What is the recommended treatment for a patient with Hepatitis C Virus (HCV) Immunoglobulin G (IgG) positive?

HCV IgG Positive: Recommended Management

All patients with HCV IgG positive should undergo confirmatory HCV RNA testing to determine if active infection is present, followed by immediate treatment with direct-acting antivirals (DAAs) if infection is confirmed, as modern regimens achieve cure rates exceeding 95-97% regardless of viral load or liver enzyme levels. 1

Initial Diagnostic Workup

When HCV IgG returns positive, the following steps are essential:

• Confirm active infection with quantitative HCV RNA testing, as anti-HCV antibodies can persist after spontaneous clearance or successful treatment 2
• Determine HCV genotype to guide optimal regimen selection and treatment duration 1, 3
• Assess liver fibrosis stage using non-invasive methods (FibroScan/elastography) or liver biopsy to determine treatment urgency 1, 3, 4
• Screen for hepatitis B (HBsAg and anti-HBc) before initiating HCV treatment, as HBV reactivation can cause fulminant hepatitis, hepatic failure, and death 1, 5
• Test for HIV coinfection, as this affects drug-drug interactions and disease progression 2, 3

Treatment Recommendations

First-Line Regimens for Confirmed Chronic HCV

For treatment-naïve patients without cirrhosis:

• Sofosbuvir/velpatasvir 400mg/100mg once daily for 12 weeks achieves 98% cure rate 1
• Glecaprevir/pibrentasvir 300mg/120mg once daily for 8 weeks is equally effective 1
• Ledipasvir/sofosbuvir 90mg/400mg once daily for 12 weeks for genotypes 1,4,5, or 6 5

For patients with compensated cirrhosis (Child-Pugh A):

• Ledipasvir/sofosbuvir for 12 weeks for treatment-naïve patients 5
• Extend to 24 weeks for treatment-experienced patients with cirrhosis 5

For decompensated cirrhosis (Child-Pugh B or C):

• Ledipasvir/sofosbuvir plus ribavirin for 12 weeks 5
• Ribavirin dosing: start at 600 mg daily, titrate to 1000 mg (<75 kg) or 1200 mg (≥75 kg) divided twice daily 5

Special Populations

Acute Hepatitis C:

• Initiate DAA therapy immediately upon diagnosis rather than waiting for spontaneous clearance, as this reduces transmission risk and prevents loss to follow-up 6
• Alternatively, pegylated interferon-α monotherapy (180 µg/week pegIFN-α2a or 1.5 µg/kg/week pegIFN-α2b) for 24 weeks achieves >90% viral eradication 2, 6

Severe Renal Disease (GFR 15-59 mL/min):

• Peginterferon alpha-2a 135 µg weekly or peginterferon alpha-2b 1 µg/kg weekly plus ribavirin 200-800 mg/day with gradual dose increase 2
• Ribavirin requires careful monitoring as it causes severe hemolytic anemia when creatinine clearance <50 mL/min 2

Hemodialysis Patients:

• Interferon alpha or peginterferon alpha monotherapy (interferon alpha 3 million units three times weekly, or pegIFN-α2a 135 µg/week, or pegIFN-α2b 1 µg/kg/week) 2
• Ribavirin combination is not recommended due to renal clearance 2

HIV Coinfection:

• Same pegylated interferon-α regimen as monoinfected patients with weight-based ribavirin (15 mg/kg/day) 2
• Consider longer treatment duration: 72 weeks for genotype 1,48 weeks for genotypes 2 and 3 2
• Avoid didanosine (contraindicated), stavudine, and zidovudine during treatment 2

HBV/HCV Coinfection:

• Treat HCV with standard therapy when HCV is the dominant cause of liver disease 2
• Initiate oral anti-HBV agents (entecavir or tenofovir) if significant HBV proliferation occurs during or after HCV treatment 2

Treatment Prioritization

Highest priority for immediate treatment:

• Advanced fibrosis (F3) or any cirrhosis (F4), as these patients face highest risk of hepatic decompensation and hepatocellular carcinoma 2, 1, 7
• Decompensated cirrhosis (Child-Pugh B or C) should be treated urgently with interferon-free regimens 2
• Clinically significant extrahepatic manifestations including symptomatic cryoglobulinemic vasculitis, HCV immune complex nephropathy, or non-Hodgkin B-cell lymphoma 2
• Individuals at risk of HCV transmission: active injection drug users, men who have sex with men with high-risk practices, women of childbearing age planning pregnancy, hemodialysis patients, incarcerated individuals 2

High priority:

• Moderate fibrosis (F2) to prevent progression to cirrhosis 2
• HIV or HBV coinfection 2
• Pre- or post-liver transplant patients 2

Monitoring During Treatment

Baseline assessment:

• Complete blood count, hepatic function panel, creatinine/GFR 1
• Quantitative HCV viral load 1

Week 4 of therapy:

• Repeat HCV RNA, CBC, creatinine, GFR, hepatic function panel 1
• If HCV RNA detectable at week 4, retest at week 6 1
• Discontinue treatment if viral load increases >10-fold (>1 log₁₀ IU/mL) at week 6 1

Post-treatment:

• Confirm cure with HCV RNA testing at 12 weeks post-treatment (SVR12), which represents permanent viral eradication in >99% of cases 1, 3

Long-Term Surveillance

For patients achieving SVR with advanced fibrosis or cirrhosis:

• Lifelong HCC surveillance with ultrasound every 6 months, as cancer risk is reduced but not eliminated 2, 1, 3
• Continue endoscopy screening for esophageal varices if cirrhosis present 1

For untreated patients or non-responders:

• Assess every 1-2 years with non-invasive fibrosis testing 2

Critical Pitfalls to Avoid

• Never delay treatment in patients with advanced fibrosis or cirrhosis, as viral eradication halts disease progression, induces fibrosis regression, reduces need for liver transplantation, and improves survival 2, 7
• Always test for HIV and HBV before initiating HCV treatment, as coinfection affects prognosis, treatment selection, and risk of HBV reactivation 1, 3, 5
• Do not withhold treatment based on high viral load or elevated liver enzymes, as modern DAAs achieve SVR rates of 95-97% regardless of baseline HCV RNA levels 1
• Active substance use is not a contraindication to treatment; consider referral to addiction medicine specialists 2, 3
• Do not use acetaminophen or alcohol during acute hepatitis 6
• Monitor for HBV reactivation during and after HCV treatment in coinfected patients, initiating nucleoside/nucleotide analogues if HBV DNA becomes detectable 1, 5