1. Before the start of therapy
n. P 31
Sixty weeks of undetectability HCV RNA after two weeks of combination therapy with ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin in a compensated cirrhosis mono-infected patient.
Imburgia C.1, Iaria C.1, Dalle Nogare E.R.1, Prestileo T.1, Sanfilippo A.1, Di Lorenzo F.1, Ficalora A.1, Buscemi C.1, Marra S.1, Corrao S.1,2
1 Infectious Diseases Unit, Department of Medicine, National Relevance and High Specialization Hospital Trust (ARNAS) Civico - Di Cristina - Benfratelli, Palermo, Italy
2 Head of Internal Medicine Department, National Relevance and High Specialization Hospital Trust (ARNAS) Civico - Di Cristina - Benfratelli, Palermo, Italy
Background
A fixed-dose tablet comprising ombitasvir (an NS5A replication complex inhibitor), paritaprevir (an NS3/4A protease inhibitor) and ritonavir (a cytochrome P450 inhibitor) in combination with dasabuvir (an NS5B polymerase inhibitor) was indicated for the treatment of chronic hepatitis C genotype 1 infection in several countries, including EU (Viekirax® and Exviera®) in 2015, according to EASL and AIFA criteria. We report a case of 60 weeks undetectability HCV RNA after two weeks of combination therapy with ombitasvir/paritaprevir/ritonavir + didasabuvir + ribavirin in a cirrhosis mono-infected patient genotype 1 b. The antiviral therapy was discontinued because of a grade 4 hyperbilirubinemia as an adverse event.
Materials and methods
A 55-year-old man was admitted to our Infectious Diseases department in October 2015 because of a chronic liver disease HCV-related (genotype 1b) for about 20 years. In 2010, he was treated with standard HCV therapy with pegylated interferon plus ribavirin for 32 weeks, interrupted for breakthrough. In October 2015, the patient returned to our attention to evaluate the start of treatment with new oral DAAs. Laboratory tests before treatment underlined normal white blood cell (WBC count 7650/mmc), platelet was /mmc, ALT 108 UI/L, AST 99 UI/L, total bilirubin 1.20 mg/dl, directed bilirubin 0.30 mg/dl, creatinine 0.73 mg/dl, albuminemia was 3,8 g/dl, and an international normalized ratio (INR) of HCV RNA was UI/mL (real time PCR ABBOTT). (table 1)
HIV Ab and HBsAg were negative. Child pugh score and MELD score were respectively A 5 and 8. The patient underwent abdomen ultrasound that was normal with diameter of spleen and portal vein within the limits. FibroScan showed a fibrosis F 4 with 45 kPa of stiffness.
EGDS highlighted esophageal varices F1. On December 2015, a first line combination antiviral therapy with ombitasvir 12,5 mg/paritaprevir 75 mg/ritonavir 50 mg 2 pills qd + dasabuvir 250 mg 1 pill bid + ribavirin 400 mg bid was started.
Table 1
Before the start of therapy
After 14 days of therapy
WBC
7650/mmc
5340/mmc
PLT
165000/mmc
154000/mmc
total bilirubine
1.20 mg/dl
22 mg/dl
directed bilirubine
0.30 mg/dl
10.70 mg/dl
ALT/AST
108/99 U/L
34/42 U/L
albumine
3.8 g/dl
3.5 g/dl
creatinine
0.73 mg/dl
0.48 mg/dl
INR
1.04
1.9
HCV RNA
UI/mL
undetectable
MELD 8 25
Results
After fourteen days from the start of the treatment, patient presented nausea, jaundice, and diarrhea and, for that, the antiviral therapy was discontinued. The exams revealed a severe hyperbilirubinemia (total bilirubin 22 mg/dl and directed bilirubin 10,70 mg/dl), ALT 34 UI/L, AST 42 UI/L, creatinine 0.48 mg/dl, albuminemia was 3,5 g/dl, and an international normalized ratio (INR) of 1.9. MELD score was 25. An abdomen ultrasound showed decompensated cirrhosis with ascites. HCV RNA after the stop of the antiviral therapy was undetected. (table 1)
Conclusions
In randomized trial TURQUOISE II a grade 4 hyperbilirubinemia (> 10 X ULN) as adverse event has never been described. The course of therapy in cirrhosis patient remains weeks. 60 weeks undetectability HCV RNA after two weeks of combination therapy with ombitasvir/paritaprevir/ritonavir + didasabuvir + ribavirin in a cirrhosis mono-infected patient genotype 1 b has never been described until now.
References
Emma D. Deeks Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir: A Review in Chronic HCV Genotype 1 Infection. Drugs 2015
Poordad F1, Hezode C, Trinh R, Kowdley KV, Zeuzem S, Agarwal K, Shiffman ML, Wedemeyer H, Berg T, Yoshida EM, Forns X, Lovell SS, Da Silva-Tillmann B, Collins CA, Campbell AL, Podsadecki T, Bernstein B. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med May 22;370(21): doi: /NEJMoa Epub 2014 Apr 11.