Patient profiled data for treatment decision-making: valuable as an add-on to hepatitis C clinical guidelines?

BACKGROUND AND AIMS: Systematic reviews and medical guidelines are widely used in clinical practice. However, these are often not up-to-date and focussed on the average patient. We therefore aimed to evaluate a guideline add-on, TherapySelector (TS), which is based on monthly updated data of all available high-quality studies, classified in specific patient profiles. METHODS: We evaluated the TS for the treatment of hepatitis C (HCV) in an international cohort of patients treated with direct-acting antivirals between 2015 and 2020. The primary outcome was the number of patients receiving one of the two preferred treatment options of the HCV TS, based on the highest level of evidence, cure rate, absence of ribavirin-associated adverse effects, and treatment duration. RESULTS: We enrolled 567 patients. The number of patients treated with one of the two preferred treatment options according to the HCV TS ranged between 27% (2015) and 60% (2020; p < 0.001). Most of the patients received a regimen with a longer treatment-duration (up to 34%) and/or addition of ribavirin (up to 14%). The effect on the expected cure-rate was minimal (1-6% higher) when the first preferred TherapySelector option was given compared to the actual treatment. CONCLUSIONS: Medical decision-making can be optimised by a guideline add-on; in HCV its use appears to minimise adverse effects and cost. The use of such an add-on might have a greater impact in diseases with suboptimal cure-rates, high costs or adverse effects, for which treatment options rely on specific patient characteristics.

The influence of ethnicity on disease outcome in patients with chronic hepatitis B infection.

Since the cultural diversity in Western Europe is growing, this study assessed whether foreign-born chronic hepatitis B (CHB) patients have more cirrhosis than Dutch- or Belgian-born patients, with a main focus on the Turkish population. Baseline characteristics (eg, socioeconomic status [SES]), biological characteristics, and disease outcome (eg, cirrhosis) were collected for all patients. Between December 2009 and January 2015, 269 CHB patients participated from the outpatient departments of three hospitals in the Netherlands, Belgium, and Turkey. Out of the 269 CHB patients, 210 were foreign-born and 59 were Dutch- or Belgian-born. Compared with Dutch- or Belgian-born patients, foreign-born patients had a higher prevalence of low SES (58% vs 31%; P = 0.001) and cirrhosis (27% vs 10%; P = 0.007). Among the Turkish population, there were no significant differences regarding the prevalence of low SES (73% vs 61%; P = 0.170), alcohol abuse (1% vs 5%; P = 0.120), anti-hepatitis C virus positivity (4% vs 0%; P = 0.344), anti-hepatitis D virus positivity (1% vs 6%; P = 0.297), and cirrhosis (37% vs 27%; P = 0.262) between patients (n = 102) living in Turkey (local) and Turkish CHB (n = 38) patients living in the Netherlands or Belgium (immigrant). In multivariate analysis, low SES (odds ratio, 5.7; 95% confidence interval, 2.3-14.5; P < 0.001) was associated with cirrhosis. In this study, foreign-born CHB patients were associated with more advanced HBV-related liver disease with 27% having cirrhosis. However, ethnicity was not associated with cirrhosis when SES was included in the multivariate analysis. The similar prevalence of cirrhosis in local Turkish compared to immigrant Turkish CHB patients is novel and warrants further investigation.

Declining Hepatitis C Virus (HCV) Incidence in Dutch Human Immunodeficiency Virus-Positive Men Who Have Sex With Men After Unrestricted Access to HCV Therapy.

Background: Direct-acting antivirals (DAAa) cure hepatitis C virus (HCV) infections in 95% of infected patients. Modeling studies predict that universal HCV treatment will lead to a decrease in the incidence of new infections but real-life data are lacking. The incidence of HCV among Dutch human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) has been high for >10 years. In 2015 DAAs became available to all Dutch HCV patients and resulted in a rapid treatment uptake in HIV-positive MSM. We assessed whether this uptake was followed by a decrease in the incidence of HCV infections. Methods: Two prospective studies of treatment for acute HCV infection enrolled patients in 17 Dutch HIV centers, having 76% of the total HIV-positive MSM population in care in the Netherlands. Patients were recruited in 2014 and 2016, the years before and after unrestricted DAA availability. We compared the HCV incidence in both years. Results: The incidence of acute HCV infection decreased from 93 infections during 8290 person-years of follow-up (PYFU) in 2014 (11.2/1000 PYFU; 95% confidence interval [CI], 9.1-13.7) to 49 during 8961 PYFU in 2016 (5.5/1000 PYFU; 4.1-7.2). The incidence rate ratio of 2016 compared with 2014 was 0.49 (95% CI, .35-.69). Simultaneously, a significant increase in the percentage positive syphilis (+2.2%) and gonorrhea (+2.8%) tests in HIV-positive MSM was observed at sexual health clinics across the Netherlands and contradicts a decrease in risk behavior as an alternative explanation. Conclusions: Unrestricted DAA availability in the Netherlands was followed by a 51% decrease in acute HCV infections among HIV-positive MSM.

Boceprevir, peginterferon and ribavirin for acute hepatitis C in HIV infected patients.

BACKGROUND & AIMS: Acute hepatitis C virus infections (AHCV) are prevalent among HIV positive men having sex with men and generally treated with pegylated interferon-alpha (PegIFN) and ribavirin (RBV) during 24weeks. The addition of a protease inhibitor could shorten therapy without loss of efficacy. METHODS: We performed an open-label, single arm study to investigate the efficacy and safety of a 12-week course of boceprevir, PegIFN and RBV for AHCV genotype 1 infections in 10 Dutch HIV treatment centers. The primary endpoint of the study was achievement of sustained virological response rate at week 12 (SVR12) in patients reaching a rapid viral response at week 4 (RVR4) and SVR12 in the intent to treat (ITT) entire study population was the most relevant secondary endpoint. RESULTS: One hundred twenty-seven AHCV patients were screened in 16 months, of which 65 AHCV genotype 1 patients were included. After spontaneous clearance in six patients and withdrawal before treatment initiation in two, 57 started therapy within 26 weeks after infection. RVR4 rate was 72%. SVR12 rate was 100% in the RVR4 group. SVR12 rate in the ITT group was 86% and comparable to the SVR12 rate of 84% in 73 historical controls treated for 24 weeks with PegIFN and RBV in the same study centers. CONCLUSION: With the addition of boceprevir to PegIFN and RBV, treatment duration of AHCV genotype 1 can be reduced to 12 weeks without loss of efficacy. Given the high drug costs and limited availability of interferon-free regimens, boceprevir PegIFN and RBV can be a considered a valid treatment option for AHCV. ClinicalTrials.gov, number NCT01912495.

Long-term follow-up of hepatitis C infection in a large cohort of patients with inherited bleeding disorders.

BACKGROUND & AIMS: Patients with inherited bleeding disorders are an interesting group to study the long-term course of chronic hepatitis C virus (HCV) infection, because of their uniform mode of infection and reliable follow-up. Our aim was to assess the long-term occurrence of adverse liver-related events in these patients. METHODS: The occurrence and determinants of end-stage liver disease (ESLD) were assessed using retrospective data of 863 HCV infected patients with inherited bleeding disorders from the Netherlands and the UK. RESULTS: Median follow-up since HCV infection was 31 years, while 30% of patients had >35 follow-up years. Nineteen percent of patients spontaneously cleared the virus and 81% developed chronic HCV infection. Of the 700 patients with chronic HCV, 90 (13%) developed ESLD. Hepatocellular carcinoma (HCC) was diagnosed in 3% of patients with chronic HCV, 41% of which occurred in the last six years. Determinants of ESLD development were age at infection (hazard ratio (HR) 1.09 per year increase), HIV co-infection (HR 10.85), history of alcohol abuse (HR 4.34) and successful antiviral treatment (HR 0.14). Of the 487 patients who were still alive at the end of follow-up, 49% did not undergo optimal conventional antiviral treatment. CONCLUSIONS: After over 30 years of HCV infection, ESLD occurred in a significant proportion of patients with inherited bleeding disorders. HCC appears to be an increasing problem. There is a significant potential for both conventional and new antiviral treatment regimens to try and limit ESLD occurrence in the future.

Acute internal medicine physicians' clinical intuition based on acute care telephone referral: A prospective study.

INTRODUCTION: In the Netherlands, most emergency department (ED) patients are referred by a general practitioner (GP) or a hospital specialist. Early risk stratification during telephone referral could allow the physician to assess the severity of the patients' illness in the prehospital setting. We aim to assess the discriminatory value of the acute internal medicine (AIM) physicians' clinical intuition based on telephone referral of ED patients to predict short-term adverse outcomes, and to investigate on which information their predictions are based. METHODS: In this prospective study, we included adult ED patients who were referred for internal medicine by a GP or a hospital specialist. Primary outcomes were hospital admission and triage category according to the Manchester Triage System (MTS). Secondary outcome was 31-day mortality. The discriminatory performance of the clinical intuition was assessed using an area under the receiver operating characteristics curve (AUC). To identify which information is important to predict adverse outcomes, we performed univariate regression analysis. Agreement between predicted and observed MTS triage category was assessed using intraclass and Spearman's correlation. RESULTS: We included 333 patients, of whom 172 (51.7%) were referred by a GP, 146 (43.8%) by a hospital specialist, and 12 (3.6%) by another health professional. The AIM physician's clinical intuition showed good discriminatory performance regarding hospital admission (AUC 0.72, 95% CI: 0.66-0.78) and 31-day mortality (AUC 0.73, 95% CI: 0.64-0.81). Univariate regression analysis showed that age ≥65 years and a sense of alarm were significant predictors. The predicted and observed triage category were similar in 45.2%, but in 92.5% the prediction did not deviate by more than one category. Intraclass and Spearman's correlation showed fair agreement between predicted and observed triage category (ICC 0.48, Spearman's 0.29). CONCLUSION: Clinical intuition based on relevant information during a telephone referral can be used to accurately predict short-term outcomes, allowing for early risk stratification in the prehospital setting and managing ED patient flow more effectively.

Cascade of care among hepatitis B patients in Maastricht, the Netherlands, 1996 to 2018.

Background & aims: There are approximately 49,000 people (0.34%) in the Netherlands with a chronic hepatitis B virus (HBV) infection. It is unclear how many are linked to care and under follow-up in hepatitis outpatient clinics. This study determined the cascade of care and identified predictors for not being linked to care and loss to follow-up in Maastricht, the Netherlands. Methods: All hepatitis B surface antigen (HBsAg)-positive patients between December 1, 1996 and September 30, 2018 were retrospectively identified. Results: In total, 644 HBsAg-positive patients were identified; of whom 75 had acute HBV infection, 471 chronic HBV infection and 98 unknown. Out of 569 individuals with a chronic/unknown HBV status, 134/569 (23.6%) were not linked to care and 58.7% (195/332 after excluding those who died or achieved HBsAg-seroclearance) were loss to follow-up (LTFU). A predictor for not being linked to care was Caucasian ethnicity (odds ratio (OR) = 2.76 (95% Confidence Interval (CI) = 1.21-6.29); p = .015). Predictors for LTFU were older age (OR = 0.97 (CI = 0.94-0.99); p = .008), HBV DNA >20,000 IU/mL (OR = 0.44 (CI = 0.21 - 0.93); p = .033) and Asian ethnicity (OR = 0.46, (CI = 0.21-1.00); p = .050). Rates of not being linked to care and LTFU decreased over time from 12.7% in 1996 to 4.4% in 2018 and from 79.2% in 1996 to 37.2% in 2018, respectively. Conclusions: A considerable amount of HBsAg-positive individuals were not linked to care or LTFU. This study indicates that ethnicity plays a role in linkage to care and follow-up. Further research is needed to elaborate on those results.

Mpox vaccination willingness, determinants, and communication needs in gay, bisexual, and other men who have sex with men, in the context of limited vaccine availability in the Netherlands (Dutch Mpox-survey).

Introduction: In the 2022 multicountry mpox (formerly named monkeypox) outbreak, several countries offered primary preventive vaccination (PPV) to people at higher risk for infection. We study vaccine acceptance and its determinants, to target and tailor public health (communication-) strategies in the context of limited vaccine supply in the Netherlands. Methods: Online survey in a convenience sample of gay, bisexual and other men who have sex with men, including transgender persons (22/07-05/09/2022, the Netherlands). We assessed determinants for being (un)willing to accept vaccination. We used multivariable multinominal regression and logistic regression analyses, calculating adjusted odds ratios (aOR) and 95 percent confidence-intervals. An open question asked for campaigning and procedural recommendations. Results: Of respondents, 81.5% (n = 1,512/1,856) were willing to accept vaccination; this was 85.2% (799/938) in vaccination-eligible people and 77.7% (713/918) in those non-eligible. Determinants for non-acceptance included: urbanization (rural: aOR:2.2;1.2-3.7; low-urban: aOR:2.4;1.4-3.9; vs. high-urban), not knowing mpox-vaccinated persons (aOR:2.4;1.6-3.4), and lack of connection to gay/queer-community (aOR:2.0;1.5-2.7). Beliefs associated with acceptance were: perception of higher risk/severity of mpox, higher protection motivation, positive outcome expectations post vaccination, and perceived positive social norms regarding vaccination. Respondents recommended better accessible communication, delivered regularly and stigma-free, with facts on mpox, vaccination and procedures, and other preventive options. Also, they recommended, "vaccine provision also at non-clinic settings, discrete/anonymous options, self-registration" to be vaccinated and other inclusive vaccine-offers (e.g., also accessible to people not in existing patient-registries). Conclusion: In the public health response to the mpox outbreak, key is a broad and equitable access to information, and to low-threshold vaccination options for those at highest risk. Communication should be uniform and transparent and tailored to beliefs, and include other preventive options. Mpox vaccine willingness was high. Public health efforts may be strengthened in less urbanized areas and reach out to those who lack relevant (community) social network influences.