Improvement of Chronic HCV Infection-Related Depression, Anxiety, and Neurocognitive Performance in Persons Achieving SVR-12

A Real-World Cohort Study

Harmanpreet Kaur; Radha K. Dhiman; Anand V. Kulkarni; Madhumita Premkumar; Virendra Singh; Ajay Kumar Duseja; Sandeep Grover; Gagandeep S. Grover; Akash Roy; Nipun Verma; Arka De; Sunil Taneja; Rohit Mehtani; Saurabh Mishra; Harpreet Kaur

Disclosures

J Viral Hepat. 2022;29(5):395-406. 

In This Article

Results

Between 18 June 2018 and 31 March 2020, we assessed 620 patients for eligibility; 85 were excluded due to the presence of HCC, 31 were unwilling to report to the nodal centre again for SVR-12 evaluation, 11 had HIV-HCV coinfection, 52 had recent/overt HE, 56 had chronic kidney disease, 6 were receiving sedatives and 2 had chronic obstructive airway disease (chronic respiratory insufficiency). We finally recruited 385 viraemic CHC patients (76.1% male, mean age 39.4 ± 14.2 years, mean HCV RNA load 5.8 log) (Figure 1). Most (69.1%) hailed from rural areas, with unsafe injection use (59.0%), prior surgery (7.1%), injection drug use (5.2%), dental procedures (4.4%) and multiple sexual partners (2.9%) being the predominant routes of presumed transmission. Educational status assessment showed majority of this cohort were literate (318, 82.5%), with 146 (38%) and 65 (16.8%) having a high school or graduate qualification, respectively. Genotype was tested in 32 patients only, as per the Punjab Model algorithm, with 59.3% having genotype 3. Of the 81 (21.0%) patients with cirrhosis, 50 (61.7%) had compensated disease. In addition, 22.1% consumed alcohol, 6.2% opium and 8.6% were current smokers. Since the nodal centre got referred cases, 113 (29.4%) had prior treatment experience. Overall SVR-12 rates were 90.6%, with cure rates 87.6% and 91.4% in patients with and without cirrhosis, respectively (p = .297). Table 1 shows the baseline parameters and characteristics of those as per their final treatment outcome.

Figure 1.

Patient enrolment chart

In patients without cirrhosis, 91.4% (278/304) of adherent patients achieved cure. Treatment failure was noted in 20 (6.7%) patients who were adherent, whereas all 6 (100%) nonadherent patients failed therapy (p < .001). In patients with cirrhosis, 66 (90.4%) of adherent patients achieved cure, and of 8 nonadherent persons, 5 (62.5%) achieved SVR-12 (p = .055). Longer duration of therapy and additional RBV may be the reason for better response in patients with cirrhosis. The number of patients with cirrhosis who received drugs for 12 and 24 weeks was 23 (28.4%) and 51 (63%), respectively, with 7 (8.6%) patients defaulting after 20 weeks of therapy. The cure rates in patients with cirrhosis who received 12, 20 and 24 weeks of therapy were 95.7%, 71.4% and 86.3%, respectively. Thus, nonadherence was associated with treatment failure (p = .023) in cirrhosis. For patients without cirrhosis, duration of treatment was noted as 8, 12, 14, 20 and 24 weeks in 6 (23.1%), 227 (74.7%), 1 (0.3%) and 67 (22.0%), respectively, in this cohort from the hub. The 24-week duration regimen was prescribed in patients with prior treatment failure with DCV on primary therapy. The cure rates were 0%, 94.3%, 0%, 100% and 91%, respectively, at 8, 12, 14, 20 and 24 weeks.

Table 2 shows the differences in the neuropsychological tests between patients who achieved cure versus those who did not at two time points (baseline and 12 weeks after treatment completion). Figure 2 shows the age- and gender-based differences in relevant cognitive scores with virological cure. Table S2 shows the differences in cognitive and neuropsychiatric performance based on the presence of cirrhosis and gender. These data may be compared with the normative scores of healthy controls and patients with NAFLD (Table S3). Overall patients who achieved SVR-12 had a significant reduction in BDI score, GAD-7, improved test scores for visual memory recall, digit span, % correct responses on Stroop test and reaction times on Stroop test with no significant changes in vigilance scores or NCT (Table S4).

Figure 2.

Results of cognitive tests based on age, gender and final outcomes at enrolment and 12 weeks after completion of therapy

Age-based differences were noted for BDI score and % correct responses on the Stroop test. Younger patients aged between 18 and 39 years performed better than those aged between 40 and 59 years and those aged ≥60 years. Figure 3 shows the gender-based differences in HRQoL domains. Women who failed to achieve SVR-12 had a marked worsening in pain (p = .019) and role limitation due to emotional health (p = .001) domains as compared to male patients who had treatment failure. In addition, women reported poor function in the pain domain as compared to men at enrolment (p = .001), which improved on achievement of SVR-12. Women also reported a worsening in the social functioning domain (p = .001) if cure was not achieved. Thus, subtle differences in HRQoL were noted based on gender and treatment outcomes as compared with healthy and diseased control normative data.

Figure 3.

Differences in the 8 HRQoL domains at enrolment and 12 weeks after completion of therapy, stratified by achievement of SVR-12, in men and women

Predictors of Outcome

On receiver operating characteristic (ROC) curve analysis, achievement of SVR-12 was associated with increased recalled visual memory targets ≥5.5 (AUC 0.708; sensitivity 62.5%, specificity 63% p = .000), and % correct Stroop test responses were >26.6% (AUC 0.918, sensitivity 94.4% specificity 80.4%, p = .000). A high BDI ≥5.5 (AUC 0.717, sensitivity 69.1%, specificity 75%, p = .000), high GAD ≥9.5 (AUC 0.606, sensitivity 69.1%, specificity 45.6%, p = .050) and low MoCA ≤26.5 (AUC 0.643, sensitivity 75.1%, specificity 45.0%, p = .005) at enrolment were paradoxically associated with a higher chance of cure. These data can be understood if we look at the dynamic change in scores. It is apparent that subjects who had a higher percentage decline in depression and anxiety scores, and improvement in cognitive test scores, especially improved reaction times in BCST ≥26.6% (AUC 0.918, sensitivity 94.3%, specificity 80.4%, p = .000) and NCT ≥44.9 (AUC 0.918, sensitivity 94.3%, specificity 80.4%, p = .000) had increased chance of achieving SVR-12 (Figure 4). BDI reduction ≥15.4% (AUC 0.876, sensitivity 95.1%, specificity 69.4%, p = .000) and GAD score reduction ≥10.10% (AUC 0.831, sensitivity 96.8%, specificity 53.8%, p = .000) were better predictors of achieving cure.

Figure 4.

Predictors of treatment cure using receiver operating characteristic (ROC) curves for pertinent variables

On binary logistic regression, we assessed the effect of age, gender, risk factor for transmission, substance abuse, baseline HCV RNA load, genotype, adherence to therapy, duration of therapy, the presence of cirrhosis, treatment experience, cognitive scores, depression, anxiety scores and HRQoL domains as predictors of outcome (Table S5). On multivariate analysis, adherence to therapy (OR 17.59; 95% CI 2.80–110.50, p = .002) was the main predictor of outcome in a model using adherence and baseline ALT in the equation. Patients who achieved greater reduction in BDI and GAD-7 and improved HRQoL domains showed higher likelihood of achieving cure (Model 2).

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