Cirrhosis and Liver Failure

Question 1

Cirrhosis

Answer 1

Late stage of progressive hepatic fibrosis

Characterized histologically by regenerative nodules surrounded by fibrous tissue

Generally irreversible

Question 2

Two types of cirrhosis

Answer 2

Compensated (no complications)

Decompensated (complications)

Question 3

Complications of Cirrhosis

Answer 3

Portal hypertension- leads to variceal hemorrhage, ascites, and encephalopathy

Liver insufficiency- encephalopathy, jaundice

Question 4

Etiologies of Cirrhosis

Answer 4

Viral
Alcoholic liver disease*
Autoimmune
Metabolic
Vascular
Non-alcoholic fatty liver disease

Question 5

What lab values should make you suspicious for cirrhosis?

Answer 5

Liver insufficiency:
Low albumin ( 1.3)
High bilirubin (> 1.5 mg/dL)

Portal hypertension:
Low platelet count (

Question 6

What imaging findings are suspicious for cirrhosis?

Answer 6

Imaging studies (CT/US/MRI):
Nodular liver
Caudate hypertrophy
Ascites
Splenomegaly
Venous collaterals
Hepatocellular carcinoma

Question 7

Model for End-Stage Liver Disease (MELD) Score

Answer 7

Mathematical survival model created from data on patients undergoing TIPS

MELD score estimates risk of 3-month mortality

Uses 3 laboratory values

- Serum total bilirubin
- Serum creatinine
- INR

Highest MELD score priority for transplant

Question 8

Calculating MELD Scores

Answer 8

6. 4 + 9.8 x log (INR) +
7. 2 x log (Cr) +
8. 8 x log (Bilirubin)

Question 9

Mechanisms of Portal Hypertension and which one is predominantly responsible for portal hypertension in cirrhosis?

Answer 9

Portal hypertension can result from:
increase in resistance to portal flow and/or
increase in portal venous inflow (Splanchnic vasodilation (increased nitric oxide))

Increased intrahepatic resistance is the initial mechanism leading to portal hypertension

Question 10

What is the site of increased resistance in cirrhosis?

Answer 10

Sinusoidal

Question 11

What are the two main things that lead to increased resistance in cirrhosis?

Answer 11

Increased intrahepatic resistance in cirrhosis is not only structural (sinusoidal fibrosis and regenerative nodules) but also functional (active vasoconstriction)

Question 12

In Portal Hypertension, what causes Splanchnic Vasodilation?

Answer 12

Increase in NO

Question 13

NO in cirrhosis

Answer 13

In Cirrhosis, Nitric Oxide (NO) Activity is Reduced and Vasoconstrictors (VC) are Increased

Question 14

What is the safest and most reproducible method to measure portal pressure?

Answer 14

measurement of the hepatic venous pressure gradient (HVPG)

Question 15

Hepatic venous pressure gradient (HVPG)

Answer 15

obtained by subtracting the free hepatic venous pressure (FHVP) from the wedged hepatic venous pressure (WHVP)

HVPG = WHVP - FHVP

Question 16

HVPG findings

Answer 16

Normal HVPG is 3-5 mmHg
HVPG is Normal in Presinusoidal Portal Hypertension
HVPG is Increased in Sinusoidal Portal Hypertension
HVPG is Increased in Post-Sinusoidal Portal Hypertension
HVPG is Normal in Post-Hepatic Portal Hypertension

Question 17

Predictors of vericeal hemorrhage

Answer 17

Variceal size (bigger more likely to bleed)
Red signs
Child B/C (measure of disease severity)

Question 18

How to reduced the Risk of Variceal Rupture

Answer 18

Decrease portal pressure, decreases transmural pressure and decreases wall tension

Question 19

Treatment for variceal bleed

Answer 19

Endoscopic variceal band ligation:
Bleeding controlled in 90%
Rebleeding rate 30%

Compared with sclerotherapy:
Less rebleeding
Lower mortality
Fewer complications
Fewer treatment sessions

Question 20

Transjugular Intrahepatic Portosystemic Shunt

Answer 20

(TIPS)

Done by interventional radiologists
Creates new communication for blood to flow through, bypassing the liver
Reduces the pressure

Good for variceal bleeding that can’t be fixed endoscopically

Done to manage refractory ascites

If on transplant list and have coagulation can use this

Complications: portal-systemic encephalopathy and liver failure.

Question 21

What to do for a pt with a variceal bleed due to liver failure

Answer 21

Immediately give a vasoconstrictors (e.g., octreotide*)

and call GI for endoscopy

Question 22

Octreotide

Answer 22

A vasoconstrictor that decreases splanchnic flow, slightly increases intraheptaic resistance and decreases portal pressure

Question 23

What is the Most Common Cause of Ascites?

Answer 23

cirrhosis (80%)

Question 24

Mechanism of ascites development

Answer 24

Result from an Increase in Nitric Oxide, leading to vasodialtion, decreased systemic vascular resistance, activation of RAAS system, Na2+ and H2O retention and ascites

Question 25

Natural History of Ascites

Answer 25

Portal Hypertension- No Ascites Uncomplicated Ascites Refractory Ascites Hepatorenal Syndrome

Question 26

What is the Most Sensitive Method to Detect Ascites?

Answer 26

Ultrasound

Question 27

Initial Workup of Ascites

Answer 27

Diagnostic Paracentesis: PMN count Culture Protien/albumin

Question 28

Serum-Ascites Albumin Gradient (SAAG) calculation

Answer 28

serum albumin minus ascites albumin (should be drawn at the same time)

Question 29

SAAG

Answer 29

correlates with sinusoidal pressure >1.1 SAAG The cutoffs for SAAG and ascites protein levels are 1.1 g/dL and 2.5 g/dL respectively. Cirrhotic ascites is typically high SAAG and low protein; cardiac ascites is high SAAG and high protein; and ascites secondary to peritoneal malignancy is typically low SAAG and high protein.

Question 30

Therapies for ascites

Answer 30

Salt restriction and Diuretics Large volume paracentesis TIPS (if refractory and low MELD score)

Question 31

Refractory Ascites

Answer 31

Occurs in ~10% of cirrhotic patients Diuretic-intractable ascites (80%): Therapeutic doses of diuretics cannot be achieved because of diuretic-induced complications Diuretic-resistant ascites (20%): No response to maximal diuretic therapy (400 mg spironolactone + 160 mg furosemide/day)

Question 32

Hepatorenal Syndrome

Answer 32

Renal failure in patients with cirrhosis, advanced liver failure and severe sinusoidal portal hypertension Absence of significant histological changes in the kidney (“functional” renal failure) Marked arteriolar vasodilation in the extra-renal circulation Marked renal vasoconstriction leading to reduced glomerular filtration rate Besides renal failure, patients with HRS have sodium and water retention Ascites is universal in patients with HRS. If ascites is absent, renal failure is more likely due to other causes Hyponatremia is almost universal in HRS. If serum sodium is normal, diagnosis of HRS is unlikely

Question 33

Types of Hepatorenal Syndrome

Answer 33

Type 1 Rapidly progressive renal failure (2 weeks) Doubling of creatinine to >2.5 or halving of creatinine clearance (CrCl) to 1.5 mg/dL or CrCl

Question 34

Major Criteria in the Diagnosis of Hepatorenal Syndrome

Answer 34

Advanced hepatic failure and portal hypertension Creatinine > 1.5 mg/dL or creatinine clearance

Question 35

Management of Hepatorenal Syndrome

Answer 35

Proven efficacy: Liver transplantation ``` Under investigation: Vasoconstrictor + albumin Transjugular intrahepatic portosystemic shunt (TIPS) Vasoconstrictor (Terlipressin) Extracorporeal albumin dialysis (ECAD) ``` Ineffective: Renal vasodilators (prostaglandin, dopamine) Hemodialysis

Question 36

Spontaneous bacterial peritonitis and hepatorenal syndrome

Answer 36

Spontaneous Bacterial Peritonitis (SBP) Complicates Ascites and Can Lead to Renal Dysfunction

Question 37

What is the Most Common Infection in Cirrhotic Patients? and what's the mechanism?

Answer 37

Spontaneous Bacterial Peritonitis (SBP) Bacterial translocation-migration of viable microorganisms from the intestinal lumen to mesenteric lymph nodes and other extraintestinal organs and sites

Question 38

Mechanisms of Bacterial Translocation

Answer 38

1. Intestinal Bacterial Overgrowth- Dysmotility Delayed transit time 2. Intestinal Permeability- Mucosal Hypoxia, Acidosis ATP depletion, NO, LPS, TNF 3. Impaired Immunity- Impaired chemotaxis, migration, phagocytic function, complement deficiency, etc.

Question 39

Microorganisms in SBP and treatment

Answer 39

Gram negative bacilli (72%) cephalosporins NO aminoglycosides

Question 40

Recurrence of Spontaneous Bacterial Peritonitis

Answer 40

Common!! 70% chance of developing another episode within the first year So prophylaxis

Question 41

Hepatic Encephalopathy

Answer 41

Neuropsychiatric complication of cirrhosis Ammonia is the culprit ``` Results of both: Portosystemic shunt (spontaneous, surgical or radiographic) and Chronic liver failure ``` Failure to metabolize neurotoxic substances Hyperammonemia results in glutamine accumulation Alterations of astrocyte morphology and function (Alzheimer type II astrocytosis) Astrocytes only cells in brain that can metabolize ammonia

Question 42

How to diagnose hepatic encephalopathy

Answer 42

Clinical diagnosis ``` Clinical findings and history important Ammonia levels are unreliable Ammonia has poor correlation with diagnosis Measurement of ammonia not necessary Number connection test Slow dominant rhythm on EEG ```

Question 43

Treatment for encephalopathy

Answer 43

``` Identify and treat precipitating factor: Infection GI hemorrhage Prerenal azotemia Sedatives Constipation ``` lactulose or antibiotics (kill bacteria that produce ammonia) Adjustment in dietary protein (short-term if at all)

Question 44

Hepatic Encephalopathy Precipitants

Answer 44

``` Excess protein TIPS Infections Sedatives/hypnotics Diuretics GI bleeding ```