What is the risk of Hepatitis C Virus (HCV) in patients with decompensated cirrhosis due to Non-Alcoholic Steatohepatitis (NASH)?

From the Guidelines

Patients with decompensated cirrhosis due to Non-Alcoholic Steatohepatitis (NASH) are at an increased risk of complications if they acquire Hepatitis C Virus (HCV) infection, and thus, should be evaluated for HCV treatment and liver transplantation regardless of etiology. Decompensated cirrhosis due to NASH and HCV represent distinct liver conditions with overlapping clinical implications. For patients with NASH-related decompensated cirrhosis, the primary management focuses on treating the liver failure complications while addressing metabolic factors, such as weight management, diabetes control, blood pressure management, and lipid control 1.

Key Considerations

• Medications like vitamin E (800 IU daily) may benefit non-diabetic NASH patients, while pioglitazone can help diabetic patients with NASH.
• For those with both decompensated cirrhosis and HCV, direct-acting antivirals (DAAs) like sofosbuvir/velpatasvir or glecaprevir/pibrentasvir are effective, though medication choice depends on the degree of liver dysfunction 1.
• Patients with decompensated cirrhosis should be evaluated for liver transplantation regardless of etiology, as liver transplantation is the treatment of choice for patients with decompensated cirrhosis 1.
• Regular screening for hepatocellular carcinoma with ultrasound every 6 months is essential, as both conditions increase cancer risk.

Management and Treatment

The presence of both conditions accelerates liver damage, as the inflammatory processes from both NASH and HCV can synergistically worsen liver function and increase fibrosis progression. Treatment should be considered without delay in patients with significant fibrosis or cirrhosis, including decompensated cirrhosis, and in patients with clinically significant extra-hepatic manifestations 1. Additionally, patients with decompensated cirrhosis and an indication for liver transplantation with a MELD score ≥18-20 should be transplanted first and treated after transplantation, or treated before transplantation if the waiting time is more than 6 months 1.

From the FDA Drug Label

1. 2 Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease

Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including MAVYRET Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure The majority of patients with severe outcomes had evidence of advanced liver disease with moderate or severe hepatic impairment (Child-Pugh B or C) prior to initiating therapy with MAVYRET, including some patients reported as having compensated cirrhosis with mild liver impairment (Child-Pugh A) at baseline but with a prior decompensation event (i.e., prior history of ascites, variceal bleeding, encephalopathy). Rare cases of hepatic decompensation/failure were reported in patients without cirrhosis or with compensated cirrhosis (Child-Pugh A); many of these patients had evidence of portal hypertension Events also occurred in patients taking a concomitant medication not recommended for coadministration, or in patients with confounding factors such as serious liver-related medical or surgical comorbidities. Cases typically occurred within the first 4 weeks of treatment (median of 27 days) In patients with compensated cirrhosis (Child-Pugh A) or evidence of advanced liver disease such as portal hypertension, perform hepatic laboratory testing as clinically indicated; and monitor for signs and symptoms of hepatic decompensation such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage Discontinue MAVYRET in patients who develop evidence of hepatic decompensation/failure. MAVYRET is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C) or those with any history of prior hepatic decompensation [see Contraindications (4), Adverse Reactions (6.1), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].

The risk of Hepatitis C Virus (HCV) in patients with decompensated cirrhosis due to Non-Alcoholic Steatohepatitis (NASH) is not directly addressed in the provided drug label. However, the label does mention the risk of hepatic decompensation/failure in patients with evidence of advanced liver disease, including those with compensated cirrhosis (Child-Pugh A) or decompensated cirrhosis (Child-Pugh B or C).

• Key points:
  • The label reports postmarketing cases of hepatic decompensation/failure in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including MAVYRET.
  • The majority of patients with severe outcomes had evidence of advanced liver disease with moderate or severe hepatic impairment prior to initiating therapy.
  • Rare cases of hepatic decompensation/failure were reported in patients without cirrhosis or with compensated cirrhosis.
• Clinical decision:
  • The FDA drug label does not provide direct information on the risk of HCV in patients with decompensated cirrhosis due to NASH.
  • However, it does highlight the risk of hepatic decompensation/failure in patients with advanced liver disease, which may be relevant to patients with NASH.
  • Given the lack of direct information, a conservative clinical decision would be to exercise caution when treating patients with decompensated cirrhosis due to NASH with MAVYRET, and to monitor closely for signs and symptoms of hepatic decompensation. 2

From the Research

Risk of Hepatitis C Virus (HCV) in Patients with Decompensated Cirrhosis due to Non-Alcoholic Steatohepatitis (NASH)

• The risk of HCV in patients with decompensated cirrhosis due to NASH is not directly addressed in the provided studies, as they focus on the treatment and outcomes of patients with HCV-related cirrhosis or NASH-related cirrhosis separately.
• However, a study 3 compared the outcomes of patients with NASH cirrhosis and hepatitis B virus (HBV) cirrhosis after decompensation with ascites, and found that patients with NASH cirrhosis had a poorer prognosis with more complications and greater healthcare resource utilization.
• Another study 4 found that patients with advanced/decompensated HCV-related cirrhosis treated with direct-acting antivirals (DAAs) had only marginal improvements in liver function at long-term follow-up, and may remain at high risk of decompensation.
• A case report 5 described a patient with decompensated HCV-associated cirrhosis who showed improvement in liver function and disappearance of hepatic encephalopathy, ascites, and pleural effusion after treatment with sofosbuvir/velpatasvir.
• Studies 6 and 7 investigated the use of non-selective beta-blockers and emricasan, respectively, in patients with cirrhosis, but did not specifically address the risk of HCV in patients with decompensated cirrhosis due to NASH.

Treatment Outcomes for Patients with Decompensated Cirrhosis

• Treatment with DAAs can improve liver function and reduce the risk of decompensation in patients with HCV-related cirrhosis 4, 5.
• Non-selective beta-blockers can reduce the risk of first decompensation in patients with cirrhosis and clinically significant portal hypertension after etiological treatment 6.
• Emricasan, a pan-caspase inhibitor, was found to be safe but ineffective in preventing new decompensation events in patients with NASH-related decompensated cirrhosis 7.

Prognosis and Complications

• Patients with decompensated cirrhosis due to NASH have a poorer prognosis compared to those with HBV cirrhosis, with more complications and greater healthcare resource utilization 3.
• Decompensated cirrhosis is associated with a high risk of additional decompensation events and death, regardless of the underlying etiology 4, 3, 7.