Supplementary Table 1. Child-Turcotte-Pugh (CTP) classification of the severity of cirrhosis

Points*
1 / 2 / 3
Encephalopathy / None / Grade 1-2
(or precipitant-induced) / Grade 3-4
(or chronic)
Ascites / None / Mild/Moderate
(diuretic-responsive) / Severe
(diuretic-refractory)
Bilirubin (mg/dL) / <2 / 2-3 / >3
Albumin (g/dL) / >3.5 / 2.8-3.5 / <2.8
PT (seconds prolonged)
or INR / <4
<1.7 / 4-6
1.7-2.3 / >6
>2.3

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.

Supplementary Table 2. Primary prophylaxis of variceal hemorrhage in patients with medium or large esophageal varices

The following interventions are recommendedbased 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 isunder evaluation and cannot be recommended until additional information is available:

  • Carvedilol

Supplementary Table 3. Treatment of acute variceal hemorrhage

The following interventions are recommendedbased on randomized clinical trials, experimental studies, and meta-analyses:

  • Antibiotic 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

Emergency surgery or TIPS are not recommended as the first therapeutic option; they are recommended only as rescue therapies

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

Supplementary Table 4. Prevention of recurrent variceal hemorrhage

The following interventions are recommendedbased on randomized clinical trials and meta-analyses:

  • 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

Supplementary Table 5. Treatment of spontaneous bacterial peritonitis

The following interventions are recommendedbased on controlled trials or cohort studies demonstrating infection cure rates of around 90 %:

  • 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 Iintravenous 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)

Supplementary Table 6. Prevention of recurrent spontaneous bacterial peritonitis

The following interventions are recommendedbased 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

Supplementary Table 7. Treatment of uncomplicated ascites

The following interventions are recommendedbased 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

Supplementary Table 8. Treatment of hyponatremia

The following interventions are recommendedbased on controlled and uncontrolled studies as well as expert opinion:

  • Water restriction (1-1.5 L/day)
  • Diuretic discontinuation

The following interventions isnot recommended, based on expert opinion:

  • Hypertonic saline

The following interventions isunder evaluation for the treatment of hyponatremia

  • V2 receptor antagonists

Supplementary Table 9. Treatment of refractory ascites

The following interventions are recommendedbased 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 interventionsarenot 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)

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

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

Supplementary Table 12. Treatment of persistent hepatic encephalopathy

The following interventions are recommendedbased on clinical trials, and expert opinion.

  • Lactulose
  • Antibiotics such as rifaximin may be considered in patients who have failed to respond adequately to lactulose therapyRifaximin in patients intolerant to lactulose

The following interventionsarenot recommended based on expert opinion:

  • Long-term protein restriction
  • Combination therapy with rifaximin plus lactulose

The following intervention isunder evaluation and cannot be recommended until additional information is available:

  • Probiotics

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

Autoimmune hepatitis

Alpha-1 antitrypsin deficiency

DNA, deoxyribonucleic acid; HCC, hepatocellular carcinoma; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus.

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