Universal screening for viral hepatitis in all inpatients of a university internal medicine department

Introduction

There has been a growing interest throughout the international medical community in the elimination of viral hepatitis as a public health threat, exemplified by the goals set by the World Health Organization (WHO) to drastically reduce new infections (90% reduction) and deaths (65% reduction) from hepatitis B and C viruses (HBV/C) by 2030 [1]. However, many reports have highlighted difficulties in achieving these goals, mainly due to the inability to identify and diagnose significant parts of the infected population [2]. Furthermore, significant challenges remain concerning prevention and treatment in many parts of the world [3].

Many strategies have been proposed to screen both high- and average-risk populations. Strategies for high-risk populations have mainly focused on patients with human immunodeficiency virus, people who inject drugs, and incarcerated patients [4,5]. With regards to screening strategies that focus on the general population, most efforts have concentrated on age-based reminders for screening to physicians and patients, as well as opportunistic screening in patients visiting healthcare facilities [6-8]. In many countries, national recommendations involve the screening of all adults at least once during their lifetime [9,10]. Although many strategies have been effectively implemented to diagnose and treat high-risk patients, there has been no implementation of screening strategies for the general population. This study aimed to explore the efficacy of universal screening for hospitalized patients with HBV/C viruses, as a potentially easy and effective screening strategy that could aid in the global effort to eradicate viral hepatitis.

Patients and methods

Results

A total of 3914 patients were included in this study. The majority of patients were male (56.5%), with a mean age of 69.8±16.9 years. A total of 112 (2.9%) and 102 patients (2.7%) tested positive for HBsAg and anti-HCV antibodies, respectively. In addition, 1281 (32.8%) patients were positive for anti-HBc, of whom 112 (8.7%) had positive HBsAg, 952 (74.4%) had positive anti-HBs, and 217 (16.9%) had neither HBsAg nor anti-HBs positivity.

The presence of positive surface antigens was more common in patients aged 41-65 years (4.1%) than in patients over 65 years old (2.4%) and those under 40 years old (2.7%). Patients born in a foreign country accounted for 21.2% of patients with positive surface antigen, with the vast majority falling within the 41-65 age group (58.3%). In addition, the presence of prior infection (positive anti-HBc) was significantly correlated with patient age (P<0.001), with patients >65 years of age having a much higher prevalence (39.9%) than patients aged 41-65 years (20.9%) or ≤40 years (9.5%). The presence of positive anti-HCV antibodies was more common in patients aged ≤40 years (9.1%) than in patients aged 41-64 years (3.5%) or >65 years (1.6%).

During hospitalization, HBV DNA testing was performed in 65 patients (58% positive for HBsAg), with 60 patients having detectable HBV DNA (92.3%). Of these, 13 had chronic HBV infection, and 47 had chronic HBV hepatitis. In addition, 23 HBsAg-positive patients died during hospitalization (20.1%), of whom 8 had chronic HBV hepatitis. No deaths were liver-related. Finally, 28 patients (71.8%) received treatment. There was a significant correlation between age and whether the patients progressed to the next level of testing or received therapy, with patients in whom further tests or treatment were not pursued being significantly older than patients who underwent all tests and received treatment when indicated (70.2±14.7 vs. 61.6±15.4 years, P=0.017).

Among patients who tested positive for anti-HCV antibodies, 53 (52%) underwent HCV RNA testing, while 11 died during hospitalization, of whom 4 had positive HCV RNA. No deaths were liver-related. HCV RNA was detected in 29 patients (54.7%), and 13 of 25 surviving patients ultimately received treatment (52% of the eligible patients). The process, from screening to treatment initiation, is illustrated in Fig. 1. As with HBV patients, HCV patients who did not undergo further tests or treatment were significantly older than patients who underwent all tests and received treatment when indicated (57±18.1 vs. 35.8±10.2 years, P=0.007).

Figure 1 Cascade of care from screening to treatment for hepatitis B (A) and C (B)

Discussion

Our study demonstrated that HBV and HCV screening can be effective among inpatients in an internal medicine department of a tertiary hospital. Establishing such practices in hospitals worldwide may significantly enhance HBV and HCV elimination.

The percentages of patients positive for HBsAg and anti-HCV antibodies were consistent with those reported in previous Greek studies [12,13]. However, our results show a slightly higher prevalence for both HBV and HCV, potentially attributed to the fact that hospitalized patients may have significantly more disease risk factors than the general population. This is further explained by the fact that a significant percentage of anti-HCV-positive patients were under 40 years old (hospitalization at a young age is associated with substance abuse in many patients [14]) and that a substantial number of HBsAg-positive patients were born in another country. Nevertheless, concomitant screening for patients from high-risk populations can be characterized as an additional benefit of this strategy, as these patients had not been identified by other screening strategies.

Regarding the percentage of patients lost during the cascade of care who did not undergo further testing or receive treatment, the characteristics of our cohort should be taken into account. Due to the severity of chronic illnesses in patients hospitalized in an internal medicine department in Greece (owing to the absence of geriatric departments), many discharged patients have a significantly shortened life expectancy, causing further diagnostic workup or treatment to be deemed irrelevant by the attending physicians. This is highlighted by the fact that patients who did not undergo further tests or were not prescribed treatment were significantly older than patients who underwent all relevant tests and were treated when indicated. Nevertheless, efforts to minimize potential deficiencies in proceeding with the appropriate diagnostic workup, or establishing contact with patients eligible for treatment, are vital. To this end, hospital policies should formalize this type of screening and ensure that specific staff are tasked with implementing the entire cascade of care for patients identified during the initial screening.

An unintended finding of our study was the significant number of individuals with a history of HBV infection, as highlighted by the very high anti-HBc positivity rate (32.8%). In the era of immunosuppressive therapies that extend to all branches of therapeutic medicine, it is essential to consider that a significant percentage of the Greek population may require antiviral prophylaxis when initiating immunosuppressive treatment.

The overall effect of our study is reflected in the combined diagnostic rate of 5.6% among the screened patients who were positive for either anti-HCV or HBsAg. While many of these patients are not eligible for therapy, the value of maintaining follow up of patients with chronic HBV infection, and using HBV and HCV patients to screen family members, should not be overlooked. Nevertheless, even in terms of patients treated, initiating treatment in 1% (41/3921) of all patients screened is a testament to the effectiveness of this strategy.

Our study had significant limitations, especially when considering its implementation on a broader scale. As the study was conducted in a single department, the results cannot be generalized to the entire country. Moreover, the presence of patients with significant risk factors (especially substance abuse and HCV) may have led to a disproportionately high prevalence of both HBV and HCV in our cohort. The cost-effectiveness of such a strategy should also be assessed, as well as the means to avoid unnecessary testing in patients who have already been tested in another setting or have a very low life expectancy. Finally, the lack of baseline patient information, such as comorbidities, history of substance abuse, and cause for hospitalization, is a significant limitation of the study that impedes the generalization of its findings.

Mass screening of the adult population or all individuals over a certain age is becoming a common strategy in countries that have established plans for viral hepatitis elimination [8,10]. However, the effectiveness of such methods depends on their ability to perform screening. Hospitalized patients may be the most accessible population for such screening efforts, with studies in multiple countries attesting to the effectiveness of in-hospital screening [15-17]. In order to safeguard the application of such programs, individuals should be assigned to supervise the screening process and ensure that the patients complete the necessary workup and are treated accordingly. Additionally, another equally important task that must be taken into account, if such a screening program is implemented, is to ensure that family members of individuals diagnosed with the condition are also tested. Nevertheless, combined with the fact that such programs can be implemented effortlessly in many hospitals, and that a significant part of the adult population visits hospitals for emergency or scheduled examinations, this may be the first step toward mass-screening substantial parts of the adult population for HBV and HCV.

To conclude, our study shows that universal inpatient screening for HBV and HCV can be an effective strategy, and can contribute to ongoing worldwide attempts to eliminate viral hepatitis.