HCV: Direct-Acting Antivirals (DAAs)
| Drug (Brand) | Mechanism | Genotype | Key Notes |
|---|
| Sofosbuvir/velpatasvir (Epclusa) | NS5B polymerase inhibitor + NS5A inhibitor | Pan-genotypic (1โ6) | 8โ12 weeks; >95% SVR; first-line for most patients |
| Glecaprevir/pibrentasvir (Mavyret) | NS3/4A protease inhibitor + NS5A inhibitor | Pan-genotypic | 8 weeks for treatment-naive non-cirrhotic; safe in renal impairment |
| Ledipasvir/sofosbuvir (Harvoni) | NS5A inhibitor + NS5B inhibitor | Genotype 1 primarily | 12 weeks; avoid with antacids (space 4 hrs) |
| Sofosbuvir/velpatasvir/voxilaprevir (Vosevi) | NS5B + NS5A + NS3/4A inhibitors | Pan-genotypic | 12 weeks; for retreatment after NS5A inhibitor failure |
๐ฏ Boards PearlSVR12 (sustained virologic response at 12 weeks post-treatment) = cure for HCV. Screen all adults โฅ18 at least once (USPSTF Grade B). DAAs contraindicated with rifampin (induces CYP450 โ reduces DAA levels) and amiodarone + sofosbuvir (fatal bradycardia). Check for drug interactions before prescribing โ CYP3A4 and P-glycoprotein interactions are common.
HBV: Nucleoside/Nucleotide Analogues
| Drug | Mechanism | Dose | Monitoring/Adverse Effects |
|---|
| Tenofovir disoproxil fumarate (TDF, Viread) | Nucleotide reverse transcriptase inhibitor; inhibits HBV DNA polymerase | 300mg PO daily | High genetic barrier to resistance; monitor renal function (Fanconi syndrome risk), bone density; avoid if CrCl <30 |
| Tenofovir alafenamide (TAF, Vemlidy) | Same mechanism as TDF; prodrug with less renal/bone toxicity | 25mg PO daily | Preferred over TDF for patients with renal/bone disease; weight gain risk |
| Entecavir (Baraclude) | Guanosine analogue; inhibits HBV DNA polymerase at 3 steps | 0.5mg PO daily (treatment-naive); 1mg/day (lamivudine-experienced) | High genetic barrier to resistance; well-tolerated; dose adjust for renal impairment |
| Pegylated interferon alfa-2a | Immunomodulatory + antiviral; finite treatment course | 180 mcg SQ weekly ร 48 weeks | Flu-like symptoms, depression, neutropenia, thyroid dysfunction; avoid in decompensated cirrhosis |
๐ฅ When to Treat HBVTreat if: HBV DNA >2000 IU/mL + elevated ALT; or HBV DNA >20,000 + any ALT; or cirrhosis regardless of HBV DNA; or immunosuppression planned (reactivation risk). Monitor on treatment: LFTs, HBV DNA, HBeAg/anti-HBe q6 months. Goal: sustained suppression of HBV DNA. Reactivation risk: screen all patients receiving rituximab, chemotherapy, or steroids โ offer prophylaxis with entecavir or tenofovir.
Cirrhosis Medications
| Drug | Indication | Mechanism | Key Points |
|---|
| Lactulose | Hepatic encephalopathy | Non-absorbable disaccharide โ acidifies colon (NH4+ trapped) โ cathartic โ decreased ammonia absorption | Titrate to 2โ3 soft BMs/day; avoid lactulose in ileus. Side effects: bloating, diarrhea, electrolyte imbalances |
| Rifaximin (Xifaxan) | Prevention of HE recurrence (second-line or add-on to lactulose) | Non-absorbable rifamycin antibiotic โ reduces ammonia-producing gut bacteria | 550mg BID; minimal systemic absorption; expensive but well-tolerated. Preferred add-on when lactulose alone insufficient |
| Spironolactone | Ascites (first-line) | Aldosterone antagonist โ blocks Na+/K+ exchange in collecting duct โ Na/water excretion | Start 100mg/day; titrate up to 400mg. Hyperkalemia is main adverse effect. Ratio spironolactone:furosemide = 100:40 to maintain normokalemia |
| Furosemide | Ascites (combined with spironolactone) | Loop diuretic โ inhibits Na-K-2Cl cotransporter in loop of Henle | 40mg PO daily combined with spironolactone; weight loss target 0.5kg/day (no peripheral edema) or 1kg/day (with edema) |
| Ceftriaxone / Norfloxacin | SBP treatment/prophylaxis | Beta-lactam antibiotic / fluoroquinolone | SBP treatment: ceftriaxone 2g IV daily ร 5 days + albumin 1.5g/kg day 1 and 1g/kg day 3 (prevents hepatorenal syndrome). Primary prophylaxis: norfloxacin 400mg daily if ascitic protein <1.5g/dL + renal/hepatic dysfunction |
| Non-selective beta-blockers (propranolol, nadolol, carvedilol) | Variceal hemorrhage prophylaxis (primary and secondary) | Reduce portal pressure via ฮฒ1 (โHR, โCO) and ฮฒ2 (splanchnic vasoconstriction) | Titrate to HR 55โ60 bpm; carvedilol also has alpha-1 blocking effect (preferred). Contraindicated in refractory ascites, HRS |
| Terlipressin / Norepinephrine + Albumin | Hepatorenal syndrome (HRS) | Vasoconstrictors โ improve systemic and renal perfusion | Terlipressin (vasopressin analogue) + albumin = first-line for HRS-AKI. Norepinephrine can substitute. Goal: reverse HRS until transplant |
Hepatotoxic Drugs to Know
| Drug | Pattern of Hepatotoxicity | Notes |
|---|
| Acetaminophen (APAP) | Hepatocellular (centrilobular necrosis); dose-dependent at >7.5โ10g; toxic metabolite NAPQI depletes glutathione | Leading cause of acute liver failure in US. Antidote: N-acetylcysteine (NAC) โ replenishes glutathione. Use Rumack-Matthew nomogram. Max safe dose: 2g/day in heavy drinkers, 4g/day in healthy adults |
| Isoniazid (INH) | Hepatocellular; idiosyncratic; 1โ2% incidence; severe if not caught early | Monitor LFTs monthly; stop if AST/ALT >3ร ULN with symptoms or >5ร ULN asymptomatic. Give B6 (pyridoxine) to prevent neuropathy. Risk increases with age, alcohol use, slow acetylators |
| Amiodarone | Hepatocellular + steatosis (phospholipidosis); chronic use; CXR: gray-blue discoloration | Monitor LFTs every 6 months on therapy. Very long half-life (40โ55 days) |
| Statins | Transaminase elevation (usually mild, benign); rarely true hepatotoxicity | Transaminase elevation in 1โ3% โ usually mild and self-limited. True DILI rare. Do NOT routinely avoid statins in liver disease unless decompensated cirrhosis |
| Methotrexate | Hepatic fibrosis/cirrhosis with chronic use; cumulative dose-dependent | Monitor LFTs; consider liver biopsy after cumulative dose 1.5g (rheumatologic use); avoid alcohol; contraindicated in liver disease |
| Valproic acid | Microvesicular steatosis + hepatocellular necrosis; rare but fatal; children <2 especially at risk | Monitor LFTs; stop immediately if symptoms |
| Azithromycin, erythromycin | Cholestatic (intrahepatic cholestasis) | Macrolide antibiotics โ cholestasis; usually reversible |
๐ง Mnemonic โ Common DILI PatternsHepatocellular: INH, APAP, statins (mild) ยท Cholestatic: macrolides, amoxicillin-clavulanate, oral contraceptives ยท Mixed: amoxicillin-clavulanate (most common cause of DILI in US), carbamazepine ยท Fibrosis: methotrexate ยท Steatosis: amiodarone, valproate, tetracyclines
Bile Acid Therapies
| Drug | Indication | Mechanism | Key Points |
|---|
| Ursodeoxycholic acid (UDCA, Actigall) | Primary biliary cholangitis (PBC), cholesterol gallstones (dissolution), NAFLD | Hydrophilic bile acid โ displaces toxic hydrophobic bile acids, cytoprotective, choleretic | PBC: 13โ15 mg/kg/day โ slows progression; monitor ALP and bilirubin. Gallstone dissolution: requires cholesterol stones, patent cystic duct, functioning GB. Slow (6โ24 months); recurrence common. First-line for PBC. |
| Obeticholic acid (Ocaliva) | PBC (second-line) + NASH (investigational) | FXR (farnesoid X receptor) agonist โ reduces bile acid synthesis + improves lipid metabolism | Add to UDCA if inadequate response. Pruritus is main side effect. NASH trials (REGENERATE): improved fibrosis |
| Cholestyramine (bile acid sequestrant) | Pruritus from cholestasis, hyperlipidemia | Binds bile acids in gut โ prevents reabsorption โ reduces bile acid-mediated itch signaling | Give 1 hour before or 4โ6 hours after other medications (reduces absorption of many drugs including digoxin, warfarin, thyroid hormones, fat-soluble vitamins) |