What is the management of Hepatitis C (HCV) related decompensated liver cirrhosis?

From the Guidelines

Management of decompensated liver cirrhosis due to hepatitis C requires prompt antiviral therapy with direct-acting antivirals (DAAs) along with comprehensive supportive care, with the preferred regimen being sofosbuvir/velpatasvir (Epclusa) 400mg/100mg once daily for 12 weeks, as recommended by the most recent guidelines 1. The choice of antiviral therapy is crucial in these patients, and the use of protease inhibitors is contraindicated in patients with decompensated cirrhosis or with prior episodes of decompensation, due to substantially higher drug exposure and risk of toxicity 1. Some key points to consider in the management of these patients include:

• The fixed-dose combination of sofosbuvir and velpatasvir is the treatment of choice for patients with decompensated (Child-Pugh B or C) cirrhosis or with compensated (Child-Pugh A) cirrhosis with prior episodes of decompensation 1.
• For patients with genotype 3 HCV, adding ribavirin (weight-based dosing: 1000mg daily if <75kg or 1200mg daily if >75kg, divided twice daily) may be beneficial, though ribavirin requires careful monitoring due to potential anemia in these fragile patients 1.
• Beyond antiviral therapy, management includes diuretics for ascites (spironolactone 100-400mg daily with furosemide 40-160mg daily), prophylactic antibiotics for spontaneous bacterial peritonitis prevention (norfloxacin 400mg daily), beta-blockers for varices (propranolol 20-40mg twice daily or nadolol 20-40mg daily), and lactulose for hepatic encephalopathy (15-30ml three times daily, titrated to 2-3 soft bowel movements daily).
• Patients should be evaluated for liver transplantation concurrently with HCV treatment, as achieving sustained virologic response may improve liver function but won't always reverse advanced cirrhosis 1.
• Regular monitoring of liver function tests, complete blood count, and renal function is essential during treatment, with close follow-up for complications 1.

From the FDA Drug Label

No dosage adjustment of ledipasvir and sofosbuvir is recommended for patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, or C) [see Dosage and Administration (2.3), Clinical Pharmacology (12.3) and Clinical Studies (14. 5)]. Clinical and hepatic laboratory monitoring, as clinically indicated, is recommended for patients with decompensated cirrhosis receiving treatment with ledipasvir and sofosbuvir and ribavirin [see Adverse Reactions (6.1)].

The management of hepatitis C decompensated liver cirrhosis with ledipasvir and sofosbuvir does not require a dosage adjustment for patients with severe hepatic impairment (Child-Pugh Class C). However, clinical and hepatic laboratory monitoring is recommended for patients with decompensated cirrhosis receiving treatment with ledipasvir and sofosbuvir and ribavirin.

• Key points:
  • No dosage adjustment is needed for severe hepatic impairment
  • Clinical and hepatic laboratory monitoring is recommended
  • Patients with decompensated cirrhosis should be closely monitored 2

From the Research

Management of Hepatitis C Decompensated Liver Cirrhosis

• The management of hepatitis C virus (HCV) infection in patients with decompensated cirrhosis has evolved dramatically over the past few years mainly due to the availability of all-oral antiviral regimens 3.
• HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients 4.
• Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin 4.

Treatment Options

• The combinations of ledipasvir/sofosbuvir/ribavirin for 12 weeks, or daclatasvir/sofosbuvir/ribavirin for 12 weeks are safe and effective for HCV genotype 1 or 4 infection, and daclatasvir/sofosbuvir/ribavirin for 12 weeks or sofosbuvir/ribavirin for 24 weeks might be effective and safe for HCV genotype 2 or 3 infection 5.
• Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns 4.
• Single tablet fixed-dose combination of ledipasvir/sofosbuvir is also approved for gen 1 with sustained virologic response at 12 weeks (SVR12) rates ≥95% 6.

Efficacy and Safety

• Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are >80% 4.
• Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5 g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection 4.
• Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis 4.
• Treatment decisions are guided by HCV genotype, renal function, drug-drug interactions, and the severity of cirrhosis 7.

Special Considerations

• Unique issues yet remain such as the challenges with renal insufficiency, tolerability of ribavirin and risk of further hepatic decompensation with a protease inhibitor-based regimen 3.
• The major concern, in potential liver transplant candidates, is of unintended 'harm' by achieving SVR but without improvement in hepatic function to an extent where the patients might function well 3.
• Treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality 4.