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Patients with chronic delta hepatitis (CDH) exhibit higher levels of morbimortality than those with hepatitis B only, generating higher indirect costs for society. The aim of this study was to estimate the loss of productivity and costs resulting from work absenteeism and presenteeism as well as premature mortality among patients with CDH in Spain. Patients with CDH in their working age (between 20-65 years) were estimated by an epidemiological flow model that incorporated the prevalence of infection with the hepatitis B and D viruses. To calculate the costs (year-2023) of absenteeism and presenteeism (over a time horizon of 1 year) as well as premature mortality (i.e., the period from death to expected retirement age), as measured in years of productive life lost (YPLL), the human capital method was used. Specific variables pertaining to the Spanish labour market (working population with hepatitis D virus (HDV), working days, average number of hours worked and gross annual salary) were considered for each sex and age group and distinguished based on infection status. All parameters were obtained from the literature and Spanish databases. A total of 1,313 CDH patients of working ages (59% men, 41% women) and 97 patients who performed unpaid housework were identified. A total of 300,113 working hours were lost per year (29,015 hours/absenteeism and 271,098 hours/presenteeism), which entailed total annual costs of €4.5M (€536,400/absenteeism and €3.9M/presenteeism) related to CDH. Among patients of working ages, CDH was estimated to cause 28 annual deaths at a cost of €8.2 M, resulting in 449 YPLL at an average cost of €18,297/YPLL. The indirect costs were estimated to be € 12.7M. CDH entails significant economic burdens for society. Consideration of the indirect costs associated with CDH is crucial with respect to the design of public health policies and interventions.

Pegylated interferon (peginterferon) alfa 2a or 2b plus ribavirin regimens were the standard of care in patients with hepatitis C virus (HCV) infection, but the sustained virological response can be suboptimum in patients with HCV genotype 1 infection. The efficacy, safety, and tolerability of the combination of simeprevir, a one-pill, once-daily, oral HCV NS3/4A protease inhibitor versus placebo, plus peginterferon alfa 2a or 2b plus ribavirin was assessed in treatment-naive patients with HCV genotype 1 infection. In the QUEST-2, phase 3 study, done at 76 sites in 14 countries (Europe, and North and South Americas), patients with confirmed chronic HCV genotype 1 infection and no history of HCV treatment were randomly assigned with a computer-generated allocation sequence in a ratio of 2:1 and stratified by HCV genotype 1 subtype and host IL28B genotype to receive simeprevir (150 mg once daily, orally), peginterferon alfa 2a (180 μg once weekly, subcutaneous injection) or 2b (according to bodyweight; 50 μg, 80 μg, 100 μg, 120 μg, or 150 μg once weekly, subcutaneous injection), plus ribavirin (1000–1200 mg/day or 800–1400 mg/day, orally; simeprevir group) or placebo (once daily, orally), peginterferon alfa 2a or 2b, plus ribavirin (placebo group) for 12 weeks, followed by just peginterferon alfa 2a or 2b plus ribavirin. Total treatment duration was 24 weeks or 48 weeks (simeprevir group) based on criteria for response-guided therapy (ie, HCV RNA <25 IU/mL undetectable or detectable at week 4 and undetectable week 12) or 48 weeks (placebo). Patients, study personnel, and the sponsor were masked to treatment assignment. The primary efficacy endpoint was sustained virological response at 12 weeks after the planned end of treatment (SVR12). Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01290679. Results from the primary (SVR12, week 60) analysis are presented. 209 (81%) of 257 patients in the simeprevir group and 67 (50%) of 134 in the placebo group had SVR12 (adjusted difference 32·2%, 95% CI 23·3–41·2; p<0·0001). The incidences of adverse events were similar in the simeprevir and placebo groups at 12 weeks (246 [96%] vs 130 [97%]) and for the entire treatment (249 [97%] vs 132 [99%]), irrespective of the peginterferon alfa used. The most common adverse events were headache, fatigue, pyrexia, and influenza-like illness at 12 weeks (95 [37%) vs 45 [34%], 89 [35%] vs 52 [39%], 78 [30%] vs 48 [36%], and 66 [26%] vs 34 [25%], respectively) and for the entire treatment (100 [39%] vs 49 [37%], 94 [37%] vs 56 [42%], 79 [31%] vs 53 [40%], and 66 [26%] vs 35 [26%], respectively). Rash and photosensitivity frequencies were higher in the simeprevir group than in the placebo group (61 [24%] vs 15 [11%] and ten [4%] vs one [<1%], respectively). There was no difference in the prevalence of anaemia between the simeprevir and placebo groups (35 [14%] vs 21 [16%], respectively, at 12 weeks, and 53 [21%] vs 37 [28%], respectively, during the entire treatment). Addition of simeprevir to either peginterferon alfa 2a or peginterferon alfa 2b plus ribavirin improved SVR in treatment-naive patients with HCV genotype 1 infection, without worsening the known adverse events associated with peginterferon alfa plus ribavirin. Janssen Infectious Diseases–Diagnostics.

Whether long-term suppression of replication of hepatitis B virus (HBV) has any beneficial effect on regression of advanced liver fibrosis associated with chronic HBV infection remains unclear. We aimed to assess the effects on fibrosis and cirrhosis of at least 5 years' treatment with tenofovir disoproxil fumarate (DF) in chronic HBV infection. After 48 weeks of randomised double-blind comparison (trials NCT00117676 and NCT00116805) of tenofovir DF with adefovir dipivoxil, participants (positive or negative for HBeAg) were eligible to enter a 7-year study of open-label tenofovir DF treatment, with a pre-specified repeat liver biopsy at week 240. We assessed histological improvement (≥2 point reduction in Knodell necroinflammatory score with no worsening of fibrosis) and regression of fibrosis (≥1 unit decrease by Ishak scoring system). Of 641 patients who received randomised treatment, 585 (91%) entered the open-label phase, and 489 (76%) completed 240 weeks. 348 patients (54%) had biopsy results at both baseline and week 240. 304 (87%) of the 348 had histological improvement, and 176 (51%) had regression of fibrosis at week 240 (p<0·0001). Of the 96 (28%) patients with cirrhosis (Ishak score 5 or 6) at baseline, 71 (74%) no longer had cirrhosis (≥1 unit decrease in score), whereas three of 252 patients without cirrhosis at baseline progressed to cirrhosis at year 5 (p<0·0001). Virological breakthrough occurred infrequently and was not due to resistance to tenofovir DF. The safety profile was favourable: 91 (16%) patients had adverse events but only nine patients had serious events related to the study drug. In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective. Long-term suppression of HBV can lead to regression of fibrosis and cirrhosis. Gilead Sciences.

The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). Most HCV patients treated with these drugs achieve viral elimination, but 1% to 15% fail to attain this objective. Treatment failures are usually related to relapse, and less often to on-treatment viral breakthrough. HCV drug resistant associated substitutions are detected in most patients who do not eliminate the virus. The risk of developing these variants depends on host- and virus-related factors, the properties of the drugs used, and the treatment strategies applied. Patients who carry Resistant Associated Substitutions (RASs) may not obtain benefits from treatment, and are at a risk of disease progression. Whether HCV RASs persist depends on their type: NS3-4A variants often disappear gradually after DAA therapy is stopped, whereas NS5A variants tend to persist for more than 2 years. The best way to prevent emergence of resistant variants is to eliminate the virus at the first treatment using highly potent DAAs with genetic barriers to resistance. For those who fail an NS5A inhibitor, deferral of treatment is recommended pending the availability of additional data if they do not have cirrhosis or reasons for urgent re-treatment. If re-treatment is needed, the most commonly used strategy is sofosbuvir as backbone therapy plus a drug from a class other than that previously used, for 24 weeks. Unless it is contraindicated, weight-based ribavirin should also be added. If available, nucleotide-based (eg, sofosbuvir) triple or quadruple DAA regimens may be considered. The optimal treatment for patients who fail an NS5A inhibitor and those with multidrug-resistant variants remains to be defined, and research efforts should continue to focus on treatment for these patients.

Tenofovir alafenamide fumarate (TAF), a new prodrug of tenofovir and a potential successor of tenofovir disoproxil fumarate (TDF), has been approved in the United States and Europe for treating adolescents and adults with chronic hepatitis B infection. TAF is formulated to deliver the active metabolite to target cells more efficiently than TDF at lower doses, thereby reducing systemic exposure to tenofovir. In patients with chronic hepatitis B, TAF appears to be as effective as TDF, with lower bone and renal toxicity. TAF has the potential advantages that dose adjustment is not required in patients with renal impairment, and monitoring can be less intense because of the better safety profile. Results from 2 large, randomized, phase 3 studies after 48 weeks of therapy have shown that TAF may be a good alternative to TDF for treating chronic hepatitis B. Whether the short-term benefits observed in these 48-week trials will translate into improvements in bone and renal health in patients receiving long-term treatment remains to be seen.

Elimination of hepatitis C virus (HCV) infection requires high diagnostic rates and universal access to treatment. Around 40% of infected individuals are unaware of their infection, which indicates that effective screening strategies are needed. We analyzed the efficiency (incremental cost-utility ratio, ICUR) of 3 HCV screening strategies: a) general population of adults, b) high-risk groups, and c) population with the highest anti-HCV prevalence plus high-risk groups. An analytical decision model, projecting progression of the disease over a lifetime, was used to establish the candidate population for HCV screening. HCV data were obtained from the literature: anti-HCV prevalence (0.56%-1.54%), viremic patients (31.5%), and percentage of undiagnosed persons among those with viremia (35%). It was assumed that most patients would be treated and have HCV therapy response (98% SVR); transition probabilities, utilities, and disease management annual costs were obtained from the literature. Efficiency over the life of patients under the National Health System perspective was measured as quality-adjusted life years (QALY) and total cost (screening, diagnosis, pharmacological and disease management). A discount rate of 3% was applied to costs and outcomes. Screening of the adult population would identify a larger number of additional chronic hepatitis C cases (N = 52,694) than screening the highest anti-HCV prevalence population plus high-risk groups (N = 42,027) or screening high-risk groups (N = 26,128). ICUR for the general population vs. high-risk groups was €8914/QALY gained per patient (€18,157 incremental cost and 2.037 QALY). ICUR for the general population vs. population with highest anti-HCV prevalence plus high-risk groups was €7,448/QALY gained per patient (€7,733 incremental cost and 1.038 QALY). These ICUR values are below the accepted efficiency threshold (€22,000-€30,000). HCV screening and treatment of the general adult population is cost-effective compared to screening of high-risk groups or the population with the highest anti-HCV prevalence plus high-risk groups.

Strong multidisciplinary support and political commitment have helped Spain become one of the countries most likely to eliminate hepatitis C. In this Comment, we set out six key elements of the Spanish elimination effort that can serve as a model elsewhere and the remaining barriers to overcome.

Background: In the past decades, global changes, including hepatitis B vaccination, hepatitis B and C antiviral therapies, and the increasing prevalence of steatotic liver disease, have influenced the landscape of liver cancer etiologies. Methods: We performed a retrospective study focused on the etiological factors of de novo hepatocellular carcinoma (HCC) diagnoses in an academic center between 2019 and 2022. Results: Among 352 consecutive patients with HCC, alcohol-related liver disease was the predominant etiology (33.3%), followed by hepatitis C (HCV) infection (30.7%). Significant associations were found between HCC etiology and patient demographics, BCLC stage at diagnosis, and cirrhosis prevalence. Conclusions: Whereas accessibility to antiviral therapy is granted, HCV infection remains as one of the main HCC etiologies. MASLD-related HCC, although growing globally, is not as relevant in our area. Strong public policies need to be implemented to prevent alcohol consumption, the main etiology of liver disease and liver cancer.

Hepatitis D virus was first described by Mario Rizzeto in 1977, and it is considered chronic viral hepatitis with the poorest prognosis. Despite its discovery almost 50 years ago, progress in its diagnosis and treatment has been scarce until recent years. The approval of bulevirtide has shed some light for patients with Chronic Hepatitis D, although important gaps regarding its use in therapy as well as about the epidemiology and diagnosis of the disease need to be addressed.

In this randomized comparison of treatment with tenofovir disoproxil fumarate or adefovir dipivoxil for 48 weeks in patients with chronic hepatitis B, tenofovir was more likely to result in viral suppression. The follow-up period was not long enough to assess the resistance patterns, risks, and benefits of long-term treatment. In this randomized comparison of treatment with tenofovir disoproxil fumarate or adefovir dipivoxil for 48 weeks in patients with chronic hepatitis B, tenofovir was more likely to result in viral suppression. Chronic hepatitis B virus (HBV) infection is a major health problem. 1 – 3 Since most patients with chronic HBV infection require long-term therapy, 4 – 6 there is a need for new drugs with potent antiviral activity and established long-term safety, as well as a proven low rate of HBV antiviral resistance, a high genetic barrier (i.e., requiring more than one amino acid substitution to confer resistance to HBV treatment), or both. The ultimate goal of treatment of chronic HBV infection is to prevent liver complications. This goal is seldom achieved through hepatitis B surface antigen (HBsAg) loss and seroconversion, which are associated . . .