What about HCV HCV reactivation HCVr Definition Increase in HCVRNA level of 1 log 10 IU mL from baseline HCVRNA following institution of cancer treatment ID: 1047919
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1. Journal Club, 29/01/2018
2. What about HCV?
3. HCV reactivation (HCVr)DefinitionIncrease in HCV-RNA level of ≥ 1 log10 IU/mL from baseline HCVRNA following institution of cancer treatment
4. Normal fluctuations in viral load within 0,5 log10 IU/mL
5. HCVr ± hepatitis flareDefinitionIncrease in ALT level to ≥ 3 times the upper limit of normal in the absence of liver infiltration by tumor, use of hepatotoxic drugs other than chemiotherapeutics, or other active systemic infection (HAV, HBV, HEV, HIV, bacterial or fungal infections).
6. HCV reactivation (HCVr)Less commonLess severe conseguences than HBV reactivationOnly a few fatal cases of fulminant hepatitis reported
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8. Retrospective study308 HCV-infected cancer patients11% had hepatitis flares during cancer treatment in 45% of the cases discontinuation of a potentially life-saving chemotherapyHCV-RNA monitoring was performed only in 22 patients
9. Endpoints of the study: Define the incidence, clinical predictors and associated outcomes of HCV reactivation in chronically infected patients undergoing chemotherapy
10. OutcomesOccurrence of HCVr and hepatitis flare from the start date of cancer treatment to 36 weeks (3 clinic visits at 12w follow-up interval) after the start dateDiscontinuation or dose reduction of chemotherapy due to hepatitis flare, liver failure, and death within 36 weeks after the start of cancer treatment
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14. On multivariable analysis, only rituximab and high-dose steroids are significantly associated with HCVr
15. HCVr was associated with a hepatitis flare in 43% of these patients (10/23)In those who developed hepatitis flare higher prevalence of genotype 2 and interleukin 28B CC genotype
16. Outcomes14 patients (14%) required cancer treatment discontinuation due to hepatitis flare: 6/23 (26%) with HCVr and 8/77 (10%) without HCVr (p: 0,08)2 cases of liver failure (none in the HCVr group): attributed to DILI8/100 patients died within 36 weeks of follow-up: 3/23 patients (13%) with HCVr and 5/77 patients (6%) without HCVr (p:0,38)
17. DiscussionUnlike HBV reactivation, HCVr seems to have an indolent course:23%of patients: HCVr43% of HCVr: hepatitis flareNo liver failure/no liver-related deaths in HCVr group
18. DiscussionDiscontinuation/dose reduction of chemotherapy Long-term oncologic conseguences?
19. Additional studies with longer follow-up are needed:Evaluate the long-term oncologic conseguences of cancer treatment modifications due to hepatitis flare associated with HCVrEvaluate the long-term conseguences of elevated HCV viral loadsConsider the possibility of «late HCVr»
20. Is pre-emptive DAA therapy indicated prior to cancer treatment?
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22. Potential benefits of HCV eradicationMinimization of drug-induced hepatotoxicityAvoid detrimental dose reductionPrevention of cancer relapse or recurrenceAvoid potentially decompensating hepatitis flaresIncrease access to clinical trials (HCV exclusion criteria in 48% of early-phase cancer clinical trials)
23. DAA therapy in cancer patients has proven to be efficacious, safe, and with minimal drug-drug interactions.
24. With the exception of patients being considered for bone marrow transplant, there are no current guidelines for the use of DAA in HCV-infected cancer patients
25. QuestionsHow cancer treatment impacts chronic liver disease related to HCV-infection?How treatment of HCV with DAAs impacts oncologic outcomes in patients undergoing cancer treatment?
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27. Hypothetical pathogenetic process of HCV-related lymphoproliferative disorders
28. Role of AVTAggressive lymphomas (DLBCL)Low grade lymphomasAVT as first line approach(etiologic treatment – EASL guidelines):HCV eradicationLong-lasting remission of lymphomaAVT after complete response to conventional chemotherapy(better DFS)
29. Aim of the study: Evaluate whether AVT with DAAs of B-NHL/HCV-infected patients in concomitance with chemotherapy is a safe therapeutic option and whether it might positively affect the outcome of NHL
30. Patients and methodsProspective observational study20 (13 males, 7 females) HCV genotype 1b-positive patients affected with DLBCL, referred to 3 hepatologic centers of South ItalyEnrollment period: June, 01 2015 – December 31, 2015Treated in concomitance with an antineoplastic treatment and with SOF/LED for 12 weeksFollow-up for 1 year after the complete remission from NHL after the first chemotherapyControl group: historical cohort of 101 HCV/DLBCL patients with similar clinical characteristics, retrospectively enrolled at the same 3 centers over the last 10 years, who didn’t undergo any AVT and had undergone similar antineoplastic therapies
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32. Only 1 patient discontinued therapy at week 9, attributed to NHL-related symptoms (grade 3 febrile neutropenia), but however achieved SVR.
33. At week 22 of follow-up 1 patient (5%) died from NHL-complications in DAA-treated patient arm, compared to 21 patients (21%) in the nontreated arm (p: 0,122)
34. Only 1 NHL relapse (5%) in DAA-treated patient arm (the same patient who died thereafter), compared to 25 relapses (25%) in the nontreated arm (p: 0,036)
35. Better DFS if:Low IPI scoreDAA treatmentOS: none of the variables reached any significance
36. No statistically significant differences in terms of SAEs and non-SAEs between the 2 arms
37. ConclusionsA combined approach of AVT and chemotherapy is safe and well toleratedIn NHL, concomitant AVT should be particularly encouraged, because eradication of the infection positively affects the outcome of NHL, improving DFS
38. Limitations of the studyShort follow-up post-SVRSmall number of patients enrolledNonrandomized study designRetrospective nature of the control armMore studies are needed to draw definitive conclusions regarding DFS and OS.
39. Take home messagesHCV reactivation in patients receiving cancer treatment has usually an indolent clinical course, but hepatitis flare can cause modifications of cancer treatment with negative effect on oncologic outcomes.The potential risk of developing HCVr should not be considered a controindication for chemotherapy.
40. Take home messagesDAA therapy in cancer patients has proven to be efficacious, safe, and with minimal drug-drug interactions.In HCV-positive NHLs, concomitant use of DAA and chemotherapy represents a useful and safe approach, able to reinforce the remission of the neoplastic disease and improve DFS.
41. Take home messagesConsidering the risk of HCVr, all patients eligible to cancer treatment should be screened not only for HBV markers, bur also for anti-HCV and (if positive) HCV-RNA.HCV treatment has to be considered before or simultaneously with chemotherapy, especially in patients with advanced liver disease or receiving regimens associated with higher risk of HCVr (such as rituximab or high-dose steroids), to optimize outcomes by avoiding changes in cancer treatment plans.Alternately, HCV-infected patients can be closely monitored and antiviral treatment initiated after HCVr is detected.
42. Guidelines?
43. Grazie per l’attenzione