What are the symptoms, complications, and treatment options for Hepatitis C (HCV) infection?

From the Guidelines

Hepatitis C treatment should prioritize direct-acting antivirals (DAAs) such as ledipasvir/sofosbuvir, elbasvir/grazoprevir, or glecaprevir/pibrentasvir for 8-12 weeks, depending on the presence of liver cirrhosis and virus genotype, as these regimens have been shown to cure over 95% of cases 1. Hepatitis C is a viral infection that primarily affects the liver, often causing no symptoms initially but can lead to serious complications over time, including liver cirrhosis, liver failure, and hepatocellular carcinoma (liver cancer). Early symptoms may include:

• Fatigue
• Jaundice
• Abdominal pain
• Nausea
• Joint pain Though many people remain asymptomatic for years, treatment is crucial to prevent long-term complications. The goals of hepatitis C treatment are to eradicate HCV and to prevent complications of liver cirrhosis, hepatocellular carcinoma, extrahepatic manifestations of HCV infection, and death 1. Treatment regimens, as recommended by the 2017 KASL clinical practice guidelines, include:
• Ledipasvir/sofosbuvir for 12 weeks
• Elbasvir/grazoprevir for 12 weeks
• Glecaprevir/pibrentasvir for 8 weeks in patients without liver cirrhosis and 12 weeks in patients with liver cirrhosis
• Sofosbuvir/velpatasvir for 12 weeks These medications work by directly blocking the virus's ability to replicate in the body. Treatment choice depends on the specific genotype of the virus, presence of cirrhosis, prior treatment history, and other medical conditions. Regular monitoring during treatment includes blood tests to check viral load and liver function. After successful treatment, most patients need follow-up testing to confirm sustained virologic response (SVR), which indicates cure 1. Even after cure, those with advanced liver disease require ongoing monitoring for complications. It is essential to note that the safety of certain medications, such as daclatasvir, ledipasvir, and asunaprevir, has not been fully evaluated in patients with severe renal impairment, and some medications are contraindicated in patients with decompensated cirrhosis 1.

From the FDA Drug Label

WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV 5.2 Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease

The treatment for Hepatitis C is glecaprevir (PO) as indicated in the drug label.

• Hepatitis C symptoms and complications are not directly addressed in the label, but it does mention the risk of Hepatic Decompensation/Failure in patients with evidence of advanced liver disease.
• The label also mentions the risk of Hepatitis B Virus Reactivation in patients coinfected with HCV and HBV 2. The treatment duration and dosage are provided in sections 2.2 and 2.3 of the label, but the symptoms and complications of Hepatitis C are not explicitly stated.

From the Research

Hepatitis C Symptoms, Complications, and Treatment

• Hepatitis C virus (HCV) infects more than 185 million individuals worldwide, with 20% of patients chronically infected progressing to cirrhosis 3
• The treatment goal is to achieve a sustained virologic response (SVR), which is the treatment goal of undetectable plasma HCV RNA 12 or 24 weeks after therapy completion 3

Treatment Options

• Patients with HCV genotype 1 should receive treatment with sofosbuvir + pegylated interferon + ribavirin due to the shorter duration of therapy and high rates of SVR (89%-90%) 3
• Simeprevir + pegylated interferon + ribavirin is an alternative for patients with HCV genotype 1 (SVR, 79%-86%) 3
• Patients with HCV genotypes 2 and 3 should receive therapy with sofosbuvir + ribavirin alone (SVR for genotype 2,12 weeks' duration: 82%-93%; SVR for genotype 3,24 weeks' duration, 80%-95%) 3
• Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is an effective and safe rescue therapy for patients with prior DAA treatment failure, with a cure rate of 95% in a Spanish cohort of 137 patients 4
• The combination of Sofosbuvir plus Velpatasvir and Glecaprevir plus Pibrentasvir, each administered over a 12-week period, were identified as the most effective and relatively safe in managing chronic hepatitis C virus genotype 2 (HCV GT2) infection, with a SVR12 of 100% (95% CI 99-100%) 5

Complications and Unmet Needs

• Viral eradication rates are pushing 100% for many HCV-infected populations, including patients with HIV/HCV coinfection, decompensated cirrhosis, liver and kidney transplants, and end-stage liver disease 6
• However, patients with liver cirrhosis infected by GT3 remain the most-difficult-to-treat group, with a lower SVR12 rate (69%) 4
• Genotypic characteristics of the virus (genotype 3) and the presence of cirrhosis are factors that decrease the rate of cure 4, 7

Real-World Effectiveness

• Real-world data show that SOF/VEL/VOX is an effective, safe rescue therapy for patients with prior DAA treatment failure, despite the presence of resistance-associated substitutions 4, 7
• In a diverse real-world cohort of heavily NS5A pretreated patients, SOF/VEL/VOX SVR rates in DAA-experienced patients were high across all genotypes, with overall SVR rates of 90.7% (429/473) for genotype 1,90.0% (18/20) for genotype 2,91.3% (42/46) for genotype 3, and 100.0% (12/12) for genotype 4 7