My hepatitis C virus (HCV) RNA is 1,420,000 IU/mL; what does this mean and how should I be evaluated and treated if I have no decompensated cirrhosis?

HCV Viral Load 1,420,000 IU/mL: Evaluation and Treatment

What This Viral Load Means

Your HCV RNA level of 1,420,000 IU/mL confirms active chronic hepatitis C infection and indicates you are a candidate for antiviral therapy. 1 This viral load is above the threshold used in older treatment algorithms (400,000–800,000 IU/mL) but is not a primary determinant of disease severity or treatment urgency—liver fibrosis stage and liver function are far more important. 1

• HCV RNA levels do not significantly correlate with the severity of hepatic inflammation or fibrosis, and show little change during chronic infection without treatment. 1
• The viral load itself does not predict treatment response with modern direct-acting antivirals (DAAs), though it was relevant in older pegylated interferon-based regimens. 1
• Quantitative HCV RNA should be measured by a sensitive assay with a lower limit of detection <15 IU/mL, ideally using real-time PCR. 1

Essential Pre-Treatment Evaluation

Before initiating therapy, you must undergo assessment of liver disease severity, HCV genotype determination, and screening for contraindications. 1

Determine Liver Fibrosis Stage

• Identifying cirrhosis is critical because it alters prognosis, treatment regimen selection, and necessitates hepatocellular carcinoma (HCC) surveillance. 1
• Fibrosis stage can be assessed by non-invasive methods initially (transient elastography or serum fibrosis markers), with liver biopsy reserved for cases of uncertainty or potential additional etiologies. 1
• Assessment should be performed regardless of ALT levels, as significant fibrosis may be present even with repeatedly normal ALT. 1

HCV Genotype and Subtype

• HCV genotype and genotype 1 subtype (1a vs. 1b) must be assessed prior to treatment initiation, as this determines the choice of therapy. 1
• Genotyping should be performed with an assay that discriminates well between subtypes 1a and 1b, as DAAs act differently according to these subtypes. 1

Screen for Co-Morbidities

• Test for HBsAg and anti-HBc to rule out hepatitis B coinfection, as HBV reactivation during HCV treatment with DAAs has caused fulminant hepatitis, hepatic failure, and death. 2, 3
• Test for HIV, as coinfection alters treatment approach. 1
• Assess for alcohol use, metabolic syndrome, diabetes, and other causes of liver disease (autoimmune hepatitis, hemochromatosis, drug-induced hepatotoxicity). 1

Treatment Indications and Prioritization

All treatment-naïve and treatment-experienced patients with compensated chronic liver disease related to HCV, who are willing to be treated and have no contraindications, should be considered for therapy. 1

Priority Groups for Immediate Treatment

• Patients with advanced fibrosis (METAVIR F3) or cirrhosis (F4) should be prioritized for treatment. 1
• Treatment is justified in patients with moderate fibrosis (METAVIR F2). 1
• Patients with clinically significant extra-hepatic manifestations (symptomatic cryoglobulinemia or HCV immune complex nephropathy) should be treated promptly. 1

Patients with Minimal Fibrosis (F0–F1)

• For patients with minimal or no fibrosis, the timing and nature of therapy is debatable, and treatment may be deferred. 1
• The decision to defer should consider patient preference, natural history and risk of progression, presence of co-morbidities including HIV coinfection, and patient age. 1
• Patients who have treatment deferred should be assessed regularly for evidence of progression. 1

Modern Treatment Options

Interferon-free, ideally ribavirin-free therapy with direct-acting antivirals (DAAs) is the current standard of care, with cure rates exceeding 95%. 1, 3, 4

• Sofosbuvir-based regimens, particularly sofosbuvir/velpatasvir, have demonstrated high sustained virologic response (SVR) rates across all HCV genotypes. 1, 2, 4
• Treatment duration is typically 12 weeks for most patients without cirrhosis or with compensated cirrhosis. 1, 2
• Pegylated interferon-alpha/ribavirin-containing regimens are now obsolete for most patients due to lower efficacy and significant side effects. 1

Special Considerations for Cirrhosis

• Patients with decompensated cirrhosis can be treated with interferon-free regimens, but should only be managed in experienced centers until further safety and efficacy data accumulate. 1
• In decompensated cirrhosis, sofosbuvir-velpatasvir with or without ribavirin for 12 weeks resulted in SVR rates of 83–94%, though treatment response is suboptimal compared to non-cirrhotic patients. 4, 5, 6
• Pegylated interferon is absolutely contraindicated in decompensated liver disease. 1

Monitoring During and After Treatment

• HCV RNA should be measured at 12 weeks after treatment completion (SVR12) using a sensitive assay (<15 IU/mL) to confirm cure. 1
• SVR12 corresponds to definitive cure of HCV infection in more than 99% of cases. 1
• During treatment, monitor for adverse events including anemia (especially with ribavirin), renal function, and hepatic decompensation. 4, 5, 6

Hepatocellular Carcinoma Surveillance

• In patients with cirrhosis, HCV eradication reduces the rate of decompensation and will reduce, albeit not abolish, the risk of HCC—surveillance for HCC should be continued. 1
• Ultrasound every 6 months is mandatory for all patients with cirrhosis, even after achieving SVR. 7, 3

Common Pitfalls to Avoid

• Do not delay treatment in patients with advanced fibrosis or cirrhosis based on viral load alone—your viral load of 1,420,000 IU/mL does not indicate more severe disease or worse prognosis than lower levels. 1
• Do not assume normal ALT levels exclude significant liver disease—fibrosis assessment is required regardless of ALT patterns. 1
• Do not start HCV treatment without first screening for hepatitis B—HBV reactivation during DAA therapy can be fatal. 2, 3
• Do not use the same laboratory for HCV RNA quantification before, during, and after treatment if possible, as different laboratories can vary in viral quantification results. 1