Lesson
Follow HCV From Exposure to Fibrosis
HCV is a positive-sense RNA virus whose error-prone replication produces genetic diversity. Acute infection can clear, but persistent viremia can drive decades of inflammation and fibrosis.
- RNA virus
- Quasispecies
- Chronicity
- Fibrosis
- HCC
virus natural history
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Map replication
The viral polyprotein is processed by NS3/4A protease, the NS5A complex organizes replication and assembly, and NS5B polymerase copies viral RNA. These targets explain modern combination therapy.
Map transmission
Blood exposure dominates, especially shared injection equipment. Perinatal, occupational, unsafe procedural, and selected sexual exposure also matter. There is no vaccine.
Map progression
Persistent inflammation can produce fibrosis, cirrhosis, portal hypertension, decompensation, and hepatocellular carcinoma. Alcohol, metabolic liver disease, HIV, and older age accelerate risk.
Treat acute infection
Current guidance uses a test-and-treat approach for confirmed acute viremia rather than waiting solely for spontaneous clearance. Immediate linkage reduces transmission and loss to follow-up.
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Lesson
Separate Exposure From Current Infection
HCV antibody documents exposure, while HCV RNA documents current infection. Reflex testing prevents a second-visit diagnostic gap.
- HCV antibody
- Reflex RNA
- Current infection
- Pregnancy
- Reinfection
screening diagnosis
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Screen broadly
CDC recommends one-time screening for all adults and testing during every pregnancy, with periodic testing for ongoing exposure and testing for anyone who requests it.
Use reflex diagnosis
Begin with an FDA-approved HCV antibody test and automatically perform nucleic-acid testing for HCV RNA when reactive. A reactive antibody with undetectable RNA does not establish current infection.
Handle early exposure
RNA can become detectable before antibody. After recent exposure or in severe immunosuppression, use RNA or repeat testing according to the timeline.
Diagnose reinfection with RNA
Antibody usually remains reactive after spontaneous clearance or cure. Use RNA for new infection when exposure continues or liver tests rise.
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Lesson
Stage Before Selecting the Pathway
Fibrosis and compensation determine whether simplified therapy applies and what follow-up survives cure.
- FIB-4
- Elastography
- Platelets
- Child-Pugh
- Simplified treatment
fibrosis eligibility
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Calculate FIB-4
FIB-4 uses age, AST, ALT, and platelet count. Current guidance accepts it as an initial noninvasive tool for simplified-treatment selection.
Integrate cirrhosis evidence
Use elastography, imaging nodularity or splenomegaly, low platelets, validated serum tests, clinical findings, and prior biopsy. Biopsy is not routinely required.
Separate compensation
Child-Pugh B or C, current or prior ascites, encephalopathy, or variceal bleeding excludes protease-inhibitor therapy and simplified pathways.
Read exclusions correctly
Prior treatment, pregnancy, HBsAg positivity, HCC, transplant, severe renal disease in selected pathways, and decompensation require another guidance section, not therapeutic abandonment.
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Lesson
Build Complementary Antiviral Pressure
DAA name stems reveal the replication target and help detect incomplete, redundant, or unsafe combinations.
- Previr
- Asvir
- Buvir
- Protease
- Polymerase
daa mechanisms
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Block protease
Glecaprevir, grazoprevir, and voxilaprevir inhibit NS3/4A processing. The previr stem is a useful clue, but liver compensation determines safety.
Block the replication complex
Pibrentasvir, velpatasvir, and ledipasvir inhibit NS5A. These potent drugs also create important resistance context after treatment failure.
Block polymerase
Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor. Dasabuvir is a nonnucleoside NS5B inhibitor. Sofosbuvir monotherapy is not adequate.
Prefer pangenotypic design
Current initial therapy often uses pangenotypic combinations, reducing the need for genotype-specific selection in eligible patients while preserving genotype testing for defined cirrhosis and retreatment contexts.
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Lesson
Deliver the Current Pangenotypic Regimen
For eligible treatment-naive adults, glecaprevir and pibrentasvir or sofosbuvir and velpatasvir anchor simplified therapy.
- Glecaprevir/pibrentasvir
- Sofosbuvir/velpatasvir
- Food
- Eight weeks
- Twelve weeks
initial regimens
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Use Mavyret correctly
Adults generally take three 100 mg and 40 mg tablets together once daily with food. Current labeling includes acute or chronic genotypes 1 through 6 in patients age 3 years or older without cirrhosis or with Child-Pugh A, using age-appropriate formulation.
Use Epclusa correctly
Adults generally take one 400 mg and 100 mg tablet daily with or without food for 12 weeks in simplified treatment. Genotype 3 with compensated cirrhosis requires baseline NS5A resistance context.
Respect liver boundaries
Mavyret is contraindicated with Child-Pugh B or C or any prior hepatic decompensation. Sofosbuvir and velpatasvir can be used with ribavirin in selected decompensated disease under expert care.
Do not preserve retired clutter
Viekira Pak and interferon-era combinations from older course material are not routine current initial regimens. Teach them as historical context, not default choices.
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Lesson
Engineer Safety Before the First Dose
A short regimen can still fail from a missed cirrhosis diagnosis, interaction, HBV reactivation, incomplete supply, or untreated coinfection.
- Medication reconciliation
- HBV triple panel
- HIV
- Pregnancy
- HCV RNA
pretreatment safety
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Collect baseline evidence
Obtain CBC, hepatic panel, kidney function, quantitative HCV RNA, and INR when cirrhosis or full monitoring guidance requires it. Add genotype when the chosen pathway needs it.
Screen coinfections
Test HIV and the HBV triple panel. If HBsAg positive, obtain HBV DNA and start indicated treatment or create prophylaxis or monitoring before DAA therapy.
Reconcile everything
Include prescriptions, over-the-counter products, supplements, acid suppressants, statins, anticoagulants, antiarrhythmics, antiseizure drugs, antiretrovirals, transplant drugs, and substances.
Confirm delivery
Verify pregnancy context, coverage, complete duration, formulation, food rule, swallowing needs, refill path, adherence routine, and a contact for any new medication.
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Lesson
Design Around the Interaction Network
DAA exposure depends on gastric pH, transporters, enzymes, liver function, and every concurrent medication.
- Acid suppression
- P-gp
- CYP
- Statins
- Amiodarone
interaction engineering
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Control gastric pH
Ledipasvir and velpatasvir need an acidic environment. Antacid separation and H2 blocker or PPI rules are product-specific, so do not invent one universal schedule.
Remove strong inducers
Rifampin, carbamazepine, phenytoin, phenobarbital, and St. John's wort can reduce exposure. Time separation does not reverse persistent induction.
Protect interacting drugs
Statins, calcineurin inhibitors, antiretrovirals, anticoagulants, and other transporter or enzyme substrates may need a hold, substitution, dose limit, or intensified monitoring.
Avoid the bradycardia stack
Sofosbuvir with amiodarone can cause serious symptomatic bradycardia. Avoid when possible or use label-directed specialist monitoring if no alternative exists.
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Lesson
Protect Every Dose and Detect Early Harm
Many uncomplicated ribavirin-free patients need focused support rather than intensive routine laboratories, while cirrhosis and interacting drugs change the plan.
- Adherence
- Hypoglycemia
- INR
- ALT
- Decompensation
monitoring delivery
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Support adherence
Review administration, missed doses, access, nausea, fatigue, new products, and injection or housing barriers without judgment. Do not wait until the end to discover a gap.
Monitor metabolic change
Improved hepatic function can lower glucose requirements and change warfarin response. Warn patients and actively monitor glucose or INR during and after treatment.
Respond to liver injury
A tenfold ALT rise, symptomatic hepatitis, increasing bilirubin or INR, jaundice, ascites, or encephalopathy requires urgent evaluation and guidance-directed interruption or escalation.
Monitor ribavirin separately
When used in selected decompensated or retreatment cases, ribavirin requires CBC and reproductive safety planning because hemolytic anemia and teratogenicity are central risks.
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Lesson
Prove Cure and Preserve What Cure Cannot Undo
SVR12 confirms cure, but fibrosis, cirrhosis, metabolic disease, alcohol exposure, and reinfection risk still determine follow-up.
- SVR12
- HCV RNA
- Cure
- Cirrhosis
- Reinfection
svr follow up
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Confirm SVR
Obtain quantitative HCV RNA and a hepatic panel 12 weeks or later after therapy. End-of-treatment negativity is encouraging but is not the cure endpoint.
Follow noncirrhotic cure
Patients without cirrhosis usually need no HCV-specific liver follow-up after SVR unless liver tests stay abnormal or another liver disease remains.
Follow cirrhotic cure
Continue HCC ultrasound with or without AFP about every six months and portal-hypertension care according to current guidance. Cure lowers but does not erase risk.
Detect reinfection
Use HCV RNA, not antibody, at least annually with ongoing risk and whenever liver tests rise. Pair testing with sterile equipment, safer sex, and harm-reduction access.
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Lesson
Keep Protease Inhibitors Out of Decompensation
Compensated and decompensated cirrhosis are different therapeutic states, not neighboring points on one simplified checklist.
- Child-Pugh A
- Child-Pugh B or C
- Protease inhibitor
- Ribavirin
- HCC
cirrhosis special
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Treat compensated disease carefully
Eligible treatment-naive Child-Pugh A patients can use simplified pangenotypic therapy after ultrasound, CTP calculation, fibrosis confirmation, laboratory review, and genotype-specific checks where required.
Exclude protease inhibitors
Glecaprevir, grazoprevir, and voxilaprevir should not be used in decompensated liver disease. Prior decompensation remains relevant even if symptoms later improve.
Use expert decompensated regimens
Sofosbuvir and velpatasvir with ribavirin is a current labeled option for selected patients. Ribavirin ineligibility, transplant timing, kidney function, and anemia require specialist design.
Maintain surveillance
Obtain HCC evaluation before therapy and continue surveillance after SVR. Address ascites, encephalopathy, varices, nutrition, transplant candidacy, and medication toxicity in parallel.
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Lesson
Reconstruct Failure and Prevent Reinfection
DAA failure is uncommon and informative. The prior regimen, resistance, interaction, adherence, liver status, and exposure history determine salvage.
- Prior DAA
- NS5A resistance
- Vosevi
- Adherence
- Harm reduction
retreatment prevention
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Reconstruct the first course
Record every component, duration, start and stop date, missed doses, interruption, food and acid rules, interacting drugs, genotype, fibrosis, and RNA response.
Use current salvage guidance
Vosevi combines sofosbuvir, velpatasvir, and voxilaprevir and has defined adult indications after selected NS5A or sofosbuvir-containing failures. It is taken once daily with food and is not used in decompensation.
Do not repeat blindly
Resistance-associated substitutions and the failed drug classes matter. Expert consultation is appropriate when the best combination or duration is unclear.
Prevent reinfection
Offer syringe services, medications for opioid use disorder, safer injection and sex counseling, wound and infection care, vaccination for HAV and HBV when susceptible, and ongoing RNA testing.
Quick check
Lesson
Close the HCV Cure Loop
A complete pathway moves from reflex diagnosis to staged treatment, uninterrupted delivery, SVR12, and the right lifelong follow-up.
- RNA
- Fibrosis
- Regimen
- Interactions
- SVR12
integrated case
Connect viral targets, fibrosis, regimen delivery, sustained response, and lifelong liver risk.
Define infection and liver state
Document antibody and RNA, acute or chronic context, FIB-4, cirrhosis evidence, Child-Pugh status, HCC evaluation, prior treatment, kidney function, pregnancy, HIV, and HBV.
Engineer the regimen
State eligibility, exact products, targets, formulation, food rule, duration, genotype or RAS need, interaction resolutions, complete supply, adherence plan, and alternative.
Engineer monitoring
Plan clinical contact, glucose, INR, liver and ribavirin safety when applicable, new-medication review, and urgent decompensation actions.
Engineer the cure transition
Schedule SVR12 RNA, HCC and portal surveillance for cirrhosis, evaluation of persistent ALT elevation, reinfection RNA testing, vaccination, and harm reduction.
Quick check
Module test
Check the connections.
Each attempt draws 10 questions from the complete 100 question bank.
Each attempt draws a fresh set and rearranges the answer choices.
References
Current clinical foundation.
Lecture material was synthesized with the following contemporary guidance. Verify local policy and current guidance before applying clinical information.