Hepatitis C virus: Difference between revisions
From IDWiki
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(added diagnosis section) |
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Line 1: | Line 1: | ||
− | == |
+ | == Background == |
+ | ===Microbiology=== |
||
− | * Enveloped single-stranded RNA virus in the genus ''Hepacivirus'' and family ''Flaviviridae'' |
||
− | * NS5A and NS5B are important non-structural proteins |
||
+ | *Enveloped single-stranded RNA virus in the genus ''Hepacivirus'' and family ''Flaviviridae'' |
||
− | == Life Cycle == |
||
+ | *NS5A and NS5B are important non-structural proteins |
||
+ | ===Life Cycle=== |
||
− | * Involves protease, polymerase, and non-structural proteins (NS5A/NS5B) |
||
+ | *Involves protease, polymerase, and non-structural proteins (NS5A/NS5B) |
||
− | == Epidemiology == |
||
+ | ===Epidemiology=== |
||
− | * Worldwide about 70 million cases |
||
− | * '''Genotype''' varies by geography |
||
− | ** Genotype 1 most common worldwide |
||
− | ** Genotype 1a and 1b common in Canada |
||
− | *** Disproportionate burden in Indigienous Canadian population in the North |
||
− | *** Very high burden of disease in Canada, causing more years of life lost in Ontario than any other infectious disease |
||
− | ** Genotype 3 more common south-east Asia and in injection drug use |
||
− | ** Genotype 4 common in Egypt (15% prevalence); Egypt has the highest burden in the world |
||
− | * In '''Canada''', about 245,000 chronic hepatitis C, about half are undiagnosed |
||
− | ** Risk factors: injection drug use (highest risk), prior transfusion, and hemophilia |
||
− | ** Increasing burden of disease as patients age and progress to cirrhosis |
||
− | * Modes of transmission |
||
− | ** Injection drug use (most important population, highest risk) |
||
− | ** Tattoos |
||
− | ** Blood transfusions before 1992 |
||
− | ** Cocaine use from blood on the straws |
||
− | ** Rarely, sexual transmission especially HIV-infected MSM |
||
− | ** Vertical transmission rare (3-5%) |
||
− | ** Iatrogenic or medical transmission, from multi-use vials |
||
+ | *Worldwide about 70 million cases |
||
− | == Pathophysiology == |
||
+ | *'''Genotype''' varies by geography |
||
+ | **Genotype 1 most common worldwide |
||
+ | **Genotype 1a and 1b common in Canada |
||
+ | ***Disproportionate burden in Indigienous Canadian population in the North |
||
+ | ***Very high burden of disease in Canada, causing more years of life lost in Ontario than any other infectious disease |
||
+ | **Genotype 3 more common south-east Asia and in injection drug use |
||
+ | **Genotype 4 common in Egypt (15% prevalence); Egypt has the highest burden in the world |
||
+ | *In '''Canada''', about 245,000 chronic hepatitis C, about half are undiagnosed |
||
+ | **Risk factors: injection drug use (highest risk), prior transfusion, and hemophilia |
||
+ | **Increasing burden of disease as patients age and progress to cirrhosis |
||
+ | *Modes of transmission |
||
+ | **Injection drug use (most important population, highest risk) |
||
+ | **Tattoos |
||
+ | **Blood transfusions before 1992 |
||
+ | **Cocaine use from blood on the straws |
||
+ | **Rarely, sexual transmission especially HIV-infected MSM |
||
+ | **Vertical transmission rare (3-5%) |
||
+ | **Iatrogenic or medical transmission, from multi-use vials |
||
+ | ===Pathophysiology=== |
||
− | * In the acute phase, the viral load and liver enzymes fluctuate over months |
||
− | ** Anti-HCV-Ab develops at 12 weeks |
||
− | ** Acute phase lasts 6 months to 2 years |
||
− | * Spontaneous clearance is rare after 2 years |
||
− | ** Anti-HCV-Ab positive and HCV RNA negative |
||
− | ** Repeat to confirm, but no need to follow it |
||
− | ** No complications, though it is a surrogate for risk behaviours |
||
− | ** ''Not'' protected from reinfection |
||
− | * If it isn't cleared, it becomes chronic |
||
− | ** Lifetime risk of cirrhosis is 50-60%, with 20% having cirrhosis at 20 years |
||
− | ** Liver cancer develops in 1-4% |
||
+ | *In the acute phase, the viral load and liver enzymes fluctuate over months |
||
− | == Clinical Presentation == |
||
+ | **Anti-HCV-Ab develops at 12 weeks |
||
+ | **Acute phase lasts 6 months to 2 years |
||
+ | *Spontaneous clearance is rare after 2 years |
||
+ | **Anti-HCV-Ab positive and HCV RNA negative |
||
+ | **Repeat to confirm, but no need to follow it |
||
+ | **No complications, though it is a surrogate for risk behaviours |
||
+ | **''Not'' protected from reinfection |
||
+ | *If it isn't cleared, it becomes chronic |
||
+ | **Lifetime risk of cirrhosis is 50-60%, with 20% having cirrhosis at 20 years |
||
+ | **Liver cancer develops in 1-4% |
||
+ | ==Clinical Presentation== |
||
− | * After exposure, may clear infection, but 70-80% become chronically infected |
||
− | * Progresses slowly and asymptomatically until they develop liver fibrosis, compensated cirrhosis, then decompensated cirrhosis |
||
− | ** ~20-25% progress to end-stage liver disease within 20 years |
||
+ | *After exposure, may clear infection, but 70-80% become chronically infected |
||
− | == Management == |
||
+ | *Progresses slowly and asymptomatically until they develop liver fibrosis, compensated cirrhosis, then decompensated cirrhosis |
||
+ | **~20-25% progress to end-stage liver disease within 20 years |
||
− | + | == Diagnosis == |
|
+ | * Screening with serology for anti-HCV antibodies followed by RNA PCR to confirm ongoing infection |
||
− | * All individuals should be considered for antiretroviral treatment |
||
+ | ** The window period for serology is about 5 to 10 weeks before antibodies are detectable |
||
− | * Assess readiness for treatment, as good adherence is necessary |
||
− | * Alcohol, drug use, and mental health disorders are ''not'' containdications to treatment |
||
+ | ==Management== |
||
− | === Initial investigations === |
||
+ | ===Decision to treat=== |
||
− | * Confirm active infection with HCV RNA then get genotype and subtype |
||
− | ** Two positive HCV RNA tests 6 months apart documents chronic infection, only needed in Ontario |
||
− | ** May need resistance testing |
||
− | ** Genotype only actually matters for cirrhosis (since we can otherwise pick a pan-genotypic regimen) |
||
− | * Baseline bloodwork, including CBC, liver enzymes, liver function, and creatinine |
||
− | * Serology to exclude HIV and HBV |
||
− | * Transferrin saturation to exclude hemochromatosis, and IgG levels to exclude autimmune hepatitis |
||
− | * Baseline liver ultrasound |
||
− | * If not clearly cirrhotic, assess liver fibrosis |
||
− | ** Bloodwork: [[AST:platelet ratio index]] (APRI), [[FIB-4]], FibroTest |
||
− | ** Imaging: FibroScan |
||
− | ** Gold standard: biopsy |
||
+ | *All individuals should be considered for antiretroviral treatment |
||
− | === Antivirals === |
||
+ | *Assess readiness for treatment, as good adherence is necessary |
||
+ | *Alcohol, drug use, and mental health disorders are ''not'' containdications to treatment |
||
+ | ===Initial investigations=== |
||
− | * Include nonstructural 3/4A (NS3/4A) serine protease (-previr), the NS5B RNA dependent RNA polymerase (-buvir) and the NS5A protein (-asvir) |
||
+ | |||
− | * Assess drug-drug interactions with [[https://www.hepdruginteractions.org/|www.hepdruginteractions.org]] |
||
+ | *Confirm active infection with HCV RNA then get genotype and subtype |
||
− | ** PPI and Epclusa/Harvoni |
||
+ | **Two positive HCV RNA tests 6 months apart documents chronic infection, only needed in Ontario |
||
− | ** Statins require dose reduction; atorvastatin and Maviret is no-no |
||
+ | **May need resistance testing |
||
− | ** Anti-epileptics except leviteracetam |
||
+ | **Genotype only actually matters for cirrhosis (since we can otherwise pick a pan-genotypic regimen) |
||
− | * Choice of treatment regimen depends on genotype, previously-failed treatments, and cirrhosis |
||
+ | *Baseline bloodwork, including CBC, liver enzymes, liver function, and creatinine |
||
− | ** All protease inhibitors (-previr) are contraindicated in decompensated cirrhosis, which refers to ascites, esophageal variceal hemorrhage, jaundice, or hepatic encephalopathy |
||
+ | *Serology to exclude HIV and HBV |
||
− | ** Sofosbuvir/velpatasvir/voxilaprevir (Vosevi) is indicated for previously-treated patients |
||
+ | *Transferrin saturation to exclude hemochromatosis, and IgG levels to exclude autimmune hepatitis |
||
+ | *Baseline liver ultrasound |
||
+ | *If not clearly cirrhotic, assess liver fibrosis |
||
+ | **Bloodwork: [[AST:platelet ratio index]] (APRI), [[FIB-4]], FibroTest |
||
+ | **Imaging: FibroScan |
||
+ | **Gold standard: biopsy |
||
+ | |||
+ | ===Antivirals=== |
||
+ | |||
+ | *Include nonstructural 3/4A (NS3/4A) serine protease (-previr), the NS5B RNA dependent RNA polymerase (-buvir) and the NS5A protein (-asvir) |
||
+ | *Assess drug-drug interactions with [[https://www.hepdruginteractions.org/|www.hepdruginteractions.org]] |
||
+ | **PPI and Epclusa/Harvoni |
||
+ | **Statins require dose reduction; atorvastatin and Maviret is no-no |
||
+ | **Anti-epileptics except leviteracetam |
||
+ | *Choice of treatment regimen depends on genotype, previously-failed treatments, and cirrhosis |
||
+ | **All protease inhibitors (-previr) are contraindicated in decompensated cirrhosis, which refers to ascites, esophageal variceal hemorrhage, jaundice, or hepatic encephalopathy |
||
+ | **Sofosbuvir/velpatasvir/voxilaprevir (Vosevi) is indicated for previously-treated patients |
||
{| class="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !Regimen |
− | ! |
+ | !1a |
− | ! |
+ | !1b |
− | ! |
+ | !2 |
− | ! |
+ | !3 |
− | ! |
+ | !4 |
− | ! |
+ | !5 |
− | ! |
+ | !6 |
|- |
|- |
||
− | | |
+ | |[[Ledipasvir]]/[[sofosbuvir]] (Harvoni) |
− | | |
+ | |12 wk ± ribavirin |
− | | |
+ | |12 wk |
− | | |
+ | |– |
− | | |
+ | |12 wk + ribavirin |
− | | |
+ | |12 wk |
− | | |
+ | |12 wk |
− | | |
+ | |12 wk |
|- |
|- |
||
− | | |
+ | |[[Elbasvir]]/[[grazoprevir]] (Zepatier) |
− | | |
+ | |12-16 wk ± ribavirin |
− | | |
+ | |12 wk |
− | | |
+ | |– |
− | | |
+ | |12 wk + sofosbuvir |
− | | |
+ | |12 wk |
− | | |
+ | |– |
− | | |
+ | |– |
|- |
|- |
||
− | | |
+ | |[[Sofosbuvir]]/[[velpatasvir]] (Epclusa) |
− | | |
+ | |12 wk |
− | | |
+ | |12 wk |
− | | |
+ | |12 wk |
− | | |
+ | |12 wk |
− | | |
+ | |12 wk |
− | | |
+ | |12 wk |
− | | |
+ | |12 wk |
|- |
|- |
||
− | | |
+ | |[[Glecaprevir]]/[[pibrentasvir]] (Maviret) |
− | | |
+ | |8 wk |
− | | |
+ | |8 wk |
− | | |
+ | |8 wk |
− | | |
+ | |8 wk |
− | | |
+ | |8 wk |
− | | |
+ | |8 wk |
− | | |
+ | |8 wk |
|- |
|- |
||
− | | |
+ | |... |
| |
| |
||
| |
| |
||
Line 140: | Line 147: | ||
|} |
|} |
||
− | * |
+ | *Epclusa 12 weeks for most, now OCB covered |
− | * |
+ | *Zepatier 12 weeks for G1 and G4 |
− | * |
+ | *Maviret 8 weeks for most; 12 weeks for cirrhosis |
− | * |
+ | *Harvoni 8 weeks if uncomplicated |
− | === |
+ | ===Experienced patients=== |
− | * |
+ | *Changes the options, mostly longer |
− | === |
+ | ===Non-pharmacologic management=== |
− | * |
+ | *Counsel to avoid sharing products like needles or razors, safe sex, avoid alcohol |
− | * |
+ | *Vaccinate for Hep A and B |
− | === |
+ | ===Follow-up=== |
− | * |
+ | *Need to confirm sustained virologic response (SVR) |
− | == |
+ | ==Screening== |
− | * |
+ | *Majority of cases of chronic hepatitis C occur in baby boomers (born 1945 to 1975), though screening for this population appears to be controversial |
− | === |
+ | ===Populations to screen=== |
− | * |
+ | *'''History of injection drug use, ever''' |
− | * |
+ | *History of incarceration |
− | * |
+ | *Received healthcare where there is a lack of IPAC |
− | * |
+ | *Blood products or organ transplantation before 1992 in Canada |
− | * |
+ | *Born or resided in a country where prevalence of HCV is >3% |
− | ** |
+ | **Central, East and South Asia |
− | ** |
+ | **Australasia and Oceania |
− | ** |
+ | **Eastern Europe |
− | ** |
+ | **Subsaharan Africa |
− | ** |
+ | **North Africa or the Middle East |
− | * |
+ | *Born to HCV positive mother |
− | * |
+ | *History of sharing personal care items or sex with an HCV-positive person |
− | * |
+ | *HIV infection |
− | * |
+ | *Received hemodialysis |
− | * |
+ | *Elevated ALT |
− | * |
+ | *'''Born between 1945 and 1975''' (baby boomers) |
− | ** |
+ | **Recommended in the US and by CASL but not by CTFPHC |
− | ==== |
+ | ====Opportunistic screening==== |
− | * |
+ | *Emergency rooms |
− | * |
+ | *Hospital inpatients |
− | * |
+ | *Substance use treatment clinics |
− | === |
+ | ===Screening procedure=== |
− | * |
+ | *Anti-HCV antibody |
− | ** |
+ | **Serum serology gold standard |
− | ** |
+ | **There are some quick point-of-care tests, like from saliva |
− | ** |
+ | **Also cheap options like dried blood spot testing, which can have RNA testing as well |
− | * |
+ | *If positive, proceed to HCV RNA |
− | ** |
+ | **May be able to do it as reflex testing |
− | * |
+ | *Should be done annually in patients who have ongoing high-risk exposures |
− | == |
+ | ==Further Reading== |
− | * |
+ | *Shah H, ''et al''. [https://doi.org/10.1503/cmaj.170453 The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver]. ''CMAJ''. 2018;190(22):E677-E687. |
− | * |
+ | *[https://doi.org/10.1093/cid/ciy585 Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection]. ''Clin Infect Dis''. 2018;67(10):1477-92. |
[[Category:Flaviviridae]] |
[[Category:Flaviviridae]] |
Revision as of 20:50, 9 July 2020
Background
Microbiology
- Enveloped single-stranded RNA virus in the genus Hepacivirus and family Flaviviridae
- NS5A and NS5B are important non-structural proteins
Life Cycle
- Involves protease, polymerase, and non-structural proteins (NS5A/NS5B)
Epidemiology
- Worldwide about 70 million cases
- Genotype varies by geography
- Genotype 1 most common worldwide
- Genotype 1a and 1b common in Canada
- Disproportionate burden in Indigienous Canadian population in the North
- Very high burden of disease in Canada, causing more years of life lost in Ontario than any other infectious disease
- Genotype 3 more common south-east Asia and in injection drug use
- Genotype 4 common in Egypt (15% prevalence); Egypt has the highest burden in the world
- In Canada, about 245,000 chronic hepatitis C, about half are undiagnosed
- Risk factors: injection drug use (highest risk), prior transfusion, and hemophilia
- Increasing burden of disease as patients age and progress to cirrhosis
- Modes of transmission
- Injection drug use (most important population, highest risk)
- Tattoos
- Blood transfusions before 1992
- Cocaine use from blood on the straws
- Rarely, sexual transmission especially HIV-infected MSM
- Vertical transmission rare (3-5%)
- Iatrogenic or medical transmission, from multi-use vials
Pathophysiology
- In the acute phase, the viral load and liver enzymes fluctuate over months
- Anti-HCV-Ab develops at 12 weeks
- Acute phase lasts 6 months to 2 years
- Spontaneous clearance is rare after 2 years
- Anti-HCV-Ab positive and HCV RNA negative
- Repeat to confirm, but no need to follow it
- No complications, though it is a surrogate for risk behaviours
- Not protected from reinfection
- If it isn't cleared, it becomes chronic
- Lifetime risk of cirrhosis is 50-60%, with 20% having cirrhosis at 20 years
- Liver cancer develops in 1-4%
Clinical Presentation
- After exposure, may clear infection, but 70-80% become chronically infected
- Progresses slowly and asymptomatically until they develop liver fibrosis, compensated cirrhosis, then decompensated cirrhosis
- ~20-25% progress to end-stage liver disease within 20 years
Diagnosis
- Screening with serology for anti-HCV antibodies followed by RNA PCR to confirm ongoing infection
- The window period for serology is about 5 to 10 weeks before antibodies are detectable
Management
Decision to treat
- All individuals should be considered for antiretroviral treatment
- Assess readiness for treatment, as good adherence is necessary
- Alcohol, drug use, and mental health disorders are not containdications to treatment
Initial investigations
- Confirm active infection with HCV RNA then get genotype and subtype
- Two positive HCV RNA tests 6 months apart documents chronic infection, only needed in Ontario
- May need resistance testing
- Genotype only actually matters for cirrhosis (since we can otherwise pick a pan-genotypic regimen)
- Baseline bloodwork, including CBC, liver enzymes, liver function, and creatinine
- Serology to exclude HIV and HBV
- Transferrin saturation to exclude hemochromatosis, and IgG levels to exclude autimmune hepatitis
- Baseline liver ultrasound
- If not clearly cirrhotic, assess liver fibrosis
- Bloodwork: AST:platelet ratio index (APRI), FIB-4, FibroTest
- Imaging: FibroScan
- Gold standard: biopsy
Antivirals
- Include nonstructural 3/4A (NS3/4A) serine protease (-previr), the NS5B RNA dependent RNA polymerase (-buvir) and the NS5A protein (-asvir)
- Assess drug-drug interactions with [[1]]
- PPI and Epclusa/Harvoni
- Statins require dose reduction; atorvastatin and Maviret is no-no
- Anti-epileptics except leviteracetam
- Choice of treatment regimen depends on genotype, previously-failed treatments, and cirrhosis
- All protease inhibitors (-previr) are contraindicated in decompensated cirrhosis, which refers to ascites, esophageal variceal hemorrhage, jaundice, or hepatic encephalopathy
- Sofosbuvir/velpatasvir/voxilaprevir (Vosevi) is indicated for previously-treated patients
Regimen | 1a | 1b | 2 | 3 | 4 | 5 | 6 |
---|---|---|---|---|---|---|---|
Ledipasvir/sofosbuvir (Harvoni) | 12 wk ± ribavirin | 12 wk | – | 12 wk + ribavirin | 12 wk | 12 wk | 12 wk |
Elbasvir/grazoprevir (Zepatier) | 12-16 wk ± ribavirin | 12 wk | – | 12 wk + sofosbuvir | 12 wk | – | – |
Sofosbuvir/velpatasvir (Epclusa) | 12 wk | 12 wk | 12 wk | 12 wk | 12 wk | 12 wk | 12 wk |
Glecaprevir/pibrentasvir (Maviret) | 8 wk | 8 wk | 8 wk | 8 wk | 8 wk | 8 wk | 8 wk |
... |
- Epclusa 12 weeks for most, now OCB covered
- Zepatier 12 weeks for G1 and G4
- Maviret 8 weeks for most; 12 weeks for cirrhosis
- Harvoni 8 weeks if uncomplicated
Experienced patients
- Changes the options, mostly longer
Non-pharmacologic management
- Counsel to avoid sharing products like needles or razors, safe sex, avoid alcohol
- Vaccinate for Hep A and B
Follow-up
- Need to confirm sustained virologic response (SVR)
Screening
- Majority of cases of chronic hepatitis C occur in baby boomers (born 1945 to 1975), though screening for this population appears to be controversial
Populations to screen
- History of injection drug use, ever
- History of incarceration
- Received healthcare where there is a lack of IPAC
- Blood products or organ transplantation before 1992 in Canada
- Born or resided in a country where prevalence of HCV is >3%
- Central, East and South Asia
- Australasia and Oceania
- Eastern Europe
- Subsaharan Africa
- North Africa or the Middle East
- Born to HCV positive mother
- History of sharing personal care items or sex with an HCV-positive person
- HIV infection
- Received hemodialysis
- Elevated ALT
- Born between 1945 and 1975 (baby boomers)
- Recommended in the US and by CASL but not by CTFPHC
Opportunistic screening
- Emergency rooms
- Hospital inpatients
- Substance use treatment clinics
Screening procedure
- Anti-HCV antibody
- Serum serology gold standard
- There are some quick point-of-care tests, like from saliva
- Also cheap options like dried blood spot testing, which can have RNA testing as well
- If positive, proceed to HCV RNA
- May be able to do it as reflex testing
- Should be done annually in patients who have ongoing high-risk exposures
Further Reading
- Shah H, et al. The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver. CMAJ. 2018;190(22):E677-E687.
- Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis. 2018;67(10):1477-92.