Hepatitis C: Difference between revisions
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'''Hepatitis C''' is "inflammation of the liver in humans caused by [[hepatitis c virus]], a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally, and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown."<ref>{{MeSH}}</ref> | '''Hepatitis C''' is "inflammation of the liver in humans caused by [[hepatitis c virus]], a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally, and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown."<ref>{{MeSH}}</ref> | ||
==Complications== | |||
In diagnosis of cirrhosis (Ishak scores, 5-6) in patients with hepatitis C, the aspartate aminotransferase to platelet ratio index (APRI) ratio > 1 suggests cirrhosis with accuracy of:<ref name="pmid23142332">{{cite journal| author=Gara N, Zhao X, Kleiner DE, Liang TJ, Hoofnagle JH, Ghany MG| title=Discordance among transient elastography, aspartate aminotransferase to platelet ratio index, and histologic assessments of liver fibrosis in patients with chronic hepatitis C. | journal=Clin Gastroenterol Hepatol | year= 2013 | volume= 11 | issue= 3 | pages= 303-308.e1 | pmid=23142332 | doi=10.1016/j.cgh.2012.10.044 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23142332 }} </ref> | |||
* Sensitivity = 79% | |||
* Specificity = 78% | |||
==Treatment== | ==Treatment== | ||
[[Clinical practice guideline]]s are available.<ref>Recommendations for Testing, Managing, and Treating Hepatitis C. Available at: http://hcvguidelines.org/</ref> | |||
Most studies have examined the outcome of sustained virologic response. The Cochrane Collaboration raises the question of whether this is an adequate outcome<ref name="pmid20839385">{{cite journal| author=Brok J, Gluud LL, Gluud C| title=Meta-analysis: ribavirin plus interferon vs. interferon monotherapy for chronic hepatitic C - an updated Cochrane review. | journal=Aliment Pharmacol Ther | year= 2010 | volume= 32 | issue= 7 | pages= 840-50 | pmid=20839385 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20839385 }} </ref> due to a trial that showed virological benefit but not clinical benefit.<ref name="pmid19052125">{{cite journal| author=Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC et al.| title=Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. | journal=N Engl J Med | year= 2008 | volume= 359 | issue= 23 | pages= 2429-41 | pmid=19052125 | doi=10.1056/NEJMoa0707615 | pmc=PMC2606037 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19052125 }} </ref> | |||
===Direct acting antiviral (DAA)=== | |||
Direct acting antiviral (DAA) also called Specifically Targeted Antiviral Therapy for HCV (STAT-C) target HCV [[viral nonstructural protein]]s essential to replication and life of the virus. | |||
====NS3 protease inhibitors==== | |||
{| class="wikitable" | {| class="wikitable" | ||
|+ [[Randomized controlled trial]]s of [[protease | |+ [[Randomized controlled trial]]s of [[protease inhibitor]]s against the NS3/4A serine protease for hepatitis C genotype 1 infection. | ||
<ref name="pmid21696308">{{cite journal| author=Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S et al.| title=Telaprevir for retreatment of HCV infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 25 | pages= 2417-28 | pmid=21696308 | doi=10.1056/NEJMoa1013086 | pmc= | url= }} </ref> | <ref name="pmid21696308">{{cite journal| author=Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S et al.| title=Telaprevir for retreatment of HCV infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 25 | pages= 2417-28 | pmid=21696308 | doi=10.1056/NEJMoa1013086 | pmc= | url= }} </ref> | ||
<ref name="pmid21696307">{{cite journal| author=Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH et al.| title=Telaprevir for previously untreated chronic hepatitis C virus infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 25 | pages= 2405-16 | pmid=21696307 | doi=10.1056/NEJMoa1012912 | pmc= | url= }} </ref> | <ref name="pmid21696307">{{cite journal| author=Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH et al.| title=Telaprevir for previously untreated chronic hepatitis C virus infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 25 | pages= 2405-16 | pmid=21696307 | doi=10.1056/NEJMoa1012912 | pmc= | url= }} </ref> | ||
| Line 15: | Line 29: | ||
| ADVANCE Study<ref name="pmid21696308"/><br/>2011|| Previously untreated patients|| telaprevir||peginterferon-ribavirin|| HCV RNA 24 weeks after last treatment|| 69% to 75%|| 44% | | ADVANCE Study<ref name="pmid21696308"/><br/>2011|| Previously untreated patients|| telaprevir||peginterferon-ribavirin|| HCV RNA 24 weeks after last treatment|| 69% to 75%|| 44% | ||
|- | |- | ||
| REALIZE Study<ref name="pmid21696307"/><br/>2011 || Previously treated patients|| telaprevir||peginterferon-ribavirin|| HCV RNA 24 weeks after last treatment|| 83% to 88% (prior | | REALIZE Study<ref name="pmid21696307"/><br/>2011 || Previously treated patients|| telaprevir||peginterferon-ribavirin|| HCV RNA 24 weeks after last treatment|| 83% to 88% (prior response)<br/>54% to 59% (prior partial response)<br/>29% to 33% (prior non-response) | ||
|| 24% (prior | || 24% (prior response)<br/>15% (prior partial response)<br/>5% (prior non-response) | ||
|- | |- | ||
| SPRINT-2 study<ref name="pmid21449783"/><br/>2011 || Previously untreated patients|| boceprevir||peginterferon-ribavirin|| HCV RNA level|| 59% to 66%|| 21% | | SPRINT-2 study<ref name="pmid21449783"/><br/>2011 || Previously untreated patients|| boceprevir||peginterferon-ribavirin|| HCV RNA level|| 59% to 66%|| 21% | ||
| Line 25: | Line 39: | ||
|} | |} | ||
Two [[protease inhibitor]]s, [[telaprevir]] and [[boceprevir]] may add benefit to standard therapy of genotype 1 infection with peginterferon and ribavirin. [[Telaprevir]] adds to peginterferon and ribavirin for previously treated<ref name="pmid21696308">{{cite journal| author=Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S et al.| title=Telaprevir for retreatment of HCV infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 25 | pages= 2417-28 | pmid=21696308 | doi=10.1056/NEJMoa1013086 | pmc= | url= }} </ref> and untreated<ref name="pmid21696307">{{cite journal| author=Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH et al.| title=Telaprevir for previously untreated chronic hepatitis C virus infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 25 | pages= 2405-16 | pmid=21696307 | doi=10.1056/NEJMoa1012912 | pmc= | url= }} </ref> patients. [[Boceprevir]] adds to peginterferon and ribavirin for previously treated<ref name="pmid21449784">{{cite journal| author=Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S et al.| title=Boceprevir for previously treated chronic HCV genotype 1 infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 13 | pages= 1207-17 | pmid=21449784 | doi=10.1056/NEJMoa1009482 | pmc= | url= }} </ref> and untreated<ref name="pmid21449783">{{cite journal| author=Poordad F, McCone J, Bacon BR, Bruno S, Manns MP, Sulkowski MS et al.| title=Boceprevir for untreated chronic HCV genotype 1 infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 13 | pages= 1195-206 | pmid=21449783 | doi=10.1056/NEJMoa1010494 | pmc= | url= }} </ref> patients. | Two NS3/4A serine [[protease inhibitor]]s, [[telaprevir]] and [[boceprevir]] may add benefit to standard therapy of genotype 1 infection with peginterferon and ribavirin. [[Telaprevir]] adds to peginterferon and ribavirin for previously treated<ref name="pmid21696308">{{cite journal| author=Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S et al.| title=Telaprevir for retreatment of HCV infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 25 | pages= 2417-28 | pmid=21696308 | doi=10.1056/NEJMoa1013086 | pmc= | url= }} </ref> and untreated<ref name="pmid21696307">{{cite journal| author=Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH et al.| title=Telaprevir for previously untreated chronic hepatitis C virus infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 25 | pages= 2405-16 | pmid=21696307 | doi=10.1056/NEJMoa1012912 | pmc= | url= }} </ref> patients. [[Boceprevir]] adds to peginterferon and ribavirin for previously treated<ref name="pmid21449784">{{cite journal| author=Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S et al.| title=Boceprevir for previously treated chronic HCV genotype 1 infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 13 | pages= 1207-17 | pmid=21449784 | doi=10.1056/NEJMoa1009482 | pmc= | url= }} </ref> and untreated<ref name="pmid21449783">{{cite journal| author=Poordad F, McCone J, Bacon BR, Bruno S, Manns MP, Sulkowski MS et al.| title=Boceprevir for untreated chronic HCV genotype 1 infection. | journal=N Engl J Med | year= 2011 | volume= 364 | issue= 13 | pages= 1195-206 | pmid=21449783 | doi=10.1056/NEJMoa1010494 | pmc= | url= }} </ref> patients. | ||
The NS3 protease inhibitor, [[asunaprevir]], might help treat hepatitis C.<ref name="pmid22256805">{{cite journal| author=Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R et al.| title=Preliminary study of two antiviral agents for hepatitis C genotype 1. | journal=N Engl J Med | year= 2012 | volume= 366 | issue= 3 | pages= 216-24 | pmid=22256805 | doi=10.1056/NEJMoa1104430 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22256805 }} </ref> | |||
The NS3/4A protease inhibitor, BI 201335, might help treat hepatitis C.<ref name="pmid21925126">{{cite journal| author=Zeuzem S, Asselah T, Angus P, Zarski JP, Larrey D, Müllhaupt B et al.| title=Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection. | journal=Gastroenterology | year= 2011 | volume= 141 | issue= 6 | pages= 2047-55; quiz e14 | pmid=21925126 | doi=10.1053/j.gastro.2011.08.051 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21925126 }} </ref> | |||
==== NS5 replication complex inhibitors==== | |||
The NS5A replication complex inhibitor, [[daclatasvir]], might help treat hepatitis C.<ref name="pmid22256805">{{cite journal| author=Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R et al.| title=Preliminary study of two antiviral agents for hepatitis C genotype 1. | journal=N Engl J Med | year= 2012 | volume= 366 | issue= 3 | pages= 216-24 | pmid=22256805 | doi=10.1056/NEJMoa1104430 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22256805 }} </ref> | |||
The NS5B replication complex inhibitor, BI 207127, might help treat hepatitis C.<ref name="pmid21925126">{{cite journal| author=Zeuzem S, Asselah T, Angus P, Zarski JP, Larrey D, Müllhaupt B et al.| title=Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection. | journal=Gastroenterology | year= 2011 | volume= 141 | issue= 6 | pages= 2047-55; quiz e14 | pmid=21925126 | doi=10.1053/j.gastro.2011.08.051 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21925126 }} </ref> | |||
==Screening== | |||
The United States Centers for Disease Control and Prevention issued draft recommendation for screening individuals born between 1945 and 1965.<ref>Centers for Disease Control and Prevention (2012) [http://www.cdc.gov/nchhstp/newsroom/HepTestingRecsPressRelease2012.html CDC Announces First Ever National Hepatitis Testing Day and Proposes that All Baby Boomers Be Tested Once for Hepatitis C]</ref> | |||
==References== | ==References== | ||
{{reflist|2}} | |||
Latest revision as of 00:14, 31 January 2014
Hepatitis C is "inflammation of the liver in humans caused by hepatitis c virus, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally, and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown."[1]
Complications
In diagnosis of cirrhosis (Ishak scores, 5-6) in patients with hepatitis C, the aspartate aminotransferase to platelet ratio index (APRI) ratio > 1 suggests cirrhosis with accuracy of:[2]
- Sensitivity = 79%
- Specificity = 78%
Treatment
Clinical practice guidelines are available.[3]
Most studies have examined the outcome of sustained virologic response. The Cochrane Collaboration raises the question of whether this is an adequate outcome[4] due to a trial that showed virological benefit but not clinical benefit.[5]
Direct acting antiviral (DAA)
Direct acting antiviral (DAA) also called Specifically Targeted Antiviral Therapy for HCV (STAT-C) target HCV viral nonstructural proteins essential to replication and life of the virus.
NS3 protease inhibitors
| Trial | Patients | Intervention | Comparison | Outcome | Results | |
|---|---|---|---|---|---|---|
| Intervention | Control | |||||
| ADVANCE Study[6] 2011 |
Previously untreated patients | telaprevir | peginterferon-ribavirin | HCV RNA 24 weeks after last treatment | 69% to 75% | 44% |
| REALIZE Study[7] 2011 |
Previously treated patients | telaprevir | peginterferon-ribavirin | HCV RNA 24 weeks after last treatment | 83% to 88% (prior response) 54% to 59% (prior partial response) 29% to 33% (prior non-response) |
24% (prior response) 15% (prior partial response) 5% (prior non-response) |
| SPRINT-2 study[8] 2011 |
Previously untreated patients | boceprevir | peginterferon-ribavirin | HCV RNA level | 59% to 66% | 21% |
| HCV RESPOND-2 study[9] 2011 |
Previously treated patients | boceprevir | peginterferon-ribavirin | HCV RNA level | 67% to 68% (nonblack patients) 42% to 53% (black patients) |
40% (nonblack patients) 23% (black patients) |
Two NS3/4A serine protease inhibitors, telaprevir and boceprevir may add benefit to standard therapy of genotype 1 infection with peginterferon and ribavirin. Telaprevir adds to peginterferon and ribavirin for previously treated[6] and untreated[7] patients. Boceprevir adds to peginterferon and ribavirin for previously treated[9] and untreated[8] patients.
The NS3 protease inhibitor, asunaprevir, might help treat hepatitis C.[10]
The NS3/4A protease inhibitor, BI 201335, might help treat hepatitis C.[11]
NS5 replication complex inhibitors
The NS5A replication complex inhibitor, daclatasvir, might help treat hepatitis C.[10]
The NS5B replication complex inhibitor, BI 207127, might help treat hepatitis C.[11]
Screening
The United States Centers for Disease Control and Prevention issued draft recommendation for screening individuals born between 1945 and 1965.[12]
References
- ↑ Anonymous (2024), Hepatitis C (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Gara N, Zhao X, Kleiner DE, Liang TJ, Hoofnagle JH, Ghany MG (2013). "Discordance among transient elastography, aspartate aminotransferase to platelet ratio index, and histologic assessments of liver fibrosis in patients with chronic hepatitis C.". Clin Gastroenterol Hepatol 11 (3): 303-308.e1. DOI:10.1016/j.cgh.2012.10.044. PMID 23142332. Research Blogging.
- ↑ Recommendations for Testing, Managing, and Treating Hepatitis C. Available at: http://hcvguidelines.org/
- ↑ Brok J, Gluud LL, Gluud C (2010). "Meta-analysis: ribavirin plus interferon vs. interferon monotherapy for chronic hepatitic C - an updated Cochrane review.". Aliment Pharmacol Ther 32 (7): 840-50. PMID 20839385. [e]
- ↑ Di Bisceglie AM, Shiffman ML, Everson GT, Lindsay KL, Everhart JE, Wright EC et al. (2008). "Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon.". N Engl J Med 359 (23): 2429-41. DOI:10.1056/NEJMoa0707615. PMID 19052125. PMC PMC2606037. Research Blogging.
- ↑ 6.0 6.1 6.2 Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S et al. (2011). "Telaprevir for retreatment of HCV infection.". N Engl J Med 364 (25): 2417-28. DOI:10.1056/NEJMoa1013086. PMID 21696308. Research Blogging.
- ↑ 7.0 7.1 7.2 Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH et al. (2011). "Telaprevir for previously untreated chronic hepatitis C virus infection.". N Engl J Med 364 (25): 2405-16. DOI:10.1056/NEJMoa1012912. PMID 21696307. Research Blogging.
- ↑ 8.0 8.1 8.2 Poordad F, McCone J, Bacon BR, Bruno S, Manns MP, Sulkowski MS et al. (2011). "Boceprevir for untreated chronic HCV genotype 1 infection.". N Engl J Med 364 (13): 1195-206. DOI:10.1056/NEJMoa1010494. PMID 21449783. Research Blogging.
- ↑ 9.0 9.1 9.2 Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S et al. (2011). "Boceprevir for previously treated chronic HCV genotype 1 infection.". N Engl J Med 364 (13): 1207-17. DOI:10.1056/NEJMoa1009482. PMID 21449784. Research Blogging.
- ↑ 10.0 10.1 Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R et al. (2012). "Preliminary study of two antiviral agents for hepatitis C genotype 1.". N Engl J Med 366 (3): 216-24. DOI:10.1056/NEJMoa1104430. PMID 22256805. Research Blogging.
- ↑ 11.0 11.1 Zeuzem S, Asselah T, Angus P, Zarski JP, Larrey D, Müllhaupt B et al. (2011). "Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection.". Gastroenterology 141 (6): 2047-55; quiz e14. DOI:10.1053/j.gastro.2011.08.051. PMID 21925126. Research Blogging.
- ↑ Centers for Disease Control and Prevention (2012) CDC Announces First Ever National Hepatitis Testing Day and Proposes that All Baby Boomers Be Tested Once for Hepatitis C