HCV pangenotypic DAA therapy in a patient with concomitant antipsychotic treatment

Presentation and history
A 43-year-old male former intra­venous drug user presented with in­cidental findings of elevated alanine transaminase (ALT) levels in Decem­ber 2021. The patient had depression and drug-induced psychosis associ­ated with previous heroin, ketamine and methamphetamine use. He was on quetiapine 300 mg daily for his psychotic symptoms, pantoprazole 40 mg daily as needed for occasional acid reflux, and simvastatin 10 mg dai­ly for hyperlipidaemia. He did not have hepatitis B virus (HBV) or human immunodeficiency virus (HIV) coinfection.

Blood tests in March 2022 revealed a high level of hepatitis C virus (HCV) RNA of 5,470,000 IU/mL, along with elevated ALT at 76 IU/L. Ultrasound (USG) screening showed coarse liver echotexture with a lobulated contour and two small liver cysts (0.4–0.6 cm), but no suspicious solid lesions. There was also splenomegaly (15.8 cm), yet no varices at the splenic hilum or any ascites were detected. FibroScan re­ported a liver stiffness measurement of 20.9 kPa and a controlled attenuation parameter of 350 dB/m. Collectively, the patient was diagnosed to have chronic hepatitis C infection with ac­tive viraemia complicated by probable cirrhosis.

Treatment and response
Considering the patient’s med­ication history, it was crucial to se­lect a suitable pangenotypic direct-acting antiviral (pDAA) and evaluate the need to adjust his comedications to minimize the risk of drug-drug in­teractions (DDIs).

After a thorough discussion, the patient was reluctant to change his antipsychotic regimen because his mood had been stable with the cur­rent long-standing quetiapine dose. Therefore, sofosbuvir/velpatasvir (SOF/VEL; 400/100 mg, one tab­let daily for 12 weeks) was started in May 2022 as it is unlikely to have clinically significant DDIs with que­tiapine.^1,2 Since the patient seldom experienced bothersome heartburn symptoms requiring pantoprazole and did not have a history of car­diovascular disease (CVD), he was advised to temporarily discontinue pantoprazole and simvastatin due to potential interactions during the 12-week course of SOF/VEL.

With the help of hepatology nurs­es who constantly followed up with the patient, complete treatment ad­herence was ascertained and good response to SOF/VEL was achieved. He achieved sustained virologic re­sponse (SVR) at 12 weeks after pDAA completion, with ALT level dropping back to 18 IU/L in October 2022. Overall, the patient tolerated SOF/VEL well without any adverse events (AEs). His mental status also remained stable throughout the HCV treatment. Subsequent oesophago­gastroduodenoscopy (OGD) screen­ing in December 2022 did not find any gastroesophageal varices.

The patient is still continuously followed up with regular screening for cirrhosis-related complications (eg, hepatocellular carcinoma [HCC] and gastroesophageal varices) arranged.

Discussion
HCV infection is a major contrib­utor to the development of chronic liver disease. SVR achievement is associated with reduced risks of all-cause mortality, liver-related mortality or transplantation, and HCC.³ pDAAs are currently offered as the first line of chronic HCV treatment due to high SVR rates, convenient once-daily oral administration, short and finite treat­ment duration (8–12 weeks), as well as good tolerability.^4,5

Despite these advantages of pDAAs, the complex profiles of chronic HCV patients often present extra challenges in treatment. In a retrospective cohort study in Hong Kong, the majority of HCV-infected patients were reported to be >55 years old (median age, 59 years), with the most common comorbidities being hypertension (47.4 percent), diabetes mellitus (26.8 percent) and CVD (8.1 percent). Seventy percent of these patients were on >1 come­dication, while 26.3 percent were on ≥3 comedications at 4 weeks prior to and during DAA treatment. Statins and antipsychotics were the most common comedications that lead to contraindications with some pDAAs due to clinically significant DDIs.¹

Furthermore, there is a growing focus on HCV-infected individuals with psychiatric conditions globally. Data have shown that ≥50 percent of HCV-infected patients suffered from a psychiatric illness, while the prevalence of HCV infection among patients with severe mental illness (8–18 percent) in the US was 4–9 times higher than that in the general population (2 percent).^6-9 Therefore, it is necessary to conduct a thorough DDI risk assessment and communi­cate well with patients regarding op­tions and foreseeable clinical impacts of pDAA on their existing comedica­tions, especially concurrent psychi­atric medications, if any, to optimize the treatment outcome by making a personalized decision.

Although SOF/VEL and gleca­previr/pibrentasvir (GLE/PIB) are both widely used pDAAs, retrospec­tive observational data from a large Spanish cohort suggested that SOF/ VEL was associated with lower risks of AEs than GLE/PIB in patients with comedications, particularly antipsy­chotics (0 percent vs 12.5 percent) and lipid-lowering drugs (5 percent vs 17.1 percent).¹⁰ HCV-infected pa­tients with concomitant use of anti­psychotics also demonstrated a low­er DDI risk with SOF/VEL vs GLE/PIB (23 percent vs 51 percent; p<0.001). Among these patients with DDIs, none in the SOF/VEL group vs 11 percent in the GLE/PIB group experi­enced DDI-related AEs. (Table) While quetiapine was the most prescribed antipsychotic in the study, a signifi­cantly lower percentage of clinical actions was reported for SOF/VEL vs GLE/PIB (5 percent vs 100 per­cent; p<0.001) in quetiapine-treated patients.¹¹ These results suggested that choosing SOF/VEL may safely allow our patient to continue his con­current antipsychotic treatment (ie, quetiapine) with less concern about significant DDIs, treatment tolerance and fluctuations in psychotic symp­tom control.

This case highlighted the importance of DDI risk assessment in chronic HCV patients, especially those with concom­itant antipsychotic use. To enhance treatment success, a thorough discus­sion with and education for patients re­ceiving pDAA treatment about potential DDIs are essential. Moreover, ensuring high treatment compliance and toler­ance by choosing an appropriate pDAA is also critical for complete HCV erad­ication.¹² The recent development of hepatology nurse service in public hos­pitals in Hong Kong has provided pow­erful support to HCV patients through regular close monitoring and education to optimize their medication adherence along the pDAA treatment course. Last but not least, in patients with advanced fibrosis, screening for cirrhosis-related complications, such as USG for HCC and OGD for gastroesophageal varices, should continue even after successful HCV eradication.¹³