Hepatic Encephalopathy, Hepatorenal Syndrome, Hepatopulmonary Syndrome, and Other Systemic Complications of Liver Disease Flashcards
The term hepatic encephalopathy (HE)
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.
the best- described neurotoxin involved in HE is ammonia,
which is produced primarily in the colon, where bacteria metabolize proteins and other nitrogen-based products into ammonia. Enterocytes synthesize ammonia from glutamine.
In cirrhosis and portal hypertension,
reduced hepatocyte function and portosystemic shunting contribute to increased circulating ammonia levels.
There are 3 major types of HE related to the underlying disease:
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
Blood ammonia levels may be a useful indicator
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
Treatment
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.
Treatment
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
Treatment
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.
Treatment
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
Treatment
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
Treatment
l-ornithine–l-aspartate, a salt of the amino
acids ornithine and aspartic acid that activates the urea cycle and
enhances ammonia clearance,
Baseline serum creatinine level
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.
AKI
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
Staging of AKI
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
Progression of AKI
Progression of AKI to a higher stage and/or need for renal replacement therapy
Regression
Regression of AKI to a lower stage
Diagnostic Criteria for Hepatorenal Syndrome*
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
Management of Hepatorenal Syndrome (HRS)
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 (
TREATMENT OF HRS
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
