Hepatitis C — fellow's quick read

Personal study digest for a new ID fellow. Recommendations are from the AASLD-IDSA HCV Guidance 2023 Update (Bhattacharya et al, Clin Infect Dis 2023). The guidance is a living document at hcvguidelines.org; the 2023 publication is a snapshot. The "What's changed since 2023" section is reviewer synthesis of newer evidence, each claim cited. Not a substitute for the full guidance.

In one line

HCV is now a curable, mostly non-specialist disease: nearly everyone gets ONE of TWO once-daily pangenotypic regimens with no pretreatment genotype, and cure (SVR12) exceeds 95%. The fellow's real work is the short list of exceptions — cirrhosis staging, decompensation, prior DAA failure, and drug interactions.

◆When to suspect / diagnose

Screen every adult ≥18 once, and every pregnancy (except settings with prevalence <0.1%). Test = HCV antibody with REFLEX HCV RNA — antibody marks exposure, RNA proves active infection (vs spontaneous/treatment-induced clearance).
Diagnose active infection by HCV RNA. Treat acute HCV the same as chronic (test-and-treat) — do not wait for spontaneous clearance, and do not use an abbreviated course (6-week courses were inferior).
Before treating, stage fibrosis noninvasively: FIB-4 >3.25, FibroScan >12.5 kPa, platelets <150,000, or nodularity/splenomegaly on imaging → presume cirrhosis. This one branch point changes duration, HCC surveillance, and drug safety.

◆Workup the fellow drives (before the first pill)

Confirm active infection (HCV RNA); stage for cirrhosis (FIB-4); check HBsAg + anti-HBc (HBV reactivation risk); baseline CBC, hepatic panel, eGFR, pregnancy status.
Drug–drug interaction check (University of Liverpool checker) — the single most important pre-treatment safety step. Common offenders: acid suppression (PPIs cut velpatasvir/ledipasvir absorption), certain statins, anticonvulsants, rifampin, and amiodarone + sofosbuvir (symptomatic bradycardia — avoid).
Genotype is NOT needed for the simplified algorithm (regimens are pangenotypic). NS5A RAS testing only for a narrow case: genotype 3 + compensated cirrhosis treated with SOF/VEL.
If cirrhotic: liver ultrasound within 6 months to exclude HCC + subclinical ascites, and start q6-month HCC surveillance — cure does not erase HCC risk.

◆Definitive therapy — the regimens

Scenario	Regimen / duration	Notes
Treatment-naive, no cirrhosis OR compensated cirrhosis (simplified)	Glecaprevir/pibrentasvir ×8 wk or sofosbuvir/velpatasvir ×12 wk	Pangenotypic; no pretreatment genotype. GLE/PIB taken with food. GLE/PIB is 8 wk even with compensated cirrhosis (EXPEDITION-8).
Genotype 3 + compensated cirrhosis	GLE/PIB ×8 wk, or SOF/VEL ×12 wk after NS5A RAS test	If baseline Y93H present: add weight-based ribavirin, or use SOF/VEL/VOX. RAS testing not needed for GLE/PIB.
Decompensated cirrhosis (Child-Pugh B/C)	Sofosbuvir/velpatasvir + weight-based ribavirin ×12 wk (or SOF/VEL ×24 wk if RBV-ineligible)	NO protease inhibitors (GLE/PIB, SOF/VEL/VOX, EBR/GZR). Low-dose RBV 600 mg if Child-Pugh C. Specialist care.
Retreatment — prior sofosbuvir/NS5A failure	Sofosbuvir/velpatasvir/voxilaprevir ×12 wk	The salvage regimen. GT3 + compensated cirrhosis: add ribavirin. Not usable in decompensation (protease inhibitor).
Children ≥3 years	GLE/PIB ×8 wk or SOF/VEL ×12 wk	Treat all HCV-infected children ≥3 y regardless of severity; pangenotypic regimens approved to age 3 (2021).

◆Duration & stopping

Most treatment-naive patients: 8 weeks (GLE/PIB) or 12 weeks (SOF/VEL). The endpoint is SVR12 = undetectable HCV RNA ≥12 weeks after finishing therapy = cure.
Minimal monitoring works — dispense the full course up front, no scheduled on-treatment labs, one remote adherence check at week 4 (MINMON: SVR 95%). Simplified patients need only a post-treatment SVR12 RNA.
Short adherence gaps (1–2 days, the most common) do not lower SVR; but <4 weeks of total therapy tanks SVR (≈50%) — complete the course.

◆Special populations

HIV/HCV coinfection: now eligible for the same simplified algorithm (new in 2023, from MINMON) — watch antiretroviral DDIs; INSTI-based regimens ease this.
Pregnancy: screen every pregnancy; DAAs are not routinely recommended — may be considered case-by-case after a risk/benefit discussion (no large safety trials).
Not eligible for "simplified" → refer/co-manage: prior HCV treatment, decompensated cirrhosis, known/suspected HCC, prior liver transplant, HBsAg-positive, or compensated cirrhosis with ESRD (eGFR <30).
People who inject drugs: active or recent use is NOT a contraindication (SVR ~95%) — treat, pair with harm reduction, and re-test RNA at least annually after cure.
HCV-viremic donor → HCV-negative recipient transplant: now routine (IRB approval no longer required). Treat early — liver graft within 1–2 weeks; non-liver (kidney/heart) prophylactic/preemptive GLE/PIB ×8 wk (MYTHIC, 100% SVR12).

◆Key decisions a fellow owns

Stage for cirrhosis (FIB-4) first — it sets duration, HCC surveillance, and whether protease inhibitors are safe.
Check HBsAg / anti-HBc before DAAs — HBV reactivation risk.
Run the Liverpool DDI check — the most common avoidable harm.
Know who is NOT simplified (list above) and route them to a specialist.
Don't shorten therapy for acute HCV, and confirm cure with an SVR12 RNA.

What's changed since 2023

Reviewer synthesis of newer evidence — not the guidance. Each claim cited; flags where the 2023 print update lags the live guidance.

HEADLINE — point-of-care HCV RNA enables same-visit "test-and-treat." The FDA authorized the first POC HCV RNA test (Cepheid Xpert HCV) with a CLIA waiver on 27 June 2024 — fingerstick, result in ~1 hour, so a patient can be diagnosed and started on DAAs in a single visit. AASLD-IDSA added a Point-of-Care Test-and-Treat Algorithm to the online guidance: start with POC RNA, dispense DAAs at the same visit, and draw blood for cirrhosis staging + HBV at diagnosis — but those results are not required before starting. Recency-sensitive — confirm current FDA/label status and local availability. FDA 27 Jun 2024 · Gastroenterol Hepatol (N Y) 2025, PMC12853733
The guidance is LIVING. The 2023 CID publication is a snapshot of hcvguidelines.org, which updates continuously; it remains the most recent comprehensive published version, but check the website for the current algorithm before quoting it. hcvguidelines.org · idsociety.org
Still current — the treatment core is stable. Universal one-time + per-pregnancy screening; universal DAA treatment for nearly all; the two pangenotypic simplified regimens (GLE/PIB 8 wk including compensated cirrhosis; SOF/VEL 12 wk); minimal monitoring. No new DAA class has been approved since 2023 and none withdrawn — the change is in the delivery model, not the drugs. EXPEDITION-8, J Hepatol 2020;72:441-449, PMID 31682879 · MINMON, Lancet Gastroenterol Hepatol 2022;7:307-317, PMID 35026142
Cure ≠ end of surveillance. Patients with cirrhosis who achieve SVR still need q6-month HCC ultrasound surveillance — an easy point to drop once the RNA clears. per AASLD-IDSA 2023 guidance

◆Anki cards minted this run

Simplified treatment-naive regimens — GLE/PIB 8 wk or SOF/VEL 12 wk, pangenotypic, including compensated cirrhosis (EXPEDITION-8).
Decompensated cirrhosis (Child-Pugh B/C) — protease inhibitors contraindicated; SOF/VEL + weight-based ribavirin.
Sofosbuvir/NS5A-failure retreatment — SOF/VEL/VOX ×12 weeks.
Currency — point-of-care HCV RNA test + same-visit test-and-treat (FDA-authorized, CLIA-waived, June 2024).

Sources: AASLD-IDSA HCV Guidance 2023 Update — Bhattacharya D, Aronsohn A, Price J, Lo Re V; Clin Infect Dis 2023 (doi:10.1093/cid/ciad319; PMID 37229695). Currency (via PubMed): EXPEDITION-8 (Brown RS Jr, J Hepatol 2020;72:441-449; doi:10.1016/j.jhep.2019.10.020; PMID 31682879); MINMON/ACTG A5360 (Solomon SS, Lancet Gastroenterol Hepatol 2022;7:307-317; doi:10.1016/S2468-1253(21)00397-6; PMID 35026142). FDA point-of-care HCV RNA authorization, 27 Jun 2024 (fda.gov). AASLD-IDSA point-of-care test-and-treat algorithm review, Gastroenterol Hepatol (N Y) 2025 (PMC12853733). Living guidance: hcvguidelines.org.