Highlights
- Recent breakthroughs offer hope for functional cures of hepatitis B and C, transforming chronic liver disease management.
- Direct-acting antivirals have revolutionized HCV treatment, achieving cure rates over 90% and improving patient quality of life.
- Continued research and enhanced access to innovative therapies are essential to overcome treatment challenges and optimize outcomes.
Summary and Background
Recent advances in hepatitis B (HBV) and hepatitis C (HCV) treatments have significantly improved patient outcomes. HBV affects millions worldwide and is a major cause of liver cirrhosis and cancer, causing about 900,000 deaths annually. Current HBV treatments suppress viral replication but rarely achieve a functional cure, defined as sustained loss of hepatitis B surface antigen (HBsAg) and undetectable viral DNA without ongoing therapy. New therapies like antisense oligonucleotides, small interfering RNAs, monoclonal antibodies, and immunomodulators show promise but need further validation.
HCV treatment has been revolutionized by direct-acting antivirals (DAAs) that target viral proteins, achieving cure rates above 90%. DAAs have replaced interferon-based therapies with safer, shorter oral regimens. Despite this, challenges such as drug resistance, access barriers, and treatment in advanced liver disease remain. These advances mark a shift from viral suppression to functional cure and eradication goals.
Advances in Hepatitis B and C Treatments
HBV therapies are evolving from viral suppression to functional cures using novel agents including entry inhibitors, monoclonal antibodies, transcription inhibitors, and immunomodulators. Sequential treatment strategies aim to reduce HBsAg before immunomodulation to enhance cure rates. Patient evaluation through clinical and imaging assessments guides therapy candidacy.
HCV treatment has advanced from interferon-based regimens to all-oral DAAs targeting NS3/4A protease, NS5A, and NS5B polymerase enzymes, achieving over 90% sustained virologic response. Remaining issues include drug interactions, resistant variants, lower efficacy in cirrhosis, and high costs. New DAAs and combination therapies are being developed to address these challenges.
Clinical Trials and Research
Clinical trials of novel HBV therapies like bepirovirsen, an antisense oligonucleotide, show significant reductions in HBsAg and viral DNA. Phase 3 studies are ongoing to evaluate combination therapy with nucleos(t)ide analogues. The GIGA-2339 recombinant antibody therapy, highly potent in preclinical studies, is entering phase 1 trials. Trial designs now focus on broader populations and stratification by viral markers to improve applicability. Combination regimens involving RNA interference and immunomodulators are under investigation to improve functional cure rates.
Impact on Patient Outcomes
DAAs have transformed HCV treatment by achieving cure rates above 90%, improving patient quality of life and reducing liver-related complications, including hepatocellular carcinoma. Early treatment initiation streamlines care and reduces costs. For HBV, current nucleos(t)ide analogues effectively suppress viral replication but rarely achieve functional cure. Novel therapies like bepirovirsen aim to improve long-term outcomes.
Challenges and Limitations
Treatment challenges include balancing clinical trial design for efficacy and generalizability, patient barriers such as adherence and awareness, provider knowledge gaps, and systemic issues like funding and access. HBV immunomodulatory therapies have safety limitations, while HCV DAAs face resistance, drug interactions, and cost barriers. Addressing these requires new antiviral agents, combination therapies, antifibrotic drugs, and expanded care models including primary care involvement.
Future Directions
Future hepatitis treatment efforts focus on overcoming resistance, improving efficacy in cirrhosis, managing drug interactions, and reducing costs. For HBV, the goal remains functional cure with novel agents including entry inhibitors, monoclonal antibodies, and RNA interference-based therapies. Combination regimens show promise, but optimization and criteria for stopping nucleos(t)ide analogues need clarification. Continued research aims to refine therapies and enhance access to achieve durable viral control and cure.
The content is provided by Sierra Knightley, Scopewires
