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The increasing number of direct-acting antiviral (DAA) regimens along with limited number of subjects and co-medications involved in clinical trials results in drug-drug interactions (DDIs) with DAAs is to be determined. We aimed to examine the prevalence and degree of DDIs between DAAs and other co-medications in a territory-wide cohort of chronic hepatitis C virus (HCV) patients.DDIs were assigned to three risk categories: Category 1-no clinically significant DDI; category 2-potential clinically significant interaction (monitoring and caution required); category 3-contraindicated (should not be co-administered).Of 2981 patients (mean age 59.3 ± 12.3 years; male 60.6%), 810 (48.8%) had genotype 1 and 552 (33.2%) genotype 6 HCV among the 1661 patients with HCV genotype tested; 769 (25.8%) received sofosbuvir/velpatasvir, 510 (17.1%) sofosbuvir/ledipasvir, and 865 (29.0%) glecaprevir/pibrentasvir. More than one-fourth (26.3%) of the patients have polypharmacy (≥ 3 co-medications) in all patients, 27.0% in patients received sofosbuvir/velpatasvir, 25.1% in elbasvir/grazoprevir, and 21.2% in glecaprevir/pibrentasvir. 2037 (68.3%) patient experienced DDI (Category 2: 53.1%; Category 3: 15.2%). The commonest drugs leading to DDIs were calcium channel blockers (31.5%) and proton pump inhibitors (23.0%) in category 2; statins (10.2%), antiplatelet/anticoagulants (3.0%) and antipsychotics (2.9%) in category 3. Changing medication was the most common response from physicians in both category 2 and 3 DDIs.The commonest co-medications leading to contraindication during DAA treatment were statins and antipsychotics. Category 2 and 3 DDIs are often managed by appropriate dose adjustments or temporary discontinuation of relevant co-medications. Careful assessment for potential DDI before DAA use is mandatory to avoid potential harmful effects.

Reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is the key ultimate goal set in essentially all treatment guidelines. There has been solid evidence supporting the relationship between serum hepatitis B virus (HBV) DNA level and risk of HCC. Antiviral treatment with oral nucleos(t)ide analogues (NAs) leads to sustained viral suppression and hence is often adopted as the secondary prevention for HCC in CHB patients. The first-generation NA, lamivudine, reduced the risk of HCC at 3 years compared to placebo; yet, its high emergence of antiviral resistance has made it no longer recommended in the international guidelines. Recent heated debate is about the two current first-line NAs—entecavir and tenofovir disoproxil fumarate (TDF)—Are they just as good to reduce HCC risk in CHB patients? A handful of cohort studies show two different kinds of observations—TDF is better than entecavir in lowering HCC risk, or these two NAs have led to similarly low risk of HCC. Tenofovir alafenamide (TAF), a modified version of TDF higher rate of ALT normalization, would be another potent nucleotide analogue is the treatment of choice for secondary prevention for HCC.