Hepatitis C Update: A Growing Challenge With Evolving Management Solutions

Transcription

1 Pts (%) Hepatitis C Update: A Growing Challenge With Evolving Management Solutions A Growing Challenge With Evolving Management Solutions Introduction Magda Houlberg, MD Chief Clinical Officer Howard Brown Health Chicago, IL Chronic Hepatitis C Is a Progressive Disease Hepatitis C Virus (HCV) in the US: Gaps in Current Practice HEALTHY LIVER FIBROTIC LIVER CIRRHOTIC LIVER 1 1% 8 6 5% 43% 4 27% Chronic hepatitis C frequently has few or no symptoms and can progress without signs for decades [1] Most pts with chronic hepatitis C are asymptomatic until serious liver complications arise [2] 1. CDC. MMWR Morb Mortal Wkly Rep. 1998;47(RR-19): Heidelbaugh JJ, et al. Am Fam Physician. 26;74: Chronic HCV Infected Diagnosed and Aware n = 3,5, 1,743, 1,514, , , , ,859 Yehia BR, et al. PLoS One. 214;9:e Access to Outpatient Care HCV RNA Confirmed 17% 16% Underwent Liver Biopsy Prescribed HCV Treatment 9% Achieved Sustained Viral Response Primary Care Clinicians Have a Critical Role in Hepatitis C Care Current All-Oral Therapies Highly Effective, Simple, Well Tolerated US prevalence of hepatitis C infection [1] 2% Average pt load for primary care clinician [2] x 2 pts Average primary care clinician has 4 pts with hepatitis C infection in his/her practice [2] Standard Interferon (IFN) 1991 Ribavirin (RBV) Peginterferon (pegifn) All-Oral Therapy Current IFN 6 Mos IFN 12 Mos IFN/RBV 6 Mos IFN/RBV 12 Mos PegIFN 12 Mos PegIFN/RBV 12 Mos PegIFN/ RBV + DAA DAA + RBV ± PegIFN All Oral DAA± RBV 1. Chak E, et al. Liver Int. 211;31: Ferrante JM, et al. Fam Med. 28;4: References in slidenotes 1

2 Prevalence of Hepatitis C Positive (%) Hepatitis C Update: A Growing Challenge With Evolving Management Solutions Case 1: 56-Yr-Old Woman Presenting to Primary Care Case 1 When and How to Screen for Hepatitis C Infection Magda Houlberg, MD Chief Clinical Officer Howard Brown Health Chicago, IL A 56-yr-old woman visits your office She has recently moved to the area following a promotion and is looking for a primary care clinician Her medical history includes migraine and anxiety She is divorced and has 2 children in college She is an exsmoker, moderate social drinker, and enjoys keeping fit She is not aware of having been tested for hepatitis C infection previously Population CDC, USPSTF, and AASLD/IDSA HCV Screening Recommendations Recommendation Age One-time screening is recommended for persons born between 1945 and 1965, without ascertainment of HCV risk [1-3] Risk One-time screening is recommended for persons with these risk factors [1,3] : History of illicit injection drug use (IDU) or intranasal illicit drug use History of long-term hemodialysis Receiving a tattoo in an unregulated facility/setting Healthcare workers upon accidental exposure Children born to anti-hcv positive mothers History of transfusion with blood or organ transplantation Were ever in prison HIV infection Chronic liver disease/hepatitis with unknown cause, including elevated liver enzymes If in primary practice, does your center routinely offer one-time hepatitis C screening to all pts born between 1945 and 1965? Yes No Annual screening is recommended for current IDUs and HIV-infected MSM [3] 1. Smith BD, et al. MMWR Recomm Rep. 212;61(RR-4): US Preventive Services Task Force. HCV Screening Guidelines Hepatitis C Prevalence is Increased in Baby Boomers Prevalence of Hepatitis C Antibody Positivity in US Population by Sex by Yr of Birth (NHANES III) [1] Screening recommended Male Female Yr of Birth Aim Provide rationale for testing Provide reassurance about testing Obtain consent Talking to Pts About Hepatitis C Testing Sample Conversation It s common The Centers for Disease Control and Prevention now recommends that people your age be tested for hepatitis C OR Hepatitis C is a virus that can cause gradual, progressive liver damage. People can have the infection for many yrs even decades without knowing it. Many people have no symptoms, so getting a blood test is the only way to know if you have hepatitis C It s curable The hepatitis C virus antibody test will help you find out if you have been exposed to the virus at any time in your life If it is alright with you, I would like to test you for hepatitis C today Iwasaki K, et al. ISPOR 21. Abstract PG17. CDC. Guide to Comprehensive Hepatitis C Counseling and Testing. 2

3 Back to Our Case Case 1 Continued Follow-up After Initial Screening A 56-yr-old woman visits your office She has recently moved to the area following a promotion and is looking for a primary care clinician Routine hepatitis C antibody test: reactive Recommended Testing Sequence for Identifying Current HCV Infection Does your practice s computer system trigger reminders based on hepatitis C antibody test results? HCV antibody test Reactive HCV RNA test Detected Current HCV infection Provide care or link to care Yes No Nonreactive Stop Not detected No current HCV infection Additional testing as appropriate CDC. MMWR Morb Mortal Wkly Rep. 213;62: Recommendations for Additional Follow-up of Initial HCV Testing Quantitative hepatitis C RNA testing prior to initiation of antiviral therapy to document baseline viral load Testing for hepatitis C genotype to guide selection of antiviral therapy Genotype 3 associated with increased risk of cirrhosis and hepatocellular carcinoma Genotypes 2, 3 may limit treatment options Genotype 1a requires testing for resistance associated substitutions (eg, NS5A), depending on treatment My approach: Ultrasound to look for portal hypertension and identify diabetes, fatty liver Counseling for HCV-Infected Individuals Prevent Hepatitis C Transmission Avoid sharing toothbrushes, dental, shaving equipment Prevent blood contact; do not donate blood Avoid illicit drugs; avoid reusing or sharing drug paraphernalia Risk of sexual transmission is low, except for people with HIV, multiple partners, or STIs Reduce Progression of Liver Disease Test for conditions that accelerate fibrosis Hepatitis B and HIV infections Evaluate for advanced fibrosis Update vaccinations Avoid alcohol 3

4 Recommendations for When and in Whom to Initiate HCV Treatment Treatment is recommended for all pts with chronic hepatitis C infection Except where life expectancy likely to be short despite treatment or transplantation Nonmodifiable Factors Fibrosis stage Inflammation grade Older age at time of infection Male sex Organ transplant Risk of accelerated fibrosis progression Viral Factors HCV genotype 3 Coinfection with hepatitis B virus or HIV Modifiable Factors Alcohol consumption Nonalcoholic fatty liver disease Obesity Insulin resistance Panel Discussion: Talking to Pts About Hepatitis C Treatment How do you counsel your hepatitis C virus infected pts to help them weigh the risks and benefits of treatment? Initiate the conversation Fatigue Type 2 diabetes mellitus Kidney disease Continue the conversation Lymphoma Hepatic complications, liver transplant If cirrhosis develops, need for hepatocellular carcinoma screening every 2 yrs Fibrosis Staging in Hepatitis Evaluation of Fibrosis: Interpreting Test Results Test Liver biopsy [1,2] Transient elastography [3,4] Noninvasive markers Child-Pugh score (based on total bilirubin, albumin, PT-INR, ascites, encephalopathy) [5] Interpretation Metavir stage : No fibrosis Metavir stage 1: Portal fibrosis Metavir stage 2: Portal fibrosis with rare septa Metavir stage 3: Advanced fibrosis Metavir stage 4: Cirrhosis look for decompensation (ascites, hepatic encephalopathy, variceal hemorrhage) Clinical impression important, exact cutoffs not well defined 7.1 kpa: Significant fibrosis (F 2) 9.5 kpa: Advanced fibrosis (F 3) 12.5 kpa: Cirrhosis (F = 4) Cutoffs vary depending on test Class A: Compensated cirrhosis Class B or C: Decompensated cirrhosis evaluate for transplant References in slidenotes. Use of Noninvasive Tests in Therapy- Naive Hepatitis C Virus Infected Pts No additional staging needed for pts with clinically evident cirrhosis Assess platelet count, INR, albumin, size of spleen on ultrasound to identify cirrhosis Hepatitis C (HIV coinfection) treatment naive Combine 2 noninvasive tests: Transient elastography + serum biomarker Discordance Concordance Case 2 Ongoing Management of Hepatitis C Infection for the Primary Care Provider EASL-ALEH. J Hepatol. 215;63: Repeat exams and No severe search for explanations fibrosis/cirrhosis Discordance No liver biopsy, Liver biopsy follow-up or antiviral if results influence treatment management (if extrahepatic manifestations) Severe fibrosis/cirrhosis No liver biopsy, antiviral treatment, screening for varices and hepatocellular carcinoma 4

5 Hepatitis C Virus RNA All-Cause Mortality (%) Liver-Related Mortality or Liver Transplantation (%) Hepatocellular Carcinoma (%) Hepatitis C Update: A Growing Challenge With Evolving Management Solutions Case 2: 45-Yr-Old Man With Hepatitis C Infection A 45-yr-old man visits your office Diagnosed hepatitis C RNA positive in 211, subsequently lost to follow-up Are biopsy results from 5 yrs ago still valid to guide hepatitis C treatment decisions? Biopsy in 211 showed Metavir stage 2 (some fibrosis) Now expresses interest in hepatitis C therapy after hearing positive reports about new oral treatments Describes current alcohol use as moderate but drinks most days Yes No Case 2: Initial Workup HCV RNA 3,5, IU/mL, genotype 1a HAV Ab negative, HBsAb/HBsAg negative, HIV negative Transient elastography 8.4 kpa (significant fibrosis, F2) Laboratory tests: WBC 35 cells/mm 3, Hb 14 g/dl, platelets 155/ L, INR 1., albumin 3.8 mg/dl, total bilirubin 1.2 mg/dl, AST 68 IU/L, ALT 64 IU/L, alkaline phosphatase 115 IU/L, creatinine 1.2 mg/dl When to Refer to an Experienced Hepatitis C Treater No Need to Refer Refer According to Provider Experience Refer No advanced fibrosis Compensated cirrhosis Decompensated cirrhosis Hepatitis C reinfection Renal impairment If required by insurance Prior treatment with peginterferon/ribavirin HIV coinfection (refer to provider with experience treating HIV) Active substance use Recurrent hepatitis C infection after liver transplantation HCV Treatment Success Is Defined as SVR or Virologic Cure Sustained virologic response = cure Hepatitis C Virologic Cure Associated With Improved Outcomes Survival Outcomes for All-Cause Mortality, Liver-Related Mortality or Liver Transplantation, and Hepatocellular Carcinoma in Pts With Chronic Hepatitis C and Advanced Hepatic Fibrosis With and Without Sustained Virologic Response (SVR) All-Cause Mortality Liver-Related Mortality or Hepatocellular Carcinoma 3 3 Liver Transplantation 3 P <.1 P <.1 P <.1 Undetectable hepatitis C virus RNA in plasma 2 1 Without SVR 2 1 Without SVR 2 1 Without SVR Start of treatment End of treatment 12 wks post treatment Viral eradication With SVR With SVR With SVR Yr Yr Yr HR:.26 (95% CI: ; P <.1) Virologic cure does not protect against reinfection van der Meer AJ, et al. JAMA. 212;38:

6 If in primary practice, do you offer hepatitis C treatment to your hepatitis C virus infected pts? If you do treat hepatitis C in your practice, do you offer treatment to pts with compensated cirrhosis? Yes No Yes, I treat cirrhotics and noncirrhotics No, I treat noncirrhotics only If you do treat hepatitis C in your practice, do you offer treatment to pts previously treated with peginterferon? Yes, I treat naive and experienced pts No, I treat naive pts only What If... Pt Had History of Injection Drug Use A 45-yr-old man visits your office Diagnosed hepatitis C RNA positive in 27, subsequently lost to follow-up Expresses interest in hepatitis C therapy after hearing positive reports about new oral treatments History of injection drug use and alcohol use No illicit drug use in the past 3 mos, describes current alcohol use as moderate but drinks most days Says he is willing to attend drug treatment program Current All-Oral Regimens for Hepatitis C Infection Current Hepatitis C Treatment Options Are More Straightforward Regimen Component Classes Approved Genotypes Grazoprevir/elbasvir Ombitasvir/paritaprevir/ritonavir Ombitasvir/paritaprevir/ritonavir + dasabuvir Sofosbuvir + daclatasvir Protease inhibitor + Protease inhibitor + Protease inhibitor + + polymerase inhibitor Nucleotide polymerase inhibitor + 1, , 3 Regimen factors may vary based on Prior treatment experience Presence of cirrhosis Hepatitis C genotype Polymorphisms associated with resistance Treatment Adjunct Ribavirin vs ribavirin free Treatment Duration 8-24 wks Sofosbuvir/ledipasvir Nucleotide polymerase inhibitor + 1, 4, 5, 6 Simeprevir + sofosbuvir Nucleotide polymerase inhibitor + protease inhibitor 1, 4 Sofosbuvir/velpatasvir Nucleotide polymerase inhibitor + 1, 2, 3, 4, 5, 6 6

7 Current HCV Treatment Options Are More Straightforward Treatment Regimens for Genotype 1 Hepatitis C Infection Regimen factors may vary based on Previous treatment experience Presence of cirrhosis Hepatitis C genotype Polymorphisms associated with resistance Some regimens (sofosbuvir/velpatasvir) effective against all genotypes Most regimens do not require testing for resistance associated substitutions Treatment Adjunct Ribavirin vs ribavirin free Treatment Duration 8-24 wks For most pts, 12-wk ribavirinfree options are available No 8-wk regimens recommended in HIV/HCV coinfection; other recommendations on treatment duration and inclusion of RBV are the same in HCV monoinfection and HIV/HCV coinfection Hepatitis C Genotype Without cirrhosis Sofosbuvir + Simeprevir NS5A = resistance associated substitutions. *8 wks of treatment can be considered in treatment-naive genotype 1 pts without cirrhosis who have pretreatment HCV RNA < 6 million IU/mL, per package insert. Do not use if Q8K positive. If pegifn/rbv experienced, add RBV (recommended) or treat for 24 wks (alternative). AASLD-IDSA HCV Guidelines 216 Recommended or Alternative Regimens for Direct-Acting Antiviral Naive Pts Sofosbuvir/ Ledipasvir Sofosbuvir + Daclatasvir Ombitasvir/ Paritaprevir/RTV + Dasabuvir Grazoprevir/ Elbasvir 1a 12 wks 8* or 12 wks 12 wks 12 wks + RBV 12 wks (no NS5A) or 16 wks + RBV (NS5A) Sofosbuvir/ Velpatasvir 12 wks 1b 12 wks 8* or 12 wks 12 wks 12 wks 12 wks 12 wks With compensated cirrhosis 1a 24 wks ± RBV * 12 wks (no NS5A) or 12 wks 24 wks ± RBV 24 wks + RBV 16 wks + RBV (NS5A) 12 wks 1b 24 wks ± RBV 12 wks 24 wks ± RBV 12 wks 12 wks 12 wks Treatment Regimens for Genotype 2-6 Hepatitis C Infection Recommendations are the same in HCV monoinfection and HIV/HCV coinfection Hepatitis C Genotype or 6 Recommended or Alternative Direct-Acting Antiviral Regimens Sofosbuvir + daclatasvir Sofosbuvir/velpatasvir Sofosbuvir + daclatasvir ribavirin Sofosbuvir/velpatasvir Ombitasvir/paritaprevir/ritonavir + ribavirin Elbasvir/grazoprevir ribavirin Sofosbuvir/ledipasvir ribavirin Sofosbuvir/velpatasvir Sofosbuvir/ledipasvir Sofosbuvir/velpatasvir Adverse Events and Drug-Drug Interactions Magda Houlberg, MD Chief Clinical Officer Howard Brown Health Chicago, IL Adverse Events Drug Drug Interactions Newer hepatitis C medications do not have same adverse events as interferon and are generally well tolerated Discuss most common adverse events and management strategies in pre-education session Headaches: nonpharmacologic management strategies, limits of OTC pain relievers and liver disease Anemia: still a concern with ribavirin; pts should be aware of symptoms and need for monitoring; could require dose reductions of hepatitis C therapy Encourage pts to report bothersome or unusual adverse events Actions Review all herbals/supplements, prescription and OTC meds, including contraceptives and proton pump inhibitors Ask about PRN usage of other drugs Consult with clinical pharmacist when possible Refer to hep-druginteractions.org Considerations Is a medication change warranted? Adjust meds now vs after regimen approved by insurance? Permanent switch vs only while on hepatitis C treatment? Some interactions may be minor Monitor labs Report symptoms Adjust timing of medication 7

8 Panel Discussion: Supporting Pts During Antiviral Therapy American Association for the Study of Liver Diseases guidance: CBC with differential and CMP at Wk 4 Hepatitis C RNA at Wk 4 and 12 wks after end of treatment My approach: If treatment is well tolerated, counsel 12 wks after treatment Post-treatment Follow-up Characteristic Recommended Follow-up After Hepatitis C Treatment Follow-up No advanced fibrosis (Metavir stage F-F2) No hepatitis C follow-up Advanced fibrosis (Metavir stage F3 or F4) Twice-yearly ultrasound surveillance for hepatocellular carcinoma If compensated cirrhosis (F4) also test for varices using baseline endoscopy Ongoing hepatitis C risk or unexplained hepatic dysfunction Test for recurrence or reinfection with quantitative hepatitis C RNA assay Persistently abnormal liver tests Test for other causes of liver disease No virologic cure Test for disease progression every 6-12 mos with hepatic function panel, CBC, and INR Consider retreatment options Key Points All pts born should be screened for hepatitis C infection Know risk-based screening recommendations Virtually all pts with hepatitis C infection should be treated, regardless of genotype and fibrosis Prevents morbidity, progression of fibrosis, hepatocellular carcinoma Many pts can be treated in primary care setting Must refer pts with decompensation Current treatments include pangenotypic and ribavirin-free options > 95% rate of cure for most genotypes Goal Is Elimination of Hepatitis C Infection Provider Education Improve Treatment Access Monitoring and Evaluation Secure Political Commitment National Planning Capacity Assessment Partnership Development Thank you! Mitruka K, et al. MMWR Morb Mortal Wkly Rep. 215;64: