Presentation. SG is a 57 yo white man diagnosed with HCV 10 years ago now contemplating retreatment PMHx:

Transcription

1 A HCV Dilemma

2 Presentation SG is a 57 yo white man diagnosed with HCV 10 years ago now contemplating retreatment PMHx: Psoriasis Mild depression 5 years prior treated with PEG/RBV for 12 months HCV PCR negative at week 16, relapsed at week 4 Complicated by exacerbation of psoriasis and anemia

3 Physical Exam Unremarkable other than BMI 24.1 GI: Mild splenomegaly Skin: plaques on the extensor surfaces of upper and lower extremities c/w psoriasis

4 Labs Liver biopsy prior to treatment (5 yrs ago) Grade 2/4, Stage ¾ HCV Genotype 1A Viral load 2,280,000 IU/mL IL28B CT WBC 6.4, Hb 15.4, Plts 137 RUQ ultrasound: possible steatosis

5 Questions 1. Would you consider retreating SG with triple therapy? What regimen would you use? Does his history of psoriasis impact this decision? Does his prior anemia impact this decision? 2. Would you repeat his liver biopsy?

6 Case Continues He elects to repeat his biopsy to be considered for a clinical trial Stage 4 EGD without varices He was given PEG/RBV/BOC for 48 weeks 2 log decline in virus after PEG/RBV lead-in Week 8 (week 4 triple therapy) he had low level viremia Treatment week 12 (week 8 of triple therapy) HCV PCR negative

7 Clinical Course Continued: Viral Response He was given PEG/RBV/BOC for 48 weeks 2 log decline in virus after PEG/RBV lead-in Week 8 (week 4 triple therapy) he had low level viremia Treatment week 12 (week 8 of triple therapy) HCV PCR negative Relapse after 4 weeks of being off of therapy

8 Clinical Course Continued: Anemia Treatment week 4 he was noted to have a 2 gram drop in Hb to 13.6 g/dl Treatment week 8 he had experienced a further decline to 10.1 g/dl Treatment week 12 (week 8 BOC/PEG/RBV) Hb dropped to 7.5 associated with fatigue and mild dyspnea requiring a blood transfusion. EPO was added and RBV was held for 7 days then dropped to 600 mg. HCV PCR negative through the remainder of therapy

9 Questions Would you retreat with TVR based therapy? Would you check a resistance panel to help guide treatment decisions? If retreated would you try to use a higher dose of RBV, starting EPO earlier and transfusing rather than decreasing RBV dose? Would you make dose modifications earlier to manage the anemia?

10 Clinical Course Continued: Rash He had stable controlled psoriasis prior to treatment initiation. At treatment week 8 he noticed a mild flare of his rash controlled with topical therapy. This remained stable throughout the remainder of his treatment course.

11 Case Continued At follow-up week 8 he called with complaints of bloating. RUQ US confirmed ascites which was easily controlled with furosemide 40 mg and spironolactone 100 mg in addition to salt restriction. After 4 weeks doses were decreased to 20 and 50 and then stopped completely due to muscle cramps. Ascites did not recur. Treatment deferred until new agents approved due to risk of decompensation.

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13 DAA failures one size may not fit all

14 History BJ is a 22 yo black woman presenting for consideration of therapy Diagnosed 1 year ago during a college physical exam Liver enzymes were mildly elevated HCV-ab positive HCV PCR positive, G1b, HCV PCR 562,000 IU

15 Case Continued Evaluated at her university and referred to hepatology PMHx: No other medical conditions Social: Minimal alcohol use Studying law

16 Case Continued Treatment was discussed Elected to be treated PEG/RBV/BOC HCV PCR negative at treatment week 8 (week 4 TT) HCV PCR positive at treatment week 16 (week 12 TT)

17 Case Continued Developed extreme itching after therapy was stopped Derm and psych evaluations done without benefit Parents suggested a second opinion She is evaluated in our office On careful questioning admits to missing several doses of her medication

18 Physical Exam BMI 19 Hgb 13.7, plts 285 ALT 56 AST 42 HCV PCR 700,000 IU

19 What would you do? Would you consider retreatment? What agent would you consider using? Order resistance testing? What can be done to improve outcomes?

20 Evidence Supports a Collaborative Care Approach to Medication Adherence in Chronic HCV Hepatologists Gastroenterologists Internists Social Workers Collaborative Care Approach NPs/PAs/RNs Medication Reimbursement Specialists Other Medical Specialists Yozviak JL, et al. International Conference on Viral Hepatitis, April 11-12, 2011, Abstract 70752, p. 27; Gujral H, et al. Clev Clin J Med 2004;71:S

21 Barriers to Chronic HCV Medication Adherence and Potential Interventions Barrier Depression Active substance abuse Lack of belief in benefits of therapy Costs of therapy Logistical/social issues Medication side effects Complex dosing regimens Potential Intervention Proactively screen for depression Use of antidepressants as needed Referral to psychiatrist if necessary Methadone maintenance programs Recommendation of 12-step programs Patient education about benefits of therapy Suggest enrollment in HCV patient class and support group Copay programs; referral to reimbursement specialist Referral to social worker to help with housing needs, transportation to clinic appointments, etc. Counseling about modifying work schedule, household chores, if possible Education about side effect management Simplified dosing regimens whenever possible Liu SS, et al. J Clin Gastroenterol 2010;44(8):e178-85; Cacoub P, et al. World J Gastroenterol 2008;14(40): ; Ghany MG, et al. Hepatology 2009;49(4): ; Gujral H, et al. Clev Clin J Med 2004;71:S33-7; Alam I, et al. Aliment Pharmacol Ther 2010;32:

22 The Role of Simplified Dosing and Adherence Systematic Review Study design Systematic review of 10 randomized, controlled trials (RCTs) on adherence to medication in various chronic diseases Two trials had insufficient data for evaluation Interventions analyzed Calendar blister packaging Calendar pill organizers With or without other interventions (e.g., patient education) Zedler BK, et al. Clin Ther 2011;33:

23 2 of 3 RCTs Showed Improved Adherence with Calendar Blister Pack Systematic Review Study Patient Population Intervention Results Becker et al Hypertension (N=86) Calendar blister pack No significant difference in adherence Schneider et al Hypertension (N=47) Calendar blister pack Significant difference in adherence in favor of calendar blister pack (P=0.039) Valenstein et al Severe mental illness (N=54) Calendar blister pack plus reminder calls and mail, patient education Significant difference in adherence in favor of blister pack, all but 1 other intervention (P<0.01) Zedler BK, et al. Clin Ther 2011;33:

24 Case Continued Retreated with PEG/RBV/TVP Went on leave from school Treatment week 4 HCV PCR negative Itching resolved by week 4 HCV PCR remained negative at treatment week 12

25 Question 1. Would you consider her eligible for RGT? She was treated for 24 weeks Remained negative 12 weeks after completing therapy. Itching has not returned.