Hepatology, in full.

Diagnose active infection with HCV antibody testing with reflex HCV RNA PCR (Rating I, A); one-time opt-out anti-HCV testing is recommended for all adults ≥18 years and with each pregnancy (I, B), with annual testing for people who inject drugs, men with HIV who have unprotected sex with men, and MSM on PrEP (IIa, C). Treatment is recommended for all persons with acute or chronic HCV infection EXCEPT those with a short life expectancy that cannot be remediated by HCV therapy, liver transplantation, or another directed therapy. Stage fibrosis noninvasively (FIB-4; biopsy not required). The simplified treatment algorithm applies only to treatment-naive adults and EXCLUDES prior HCV treatment, HBsAg positivity, current pregnancy, known or suspected HCC, prior liver transplantation, and any current or prior episode of decompensated cirrhosis; excluded patients are managed by the genotype/population-specific sections, not the simplified pathway. Treatment-naive WITHOUT cirrhosis (FIB-4 ≤3.25 and no other evidence of cirrhosis): glecaprevir 300 mg/pibrentasvir 120 mg once daily with food × 8 weeks, OR sofosbuvir 400 mg/velpatasvir 100 mg once daily × 12 weeks, both pangenotypic and equally recommended; pretreatment CBC, hepatic function panel, eGFR, quantitative HCV RNA, HIV, HBsAg, pregnancy test within 6 months, plus medication reconciliation for drug-drug interactions. Treatment-naive WITH compensated cirrhosis (Child-Pugh A): glecaprevir/pibrentasvir × 8 weeks for genotypes 1-6, OR sofosbuvir/velpatasvir × 12 weeks for genotypes 1, 2, 4, 5, and 6 only, in genotype 3 with compensated cirrhosis, baseline NS5A resistance testing is required before sofosbuvir/velpatasvir and the presence of Y93H changes the regimen; pretreatment labs within 3 months plus CTP score and liver ultrasound within 6 months. On treatment, no routine laboratory monitoring is required except counseling diabetic patients about hypoglycemia and monitoring INR in patients on warfarin. Decompensated cirrhosis (CTP class B or C, or any prior decompensation): refer to a practitioner with expertise, ideally at a liver transplant center; ALL protease-inhibitor-containing regimens (glecaprevir, grazoprevir, voxilaprevir) are contraindicated. Ribavirin-eligible, treatment-naive: sofosbuvir/velpatasvir + weight-based ribavirin × 12 weeks (all genotypes), or ledipasvir/sofosbuvir + ribavirin × 12 weeks for genotypes 1, 4, 5, 6; ribavirin-ineligible: sofosbuvir/velpatasvir (or ledipasvir/sofosbuvir for GT 1, 4, 5, 6) × 24 weeks without ribavirin; prior sofosbuvir-based or NS5A inhibitor-based treatment failure: sofosbuvir/velpatasvir + weight-based ribavirin × 24 weeks. In CTP class C, start ribavirin at 600 mg/day and increase as tolerated toward weight-based dosing. Cure is defined by quantitative HCV RNA undetectable ≥12 weeks after completing therapy (SVR12), checked with a hepatic function panel; patients without cirrhosis who achieve SVR need no further liver-related follow-up, while patients with cirrhosis continue HCC ultrasound surveillance every 6 months and variceal screening per AASLD guidelines after SVR. Repeat annual HCV RNA testing in anyone with ongoing exposure risk.