Hepatic Encephalopathy, Hepatorenal Syndrome, Hepatopulmonary Syndrome, and Other Systemic Complications of Liver Disease

Question 1

The term hepatic encephalopathy (HE)

Answer 1

encompasses a wide array of transient and subtle reversible neurologic and psychiatric manifestations usually found in patients with chronic liver dis- ease and portal hypertension, but also seen in patients with ALF.

Question 2

the best- described neurotoxin involved in HE is ammonia,

Answer 2

which is produced primarily in the colon, where bacteria metabolize proteins and other nitrogen-based products into ammonia. Enterocytes synthesize ammonia from glutamine.

Question 3

In cirrhosis and portal hypertension,

Answer 3

reduced hepatocyte function and portosystemic shunting contribute to increased circulating ammonia levels.

Question 4

There are 3 major types of HE related to the underlying disease:

Answer 4

type A, associated with ALF;
type B, associated with portosystemic shunts in the absence of liver disease;

type C, associated with chronic and end-stage liver dis- ease and portal hypertension

Type C HE is the most common type and has historically been graded from 0 to 4 based on the West Haven criteria

Question 5

Blood ammonia levels may be a useful indicator

Answer 5

of HE in the absence of cirrhosis and portal hypertension, seen in patients with metabolic disorders that influence ammonia generation or metabolism, such as urea cycle disorders and disorders of proline metabolism

Question 6

Treatment

Answer 6

Nonabsorbable disaccharides have been the cornerstone of the treatment of HE.

Oral lactulose or lactitol (the latter is not available in the USA) are metabolized by colonic bacteria to byproducts that appear to have beneficial effects by causing catharsis and reducing intestinal pH, thereby inhibiting ammonia absorption.

Question 7

Treatment

Answer 7

Oral antibiotics have also been used to treat HE, with the aim of modifying the intestinal flora and lowering stool pH to enhance the excretion of ammonia.

Antibiotics are generally used as second-line agents after lactulose or in patients who are intolerant of nonabsorbable disaccharides.

Rifaximin given orally in a dose of 550 mg twice daily was approved in 2010 for the treatment of chronic HE and reduction in the risk of recurrence of overt HE in patients with advanced liver disease

Question 8

Treatment

Answer 8

Acarbose, an intestinal α-glucosidase inhibitor used to treat type 2 diabetes mellitus, inhibits the intestinal absorption of carbohydrates and glucose and results in their enhanced delivery to the colon.

As a result, the ratio of saccharolytic to proteolytic bacterial flora is increased, and blood ammonia levels are decreased.

Question 9

Treatment

Answer 9

Administration
of zinc, which has been used because zinc deficiency is common
in patients with cirrhosis and because zinc increases the activity of ornithine transcarbamylase, an enzyme in the urea cycle,
may also improve HE;

however, clear efficacy has not been established

Question 10

Treatment

Answer 10

Extracorporeal albumin dialysis using the molecular
adsorbent recirculating system (MARS) has resulted in a reduction in blood ammonia levels and improvement in severe HE
in patients with acute-on-chronic liver failure

Question 11

Treatment

Answer 11

l-ornithine–l-aspartate, a salt of the amino
acids ornithine and aspartic acid that activates the urea cycle and
enhances ammonia clearance,

Question 12

Baseline serum creatinine level

Answer 12

A value obtained in the previous 3 months can be used as baseline; however, in patients with multiple values in previous 3 months the value closest to the admission creatinine should be used.
In patients without a previous serum creatinine determination, the admission value should be used as the baseline.

Question 13

AKI

Answer 13

A 50% increase in the serum creatinine level from baseline that is known or presumed to have occurred within the 7 days prior
OR
A rise of 0.3 mg/dL (26.4 μmol/L) in the serum creatinine level in <48 hr

Question 14

Staging of AKI

Answer 14

Stage 1: A rise in the serum creatinine level of 0.3 mg/dL (26.4 μmol/L) or an increase in serum creatinine ≥1.5-fold to 2-fold above baseline
Stage 2: A rise in the serum creatinine level of >2-fold to 3-fold above baseline
Stage 3: A rise in the serum creatinine level of >3-fold above baseline or a serum creatinine level of 4 mg/dL (353.6 μmol/L)
with an acute increase of ≥0.3 mg/dL (26.4 μmol/L) or initiation of renal replacement therapy

Question 15

Progression of AKI

Answer 15

Progression of AKI to a higher stage and/or need for renal replacement therapy

Regression
Regression of AKI to a lower stage

Question 16

Diagnostic Criteria for Hepatorenal Syndrome*

Answer 16

Cirrhosis with ascites

Diagnosis of AKI according to International Club of Ascites-AKI criteria

No or insufficient response in 48 hr after diuretic withdrawal and adequate volume expansion with IV albumin

Absence of shock

No evidence of recent use of nephrotoxic agents

Absence of intrinsic renal disease

Question 17

Management of Hepatorenal Syndrome (HRS)

Answer 17

PREVENT VARICEAL BLEEDING:
Measures to prevent variceal bleeding (e.g., β-receptor blocking agent, band ligation)
Pentoxifylline for severe alcohol-associated hepatitis
Prevention of HRS
Avoidance of intravascular volume depletion (diuretics, lactulose, GI bleeding, large-volume paracentesis without adequate volume repletion)
Judicious management of nephrotoxins (ACEIs, ARBs, NSAIDs, antibiotics)
Prompt diagnosis and treatment of infections (SBP, sepsis) SBP prophylaxis (

Question 18

TREATMENT OF HRS

Answer 18

Discontinuation of all nephrotoxic agents (ACEIs, ARBs, NSAIDs, diuretics)
Antibiotics for infections
IV albumin—bolus of 1 g/kg/day on presentation (maximum dose,
100 g daily). Continue at a dose of 20-60 g daily as required to maintain the central venous pressure between 10 and 15 cm H2O
Vasopressor therapy (in addition to albumin): Terlipressin*—start at 1 mg IV every 4 hr and increase up to
2 mg IV every 4 hr if the baseline serum creatinine level does not improve by 25% at day 3 of therapy
OR
Midodrine and octreotide—begin midodrine at 2.5-5 mg orally 3
times daily and increase to a maximum dose of 15 mg 3 times daily. Titrate to an MAP increase of at least 15 mm Hg; begin octreotide at 100 μg subcutaneously 3 times daily and in- crease to a maximum dose of 200 μg subcutaneously 3 times daily, or begin octreotide with a 25 μg IV bolus and continue at a rate of 25 μg/hr
OR
Norepinephrine—0.1-0.7 μg/kg/min as an IV infusion. Increase by 0.05 μg/kg/min every 4 hr and titrate to an MAP increase of at least 10 mm Hg
The duration of vasopressor treatment is generally a maximum of 2 weeks until HRS reverses or LT is performed
Evaluation of patient for LT