Pharmacotherapy of cirrhosis

byAbdelwahab Ward, BS Pharm, PharmD - last updated
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Overview ã…¡ Cirrhosis is defined as diffuse injury to liver characterized by destruction of hepatocytes and their replacement by fibrous tissue. Typically, the disease develops slowly over months or years. Early on, there are often no symptoms. As the disease worsens, a person may become tired, weak, itchy, have swelling in the lower legs, develop yellow skin (elevated bilirubin), bruise easily, have fluid buildup in the abdomen, or develop spider-like blood vessels on the skin. The fluid build-up in the abdomen may become spontaneously infected. Other serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus or dilated stomach veins, and liver cancer. Hepatic encephalopathy results in confusion and may lead to unconsciousness.

     Pathophysiology. Elevation of portal blood pressure because of fibrotic changes within hepatic sinusoids, changes in levels of vasodilatory and vasoconstrictor mediators, and increase in blood flow to splanchnic vasculature. Resistance to blood flow contributes to portal hypertension and the development of varices, ascites, hepatic encephalopathy (HE), and coagulopathy. Portal hypertension characterized by...
  1. Hypervolemia
  2. Increased cardiac index
  3. Hypotension
  4. Decreased systemic vascular resistance

DIAGNOSIS

Means of confirmation and diagnosis. Child–Pugh classification system to assess and define severity of cirrhosis (see Table 1). 

Laboratory tests. Routine liver function tests include alkaline phosphatase, bilirubin, aspartate transaminase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (GGT), albumin and prothrombin time (PT). Complete blood count (CBC), thrombocytopenia relatively common feature in chronic liver disease. 

Table (1). Child-Pugh Score
Component Score Given for Observed Findings
1 2 3
Encephalopathy grade None 1 to 2 3 to 4
Ascites None Mild or controlled by diuretics Moderate or refractory despite diuretics
Albumin (g/dL) > 3.5 2.8 to 3.5 < 2.8
Total bilirubin (mg/dL) < 2 (< 34 micromoles/L) 2 to 3 (34 to 50 micromoles/L) > 3 (> 50 micromoles/L)
ـــــ or
Modified total bilirubin < 4 4 to 7 > 7
Prothrombin time (seconds prolonged) < 4 4 to 6 > 6
ـــــ or
INR < 1.7 1.7 to 2.3 > 2.3
Child-Pugh Classification
 Class A (mild hepatic impairment): Score 5 to 6
Class B (moderate hepatic impairment): Score 7 to 9
Class C (severe hepatic impairment): Score 10 to 15

PHARMACOTHERAPY

Table (2). Pharmacotherapy for complications of cirrhosis
Clinical condition Pharmacotherapy Comments
Ascites
  • Spironolactone (Aldactone) 100–400 mg daily
  • Furosemide (Lasix) 40–100 mg daily
  • Albumin 20% 8 g/L of fluid removed via paracentesis
 Spironolactone directly targets hyperaldosteronism; one of the primary causes of ascites formation

Furosemide used for additional fluid removal; preferentially decreases vascular/peripheral fluid vs. peritoneal fluid; use caution with intravascular volume depletion

Ratio of 100:40 mg spironolactone; furosemide helps maintain potassium balance

Only give albumin, if ≥ 5 L fluid removed via paracentesis
Hepatic encephalopathy (HE)
  • Lactulose (Duphalac) 15–45 mL TID up to every 1–2 hr
  • Rifaximin (Gastrobiotic) 400 mg TID; max 1,200 mg/day
 Titrate lactulose to 3–4 soft bowel movements/day or as tolerated by patient

Ammonia levels do not correlate with level of impairment; assess patient symptoms

Consider rifaximin in those refractory to or intolerant of lactulose
Hepatorenal syndrome (HRS)
  • Albumin 20% 1 g/kg day 1; then 20–40 g/day
  • Midodrine 5–7.5 mg TID up to 12.5 mg TID
  • Octreotide (Sandostatin) 100 μg subcutaneous TID up to 200 μg TID
 Discontinue if ≥ 4.5 g/L serum albumin
Portal hypertension
  • Propranolol (Inderal) 10 mg BID up to 80 mg/day
  • Nadolol 20 mg daily up to 160 mg daily
 Decrease risk of variceal bleeding secondary to portal hypertension

Goal: Decrease HR by 25% or to 55–60 BPM (noninvasive surrogate marker for portal hypertension)

Initiate at low doses and titrate slowly; cirrhotic patients often have low BP at baseline
Spontaneous bacterial peritonitis (SBP)
  • Cefotaxime (Cefotax) 2 g IV every 8 hr
  • Ceftriaxone (Rocephin) 1 g IV every 12 hr or 2 g every 24 hr
  • Piperacillin/tazobactam (Tazocin) 4.5 g IV every 6 hr
  • Albumin 20% 1.5 g/kg on day 1; 1 g/kg day 3
 Primarily Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae

Alternative prophylactic ceftriaxone dose during variceal bleeding is 1 g IV daily

Albumin decreases incidence of HRS in patients with SBP
Long-term SBP prophylaxis
  • Ciprofloxacin (Ciprofar) 750 mg every week
  • Trimethoprim/sulfamethoxazole (Septrin DS) 1 tab 5 doses per week (Monday through Friday)
 Decreases mortality in those with prior episode of SBP

Daily vs. intermittent therapy may be preferred due to resistance concerns
Variceal bleeding Octreotide (Sandostatin) 50–100 mg IV bolus, then 25–50 mg/hr continuous infusion Duration controversial; continue at least 24 h after banding of varices; some recommend 5 days total

Prophylactic antibiotics recommended during acute variceal bleeding with or without ascites

REFERENCES

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