1
Supplementary Table 1. Child-Turcotte-Pugh (CTP) classification of the severity of cirrhosis
Encephalopathy
1
None
Ascites
None
Points*
2
3
Grade 1-2
Grade 3-4
(or precipitant(or chronic)
induced)
Mild/Moderate
Severe
(diuretic-responsive)
(diuretic-refractory)
2-3
>3
2.8-3.5
<2.8
4-6
>6
1.7-2.3
>2.3
Bilirubin (mg/dL)
<2
Albumin (g/dL)
>3.5
PT
(seconds
<4
prolonged)
<1.7
or INR
PT=Prothrombin time; INR=international normalized ratio.
* 5-6 points= CTP class A; 7-9 points = CTP class B; 10-15 points = CTP class C.
2
Supplementary Table 2. Primary prophylaxis of variceal hemorrhage in patients with
medium or large esophageal varices
The following interventions are recommended based on RCTs demonstrating delay in time to
first variceal hemorrhage:
 Nonselective -blockers (propranolol, nadolol) or
 Endoscopic variceal ligation (EVL)
The following interventions are not recommended based on RCTs demonstrating that other
interventions are either more effective or safer:
 Nitrates alone
 Endoscopic sclerotherapy
 Shunt surgery/TIPS
 Combination NSBB/EVL
 Combination NSBB/nitrates
 Combination NSBB/diuretics
The following interventions is under evaluation and cannot be recommended until additional
information is available:
 Carvedilol
3
Supplementary Table 3. Treatment of acute variceal hemorrhage
The following interventions are recommended based on randomized clinical trials,
experimental studies, and meta-analyses:
 Short-term antibiotic prophylaxis
 Conservative blood replacement (target hemoglobin ~8 g/dl)
 Diagnostic endoscopy within 12 hours of admission
 Combination pharmacological and endoscopic therapy if variceal source is confirmed
 In case of failure to control bleeding or early rebleeding, a prompt decision for rescue
therapy should be made (no more than two sessions of endoscopic therapy)
 Rescue therapies: TIPS or shunt surgery
The following interventions are not recommended based on randomized clinical trials or
uncontrolled studies demonstrating that other interventions are either more effective or safer:
 Recombinant Factor VIIa
 Balloon tamponade should be used only as a bridge to rescue therapy
The following interventions are under evaluation and cannot be recommended until additional
information is available:
 Early TIPS placement (within 24-48 hours) in high-risk patients
 Esophageal stenting as a temporizing measure in intractable bleeding
4
Supplementary Table 4. Prevention of recurrent variceal hemorrhage
The following interventions are recommended based on randomized clinical trials and metaanalyses:
 Nonselective -blockers (propranolol, nadolol) plus endoscopic variceal ligation
 Nonselective -blockers plus nitrates (e.g. isosorbide mononitrate)
 Rescue therapies: TIPS or shunt surgery
The following interventions are not recommended based on clinical trials demonstrating that
other interventions are either more effective or safer:
 Nonselective -blockers alone
 Sclerotherapy
 EVL alone
 EVL plus sclerotherapy
5
Supplementary Table 5. Treatment of spontaneous bacterial peritonitis
The following interventions are recommended based on controlled trials or cohort studies
 Intravenous cefotaxime or other third-generation cephalosporins such as ceftriaxone
for a duration of 5 to 8 days
 Intravenous ampicillin/sulbactam is an alternative
 In patients with community-acquired SBP, no renal dysfunction, no encephalopathy,
and a low prevalence of quinolone-resistant organisms, an orally administered widely
bioavailable quinolone (ciprofloxacin, levofloxacin) is an alternative
 In patients with nosocomial (hospital-acquired) SBP, the use of extended spectrum
antibiotics (e.g. carbapenems, piperacillin/tazobactam) as initial empirical therapy
should be considered
 Concomitant (to antibiotics) use of intravenous albumin in patients with high risk of
developing renal dysfunction (bilirubin >4 mg/dL, BUN >30 mg/dL or creatinine
>1.0 mg/dL)
The following interventions are not recommended based on clinical trials, uncontrolled studies
demonstrating that other interventions are either more effective or safer, as well as theoretical
considerations:


Aminoglycoside-containing antibiotic combinations
Procedures and medications that will decrease intravascular effective volume (e.g.,
large volume paracentesis, diuretics)
6
Supplementary Table 6. Prevention of recurrent spontaneous bacterial peritonitis
The following interventions are recommended based on randomized clinical trials or expert
opinion:
 Oral norfloxacin at a dose of 400 mg q.d. (not on VA National Formulary)
 Oral ciprofloxacin or levofloxacin at a dose of 250 mg q.d. (empirical dose)
 Oral trimethoprim/sulfamethoxazole
The following intervention is not recommended based on clinical trials or uncontrolled studies
demonstrating that other interventions are either more effective or safer:
 Weekly administration of quinolones
7
Supplementary Table 7. Treatment of uncomplicated ascites
The following interventions are recommended based on controlled and uncontrolled studies as
well as expert opinion:
 Salt restriction
 Spironolactone with or without furosemide
 Large-volume paracentesis plus albumin in hospitalized patients with tense ascites in
whom other complications have been resolved
 Antibiotic prophylaxis in high-risk patients (see text)
The following interventions are not recommended, based on clinical trials demonstrating that
other measures are either more effective or safe as well as expert opinion:
 Furosemide alone
 Intravenous diuretics
The following interventions are under evaluation for the treatment of uncomplicated ascites
 Clonidine
 V2 receptor antagonists
8
Supplementary Table 8. Treatment of hyponatremia
The following interventions are recommended based on controlled and uncontrolled studies as
well as expert opinion:
 Water restriction (1-1.5 L/day)
 Diuretic discontinuation
The following interventions is not recommended, based on expert opinion:
 Hypertonic saline
The following interventions is under evaluation for the treatment of hyponatremia
 V2 receptor antagonists
9
Supplementary Table 9. Treatment of refractory ascites
The following interventions are recommended based on randomized controlled studies:
 LVP plus albumin, associated with salt restriction and diuretics
 In patients in whom <5 L is extracted, plasma volume expansion may not be
necessary
 In patients requiring frequent LVP, TIPS is an option
 In patients requiring frequent LVP, who are not TIPS or transplant candidates, PVS is
an option
The following interventions are not recommended based on controlled clinical trials
demonstrating that other interventions are either more effective or safer:
 PVS or TIPS as first-line therapy
 TIPS in patients with serum bilirubin > 3 mg/dL, a CTP score > 11, age > 70 years, or
evidence of heart failure
The following interventions are under evaluation for the treatment of refractory ascites
 Clonidine
 V2-receptor antagonists
 Vasoconstrictors (midodrine, terlipressin)
10
Supplementary Table 10. Treatment of hepatorenal syndrome
The following interventions are recommended based on clinical trials and expert opinion
 Liver transplant
 Systemic vasoconstrictors plus albumin
The following interventions are not recommended based on clinical trials demonstrating a lack
of benefit compared to no therapy or placebo therapy
 Octreotide alone
 Prostaglandins
 Dopamine
 Dialysis
The following interventions are under evaluation and cannot be recommended until additional
information is available:
 TIPS
 MARS
11
Supplementay Table 11. Treatment of episodic hepatic encephalopathy
The following interventions are recommended based on clinical trials and expert opinion
 Identification and treatment of precipitating event
 Lactulose (oral or by enema)
 Rifaximin in patients intolerant to lactulose
The following interventions are under evaluation and cannot be recommended until additional
information is available:
 Flumazenil, ornithine aspartate, bromocriptine
 Extracorporeal albumin dialysis
12
Supplementary Table 12. Treatment of persistent hepatic encephalopathy
The following interventions are recommended based on clinical trials, and expert opinion.
 Lactulose
 Rifaximin in patients intolerant to lactulose
The following interventions are not recommended based on expert opinion:
 Long-term protein restriction
 Combination therapy with rifaximin plus lactulose
The following intervention is under evaluation and cannot be recommended until additional
information is available:
 Probiotics
13
Supplementary Table 13. Patients in Whom HCC Surveillance is Recommended [244]
Hepatitis B carriers (HBsAg-positive patients)
Asian males  40 years
Asian females  50 years
All cirrhotic hepatitis B carriers (HBsAg-positive)
Family history of HCC
Africans over age 20
Other non-cirrhotic hepatitis B carriers – risk of HCC varies based on severity of underlying
disease, current and past inflammatory activity, and HBV DNA level
Non-HBV cirrhosis
Hepatitis C
Alcoholic cirrhosis
Genetic hemochromatosis
Primary biliary cirrhosis
Non-alcoholic steatohepatitis
Surveillance is recommended even though
Autoimmune hepatitis
data is lacking on its benefit
Alpha-1 antitrypsin deficiency
DNA, deoxyribonucleic acid; HCC, hepatocellular carcinoma; HBsAg, hepatitis B surface
antigen; HBV, hepatitis B virus.
14
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