-hypertrophic (dysmorphic liver)

o Consistency: hard

o Front edge: sharp

o Irregular front surface

o Non-sensitive
 2. Signs of PH:

o Abdominal collateral venous circulation

o Repermeabilization of the ombilical vein

o Splenomegaly

o Ascites

C. SIGNS OF HEPATOCELLULAR INSUFFICIENCY

1. Skin signs:

o Stellate angiomas

o Palmar erythrosis

o White nails, Digital hippocratism

2. Endocrine signs:

o In men: Hypogonadism, Gynecomastia, Reduced hair growth, Sexual impotence

o In women: amenorrhea and infertility

3. Hematological:

o Anemic syndrome

o Coagulation disorder resulting in:

 Epistaxis

 Gingivorrhagia

4. Clinical signs specific to each etiology

V. FURTHER TESTS

1. Biological tests:

o Can be normal

o CBC: signs of hypersplenism: Isolated thrombocytopenia, Bicytopenia or

pancytopenia

o Liver function tests:

 Cytolysis: depending on disease activity

 Cholestasis: GGT, PAL: normal or increased

 Bilirubin: Normal or slightly elevated

 HC deficiency: depending on the degree of HC deficiency:

 Prothrombin: normal > 70% or low

  Factor V: normal or low

 Albuminemia: normal, hypoalbuminemia

 EPP: ß γ block (Beta-Gamma block), hypergamaglobulinemia

 Alpha-feto-protein: >400ng/ml: suggests HCC

2. Abdominal ultrasound coupled with Doppler:

o Systematic: repeated every 6 months (HCC screening)

o Indirect and non-specific signs of cirrhosis:

 Change in liver volume

 Contours sometimes bumpy

 Heterogeneous parenchyma appearance

o Signs of PH:

 Dilatation of the portal vein and splenic vein

 Splenomegaly with tortuous splenic vein

 Collateral venous circulation around

 Spleno-renal shunt

 Ascites, if present and abundant

3. Endoscopy: UGI:

o Esophageal varices:

 Stage I: Varicose vein disappears on insufflation

 Stage II: Non-confluent varicose veins that do not disappear after insufflation

 Stage III: Varicose veins that do not disappear after insufflation and are
confluent

4. Assessment of hepatic fibrosis:

o Liver biopsy:

 Diagnosis

 Sometimes specifies the origin of cirrhosis

 If clinical, biological, and imaging findings are suggestive: liver biopsy is not
essential

o Ultrasonic pulse elastometry:

 Direct physical approach

 Measures the degree of elasticity of the liver, using a modified ultrasound

probe
  To assess liver fibrosis

5. Scanner/MRI:

o Not mandatory for diagnosis of cirrhosis

o Better than ultrasound for detecting liver cancer (HCC)

o But always with injection ++++

VI. MAIN ETIOLOGIES

1. Chronic viral hepatitis:

o VHC: C virus antibodies, PCR RNA C

o VHB: HBsAg +, anti HBc antibodies +, PCR DNA B

o VHD: In addition to B positive, anti delta antibodies/PCR RNA D

2. Toxic hepatitis: Chronic alcoholism

3. Chronic autoimmune hepatitis:

o Serology: antinuclear antibodies, smooth muscle antibodies, LKM1 antibodies

o Histology: by liver biopsy

4. Cirrhosis complicating NASH ++++

5. Cholestatic biliary disorders:

o Primary biliary cholangitis: anti-mitochondrial M2 antibodies

o Primary sclerosing cholangitis: PSC

6. Hereditary diseases:

o Wilson's disease

o Hemochromatosis

o Alpha-1 antitrypsin deficiency

7. Celiac disease

8. Hemodynamic causes:

o Cardiac liver

o Budd-Chiari syndrome

9. Others:

o Sarcoidosis, syphilis, bilharziosis

VII. COMPLICATIONS: DECOMPENSATED CIRRHOSIS

1. Digestive hemorrhage:

o Hematemesis and/or melena ++++

o Rectorrhagia with shock due to:

 Rupture of varices

 Hypertensive gastropathy

 Gastric or duodenal ulcer

2. Hepatic encephalopathy:

o Increasing severity: up to coma through 4 stages:

 Stage I: Asterixis (flapping tremor)

 Stage II: Temporo-spatial disorientation

 Stage III: mild coma

 Stage IV: deep coma

o Always look for a trigger: ++++

 Digestive hemorrhage

 Infection, especially of ascites fluid

 Medications: sedatives, diuretics

 Hydroelectrolytic disorders: hyponatremia

3. Ascites: frequent +++ complication

o Due to: PH and/or hepatocellular deficiency

o Diagnosis often clinical:

 Grade 1: Minimal: discovered by ultrasound

 Grade 2: Medium abundance: matity on the flanks centered by a sonority

 Grade 3: High abundance:

 Very distended abdomen

 Everted umbilicus

 Diffuse matity

 Signs of intolerance: Pain/Dyspnea

4. Hepatocellular carcinoma (HCC): ++++

o Complications that may reveal cirrhosis

o Discovered during screening: ultrasound/aFP:

 Can be single or multiple

  Abdominal ultrasound: confirms the solid nature of the tumor

 Angio-CT: suggestive appearance: focal hyperdense lesion in the arterial

phase with washout in the portal phase

 Others: Angio-MRI +++

 Histology: guided ultrasound or scannoguided: confirms diagnosis

5. Icterus:

o Jaundice with predominant conjugated bilirubin

o Due to impaired bilirubin excretion

o Multiple causes, the main one: HC deficiency

6. Infectious complications: ++++

o Due to reduced immune defenses

o Infection of ascites fluid, lungs, urinary tract

7. Hepatorenal syndrome (HRS): Renal failure

o Diagnosis criteria:

 End-stage cirrhosis with HC deficiency

 Refractory ascites and oliguria < 500ml/24h

 No improvement in renal function after 2 days of:

 Stopping diuretics

 Volume expansion with albumin

 Severe prognosis

8. Pulmonary complications: 3 types:

o Hydrothorax: mostly on the right in 90% of cases

o Portopulmonary hypertension

o Hepatopulmonary syndrome: Cirrhosis + hypoxia + diffuse dilatation of pulmonary

vessels

9. Tendency to hypoglycemia:

o Observed in cirrhosis with severe HC deficiency

10. Cardiac complications:

o 30 to 60% of cirrhotics develop:

 Increased cardiac output

 Reduced peripheral vascular resistance

11. Biliary lithiasis

 12. Gastro-duodenal ulcer

VIII. EVOLUTION AND PROGNOSIS

1. Child-Pugh score: sum of points for all items

2. MELD score:

o From 3 values: total bilirubin, creatinine, and INR

o 15: liver transplant

IX. TREATMENT

A. Etiological treatment: ++++

 Alcohol withdrawal, discontinuation of hepatotoxic drugs

 VHB: Lamivudine, Adefovir, Tenofovir, etc.

 VHC: DAAs (Direct-acting antivirals)

 AIH: corticosteroids and/or immunosuppressants

 PBC, PSC: Acide Urso Désoxy Cholique: AUDC

 Hemochromatosis: bloodletting

 Wilson: D-penicillamine, etc.

B. Liver transplantation: ++++

 Indications:

o Advanced cirrhosis

o Complications of cirrhosis not controlled by other treatments

o Neoplastic grafting (hepatocellular carcinoma)

C. Treatment of complications

1. Digestive hemorrhage:

o EV rupture: Vasopressors (somatostatin)

o EV ligation, Blakemore probe

o Biological glue for gastric varices

o Preventive treatment of rupture:

 Non-cardio selective B-blockers: propranolol or Carvedilol

 EV binding

2. Hepatic encephalopathy:
 o Preventive treatment:

 Ban on sedatives: benzodiazepines

 Lactulose:

 Decrease in colonic pH

 Reduced colonic ammonium absorption

o Curative treatment:

 Treatment of triggering factors

3. Ascites fluid infection:

o Diagnosis:

 Biochemistry: on request:

 White blood cell count with cytological formula

 NPC count: If NPC > 250/mm3 = ascites infection

o Processing is based on:

 Antibiotic therapy: 3rd generation cephalosporin, protected amoxicillin, or

fluoroquinolone

 AND on perfusion of albumin +++

4. Ascites +++

o Low-salt diet: 2 to 3 g/d Na

o Diuretics:

 Spironolactone: anti-aldosterone: Gradual dose of 100 to 250 mg/d taken

once in the morning

 May be combined with: Furosemide: 40 to 80mg/d

o Evacuation ascites puncture: if grade III:

 Puncture of 5 to 6 L or more

 AND: Perfusion Albumin 20%:

 Monitoring: State of consciousness, weight, diuresis

5. Refractory ascites:

o If treatment with diuretics fails:

 Albumin infusion

 Evacuation punctures

 Peritoneo-jugular shunt

 Liver transplantation +++

  TIPS +++ (transjugular intrahepatic portosystemic shunt) installed under
radiological control

6. Hepatocellular carcinoma (HCC):

o Curative treatment:

 Surgical TRT: liver transplant

 Percutaneous TRT: alcoholization, radiofrequency

o Palliative treatment:

 Chemo-embolization

 Medical TRT: Systemic chemotherapy, e.g., Sorafenib

7. HRS: The ideal treatment is Liver transplant

X ### X. MONITORING

 Clinical, biological, ultrasound, and endoscopic evaluations

 Periodic investigation of complications

 Screening for hepatocellular carcinoma by:

o Alpha-feto protein assay

o Liver ultrasound every 6 months

 Esophageal varices monitoring:

o UGI/3 years: if no EV

o Beta blockers if no contraindications

PORTAL HYPERTENSION (PH)

I. DEFINITION

 Normal portal pressure: 7 to 10 mm Hg

 Hemodynamic definition:

o Portal venous pressure ≥ 15 mmHg

o Pressure gradient between portal and vena cava > 5 mmHg

 Hyperpressure due to obstruction of the portosystemic circulation

 Indirect signs:

o Clinical manifestations: CVC, SMG

o Endoscopic: EV, GV
 o Radiology: CVC, spleno-renal shunts, etc.

o Biological: thrombocytopenia < 120,000/mm3

II. PATHOPHYSIOLOGY

 Consequences of PH:

o Splenomegaly

o Vein dilatation

o Development of collateral circulation (+++)

o Porto-systemic shunts = communication between portal and vena cava territories

(superior, inferior, anterior, and posterior shunts)

III. CLASSIFICATION

 Depending on the site of the obstacle or block: 3 types of PH

o At the PV level and/or its related vessels: Subhepatic or subhepatic PH

o Portal venules and sinusoidal capillaries: Intrahepatic PH

o In the suprahepatic vein or inferior vena cava: Suprahepatic or suprahepatic PH

IV. POSITIVE DIAGNOSIS

1. Circumstances of identifying the disease:

o Most often latent and asymptomatic

o Discovered during workup for causative disease

o Biological manifestations of hypersplenism

2. Functional signs:

o Feeling of gravity in the left hypochondrium (SMG)

o Acute abdominal or back pain (thrombosis)

o Increased abdominal volume (ascites)

o Occurrence of complications:

 Upper gastrointestinal bleeding

 Hepatic encephalopathy

 Ascites, especially if grade II or III

3. Physical signs:
 o Abdominal porto-caval CVCs: +++

 Dilated veins:

 Basi-thoracic or thoracic

 And/or on the flanks

 And/or hypogastric

 Significant periumbilical venous dilatation: Cruveilhier-Baumgarten syndrome

 Their absence does not eliminate these blocks

 Exclusive to supra- and intra-hepatic blocks

4. Splenomegaly:

o Frequent but not constant

5. Liver:

o Normal morphology or modified if cirrhosis or thrombosis

6. Signs of hepatocellular insufficiency: if cirrhosis:

o Mucocutaneous: palmar erythrosis, stellate angiomas, white nails, digital

hippocratism

o Endocrine: gynecomastia, reduced hair growth

o Hemorrhagic syndrome

7. Complications:

o If port-cave pressure gradient is > 12mm Hg

 Upper gastrointestinal bleeding:

 Rupture of esophageal varices

 Ruptured gastric varices

 Ascites

 Hepatic encephalopathy

V. RADIOLOGICAL EXAMINATIONS

1. Abdominal ultrasound + Doppler:

o Important test for the diagnosis of PH, simple and non-invasive

o Diagnosis of PH:

 Increase in PV diameter greater than 15 mm

 Visualization of porto-systemic collaterals ++

  Splenomegaly with tortuous SV and/or surrounding CVC

o Allows diagnosis of obstacle level

2. Abdominal computed tomography: angio-CT:

o Not necessary in the assessment of portal hypertension

o Interest in portal thrombosis

VI. ENDOSCOPY: UGI

1. Varices:

o Oesophageal: EV: Location: lower third of the oesophagus

 Three stages:

 Stage I: cord disappears on insufflation

 Stage II: varicose veins that do not disappear with insufflation but are
not confluent

 Stage III: Confluent varicose veins that do not disappear with

insufflation

 Presence or absence of red-color signs (risk of hemorrhage)

2. Gastric:

o GOV: GOV1 and GOV2

o IGV: IGV1 and IGV2

3. Ectopic: rectal, colonic, etc.

4. Gastric mucosal abnormalities:

o Congestive gastropathy:

 Erythematous mosaic gastritis

 Moderate, severe

 Diffuse but usually fundus

o Antral vascular ectasia:

 Red macules with a watermelon appearance

 Erosions

 Peptic ulcers

VII. CAUSES OF PH
  Classified according to the level of the obstacle upstream of which portal hypertension
develops:

o Suprahepatic PH

o Intrahepatic PH

o Subhepatic PH

A. INTRA-HEPATIC PH

 The most frequent block +++

1. Cirrhosis +++:

 Viral: B, B-D, C

 Alcoholic

 Autoimmune

 Primary or secondary biliary

 Rare causes: hepatic sarcoidosis, massive steatosis, NASH, celiac disease,

Wilson, hemochromatosis, etc.

2. Non-cirrhosis: Non-cirrhotic PH:

 Hepatic sarcoidosis, hepatic tuberculosis

 Massive steatosis, NASH

 Amyloidosis

 Malignant hemopathy

 Secondary liver cancer

 Porto-sinusoidal vascular disease (PSVD): a new feature

B. SUPRA-HEPATIC PH

 Budd-Chiari syndrome

o Obstruction of at least 2 suprahepatic veins and/or IVC

2. Primitive: venous obstruction caused by thrombogenic conditions:

 Myeloproliferative disorders

 Anti-phospholipid syndromes

 Thrombophilia

 Vasculitis: Behçet, IBD, celiac disease, etc.

3. Secondary:

 Endoluminal tumor invasion

 HCC +++
  Kidney or adrenal cancer

 Extrinsic compression of the V sus-H and/or IVC:

 Hepatic hydatid cyst

 Liver abscesses: amebic or pyogenic

4. Cardiac causes:

 Restrictive cardiomyopathy, restrictive pericarditis

C. SUB-HEPATIC HTP

 Obstruction of the portal vein (+++) and/or one of its efferent branches by:

1. Venous thrombosis:

 Thrombogenic conditions: same as suprahepatic

 Pylephlebitis secondary to an infectious focus in the portal territory:

appendicitis, diverticulitis, pancreatitis, IBD, surgery, etc.

2. Tumor invasion: any neighboring cancer

3. Extrinsic compression:

 Dominated by hepatocellular carcinoma (HCC) (+++)

 Neoplastic or tubercular ADP

IX. TREATMENT

 Purpose: Treatment of the causative disease and treatment of complications

A. Digestive bleeding:

1. Emergency treatment:

o Stabilization of hemodynamic factors: +++

o Vasopressin and derivatives

o Somatostatin and derivatives

2. Endoscopic treatment:

o Mainly: Ligation of esophageal varices

3. Preventive treatment of recurrent bleeding:

o Non-cardio selective B-blockers: propranolol, Carvedilol

o If no contraindications: bradycardia

o Primary prophylaxis: without prior bleeding

o Secondary prophylaxis: after vein ligation

 o EV binding

4. Others:

o TIPS

o Surgical treatment: Portal shunts if bleeding is uncontrolled

o Porto-splenic anastomoses, Porto-cava anastomoses