A 13-year-old boy presents to the pediatrician with yellow discoloration of the sclerae since yesterday, and dark-colored urine for 2 days. A detailed history is taken and reveals that he had a cough, cold, and fever the week before the onset of the current symptoms, and was treated with over-the-counter medications. He reports an improvement in his upper respiratory symptoms but has been experiencing fatigue, nausea, and poor appetite since then. There is no past history of recurrent nausea, vomiting, jaundice or abdominal pain, and he has not received any blood transfusion. In addition, he frequently eats at a roadside restaurant near his school. His growth and development are normal for his age and sex. The temperature is 37.9°C (100.2°F), pulse is 96/min, blood pressure is 110/70 mm Hg, and the respiratory rate is 22/min. The physical examination shows icterus. The examination of the abdomen reveals tender hepatomegaly with the liver having a firm, sharp, and smooth edge. The laboratory test results are as follows: Hemoglobin 14.2 g/dL WBC (white blood cell) 10,500/mm3 Differential leukocyte count Segmented neutrophils 56% Bands 4% Lymphocytes 35% Eosinophils 2% Basophils 0% Monocytes 3% Platelet count 270,000/mm3 Serum total bilirubin 8.4 mg/dL Serum direct bilirubin 7.8 mg/dL Serum alanine aminotransferase 350 U/L Serum alkaline phosphatase 95 U/L Prothrombin time 20 seconds Which of the following laboratory tests is most likely used to diagnose the condition of this patient?

Quantitative assay for glucose-6-phosphate dehydrogenase (G6PD) activity

Direct-acting antivirals for HCV for USMLE Step 1: High-Yield Microbiology Lessons

DAA Classes - HCV's Kryptonite

Direct-acting antivirals (DAAs) target specific non-structural (NS) proteins in the HCV replication cycle, effectively halting viral production. The main classes are distinguished by their target and suffix.

HCV replication cycle and DAA targets in a hepatocyte

Class	Target	Suffix	Example
NS3/4A Protease Inhibitor	Proteolytic cleavage	-previr	Grazoprevir
NS5A Inhibitor	Viral replication/assembly	-asvir	Ledipasvir
NS5B Polymerase Inhibitor	RNA synthesis	-buvir	Sofosbuvir

⭐ Sofosbuvir is a nucleotide analog NS5B inhibitor, giving it a high barrier to resistance and pangenotypic activity.

The Antiviral Arsenal - Know Your Suffixes

Direct-acting antivirals (DAAs) are the cornerstone of modern HCV therapy, targeting specific non-structural (NS) proteins. Classification by suffix is key to identifying their mechanism.

📌 Mnemonic: -previr (Protease), -asvir (NS5A), -buvir (NS5B).

Drug Class	Suffix	Examples	Key Features
NS3/4A Protease Inhibitors	-previr	Glecaprevir, Grazoprevir	Inhibit the viral protease, preventing cleavage of the HCV polyprotein into mature forms.
NS5A Inhibitors	-asvir	Ledipasvir, Pibrentasvir	Block the NS5A protein, which is critical for viral RNA replication and virion assembly.
NS5B Polymerase Inhibitors	-buvir	Sofosbuvir, Dasabuvir	Inhibit the RNA-dependent RNA polymerase (NS5B), terminating the viral RNA chain.

Clinical Strategy - Regimens & Risks

Pangenotypic Regimens: Preferred for simplifying treatment; effective across all genotypes.
- Glecaprevir/Pibrentasvir
- Sofosbuvir/Velpatasvir
Pre-Treatment Essentials:
- Screen for HBV (HBsAg, anti-HBc) to assess reactivation risk.
- Assess for cirrhosis (e.g., FibroScan) to determine treatment duration.
Adverse Effects & Warnings:
- Common: Headache, fatigue, nausea.
- ⚠️ Black Box Warning: Risk of HBV reactivation in co-infected patients. May lead to fulminant hepatitis.

⭐ Sustained Virologic Response (SVR) at 12 weeks post-therapy is the marker for cure, achieved in >95% of patients with modern DAA regimens.

Direct-acting antivirals (DAAs) target specific HCV non-structural proteins (NS3/4A protease, NS5A, NS5B polymerase).

Drug names indicate their target: -previr (protease), -asvir (NS5A), and -buvir (polymerase).

Combination therapy is standard to prevent resistance and achieve >95% cure rates (SVR).

DAAs are pangenotypic, effective against all major HCV genotypes.

Key adverse effects are minimal, typically headache and fatigue.

⚠️ Always screen for HBV before initiating DAA therapy due to the risk of HBV reactivation.

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