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Simplification of hepatitis C management: Role of an 8-week oral DAA regimen

Prof. Ching-Lung Lai
Department of Medicine
University of Hong Kong
09 Jun 2020
Introduction of highly effective direct-acting antivirals (DAAs) has dramatically changed the landscape of chronic hepatitis C virus (HCV) infection treatment. Professor Ching-Lung Lai of the Department of Medicine, University of Hong Kong, discussed with MIMS Doctor how the oral glecaprevir (300 mg)/pibrentasvir (120 mg) (G/P) combination regimen, given for only 8 weeks, can simplify HCV infection management and improve treatment adherence, including in the key high-risk population of people who inject drugs (PWID). 

Barriers to simplification of hepatitis C management

With the availability of highly effective DAAs and enhanced patient access to HCV care, the WHO goal of elimination of HCV infection as a public health threat by the year 2030 seems feasible. [WHO Global Hepatitis Report 2017:]

“In Hong Kong, patient identification and treatment adherence are the main barriers to achieving this goal,” noted Lai. “Furthermore, only patients with significant liver fibrosis [F2–3] or cirrhosis [F4] are prioritized to receive subsidized DAA treatment at public hospitals, despite WHO’s recommendations that all HCV-infected patients should receive treatment, irrespective of disease stage.” [WHO, 2018, Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection:]

An 8-week DAA regimen for treatment-naïve non-GT3 patients with compensated cirrhosis

In Hong Kong, the oral G/P combination regimen is currently indicated for 8 weeks in treatment-naïve patients aged ≥12 years with chronic HCV genotype (GT) 1, 2, 4, 5 or 6 infection and compensated liver disease (with or without cirrhosis). [Maviret Hong Kong Prescribing Information, Aug 2019]

Recently published results of the single-arm, multicentre, phase IIIb EXPEDITION-8 trial (n=343) showed that 8-week treatment with the G/P combination led to high rates of sustained virological response at post-treatment week 12 (SVR12) in treatment-naïve patients with chronic HCV GT1–6 infection and compensated cirrhosis. (Figure) [J Hepatol 2020;72:441-449]


The 8-week treatment duration for the G/P regimen is consistent with the simplified HCV treatment algorithm for treatment-naïve adults with compensated cirrhosis proposed in the latest American Association for the Study of Liver Diseases/Infectious Diseases Society of America (AASLD/IDSA) HCV guidelines.  [AASLD/IDSA, Recommendations for testing, managing, and treating hepatitis C:]

“In addition to the shortened 8-week treatment course, the oral G/P combination offers a ribavirin-free option, allowing further treatment simplification in more patients,” highlighted Lai.

Prioritizing PWID for HCV elimination

“In Hong Kong, illicit intravenous [IV] drug use is currently the most significant risk factor for HCV transmission,” said Lai. A recently published systematic review and meta-analysis reported an 81.7 percent prevalence of HCV antibody among PWID in Hong Kong. [Int J Drug Policy 2019;70:87-93]

“Screening for HCV infection is available at the Department of Health’s methadone clinics and Hospital Authority’s halfway houses. However, active IV drug users are generally reluctant to come forward for HCV screening, and this is a major challenge in case identification within the PWID population,” noted Lai. “Through social workers, church outreach programmes and public advertising campaigns, PWID could receive enhanced education and counselling on the safety and excellent cure rates of DAAs, and be encouraged to come forward for HCV testing.”

Lai agreed that an outreach service model, such as the DeLIVER Care Van – a mobile medical unit delivering targeted HCV screening through street outreach, community events and methadone clinic service to PWID in California, US, as well as liver fibrosis staging to those who screened positive – might be a feasible option in Hong Kong for identifying and diagnosing HCV infection among PWID and linking them to care. [Price J, AASLD 2019, abstract 0594]

G/P’s efficacy in PWID and patients with suboptimal adherence

An Austrian real-world study demonstrated that PWID at high risk of nonadherence to treatment achieved high SVR12 rates when G/P therapy was medically supervised. [PLoSONE 2020;15:e0229239] “Social workers and churches in Hong Kong could play that role to ensure treatment adherence within this special population,” Lai suggested.

In an analysis of data from 13 phase III clinical trials and real-world studies, G/P therapy demonstrated similar rates of treatment completion and SVR12 in patients with recent, former, or no history of illicit drug use. [Aghemo A, et al, AASLD 2019, abstract 1549]

A pooled analysis of 10 phase III studies showed high overall adherence to G/P therapy for 8 weeks or 12 weeks in treatment-naïve patients with HCV GT1–6 infection, with a modest decline in adherence observed with 12 weeks of treatment. However, SVR12 rates remained high with 8- or 12-week therapy, indicating that suboptimal adherence may not compromise treatment outcomes with G/P. [Jacobson IM, et al, AASLD 2019, abstract 1515]

Another pooled analysis of 13 phase III clinical studies that investigated the impact of short-term G/P treatment interruption in patients treated for 8 or 12 weeks also reported high SVR12 rates irrespective of treatment interruption. No patients who interrupted G/P treatment experienced virologic failure. [Zamor P, et al, AASLD 2019, abstract 1553]

DAA sequencing in the context of salvage therapy

The sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) combination is recognized as an effective salvage therapy for patients with chronic HCV infection who have failed a previous DAA regimen. [Infect Drug Resist 2019;12:2259-2268]

Data from a Canadian prospective registry showed reduced response to SOF/VEL/VOX in patients who had received prior therapy with SOF/VEL (n=26) vs other DAA regimens (n=90) (SVR12, 88.4 percent vs 97.2–100 percent). [Onofrio F, et al, AASLD 2019, abstract 1631]

“However, the number of patients in the SOF/VEL subgroup was small,” said Lai. As such, further studies may be needed to determine whether a non–SOF-based regimen (eg, G/P) may be considered in the first-line setting to maintain high SVR12 rates after salvage therapy with SOF/VEL/VOX.


The shortened 8-week treatment duration for G/P in treatment-naïve, compensated cirrhotic non-GT3 patients with HCV infection allows treatment simplification as recommended by international guidelines.

PWID have a very high HCV burden and should be prioritized in HCV elimination efforts. Mobile community-based HCV testing strategies can enhance targeted screening and linkage to care in this vulnerable population.

The G/P combination is very effective even in cases of suboptimal adherence or short-term treatment interruption, and thus provides reassurance when treating PWID with chronic HCV infection.

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Most Read Articles
22 Nov 2019
In patients with Lynch syndrome, chromoendoscopy (ChE) allows for the detection of more lesions than white light endoscopy (WLE), especially in terms of adenomas, flat lesions and proximal lesions, reports a recent meta-analysis.