WHEN HCV TREATMENT IS DEFERRED

WV HEPC ECHO PROJECT

October 13, 2016

WHEN HCV TREATMENT IS DEFERRED

�  Reminder - treatment is recommended for all patients with chronic HCV infection

�  Except short life expectancies that cannot be remediated by treating HCV or transplantation

�  Abandon the “triage approach”

�  Due to cost concerns of HCV treatments, prioritizing patients who may benefit most from HCV antiviral treatment had been advised previously

�  Based on the degree of liver disease, extra-hepatic manifestations, risk of transmission

WHEN HCV TREATMENT IS DEFERRED

�  Reasoning behind the current treatment recommendations: �  (i.e. why to treat most patients …)

�  Prevent progression of liver fibrosis and resultant chronic liver disease and risk for development of hepatocellular cancer

�  Decreased all-cause morbidity and mortality

�  Quality-of-life improvements for patients treated regardless of baseline fibrosis

�  Improve or prevent extra-hepatic complications

� Diabetes mellitus, cardiovascular disease, renal disease, and B-cell non-Hodgkin lymphoma, etc.

�  Prevention HCV transmission

WHEN HCV TREATMENT IS DEFERRED

�  HCVGuidelines.org

�  “Deferral practices based on fibrosis stage alone are inadequate and shortsighted”

WHEN HCV TREATMENT IS DEFERRED

�  Despite current guidance to “treat everyone”, patient selection should still be individualized after appropriate patient centered evaluation:

Example of issues that might impact patient selection for treatment:

�  Patient capacity to comply with treatment

�  Risk of re-infection

�  Medication interactions

�  Pregnancy and/or willingness to avoid getting pregnant while on treatment (esp. if ribavirin used)

�  Safety to patient (concern if decompensated cirrhotic)

�  Failure of prior treatment regimens

�  Access to medication (insurance)

WHEN HCV TREATMENT IS DEFERRED

�  Care for the HCV infected individual

�  Ongoing education

�  Natural hx

�  Transmission prevention

�  Address risk factor for HCV acquisition

�  Update labs

�  HCC / Varices Screening if needed

�  Vaccination

�  Assess for symptoms

�  Hepatotoxin avoidance

WHEN HCV TREATMENT IS DEFERRED

�  Hepatitis C Natural History Education �  AASLD guidelines: the risk of developing cirrhosis ranges from 5 to

25% over a period of 25 to 30 years

�  Can often alleviate fears with education – usually “decades not days” needed for Hepatitis C to cause significant liver damage

WHEN HCV TREATMENT IS DEFERRED �  Transmission prevention education

�  Blood donation

�  Patients should be advised to never donate blood or semen

�  Transmission to household contacts

�  Avoid sharing toothbrushes, other dental devices, sharp items used for personal hygiene, cover any bleeding wounds

�  Drug use

�  Cessation of drug use, avoid reusing or sharing syringes and needles/paraphernalia

�  Sexual transmission

�  Especially men who have sex with men

�  Pregnancy

�  Risk of vertical transmission

WHEN HCV TREATMENT IS DEFERRED �  Address risk factor for HCV acquisition

�  Often it is the patient’s addiction that causes the most harm

�  A 2011 study showed that the leading cause of death in patients with Hepatitis C was not liver-related illnesses1

� 72% of deaths were the result of drug overdose or suicide

1. J. Hepatol, 2011 May; 54(5): 879-86. Trends in mortality after diagnosis of hepatitis B or C infection: 1992-2006.

WHEN HCV TREATMENT IS DEFERRED

�  Keep labs up to date �  Routine Labs and Imaging -- see Jay’s intake form

�  Ongoing screening for Co-infections

�  Follow markers of Liver Fibrosis �  Various modalities:

�  Liver biopsy

� Serum biomarkers of fibrosis (examples: Fibrosure, FibroTest)

� Vibration-controlled transient liver elastography (example: FibroScan)

� AST-to-Platelet Ratio Index (APRI) or  Fibrosis 4 score (FIB-4)

� Common approach to fibrosis assessment is to combine info from clinical assessment and non-invasive modalities

WHEN HCV TREATMENT IS DEFERRED �  Screening for hepatocellular cancer when warranted

�  Patients with advanced fibrosis or cirrhosis (F3/F4)

�  The 2010 American Association for the Study of Liver Diseases (AASLD) guideline on the management of hepatocellular carcinoma (HCC)

�  Recommends that surveillance be performed using ultrasonography at six-month intervals

�  The combined use of Alpha-fetoprotein (AFP) and ultrasonography is not recommended by the AASLD

WHEN HCV TREATMENT IS DEFERRED �  Vaccinations

�  Patients with Hepatitis C should receive any immunization that is recommended for a healthy individual of their age

�  Advisory Committee on Immunization Practices (ACIP) recommends the following for patients with chronic liver disease: �  Hepatitis A

�  Hepatitis B

�  Pneumococcal vaccine

�  Yearly influenza vaccine

�  Tetanus, diphtheria, and acellular pertussis

WHEN HCV TREATMENT IS DEFERRED �  Assess for HCV symptoms

�  Chronic HCV is usually asymptomatic

�  The most frequent complaint in patients with chronic hepatitis C is fatigue

�  Other common complaints include nausea, anorexia, myalgias, arthralgias, and abdominal pain

�  Patients may also present with symptoms and signs of chronic liver disease and cirrhosis

�  Chronic infection with hepatitis C has also been associated with many extra-hepatic manifestations

�  Specific examples include cryoglobulinemia, porphyria cutanea tarda, leukocytoclastic vasculitis, glomerulonephritis, lymphoma, diabetes, and autoimmune disorders

WHEN HCV TREATMENT IS DEFERRED

�  Avoidance of Hepatotoxins �  Alcohol and HCV act together to promoting progression to cirrhosis

and increasing the risk of hepatocellular carcinoma �  A safe threshold of alcohol consumption has not been established �  Therefore abstinence of alcohol in patients with chronic HCV is

suggested

�  NSAIDS should be avoided in patients at risk for GI bleeding (cirrhotic patients)

�  Acetaminophen, but should not exceed 2 g per 24 hours �  Ask about herbal and alternative therapies or other supplement use 

WHEN HCV TREATMENT IS DEFERRED

�  HCVGuidelines.org

�  “Ongoing assessment of liver disease is recommended for persons in whom therapy is deferred.” Rating: Class I, Level C

WHEN HCV TREATMENT IS DEFERRED

�  Fibrosis progression varies markedly between individuals

�  Variables:

�  Host

�  Environmental

�  Viral

WHEN HCV TREATMENT IS DEFERRED

Host ViralNon-modifiable Fibrosis stage Inflammation grade Older age at time of infection Male sex Organ transplant / immune suppression Modifiable Alcohol consumption Nonalcoholic fatty liver disease Obesity Insulin resistance

HCV genotype 3 Coinfection with hepatitis B virus or HIV

Note: Level of HCV RNA does not correlate with stage of disease

When and in Whom to Initiate HCV Therapy Table 1. Factors Associated With Accelerated Fibrosis Progression

WHEN HCV TREATMENT IS DEFERRED

�  Fibrosis may not progress linearly

�  Some individuals may progress slowly for many years followed by an acceleration of fibrosis progression

�  Often those aged >50 years

�  Others may never develop substantial liver fibrosis despite longstanding infection

WHEN HCV TREATMENT IS DEFERRED

�  Presence of existing fibrosis is a strong risk factor for future fibrosis progression �  Fibrosis results from chronic hepatic necroinflammation

�  Watch for higher “activity grade” �  Associated with more rapid fibrosis progression

�  Liver biopsy or fibrosure

� Higher serum transaminase values

� However, even patients with normal ALT levels may develop substantial liver fibrosis

�  Remember the limitations of non-invasive assessment of fibrosis �  Even liver biopsy not perfect

WHEN HCV TREATMENT IS DEFERRED

�  Extraheptatic complications may not be tied to fibrosis stage

�  Examples:

�  Diabetes mellitus

�  Cardiovascular disease

�  Renal disease

�  B-cell non-Hodgkin lymphoma

�  So must be assessed for routinely when therapy deferred

WHEN HCV TREATMENT IS DEFERRED

�  How often to see/re-assess patients

�  “An ideal interval for assessment has not been established”

�  Annual evaluation is appropriate to discuss modifiable risk factors and to update testing for hepatic function and markers for disease progression

�  For all individuals with advanced fibrosis, liver cancer screening dictates a minimum of evaluation every 6 month

�  For individuals with risk factors for rapid progression, every 6 months seems reasonable