What is the appropriate treatment for a patient diagnosed with hepatitis?

Treatment of Hepatitis

Hepatitis C Treatment

For chronic hepatitis C, direct-acting antiviral regimens with sofosbuvir-based combinations are the standard of care, achieving sustained virologic response rates exceeding 90% across all genotypes. 1

Genotype-Specific Treatment Regimens

Genotype 1 HCV Without Cirrhosis

• Ledipasvir (90 mg)/sofosbuvir (400 mg) fixed-dose combination daily for 12 weeks is the preferred first-line regimen 1
• Alternative options include paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus dasabuvir (250 mg) twice daily for 12 weeks 1
• Sofosbuvir (400 mg) plus simeprevir (150 mg) daily for 12 weeks is also effective 1

Genotype 1 HCV With Cirrhosis

• Extend ledipasvir/sofosbuvir to 24 weeks for patients with cirrhosis 1
• Alternatively, use ledipasvir/sofosbuvir plus weight-based ribavirin (1000 mg if <75 kg or 1200 mg if ≥75 kg) for 12 weeks 1

Genotype 2 HCV

• Sofosbuvir (400 mg) plus weight-based ribavirin daily for 12 weeks for both treatment-naïve and treatment-experienced patients without cirrhosis or with compensated cirrhosis 1, 2

Genotype 3 HCV

• Sofosbuvir (400 mg) plus weight-based ribavirin daily for 24 weeks for both treatment-naïve and treatment-experienced patients 1, 2

Critical Pre-Treatment Testing

All patients must be tested for hepatitis B virus (HBV) coinfection before initiating HCV treatment by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc). 2 This is mandatory because HBV reactivation has resulted in fulminant hepatitis, hepatic failure, and death in HCV/HBV coinfected patients receiving direct-acting antivirals without concurrent HBV therapy 2

Treatment Failures and Retreatment

Prior Interferon-Based Regimen Failure

• Patients without cirrhosis: ledipasvir/sofosbuvir for 12 weeks 1
• Patients with cirrhosis: ledipasvir/sofosbuvir for 24 weeks OR ledipasvir/sofosbuvir plus weight-based ribavirin for 12 weeks 1

Prior Sofosbuvir-Containing Regimen Failure

• Patients with cirrhosis requiring urgent treatment: ledipasvir/sofosbuvir plus weight-based ribavirin for 24 weeks 1
• Patients without cirrhosis requiring urgent treatment: ledipasvir/sofosbuvir plus weight-based ribavirin for 12 weeks 1
• Patients without urgent need should defer therapy until additional data are available or enroll in clinical trials 1

Special Populations

Patients Ineligible for Interferon

• Sofosbuvir plus ribavirin for 24 weeks can be considered for genotype 1 patients who cannot receive interferon-based regimens 2

Patients Awaiting Liver Transplantation

• Administer sofosbuvir plus ribavirin for up to 48 weeks or until transplantation to prevent post-transplant HCV reinfection 2

Critical Drug Interactions and Contraindications

Coadministration of amiodarone with sofosbuvir-containing regimens is not recommended due to risk of serious symptomatic bradycardia, including fatal cardiac arrest 2 If no alternative exists, cardiac monitoring in an inpatient setting for the first 48 hours is mandatory, followed by daily heart rate monitoring for at least 2 weeks 2

P-glycoprotein inducers (rifampin, St. John's wort) must not be used with sofosbuvir as they significantly decrease drug concentrations and reduce therapeutic efficacy 2

Renal Impairment Considerations

No dosage recommendation exists for patients with severe renal impairment (eGFR <30 mL/min/1.73m²) or end-stage renal disease due to up to 20-fold higher exposures of sofosbuvir metabolites 2

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Hepatitis B Treatment

Monotherapy with entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) is the preferred first-line treatment for chronic hepatitis B, achieving viral suppression in >90% of patients at 12 months. 3

Treatment Indications by Disease Phase

HBeAg-Positive Chronic Hepatitis B

• Treat if HBV DNA ≥20,000 IU/mL AND serum ALT >2× ULN OR moderate histological lesions on biopsy 3
• Treatment can be delayed 3-6 months in compensated disease to allow for potential spontaneous HBeAg seroconversion 3

HBeAg-Negative Chronic Hepatitis B

• Treat if HBV DNA ≥2,000 IU/mL AND serum ALT >2× ULN OR moderate histological lesions on biopsy 3
• These patients typically require long-term or indefinite treatment 3

Compensated Cirrhosis

• All cirrhotic patients with detectable HBV DNA should be treated with entecavir or tenofovir regardless of ALT levels 3
• ALT should not guide treatment decisions in cirrhosis, as these patients already have significant fibrosis and frequently have near-normal ALT 3

Decompensated Cirrhosis

• Treat immediately with entecavir or tenofovir regardless of HBV DNA level 3
• Pegylated interferon-alfa is absolutely contraindicated due to risk of liver failure 3
• Coordinate with transplant centers and refer for liver transplantation evaluation 3

Preferred Medication Dosing

Tenofovir alafenamide (TAF) 25 mg orally once daily has a superior safety profile regarding renal and bone toxicity compared to TDF, with similar antiviral efficacy 3

Long-Term Management

• Most patients require long-term or indefinite therapy, as HBsAg loss occurs in only 1-12% even after years of treatment 3
• Monitor HBV DNA and ALT every 3-6 months during therapy to assess virological and biochemical response 3
• Assess renal function periodically if using tenofovir-based therapy 3

Special Populations

Pregnant Women

• Tenofovir is preferred during pregnancy for prevention of mother-to-child transmission in women with high viremia 3

Patients Requiring Immunosuppression

• Treatment is indicated for prevention of HBV reactivation in patients requiring immunosuppression or chemotherapy 3

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Acute Hepatitis A Treatment

Acute hepatitis A is self-limited and requires only supportive care, with complete clinical recovery occurring in nearly all adult patients by 6 months. 1, 4

Clinical Management

• Monitor liver function tests and serum bilirubin during the acute phase 4
• Serum aminotransferases typically decrease by approximately 75% per week after peak levels 4
• Jaundice persists for <2 weeks in approximately 85% of cases 4
• Chronic hepatitis does not occur with hepatitis A infection 4

Infection Control

• Enteric precautions are required only during the first two weeks of illness and one week after onset of jaundice 5
• Maximal viral excretion occurs before jaundice onset, so isolation after hospitalization has limited benefit 6
• Standard blood and body fluid precautions apply 5

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Immune Checkpoint Inhibitor-Induced Hepatitis

Grade 1 (AST/ALT 1-3× ULN or Bilirubin 1-1.5× ULN)

• Monitor liver chemistries once or twice weekly without treatment delay 1, 7
• Continue immune checkpoint inhibitor (ICI) therapy 1

Grade 2 (AST/ALT >3-5× ULN or Bilirubin >1.5-3× ULN)

• Hold all potentially hepatotoxic medications and discontinue non-essential drugs 1, 7
• Consult gastroenterology or hepatology 1, 7
• Prednisone 0.5-1.0 mg/kg/day may be administered only if clinical symptoms of severe liver toxicity are present 1, 7
• ICI may be resumed if patient recovers to grade 1 hepatitis with steroid dose ≤10 mg prednisone daily 1

Grade 3 (AST/ALT >5-20× ULN or Bilirubin >3-10× ULN)

• Discontinue ICI therapy and initiate glucocorticoids at 1-2 mg/kg methylprednisolone or equivalent 1
• Urgent gastroenterology/hepatology consultation is required 1
• Consider liver biopsy and hospitalization on a case-by-case basis 1
• Plan 4-6 week steroid taper 1
• If no response within 3-5 days, add second-line immunomodulators (azathioprine, mycophenolate mofetil, or tacrolimus) 1
• Infliximab should be used with caution due to potential idiosyncratic liver toxicity 1

Grade 4 (AST/ALT >20× ULN or Bilirubin >10× ULN or Hepatic Decompensation)

• Hospitalize at a referral center with liver failure expertise 1
• Permanently discontinue ICI treatment 1
• Start 2 mg/kg/day methylprednisolone with planned 4-6 week taper 1
• If transaminases do not drop by at least 50% in 3 days, start secondary immunosuppression with azathioprine, mycophenolate mofetil, or tacrolimus 1
• Antithymocyte globulin is reserved for refractory and severe cases only 1