Sustained Virologic Response After 6 Weeks of Therapy With a First-Generation Hepatitis C Virus Protease Inhibitor

To the Editor—Patients with hepatitis C virus (HCV) genotype 1 infection should receive 12 weeks of triple combination therapy with the first-generation HCV protease inhibitor telaprevir, pegylated interferon (peg-IFN) alfa-2a or alfa-2b, and ribavirin (RBV), followed by 12 or 36 weeks of double therapy with peg-IFN and RBV [1]. We report a case of sustained virologic response (SVR) achieved after only 6 weeks of triple combination treatment.

A 53-year-old white woman with history of breast cancer was treated with surgery, adjuvant chemotherapy, and radiation in 2010, followed by hormonal therapy with letrozole. During a routine follow-up at another facility, elevated transaminases were detected and further investigation led to the diagnosis of chronic HCV infection that was probably acquired 30 years before current presentation. She was infected with HCV genotype 1b, and host genotyping revealed the IL28B CC allele. Liver biopsy showed bridging fibrosis.

The patient was initiated on telaprevir, peg-IFN alfa-2a, and RBV. Concurrent medications included hydrochlorothiazide and lisinopril for hypertension. Letrozole was discontinued a few weeks before antiviral treatment initiation, to avoid potential drug interactions. On week 4 of treatment, the HCV load was undetectable (rapid virological response [RVR]). Two weeks later, the patient presented with shortness of breath, anemia, thrombocytopenia, rash, and acute renal failure. HCV treatment was discontinued because of severe renal dysfunction. During the first 2 weeks off therapy, the hematologic toxic effects worsened, necessitating hospital admission, use of hematopoietic growth factors, and red blood cell transfusion (Figure 1).

Figure 1.

Outcome and laboratory abnormalities in a patient successfully treated with 6 weeks of telaprevir-based therapy. ^aHepatitis C virus was measured with the transcription-mediated amplification method. Abbreviations: HCV, hepatitis C virus; Rx, treatment; SVR24, sustained virologic response after 24 weeks off treatment; WBC, white blood cells.

The patient was referred to our institution for investigation of possible myelodysplastic syndrome. Bone marrow biopsy revealed no evidence of malignancy, and the abnormal laboratory parameters were attributed to HCV treatment. In the following weeks, the patient improved and all laboratory parameters normalized. The HCV load remained undetectable at 24 weeks after cessation of HCV treatment (SVR24).

Telaprevir-containing therapy is very effective, but is often associated with the development of severe side effects [1]. This treatment combination is also associated with renal impairment, which leads to more pronounced anemia from decreased RBV elimination [2]. The half-life of RBV ranges from 100 hours normally to 500 hours in patients with decreased renal function [3]. The renal impairment our patient developed might have contributed to her severe anemia by prolonging RBV exposure after treatment cessation. The fact that the anemia worsened even after treatment discontinuation supports this hypothesis. On the other hand, extended RBV exposure might have led to the patient's favorable virologic outcome.

In regard to positive predictors of response to HCV treatment, our patient had several: female sex, white race, HCV-1b genotype infection, IL28B CC allele, low baseline viral load, no cirrhosis or steatosis, and RVR [4]. We found 2 reports of patients with SVR after shortened duration of telaprevir-based therapy (Table 1) [5, 6]. The common characteristics of these patients and our patient include non–African American race, HCV-1b genotype, and absence of cirrhosis.

Table 1.

Reported Cases of Sustained Virologic Response After Short-Duration Telaprevir-Based Therapy

Characteristic	Case 1 (Present Case)	Case 2 [5]	Case 3 [6]
Age, y	53	28	66
Sex	Female	Male	Male
Race	White	Whitea	Asian
Body mass index, kg/m2	33	26a	23
Comorbidities	Obesity, cancer survivor	HIV coinfection	None
HCV genotype	1b	1b	1b
IL28B polymorphism	CC	CT	CC
Cirrhosis	No	Noa	No
Baseline viral load, IU/mL	94 620	>69 000 000	3 502 804
Previous HCV treatment	Naive	Nonresponder	Naive
Total treatment duration	6 wk	24 wkb	4 wk
Telaprevir dose Peg-IFN dose Ribavirin dose	750 mg TID 180 µg once/wk 600 mg BID	750 mg TID 180 µg once/wk 600 mg qAM/400 mg qPM	750 mg TID 180 µg once/wk 600 mg qAM/400 mg qPM
Reason for withdrawal	Acute renal failure	Lost to follow-up	Acute renal failure
RVR	Yes	Yesa	No
SVR	SVR24	SVR24	SVR24

Abbreviations: BID, twice daily; HCV, hepatitis C virus; HIV, human immunodeficiency virus; peg-IFN, pegylated interferon; qAM, every morning; qPM, every evening; RVR, rapid virologic response; SVR, sustained virologic response; SVR24, SVR for 24 weeks; TID, 3 times daily.

^a Additional information provided by corresponding author Dr E. Cachay [5] (personal communication).

^b Instead of the 48 weeks recommended for HIV-coinfected patients and nonresponders.

The interim analysis of an exploratory multicenter study designed to evaluate the efficacy of 12-week-total telaprevir-based therapy in patients with HCV genotype 1, either treatment-naive or with relapse after treatment, showed an SVR of 87% (74 of 85 subjects) among noncirrhotic patients with the IL28B CC genotype who had achieved RVR [7].

In conclusion, the addition of first-generation protease inhibitors to the anti-HCV treatment armamentarium has improved outcomes of patients infected with genotype 1 HCV [1]. Unfortunately, these regimens are frequently associated with serious adverse events. The present report describes the common characteristics of patients successfully treated after short-duration telaprevir-based therapy.