Impact of Hepatitis C Virus Treatment on the Risk of Non-hepatic Cancers Among Hepatitis C Virus-infected Patients in the US

Wei Wang; Vincent Lo Re III; Yi Guo; Hong Xiao; Joshua Brown; Haesuk Park

Disclosures

Aliment Pharmacol Ther. 2020;52(10):1592-1602. 

In This Article

Results

Patients Characteristics and Treatment Pattern

We identified 62 078 patients with newly diagnosed HCV who met our inclusion/exclusion criteria between January 2005 and December 2016. Of the 62 078 HCV patients, 44 776 (72%) did not receive any HCV treatment, and 17 302 (28%) initiated HCV treatment. Of the later, 15 322 (25% of the 62 078) further completed a minimally effective treatment, and 1446 patients (2% of the 62 078) experienced therapy switching. Among HCV patients who initiated HCV treatment (n = 17 302), 6738, 3232, and 7332 patients received dual therapy, triple therapy, and all-oral therapy respectively. About 82% (n = 5553) of patients who initiated dual therapy completed a minimally effective treatment. The corresponding number was 83% (n = 2678) for patients with triple therapy, and 97% (n = 7091) for patients with all-oral therapy (Figure 2).

Figure 2.

Selection of study patients. Abbreviations: CCAE, commercial claims and encounters; MDCR, medicare supplemental and coordination of benefits; HCV, hepatitis C virus

Patients in the all-oral therapy group were older (mean age: 53.8), had a significantly higher CCI (eg 11.3% had CCI ≥ 4), had more advanced liver disease (ie 5.5% had cirrhosis; 3.1% had decompensated cirrhosis), and had more comorbidities (eg 2.9% had CKD; 17.1% had diabetes; 2.7% had HIV; 5.8% were obese; 19.4% smoked) compared to patients in either the dual or triple therapy groups. However, patients in the no treatment group were more likely to have alcohol use disorder (7.7%), drug use disorder (16.8%) and contraindications to pegylated interferon and ribavirin such as schizophrenia (3.4%), depression (15.0%), epilepsy (1.1%), and anaemia (9.9%) than patients in any other therapy groups (Table 1). The mean time from HCV diagnosis to treatment initiation in the all-oral therapy group was 33.1 months [standard deviation (SD): 32.4 months], which was significantly longer than those in other therapy groups [dual therapy: 8.4 (SD 11.3); triple therapy: 18.7 (SD 21.3)] (Table 1).

HCV Treatment Effect on Non-hepatic Cancer Outcomes

Table 2 shows the risk of developing non-hepatic cancers among HCV-infected patients who initiated HCV treatment, completed a minimally effective treatment, or had no treatment. The majority of the non-hepatic cancer events (74%) occurred in patients who received no HCV treatment, with an incidence rate of 23.3 per 1000 person-years. The non-hepatic cancer incidence rate was significantly lower among patients who initiated treatment (20.1 per 100 000 person-years) and who completed a minimally effective treatment (19.7 per 1000 person-years). After adjusting for sex, commercial insurance type, CCI and health service utilisation, as well as the time-dependent covariates of age, HCV disease duration, comorbidities and medication use, we found that HCV patients who initiated treatment had a signficantly reduced risk of incident non-hepatic cancer compared to those who received no treatment (HR = 0.89; 95% Cl = 0.82–0.96). The reduction was slightly greater among patients who completed a minimally effective treatment (HR = 0.87; 95% Cl = 0.80- 0.95).

In the subgroup analysis when stratifying patients by sex, age, cirrhosis and diabetes, we found that the association between receiving HCV treatment and a reduced risk of non-hepatic cancers was significant among patients who were male (TX initiation, HR = 0.88; 95% Cl = 0.79–0.97; Effective TX, HR = 0.85; 95% Cl = 0.77–0.95), aged between 50 and 65 (TX initiation, HR = 0.86; 95% Cl = 0.79–0.95; Effective TX, HR = 0.84; 95% Cl = 0.75–0.93), without cirrhosis (TX initiation, HR = 0.86; 95% Cl = 0.78–0.95; Effective TX, HR = 0.87; 95% Cl = 0.78–0.97), and without diabetes (TX initiation, HR = 0.85; 95% Cl = 0.77–0.94; Effective TX, HR = 0.85; 95% Cl = 0.76–0.94) (Table 2). Although HCV treatment initiation among cirrhotic patients did not significantly decrease the risk of non-hepatic cancers (HR = 0.91; 95% Cl = 0.79–1.06), completion of a minimally effective treatment was associated with a significant cancer risk reduction (HR = 0.85; 95% Cl = 0.72–0.99).

HCV Treatment Effect on Non-hepatic Cancer Outcomes by Cancer Types

We summarised the treatment effect on selected types of non-hepatic cancers in Figure 3 and Table S6. After adjusting for baseline and time-dependent covariates, we found that HCV patients who initiated treatment had a 23% decrease in the risk of developing lung cancers compared to those who received no treatment (HR = 0.77; 95% Cl = 0.58–0.99). Among patients who received a minimally effective treatment, the decrease in the risk was 25% for lung cancers (HR = 0.75; 95% Cl = 0.55- 0.99), and 45% for pancreatic cancers (HR = 0.55; 95% Cl = 0.31- 0.97). However, there was no significant treatment effect found on the risk reduction for other cancer types.

Figure 3.

Incidence rate and hazard ratio for non-hepatic cancer in treated vs untreated chronic hepatitis C-infected patients by cancer type. Abbreviations: TX, treatment; CI, confidence interval; TX initiation, Treatment initiation; Effective TX, Minimally effective treatment. Note: Patients' sex, insurance type, Charlson Comorbidity Index (CCI) and health service utilisation at baseline were adjusted in Cox proportional-hazards models. Patients' age, treatment exposure, comorbidities and drug use were adjusted as time-dependent covariates in the models. The number of patients initiated all therapy were 17 302; The number of patients with Minimum effective treatment of all therapy was 15 322. There were 44 776 HCV patients having no treatment

HCV Treatment Effects on Non-hepatic Cancer Outcomes by Therapy Type

In the subgroup analysis stratified by therapy type, the association between HCV treatment and the risks of non-hepatic cancers was significant in the dual therapy group (TX initiation, HR = 0.87; 95% Cl = 0.78–0.97; Effective TX, HR = 0.87; 95% Cl = 0.77–0.98), but not in the triple therapy or all-oral therapy groups. Although we identified a lower incidence of non-hepatic cancers among patients who received triple therapy, especially those who completed a minimally effective triple therapy, compared to untreated patients, the adjusted results were not statistically significant (Table 3). When we further stratified triple therapies by first and second generation, the findings remained consistent with the overall triple therapy results (Table 4).

In the sensitivity analysis, we used the truncated datasets, 2011–2016 and 2013–2016 dataset, to examine the impact of triple therapy and all-oral therapy. We identified 20 503 and 8444 newly diagnosed HCV patients respectively (Table 4). In the triple therapy subgroup analysis with the 2011–2016 dataset, we found that the initiation of triple therapy did not significantly decrease the risk of non-hepatic cancers (HR = 0.84; 95% Cl = 0.67–1.05), but the completion of a minimally effective triple therapy was associated with a significant cancer risk reduction (HR = 0.76; 95% Cl = 0.58–0.98). The mean follow-up time after treatment initiation was 29 months and 13 months for patients with triple and all-oral therapy, respectively, which were much shorter compared to the follow-up time for patients on dual therapy (47 months) and no treatment (42 months). Due to shorter follow-up time, for all-oral therapy subgroup analysis in the 2013–2016 dataset, there was no significant treatment effect found.

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