Pharmacotherapy of cirrhosis

Overview ㅡ 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 figure 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.

Figure (1)

Child–Pugh classification system.

Pharmacotherapy

Pharmacotherapy for complications of cirrhosis involves various medications tailored to specific clinical conditions. For ascites, spironolactone (Aldactone) is prescribed at 100–400 mg daily, targeting hyperaldosteronism, a primary cause of ascites formation. Furosemide (Lasix), at 40–100 mg daily, aids in additional fluid removal, mainly from vascular and peripheral areas, while maintaining potassium balance in a 100:40 mg ratio with spironolactone. Albumin 20% is administered at 8 g/L of fluid removed via paracentesis, but only if 5 liters or more is removed.

In hepatic encephalopathy (HE), lactulose (Duphalac) is given at 15–45 mL three times daily, titrated to achieve 3–4 soft bowel movements daily. Rifaximin (Gastrobiotic), at 400 mg three times daily, is considered for those intolerant to lactulose, with a maximum dosage of 1,200 mg/day. Ammonia levels do not correlate with impairment severity; thus, patient symptoms should guide treatment.

For hepatorenal syndrome (HRS), albumin 20% is administered at 1 g/kg on day one, followed by 20–40 g/day. Midodrine is dosed at 5–7.5 mg three times daily, up to 12.5 mg TID, while octreotide (Sandostatin) is given at 100 μg subcutaneously three times daily, up to 200 μg TID. Treatment should be discontinued if serum albumin levels reach 4.5 g/L or higher.

Portal hypertension management involves propranolol (Inderal) at 10 mg twice daily, up to 80 mg/day, or nadolol at 20 mg daily, up to 160 mg daily. The goal is to reduce heart rate by 25% or to 55–60 BPM, a noninvasive marker for portal hypertension. Medications should be initiated at low doses and titrated slowly due to baseline low blood pressure in cirrhotic patients.

Spontaneous bacterial peritonitis (SBP) is treated with cefotaxime (Cefotax) at 2 g IV every 8 hours, ceftriaxone (Rocephin) at 1 g IV every 12 hours or 2 g every 24 hours, or piperacillin/tazobactam (Tazocin) at 4.5 g IV every 6 hours. Albumin 20% is given at 1.5 g/kg on day one and 1 g/kg on day three, reducing the incidence of HRS in SBP patients. Pathogens typically include Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae.

For long-term SBP prophylaxis, ciprofloxacin (Ciprofar) is dosed at 750 mg weekly, or trimethoprim/sulfamethoxazole (Septrin DS) is given as one tablet five times per week. This regimen decreases mortality in patients with a prior SBP episode, with daily versus intermittent therapy being preferred due to resistance concerns.

In cases of variceal bleeding, octreotide (Sandostatin) is administered at 50–100 mg IV bolus, followed by a continuous infusion of 25–50 mg/hour. Treatment duration is controversial but should continue at least 24 hours post-variceal banding, with some recommending up to five days. Prophylactic antibiotics are recommended during acute variceal bleeding, irrespective of ascites presence.

References

• Cirrhosis - Symptoms, Diagnosis and Treatment | BMJ Best Practice (bestpractice.bmj.com, 2020). Available at: https://bestpractice.bmj.com/topics/en-gb/278?q=Cirrhosis&c=suggested

  S. Ge P, 'Treatment of Patients with Cirrhosis | NEJM' (New England Journal of Medicine, 2016). Available at: https://www.nejm.org/doi/full/10.1056/nejmra1504367