Use of Healthcare Resources and Drug Expenditure Before and After Treatment of Chronic Hepatitis C With Direct Antiviral Agents

Mercedes Vergara; Mireia Miquel; Emili Vela; Montserrat Cleries; Caridad Pontes; Alba Prat; Montse Rué


J Viral Hepat. 2021;28(5):728-738. 

In This Article


Our study demonstrates that patients with CHC treated with DAA showed a decrease in length of hospital stay as well as rate of hospitalization due to decompensated liver disease. This finding is important since CHC is still the main cause of cirrhosis burden worldwide, particularly in low-income countries.[28] A previous study by our group demonstrated that the main expenditure in patients with cirrhosis was hospitalization; its weight in the total expenditure increased with disease decompensation.[29] Desai et al analysed hospitalizations from cirrhosis from 2008 to 2014.[20] Hospitalization costs increased 30.2% from 2008 to 2014, and cirrhosis admissions increased 36% and 24%, respectively, for patients with decompensated and compensated cirrhosis during this period. In our study, the decrease in hospitalizations due to cirrhosis complications means a change in the natural history of the disease in patients with cirrhosis secondary to CHC. In line with these results, the introduction of DAA has also led to a significant decrease in liver transplants worldwide.[30] In Catalonia, the percentage of CHC-positive liver transplant recipients decreased from 52.4% in 1993 to 29% in 2017.[31]

These changes were more relevant on subgroup analysis by fibrosis stage or morbidity burden. As morbidity or fibrosis stage increased, there was a more pronounced decrease in hospitalization for complications of cirrhosis and outpatient visits. Almost half of the patients in our cohort had cirrhosis (compensated or decompensated), which meant a more pronounced decrease in healthcare resource use. The high number of patients with cirrhosis included relates to the study period, as it was conducted when DAA treatment was prioritized for patients with advanced fibrosis or cirrhosis.

Another interesting result of this study was the increased relative risk of antineoplastic medication use. When analysed by subgroup, this use increased with more advanced fibrosis stage and higher morbidity risk. These results may have different explanations. Some authors have hypothesized on an increase in malignancies after DAA treatment, a somewhat controversial point with differing reported results. Khoury et al treated 431 patients with DAA.[32] In their cohort, the rate of malignancies was 696 per 100,000 for lymphoma and 232 per 100,000 for each of the other malignancies such as laryngeal carcinoma, pancreatic adenocarcinoma, cervical carcinoma, lung carcinoma, recurrent transitional cell carcinoma of the urinary bladder and metastatic breast cancer, while the incidence in the general population is 20, 8.8, 1.7, 44.7, 142 and 89.7 per 100,000, respectively.[32] Kim et al published trends in mortality from extrahepatic complications of viral hepatitis in the United States. They performed a population-based study using US Census and the National Center for Health Statistics mortality records from 2007 through 2017. They found that after widespread use of DAA agents, cause-specific mortality from extrahepatic cancers increased, whereas mortality from cardiovascular disease or diabetes increased only among patients with CHC infection.[33] Other factors may be relevant: for example, some authors have hypothesized that the elimination of hepatitis C increases the probability of being treated with chemotherapy.[34] Such a hypothesis would link with our findings that antineoplastic drug use had a more pronounced increase in the subgroups of patients with high-risk morbidity or advanced fibrosis with compensated or decompensated cirrhosis. Disease improvement after treatment may lead to more options for chemotherapy treatment. Selection bias is another possible reason: there may have been patients with CHC who could have developed cancer and died of it before their CHC was treated. Extensive prospective studies will be necessary to be able to draw firm conclusions. Our study also demonstrates that co-infection with HIV did not affect the use of healthcare resources.

Our study has some limitations. All DAA treatments were given via public healthcare resources, but some of the pre- and post-treatment expenditures could have occurred in private centres and therefore not been registered, although most of the population in our region uses public health care. Another limitation is the follow-up time (24 months after treatment), which may have been too short to allow differences or trends to be seen. It could be postulated that health benefits after CHC cure may increase over time. Another bias was that almost half of the included patients had advanced fibrosis stage or cirrhosis, which could have overestimated the decrease in healthcare resource expenditure. The study period included the early years of antiviral treatment and, due to the cost of DAA, there was a predominance of patients with severe disease. In recent years, the type of patient with CHC treated with DAA has changed to include those with less advanced fibrosis and lower morbidity, which could have limited the decrease in healthcare resource use. It would be interesting to know if this trend will persist.

In conclusion, our study demonstrates that in patients with CHC, following treatment with DAA, there was a decrease in use of some healthcare resources: length of hospital stay, hospitalization due to cirrhosis complications, outpatient visits and number of invoices. However, chemotherapy use increased significantly, especially in patients with high-risk morbidity and cirrhosis.