What is the recommended treatment for a patient with high Hepatitis C Virus (HCV) RNA levels, low 25-hydroxyvitamin D (25OH Vitamin D) levels, and positive Hepatitis B Surface Antigen (Hepatitis B Surface Antigen) status?

HCV Treatment in HBV-Coinfected Patient with Low Vitamin D

This patient requires immediate direct-acting antiviral (DAA) therapy for HCV while simultaneously initiating HBV nucleoside/nucleotide analogue prophylaxis due to positive HBsAg status, with vitamin D supplementation as an adjunct. 1, 2

Critical Initial Actions

HBV Reactivation Prevention (Highest Priority)

• Start HBV nucleoside/nucleotide analogue therapy immediately before or concurrent with HCV treatment because this patient is HBsAg-positive, placing them at significant risk for HBV reactivation during HCV DAA therapy, which can result in fulminant hepatitis, hepatic failure, and death 1, 2
• The FDA boxed warning for DAAs specifically mandates testing for HBsAg and anti-HBc before HCV treatment initiation 2
• Monitor ALT levels monthly during and after HCV treatment to detect HBV reactivation early 1

Complete HCV Characterization

• Obtain HCV genotype immediately (currently "In Process" in your labs) as this determines the specific DAA regimen and treatment duration 3, 1, 4
• Assess liver fibrosis stage using non-invasive methods (FibroScan, APRI, FIB-4) to determine treatment urgency and duration 4
• The declining viral load (3000 IU/mL two years ago to 1890 IU/mL currently) suggests chronic infection rather than acute hepatitis 3

HCV Treatment Regimen Selection

Once Genotype Results Available

For treatment-naïve patients without cirrhosis or with compensated cirrhosis:

• Most HCV genotypes (1-6): 8 weeks of glecaprevir/pibrentasvir (MAVYRET) taken with food 2
• Alternative regimens include sofosbuvir-based combinations depending on genotype 3

If genotype 4:

• Sofosbuvir 400 mg daily plus daclatasvir 60 mg daily for 12 weeks in treatment-naïve patients 3
• Consider adding weight-based ribavirin (1000-1200 mg based on body weight) if cirrhosis is present 3

Treatment Monitoring Schedule

• HCV RNA at baseline, week 2 (adherence check), week 4, end of treatment, and 12 weeks post-treatment for SVR12 confirmation 3, 4
• Monthly ALT monitoring specifically for HBV reactivation surveillance 1
• HBV DNA levels if they become detectable during treatment 1

Vitamin D Management

Supplementation Strategy

• Initiate vitamin D3 2000 IU daily immediately as the current level of 20 ng/mL is insufficient (target >32 ng/mL) 5
• Low vitamin D levels (especially <15 ng/mL) independently predict poor HCV treatment outcomes 5
• In one randomized trial of HCV genotype 2-3 patients, vitamin D supplementation improved SVR from 77% to 95% 5
• Recheck vitamin D levels at 12 weeks to ensure adequate repletion (target 34 ng/mL or higher) 5

Critical Pitfalls to Avoid

Do Not Delay HBV Prophylaxis

• Failure to provide concurrent HBV nucleoside/nucleotide analogue therapy in this HBsAg-positive patient could result in fatal hepatitis flares 1, 2
• Approximately two-thirds of HBV-HCV coinfected patients experience HBV DNA increases during DAA therapy, though most remain asymptomatic 1

Do Not Use Outdated Interferon-Based Regimens

• The 2011-2014 guidelines recommending pegylated interferon plus ribavirin are obsolete 3
• Modern DAA regimens achieve >95% cure rates with minimal side effects and shorter duration 3, 2

Do Not Overlook HIV Status

• Confirm HIV status if not already documented, as HIV coinfection affects prognosis and treatment approach 1, 4

Post-Treatment Surveillance

• Continue HBV monitoring indefinitely, particularly in the first 12 weeks after HCV treatment completion 1
• If cirrhosis is present, continue HCC surveillance every 6 months even after achieving SVR 3, 4
• The positive hepatitis B core antibody with adequate surface antibody (19.8) suggests past exposure with immunity, but the positive HBsAg indicates chronic HBV infection requiring ongoing management 1