Late presentation of chronic HBV and HCV patients seeking specialist care for the first time in Spain: a 2-year registry review

Late presentation to the care of a hepatitis specialist (hepatic units or gastroenterologists) continues to be a challenge in Spain, with almost a quarter of patients in this study from 11 major university hospitals presenting first advanced liver disease or advanced liver disease. consultation with a liver specialist. Patients with chronic hepatitis C infection were late for treatment more frequently than those with hepatitis B and were mainly people born in Spain.

Late presentation to care leads to more advanced disease progression at baseline, making treatment (both for HBV and HCV) and subsequent cure (for HCV) more difficult. In Spain, cirrhosis and other chronic liver diseases caused by HCV and HBV accounted for 1,598 deaths (0.38% of the total) and 618 (0.15%) deaths in 2017, respectively. Liver cancer accounted for 2,860 (0.69%) deaths from HCV and 409 (0.1%) deaths from HBV in the same year.17. Health systems need to ensure that those in need of treatment are screened, diagnosed and referred to specialist care before their liver disease progresses and causes significant liver damage.18. In the case of human immunodeficiency virus (HIV), a definition of late presentation at diagnosis has facilitated monitoring and identification of risk factors for late presentation of HIV.19 in addition to monitoring trends over time20.

Delayed link to care or loss of follow-up after referral to specialist care is a significant barrier to prompt initiation of treatment21 and poses additional risk to ALD and LSLD. A late referral for specialist treatment from primary care, where viral hepatitis is often diagnosed, prolongs the length of time individuals live on or untreated with either disease, putting highlight the gaps in the health system. Not only should viral hepatitis screening be strengthened at the primary care level, but the referral pathway must be improved. In our study, we identified patients referred by other specialists from the same hospital or from other gastroenterology and hepatology departments from other hospitals. The first suggests that referral processes in hospitals need to be strengthened, which is a failure of healthcare. The latter perhaps highlights that some patients may have liver conditions that are difficult to treat, rather than presenting late for viral hepatitis care. This nuance should be taken into account by health care providers when initiating care, when, despite presenting an ALD or LSLD, patients may not initially have presented late for the treatment. care. Strong care pathways (e.g. referral processes) are a particular challenge during the ongoing COVID-19 pandemic, as primary care centers in Spain are overloaded with COVID-19 cases and may have fewer capacities and resources to cope with other morbidities, including viral hepatitis. In our study, the average year of diagnosis for patients was 2011; 7 to 8 years before obtaining specialized care with a gastroenterologist or a hepatologist despite the fact that he may have been hospitalized for comorbidities. Patients who present with hepatocellular carcinoma at the first consultation with a specialist begin treatment after the impact of a prolonged and untreated infection with viral hepatitis has already resulted in irreversible liver damage. Deaths from cirrhosis accounted for 2.4% of total deaths worldwide in 201722. In a single-center study in Denmark, 5.3% (28/527) of late-presenting patients (n = 169) had LSLD at the first visit23. Our study reported a similar prevalence of LSLD (5.8%), of which 55 patients presented with HCC at the first consultation between the years 2018 and 2019. Similarly, in a study using patients with HCC related to the newly diagnosed hepatitis B (n = 1276) in Korea, Sinn et al. reported that in 2013, 23.1% of patients with newly diagnosed HCC cases had no clinic visits prior to their HCC diagnosis24. In contrast, in 2003, this prevalence was 50.9%, underscoring the impact of effective targeted screening in Korea. However, any proportion of LP, and especially HCC at the first consultation, emphasizes that timely diagnosis and referral must be optimized and targeted as a public health challenge.

In the study by Sinn et al.24, the authors reported that a lower income was associated with a higher risk of LP. Our study did not collect income level variables; however, it would be interesting to further explore the potential barriers to accessing specialist care in Spain, which could include socio-economic barriers. Health care is free and universal for all legal residents of Spain in all the autonomous communities of the country, so the cost of care should not be a main factor contributing to LP in care. However, HBV patients were predominantly foreign-born, especially from countries in sub-Saharan Africa and Asia. Migrants who have an irregular legal status in the country would not have the right to access the public health system, which could be a risk factor contributing to the 15.0% of LP HBV cases in our study. In addition, 35% of all HBV patients who presented late for treatment were not of Spanish origin, which underlines the importance of early detection of HBV among migrant populations residing in Spain. In addition, HBV vaccination coverage of foreign-born people was not well reported in all centers, with almost 50% reporting incorrect vaccination in patients and an additional 40.8% missing values ​​(data not reported in the results). Incomplete or incorrect HBV vaccination in patients arriving in Spain from endemic countries should suggest the urgency of rapid HBV screening. Appropriate immunization coverage reports will consolidate current monitoring and surveillance methods and may detect gaps in testing and referral services.

In contrast, patients infected with HCV were predominantly of Spanish origin (87.3%) and had a history of past or current injection drug use (27.1%). ALD was reported in 26.9% of patients with HCV, similar to those described in another cohort study (GECCO cohort, Germany) which reported an ALD prevalence of 32.5%25. However, 210/863 of the patients included in the GECCO cohort were co-infected with HIV / HCV. HIV patients are increasingly aware of their status and are regularly cared for, which suggests that HCV testing would be done in a timely manner, thereby reducing the risk of CR. Integrated care is a reported best practice for increasing detection, management and monitoring of treatment for HCV care26 and in Spain, elimination of HCV among people infected with HIV / HCV is achievable27, as is the case in other settings28. Among those who had a mode of transmission documented in our study, injection drug use was the most common route of HCV infection. Targeted interventions for this key population should be implemented if they are lacking in particular and wide-ranging regions to achieve the WHO elimination goals by 2030.

Notably, however, our study also had a large proportion of unknown modes of transmission, for both HBV and HCV patients. This poses a particular challenge when designing targeted interventions for key populations, as described in the Spanish Ministry of Health screening guidelines.29. Age was identified as a risk factor for LP and the presence of hepatocellular carcinoma in our study, which may serve as a basis for increased screening among older groups, including several generations, similar to what is recommended in the United States30.

Current models of patient-centered care exist across Spain to increase testing and linkages to care for people who inject drugs. These models of care have high cure rates and should be extended, especially since the normal care pathways with referral systems in the Spanish hospital system show large proportions of LP and referral origins not followed. These models of care often use point-of-care testing31 or reflex test32, helping to reduce the potential lost to follow-up.

Our results can be used to identify vulnerable groups (eg injecting drug users and migrants); risk factors and characteristics (eg age) that contribute to LP; monitor the effectiveness of ongoing interventions in the region; and potentially initiate additional studies and improve rapid access to treatment. Since hospitals serving various Spanish cities were included in this study, further studies examining potential barriers to specialist care are warranted.

The main advantages of our study are that it is a multicenter study with a large number of patients included over a period of two years. However, the study has several limitations such as inconsistency in data quality, including missing data for some variables between centers. In addition, the confusion between late presentation to care and late presentation to treatment should be highlighted. While our study focused on describing the late presentation to specialist care because liver specialists are appointed to oversee the treatment and care of patients with viral hepatitis in Spain, the data also shows that some patients may have been treated in other specialties before reaching the appropriate specialty for their management of viral hepatitis. In addition, the stage of fibrosis was reported by each participating hospital using different methods of staging the liver by each. Our data cannot reflect the accuracy of every stage of fibrosis reported; hospitals classified their patients’ stage of fibrosis using one of the methods described in “Complementary material”.


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