Liver Cirrhosis and Complications

Question 1

Who first introduced the term cirrhosis

Answer 1

Rene Laennec

Question 2

What is the common cause of liver cirrhosis in Ghana

Answer 2

HBV

Question 3

What is liver cirrhosis

Answer 3

It is the abnormal response of the liver to any chronic injury eg. viral hepatitis, alcohol. Diffuse fibrosis of the liver with nodule formation. Distortion of hepatic architecture by fibrosis and attempted regeneration leads to loss of function, portal hypertension, and potential hepatocellular malignancy

Question 4

What are some etiologies of liver cirrhosis

Answer 4

Viral
Prolonged cholestasis
Hepatic venous outflow obstruction syndromes
Autoimmune
Toxins and Drugs eg. Methotrexate, Amiodarone
Alcohol
Metabolic (hemochromatosis, Wilson’s disease, NASH)
Genetic (alpha 1 antitrypsin deficiency)

Question 5

What is the pathophysiology of liver cirrhosis

Answer 5

Irreversible/reversible chronic injury of the hepatic parenchyma which include progressive and widespread death of liver cells associated with inflammation and fibrosis
Extensive fibrosis - distortion of the hepatic architecture and development of portosystemic vascular shunts
Formation of regenerative nodules due to the proliferation of surviving hepatocytes

Question 6

What are the morphological classifications of liver cirrhosis

Answer 6

Relatively nonspecific with regard to etiology
Micronodular cirrhosis- Nodules < 3mm in diameter caused by alcohol, hemochromatosis, cholestatic causes of cirrhosis, and hepatic venous outflow obstruction
Macronodular cirrhosis- Nodules > 3mm in diameter secondary to chronic viral hepatitis
The morphologic appearance of the liver may change as the liver disease progresses
Micronodular cirrhosis usually progresses to macronodular cirrhosis
Serological markers available today are more specific than morphological appearance of the liver for determining the etiology of cirrhosis
Accurate assessment of liver morphology may only be achieved at surgery, laparoscopy, or autopsy

Question 7

What are the four clinical stages of liver cirrhosis

Answer 7

Stage 1 – Absence of both varices and ascites
Stage 2 - Presence of varices without bleeding & no ascites
Stage 3 – Ascites with or without oesophageal varices
Stage 4 – Variceal bleeding with or without ascites

Stage 1 & 2 – Compensated Cirrhosis
Stage3 & 4 – Decompensated Cirrhosis

Question 8

What are the two main classifications of liver cirrhosis

Answer 8

Compensated (Complications absent) Decompensated (Complications eg.variceal haemorrhage, ascites, encephalopathy,HCC) → most deaths

Question 9

How do you diagnose liver cirrhosis

Answer 9

Most common measured laboratory test classified as LFTs include
-the enzyme tests (principally the serum aminotransferases, alkaline phosphatase, and gamma glutamyl transpeptidase), serum bilirubin
-tests of synthetic function (principally the serum albumin concentration and prothrombin time)
•Imaging Modalities - Ultrasound can suggest the presence of cirrhosis and detects complications of cirrhosis
•Liver biopsy
-Obtained by either a percutaneous, transjugular, laparoscopic, or radiographically-guided fine-needle approach
-Sensitivity - 80 to 100% not necessary if the clinical, laboratory, and radiologic data strongly suggest the presence of cirrhosis
-May reveal the underlying cause of cirrhosis

Question 10

How do you treat liver cirrhosis

Answer 10

Treat the underlying cause
Treat the complication

Question 11

What are some complications of liver cirrhosis

Answer 11

Ascites
Spontaneous Bacterial Peritonitis/ Other infections
Hepatorenal syndrome
Varices/hemorrhage
Hepatopulmonary syndrome
Other Pulmonary syndromes
Hepatic hydrothorax
Porto pulmonary HTN
Hepatic Encephalopathy
Hepatocellular carcinoma
Anaemia, thrombocytopenia and coagulopathy
Malnutrition
Cirrhotic cardiomyopathy

Question 12

What are some routine tests performed on ascitic fluid

Answer 12

Cell count and differential
Albumin concentration
Total protein concentration
Culture in blood culture bottles

Question 13

What are some optional tests to perform on ascitic fluid

Answer 13

Glucose concentration
LDH concentration
Gram stain
Amylase concentration

Question 14

How is ascites treated

Answer 14

Dietary sodium restriction
Limiting sodium intake to 88 meq (2000 mg) per day
The most successful therapeutic regimen is the combination of single morning oral doses of Spironolactone and Furosemide, beginning with 100 mg and 40 mg

Two major concerns with diuretic therapy for cirrhotic ascites:
Overly rapid removal of fluid
Progressive electrolyte imbalance

Question 15

Up to 20% of patients with cirrhotic ascites fail medical management. Why

Answer 15

Incorrect use of diuretics
Dietary sodium abuse
Hepatic Hydrothorax (do not place a chest tube or attempt pleurodesis, most cases respond to an increase in diuretics, refractory cases may require TIPS)
Hyponatremia
SBP
True refractory ascites

Question 16

What is spontaneous bacterial peritonitis (SBP)

Answer 16

Infection of ascitic fluid. The most common bacteria causing SBP are gram-negative bacteria- Escherichia coli and Klebsiella pneumoniae, gram-positive bacteria- Streptococcus pneumoniae
It usually results from a single organism (finding mixed flora on culture suggests a perforated abdominal viscus or contaminated specimen)
Almost always seen in the setting of end-stage liver disease
The diagnosis is established by
A positive ascitic fluid bacterial culture
Elevated ascitic fluid absolute polymorphonuclear leukocyte (PMN) count (>250 cells/mm3)

Question 17

What are some clinical manifestations of SBP

Answer 17

Fever
Abdominal pain
Abdominal tenderness
Altered mental status

Question 18

What is the preferred antibiotic prophylaxis for SBP

Answer 18

Norfloxacin 400mg twice a day orally for 7 days

Question 19

What is the hepatorenal syndrome

Answer 19

Acute renal failure due to advanced liver disease (Cirrhosis, Severe Alcoholic Hepatitis, Fulminant Hepatic Failure). It presents with rapid and progressive renal insufficiency. It is most commonly precipitated by SBP
It is often associated with diuretic resistant ascites

Question 20

What are the drug treatments for HRS

Answer 20

Midodrine (Selective alpha-1 adrenergic agonist, Systemic vasoconstrictor)
Octreotide (Inhibitor of endogenous vasodilator release)

Midodrine 7.5-12.5 mg tid plus octreotide 100-200 mcg tid with daily albumin infusion associated with reduced mortality in one uncontrolled trial

Question 21

HRS is characterized by

Answer 21

Oliguria
Benign urine sediment
Very low rate of sodium excretion
Progressive rise in the plasma creatinine concentration
Reduction in GFR often clinically masked
Prognosis is poor unless hepatic function improves
Nephrotoxic agents and overdiuresis can precipitate HRS

Question 22

………….. are a direct consequence of portal hypertension

Answer 22

Gastroesophageal varices

Question 23

How do you manage variceal bleeding

Answer 23

Primary Prophylaxis (Pharmacologic, Endoscopic)
Acute Variceal Hemorrhage (Pharmacologic, Endoscopic, TIPS)
Secondary Prophylaxis (Pharmacologic, Endoscopic, TIPS)

Question 24

What is the treatment for variceal bleeding

Answer 24

General Management:
IV access and fluid resuscitation
Antibiotic prophylaxis- Recommended antibiotics include oral norfloxacin, ciprofloxin, ofloxacin, and amoxicillin clavulanate, ceftriaxone IV
Correct coagulopathy
Do not overtransfuse (hemoglobin ~ 7-8 g/dL)
Empiric lactulose?

Specific therapy:
Pharmacological therapy: octreotide, vasopressin + nitroglycerin
Early endoscopic therapy: band ligation
Shunt therapy: TIPS, surgical shunt

Question 25

What are the pharmacological treatment for acute variceal hemorrhage

Answer 25

Octreotide:
50 microgram bolus and 25-50 mcg/hr for up to 5 days (range 2-5 days)
Vasopressin:
Too dangerous for empiric initial therapy
Continuous infusion 0.2-0.4 U/min up to 1.0 U/min
Recommended only in combination with i.v. TNG: 10-50 mcg/min
Titrate TNG infusion to maintain systolic BP >90 mmHg
Continuous vasopressin> 24 hr not recommended

Question 26

What are some non-pharmacological treatment of acute vacriceal hemorrhage

Answer 26

Endoscopic Band Ligation:
Gastric varices that are continuous with esophageal varices and extend along the lesser curve (GOV1) should be treated in the same way as esophageal varices
Transjugular Intrahepatic Portal-systemic Shunting (TIPS)

•Mostly Historical Interest
•Sengstaken-Blakemore Tube
•Embolization of varices
•Portacaval shunt surgery