Racelis, Melinna Giann A. Dra.
Delos Santos-Lucero’s Didactics on Liver Cirrhosis and its Complications
Learning Points 04March22
1. Definitions, General Pathologic Features, And Staging
Definition and General Histopathologic
Features
o - Cirrhosis: defined histopathologically
o -Development of fibrosis > architectural distortion with the formation of regenerative nodules >
effects: 1) decrease in hepatocellular mass and function, 2) alteration of blood flow
Discontinuation or cessation of elicit factor like alcohol may improve the patient’s condition
STAGING
Child-Turcotte-Pugh classifications has limitations that ascites is vulnerable to subjectiveness; abnormal laboratory
findings ranges alsp fall in one equivalent score
ETIOLOGY
2. Pathologic features
Nodules: <3mm in diameter (micronodular)
Cessation of alcohol > larger nodules may form (mixed micronodular and macronodular cirrhosis)
3. Pathogenesis
Ethanol is absorbed in intestine and at small extent at the stomach and there are three enzymes responsible
in pathogenesis of alcoholic liver disease include ADH, ALDH and catalase. Acetaldehyde from ethanol via
enzyme ADH is the most common pathway. Oxidative damage occurs due to formation of ROS as acetaldehyde
is highly reactive and interrupt many pathways. Kupffer cells may also be activated. In destruction of
hepatocytes, liver may also shrink in size.
4. Clinical Features
a. Nonspecific symptoms:
i. Vague right upper quadrant abdominal pain
ii. Fever
iii. nausea and vomiting
iv. Diarrhea
v. Anorexia
vi. Malaise
b. Specific complications of chronic liver disease
i. ascites,
ii. edema,
iii. Upper gastrointestinal (GI)
iv. Hemorrhage
v. Jaundice
vi. Encephalopathy
c. Physical Examination
Hepatomegaly
Splenomegaly
Scleral icterus
Palmar erythema
Spider angiomas
Parotid gland enlargement
Digital clubbing
Muscle wasting
Edema and ascites
d. Physical Examination
i. Men
1. Decreased body hair
2. Gynecomastia
3. Testicular atrophy
ii. Women
1. menstrual irregularities / amenorrheic
2. Amenorrhea in women may be reversible if alcohol is discontinued
5. Laboratory Tests
a. Anemia (Zieve's syndrome)
b. Thrombocytopenia
c. Serum total bilirubin: normal or elevated
d. Direct bilirubin: mildly elevated
e. Prothrombin time: prolonged
f. ALT, AST: elevated
At early stages of liver diseases laboratory values may be normal but in later stages hypersplenism from
portal hypertension may lead to anemia. Anemia can also be caused by decreased bone marrow proliferation
Direct bilirubin is mildly elevated but if it worsens, we can see highly elevated direct bilirubinProlonged
prothrombin time and patient is no longer respondent to vitamin K treatment.ALT AST Ratio is 2:1
6. Diagnosis
Liver biopsy - If patient continues to drink in presence of alcoholic hepatitis, biopsy should be done 6
months after cessation of alcohol in order to detect residual reversible process
7. Treatment
Abstinence from alcohol
Acamprosate calcium
Good nutrition
Long-term medical supervision
Treatment: abstinence is the cornerstone management
Specific management and treatment:
o Glucocorticoids: severe alcoholic hepatitis without infection
o - Restricted to patients with a Discriminant Factor (DF) value of >32
o - DF = serum total bilirubin + (PT - control) × 4.6
o - Oral pentoxifylline
o - Parenteral infliximab or etanercept
Specific treatment included glucocorticoids in absence of infection but is restricted in patients with discriminating factor
of greater than 32 In patient whose value is more than 32, small studies proved that there is improved survival in 28 days
to those who are treated with GCS. Oral pentoxifyline is easier to administer than glucocorticoids
Anabolic steroids
Propylthiouracil
Antioxidants
- Colchicine
Penicillamine
Acetaminophen is discouraged (can consume <2g)
8. COMPLICATIONS OF CIRRHOSIS
a. General features of the following cirrhosis complications (splenomegaly and hypersplenism, hepatorenal
syndrome, malnutrition in cirrhosis, coagulapathies, bone disease)
b. Management of the following cirrhosis complications (portal hypertension, ascites, SBP, hepatic
encephalopathy
c. Major Complications of Cirrhosis
9. Portal hypertension: elevation of the hepatic venous pressure gradient (HVPG) to >5 mmHg
a. Causes: increased intrahepatic resistance to the passage of blood flow through the liver; increased
splanchnic blood flow secondary to vasodilation within the splanchnic vascular bed
b. Directly responsible for the two major complications of cirrhosis
i. variceal hemorrhage
ii. ascites
Postheptic causes include Hepatic veins draining to the heart
Hepatic classification of portal hypertension accounts for majority of cirrhosis complications as they can presinusoidal or
sinusoidal
The larger the size of varix correspond to severity
Clinical Features:
Upper Gl bleeding (Esophageal varices)
Ascites
Peripheral edema
Enlarged spleen > thrombocytopenia leukocytopenia
- Upper Gl bleeding (Esophageal varices)
- Screening for known cirrhotics: endoscopy
- 5-15% of cirrhotics per year develop varices > 1/3 will develop bleeding
- Factors that predict the risk of bleeding
severity of cirrhosis
- Height of wedged-hepatic vein pressure
- Size and location of the varix
-endoscopic stigmata: red wale signs, hematocystic spots, diffuse erythema, bluish color, cherry
red spots, or white-nipple spots
- ascites
Diagnosis (Upper Gl bleeding (Esophageal varices)
o Endoscopy
o CT scan
o MRI
Imaging methods to detect present of collateral circulation
Upper Gl bleeding (Esophageal varices) Treatment:
o Primary prophylaxis:
- routine endoscopy
- Nonselective beta blockers (propanolol, nadolol)
- Variceal band ligation / varice al sclerotherapy
Prevention of rebleeding
o - routine endoscopy
o - Nonselective beta blockers (propanolol, nadolol) *propranolol can exacerbate hypotension further
hence it is not given, also cirrhotic patients are in procoagulant state hence the only time that we watch
out for bleeding is when the INR is >20
o - Variceal band ligation / varice al sclerotherapy
Prevention of rebleeding Upper Gl bleeding (Esophageal varices)
- Treatment:
- Acute variceal hemorrhage:
vasoconstricting agents
- somatostatin
- Octreotide (50-100ug/h by continuous infusion
-Balloon tamponade (Sengstaken-Blakemore tube or Minnesota tube)
-Transiugular intrahepatic portosystemic shunt (TIPS)
Non selective beta blockers propranolol and nadolol studies patient treated with it have lower incidence of variceal
hemorrhage; Somatostain 3mg in 500 ml solution and administer 40 ml bolus; Somatostatin another 3 mg in 500ml
PNSS;Acute varicella hemorrhage is also treated with ballon tamponade to patients who cannot undergo endoscopic
therapy right away;If bleeding continues we can also use TIPS.
10. Splenomegaly and Hypersplenism
Clinical Features:
Enlarged spleen
- Thrombocytopenia
- Leukopenia
- Left-sided and left upper quadrant abdominal pain
Treatment:
No specific treatment
- Splenectomy
11. Ascites
Accumulation of fluid within the peritoneal cavity
Most common cause: portal hypertension
Sodium retention is also a response when there is arterial under filling that will aggravate or worsen volume of ascites
another contributing factor is hypoalbuminemia due to decrease synthetic function of cirrhotic liver. Supine position on
either left or right side if there is movement in percussion It is positive shifting dullness . Patients presenting with ascites
for the first time, paracentesis is indicated and serum ascites to albumin gradient or SAAG now replaces the classification
of transudative or exudative fluid and patients. With liver cirrhosis, we expect them to have >1.1 g/dL SAAG and if it is
less than 1.1 infectious agent or malignancy can be considered
Clinical Features:
o Increased abdominal girth
o Peripheral edema
o Shortness of breath
o Hepatic hydrothorax
o Malnourished
o Muscle wasting
o Excessive fatigue and weakness
Diagnosis
Bulging flanks
- (+) fluid wave
- (+) shifting dullness
Imaging
- Ultrasound
CT scan
Diagnostics
o Paracentesis: total protein and albumin content, blood cell counts with differential, and cultures,
amylase, cytology
o Serum-ascites-to-albumin gradient (SAAG)
>1.1g/dL: portal hypertension
<1.1g/dL: infectious or malignant
if very low: increased risk for SBP
Treatment:
- Sodium restriction (<2g/day)
- Diuretics
- Spironolactone 100-200mg/ d single dose Up to 400-600mg/d
- Furosmide 40-80mg/d up to 120-160mg/d
Refractory Ascites
o Still with ascites even with the maximum dosages of diuretics who are compliant
with a low sodium diet
- Treatment: paracentesis
- TIPS
12. Spontaneous Bacterial Peritonitis
Severe complication of ascites
Spontaneous infection of the ascitic fluid without an intraabdominal source
Pathogenesis: bacterial translocation
Most common organisms:
- Escherichia coli and other gut bacteria
Other organisms:
- Streptococcus viridans
- Staphylococcus aureus
> Enterococcus Sp.,
Diagnosis:
Absolute neutrophil count: >250uL
Clinical Features:
- Fever
- Altered mental status
elevated white blood cell count
abdominal pain or discomfort
Treatment:
Third-generation cephalosporin
13. Hepatorenal Syndrome
form of functional renal failure without renal pathology with advanced cirrhosis or acute liver failure
Marked disturbance in arterial renal circulation:
- increased in vascular resistance
- Reduction in systemic vascular resistance
Diagnosis: Presence of large amount of ascites with progressive increase in creatinine
14. Hepatic Encephalopathy
Clinical Features:
- Changes in mental status: confused or change in personality/behavior
- Brain edema (swelling of the gray matter) > Cerebral herniation
- Asterixis
Causes: Electrolyte disturbance (Hypokalemia)
15. Bone Disease in Cirrhosis
Osteoporosis: malabsorption of Vitamin D and decreased calcium ingestion
Diagnosis: Dual x-ray absorptiometry (DEXA)
Treatment: biphosphonates
16. Malnutrition
Catabolic state
Factors: poor dietary intake
Alterations in gut nutrient absorption
Alterations in protein metabolism
Treatment: dietary supplementation
17. Abnormalities in Coagulation
decreased synthesis of clotting factors and impaired clearance of anticoagulants
Decreased synthesis of Vitamin K-dependent clotting factors: Factor II. VII IX X
Treatment: IV/IM vitamin K
