1 / 56

Camden ME

Camden ME. Kansas City Risk Selectors. Hepatitis C in 2018 Advances in evaluation and treatment March 6, 2018 Bruce W. Henricks, M.D. FACP. Causes of Chronic Liver Disease. Prevalence of Hepatitis C. Worldwide ~ 170 million infected, 71 million have chronic HCV.

Leo
Download Presentation

Camden ME

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Camden ME

  2. Kansas City Risk Selectors Hepatitis C in 2018 Advances in evaluation and treatment March 6, 2018 Bruce W. Henricks, M.D. FACP

  3. Causes of Chronic Liver Disease

  4. Prevalence of Hepatitis C • Worldwide • ~ 170 million infected, 71 million have chronic HCV

  5. Prevalence of Hepatitis C • Since the identification of the hepatitis C virus (HCV) in 1989 • The number of HCV cases in the U.S. has fallen 80% • About 2.7 to 3.9 million estimated to be infected in the U.S. • ~1.6% of the population are living with HCV • ~76% + for HCV were born between 1945 and 1965

  6. Natural history of HCV

  7. Prevalence of Hepatitis C • HCV in the U.S. • HCV accounts for • 20% of all acute cases of hepatitis • ~ 30,000 new acute HCV infections in 2016 • 8000-10,000 deaths per year • 4.58 deaths per 100,000 • The death rate now exceeds that of HIV at 4.16 per 100,000 • Accounts for 40% of liver transplants- (95% are re-infected) • About 50% infected with HCV are unaware of their diagnosis

  8. Prevalence of Hepatitis C • HCV in the U.S. • About 17% of HCV(+) patients are late diagnoses • Cirrhosis or hepatic decompensation are already present • ~50-60% of the new cases of HCV occur in people with histories of injection drug abuse • HCV rate in those born from 1945 to 1965 • 6 times higher than those born in other years • 2012 CDC guidelines recommend routine screening for individuals born in those 2 decades

  9. HCV Sources of Infection

  10. A recent Quick Quote • 58 M $5 Million • HCV since his 30’s • Naïve to treatment until June 2017 • Harvoni completed in late September 2017 • U/S based transient elastography suggests F1 • FibroSure supports F2 • S/t his PCR post-Harvoni 12 weeks later being negative in January 2018 • Is he STD?

  11. HCV Characteristics • Hepatitis C • A spherical, enveloped single-stranded RNA virus • Closely related to viruses of • Hepatitis G • Dengue • Yellow fever • HCV can produce 10 trillion new viral particles each day • Worsened by daily alcohol consumption

  12. Transmission of HCV • Those at highest risk • Illicit injection drug users (IDUs)- 60% of new HCV • In developed countries • 1/3 of young IDUs (aged 18-30) are HCV infected • Older or former IDUs have a prevalence of 70%-90% infected • Other exposures of lower HCV risk • Needle-stick injuries- about 3 % • Maternal-fetal transmission- less than 5 % • In 10% no risk factor can be identified

  13. Transmission of HCV • Other exposures of lower risk, cont. • Via tattooing, sharing razors, acupuncture • Transfusion-associated HCV • Blood pool screened since 1990 • Using polymerase chain reaction (PCR) • < 1 per 2 million units transfused • Window after infection, to detection • Can be 1 to 2 weeks with PCR Immune response to HCV

  14. HCV Genotypes • HCV has • 6 genotypes, with numerous subtypes • Genotype 1 the major form worldwide, 40-80% of all HCV • Genotype 1a and 1b occurs in3/4s of U.S. HCV cases • Genotypes 2a, 2b, 2c occur in (10-15%) of U.S. cases • Genotypes 3a and 3b in (4-6% of cases) • Most prevalent in India, Pakistan, SE Asia, and Scotland • Genotypes 4, 5, and 6 < 5% of U.S. cases

  15. Factors influencing HCV incidence • In U.S. • HCV more common in minority populations • No gender preponderance • 65% of persons with HCV are 30-49 years • Being infected while younger has a somewhat better prognosis • Infection uncommon in those 20 and younger • Unless IV Drug abuse

  16. HCV Prognostic factors • Chronic HCV • Likelihood of progression influenced by • The natural h/o HCV in that individual + their environment • Alcohol use • Male sex • Ages 40 to 55 years at time of initial infection • Cumulative impact of hepatic toxins (alcohol, meds, environmental exposure, etc) on the liver over time • BMIs > 30 • Concomitant hepatitis, or conditions with iron excess • Immunosuppression, or HIV co-infection

  17. HCV evaluation-Liver biopsy • Sampling size small- 1-2 mm x 7 to 15 mm • Risk of sampling errors from so small a biopsy • Discrepancies in interpretation by pathologists • Invasive, ..associated with complications / unwelcome by pts

  18. Liver Biopsy • Only reliable way to assess current condition • Still may not be predictive of the future course • The biopsy evaluates the extent of hepatic damage • Two important features (Batt’s –Ludwig scoring) • The severity of inflammation or “Grade” • Expressed on a scale of “0 to 4” • Extent of fibrosis or “Stage” • Expressed on a scale of “0 to 4” • Stage 0 no fibrosis…… to Stage 4 cirrhosis

  19. Liver Biopsy scoring • Score given to the degree of Grade + Stage • The higher the (Knodell) score the more severe the inflammation / fibrosis • Scores of 4 or less = mild inflammation / fibrosis • Regardless of the system used, when the fibrosis is >“mild” the prognosis worsens • May evolve to peri-portal fibrosis with fibrous septa • “Bridging fibrosis” • Respected as a precursor of cirrhosis and likely RNA

  20. Mt. Washington, NH 1934, winds of 231mph

  21. Understanding hepatic fibrosis • Hepatic fibrosis • Initially thought to be irreversible….. NO longer • A dynamic process with the potential for significant resolution • The molecular understanding of fibrogenesis and fibrosis regression and how they interact in relation to chronic inflammation has changed • Though it is difficult to predict the net rate or degree of change • Is now recognized as a variable process with the potential for significant resolution

  22. Hepatic Fibrosis • What’s the natural history of fibrosis? • Meta-analysis data from multiple large studies: • The fibrosis remained stable in 46% • The fibrosis improved in 21% • The fibrosis progressed in 33%, …..commonly in NASH • Non-alcoholic steatohepatitis • In about 2/3’s the fibrosis will remain stable or regress

  23. METAVIR Scoring • Stages of fibrosis • F0: normal liver with no fibrosis • F1: portal fibrosis without septa • F2: a few septa present • ( > or = F2considered significant fibrosis) • F3: numerous septa, but w/o cirrhosis • F4: cirrhosis

  24. Evaluating Hepatic Fibrosis- HCV • Limitations of liver biopsy have led to the development of new non-invasive tests • Serve as estimates of the amount of fibrosis present • Non-invasive options have arisen from work on the evaluation of viral hepatitis • Particularly with HCV • Degree of fibrosis impacts therapeutic options and treatment • Both initial and retreatment protocols

  25. Non-invasive Testing for Fibrosis • Two general categories of testing • Serologic blood tests • Are more readily available • Considerable progress made in improving their accuracy • Radiologic tests • Either type of testing does not replace or approximate the value of a good liver biopsy • Clinically they can be used in combination • ( Hepascore + ultrasonography, as examples)

  26. Fibrosis- serologic testing • Available options in the U.S. (cost ~$250/test) • FibroTest/FibroSure • Hepascore • Fibrospect • AST to platelet ratio (APRI) • Calculated from routine laboratory tests • The blood tests above have been the most studied

  27. HCV Case #1 • 49 F • HCV genotype 1a since the early 1990s • Failed Peginterferon + Riba in 2002 • Had a third liver biopsy in 2009 • Stage 1 minimal fibrosis • FibroSure suggests F2 only • November of 2017, has stopped occasional alcohol • Minimal elevation in LFTs • A good candidate for new direct acting anti-virals • Insurance company reviewing coverage

  28. Fibrosis-serologic testing • Limitations • Tests reflect liver matrix (architecture) turnover • Values elevated by surrounding hepatic inflammation • None of the markers are liver-specific • They are only a surrogate, an “estimate of fibrosis” • NOT a specific biomarker • None has emerged as the standard

  29. Fibrosis-serologic estimates • Consensus • They have a good ability to differentiate • Significant fibrosis (F2 to F4) from those without (F0 to F1) • They don’t reliably differentiate between the different fibrotic stages • F1, vs, F2, or F3, etc • Sensitivity in a range of 60-75%, Specificity 80-90% • Tend to be a better tests when F3 or F4 fibrosis present • F4- sensitivity of 87% specificity of 91%

  30. Fibrosis -serologic estimates • Where can they help guide us? • Most useful at both extremes of METAVIR scoring • When there is little or no fibrosis (F0 to F1) • When there is F3 or greater fibrosis present • Reminder- (Fibrosis at F2 or greater cause for concern)

  31. Non-invasive tests of fibrosis • Radiologic • Ultrasound-based transient elastography (UTE) • Magnetic resonance elastography (MRE) • Scans the whole liver, but much more expensive • Mechanical excitation principles • Fibrotic tissue differs from healthy liver tissue in the way it responds to excitation by sound waves • Waves propagate/move faster in fibrotic, or “stiffer” hepatic tissue

  32. Non-invasive tests of fibrosis • Radiologic • Ultrasound-based transient elastography (UTE) • Accuracy • =/>F2 sensitivity of 70%, specificity of 84% • F4 sensitivity of 87%, specificity of 91% • Serologic tests • Compare favorably as valid tests • Value of the test goes up as (F score) increases • F4 sensitivity approaches 87%, sensitivity > 90%

  33. Fatty Liver, or Steatosis on U/S

  34. U/S elastography of the liver

  35. MR elastography

  36. Non-invasive estimates of fibrosis • May be used in combination • Expect to see both in future aps reviews, particularly the serologic and in Hep C cases • Dependent upon • Local availability • MD preference, expertise improving over time and usage • Serologic test + Radiologic scan • UTE + Hepascore • Both most readily available

  37. Treatment of HCV, in 2012 0% 18%

  38. HCV review in November 2013 • Expect antivirals to dominate HCV therapy the next 5 years • Sofosbuvir May 2013 • Simeprevir (FDA review 10-13) • Oral therapy with Ribavirin, 80% response rates • A simple oral regimen that becomes a reality will • Significantly reduce HCV morbidity and mortality

  39. Treatment of Acute Hepatitis C • When identified in first 1-6 months of infection • Pegylated interferon + Ribavirin used previously • In 2013, the treatment of choice • Effective in nearly 90% • Currently treat as chronic HCV and use new direct anti-virals • d/t efficacy and oral route of Tx • Unfortunately, early discovery is quite rare • Since most are asymptomatic or only have vague transient symptoms • Helps explain the true burden of chronic Hepatitis C

  40. Treatment of Chronic HCV • Main goal, get a sustained viral response (SVR) • To achieve a SVR, and …… prevent progression • Defined as an absence of HCV-RNA via PCR at least 3 mo (12 weeks) after the discontinuation of therapy • Was 6 months with INF-based therapies • Some clinicians will repeat a PCR at 24 weeks post-Tx • Once at a SVR or SVR12 • 97 to 100% chance of being HCV RNA negative long term and thus a “cure”

  41. A view atop Mt. Willard, NH

  42. Current therapies in HCV • Direct-acting antivirals (DAAs) • Target the nonstructural proteins of HCV • Disrupt viral replication and the infection • Advantages • Highly effective where 94-99% will achieve a SVR • Well tolerated • All-oral regimens • Behavior and diet • During Tx complete avoidance of alcohol recommended • Benefit of 2-3 cups of coffee • Lessens mortality / hospitalizations across a spectrum of liver disease

  43. DAAs: multiple points of viral attack Sofosbuvir Ledipasvir

  44. Current therapies in HCV • Preferred regimens used for 12 weeks • Mavyret • (Glecaprevir + pibrentasvir) 3 pills once daily, $39,600 • May be used for 8 weeks in F0 to F3 • Epclusa • (Sofosbuvir + velpatasvir) 1 pill/day, $74,760 • Harvoni- (< 17 months ago the drug of choice) • (Ledipasvir + sofosbuvir) in a single pill/ day, $94,500 • May be used just (8 weeks) in • Naïve pt. w/o cirrhosis and viral load of < 6 million intl units/ ml

  45. Current therapies in HCV • Preferred8 week regimen- Mavyret • N Eng J Med, 2018 Jan 25 (1350 patients) • Latest FDA approved treatment • HCV patients without cirrhosis in genotypes 1 and 3 • In genotype 1 SVR after 8 weeks in 99.1% SVR after 12 weeks in 99.7% • In genotype 3 SVR after 8 weeks in 95% SVR after 12 weeks in 97% Discontinuation rate d/t drug was < 1% in all groups

  46. Current therapies in HCV • HCV genotypes 1 and 2 account for 90% of the U.S. cases • Mavyret • Epclusa • Harvoni • All can be used across • METAVIR scores F0 to F4 • Treatment history: naïve or those retreated • Genotypes 1, 2, or 3

  47. Current therapies in HCV • Other first-line regimens used for 12 weeks • Zepatier • Elbasvir + grazoprevir 1 pill/ day $54,600 • Viekira Pak-(4 drug combination) • Ombitasvir + paritaprevier + ritonavir + dasabuvir (with or w/o ribavirin) 2 pills/day $83, 319 • Numerous DAA regimen algorithms • Are available across F scores, genotypes, etc.

  48. Current therapies in HCV • Priority patients for DAA therapy • Those with • Advanced fibrosis, ( F2 or >) • Liver transplant recipients • Re-infection rate with HCV approaches 95% • Severe extra-hepatic manifestations of HCV infection • Renal • Hematological • Diabetics with HCV

  49. Underwriting Hepatitis C • Recognize that the stages of fibrosis have the potential to improve or resolve • Particularly with a SVR post-treatment • Accept the fact; we will won’t see as many liver biopsies as we used to, or want • Non-invasive substitutes will very likely increase • Serologic and radiologic tests • FibroSure, FibroSpect, Hepascore …….etc • U/S-based transient elastography (UTE) • Value of knowing < F2 vs > F2

  50. Underwriting Hepatitis C • Hep C cases with DAAs are here now • Mavyret and Epclusa will be popular • Due to their efficacy and being once daily • More favorably priced than Harvoni • 94-99% will achieve a SVR • Other DAAs and regimens will continue to evolve • Availability to receive DAAs varies and should improve

More Related