Hepatitis C natural history: Difference between revisions
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__NOTOC__ | |||
{{Hepatitis C}} | {{Hepatitis C}} | ||
{{CMG}} | {{CMG}}; '''Associate Editor(s)-In-Chief:''' [[User:YazanDaaboul|Yazan Daaboul]], [[User:Sergekorjian|Serge Korjian]], {{JA}} | ||
==Overview== | |||
The majority of individuals infected with [[HCV]] will become chronic carriers. The primary and most severe complications of HCV are [[hepatic]], namely [[liver cirrhosis]] years after the onset of infection and the consequent development of [[hepatocellular carcinoma]]. Other classical extra-hepatic manifestations (e.g., [[cryoglobulinemia]], [[lichen planus]], [[membranoproliferative glomerulonephritis]], and [[porphyria cutanea tarda]]) are also complications of [[chronic HCV infection]]. Treatment is necessary for patients with chronic stable HCV infection; otherwise, the prognosis is poor and progression of the disease is potentially fatal. | |||
==Natural History== | ==Natural History== | ||
Upon exposure, HCV causes an acute phase that is | Upon exposure, HCV causes an acute phase that is asymptomatic in approximately 80% of cases. Acute HCV persists for less than 6 months. In 15-45% of cases, HCV is an isolated acute infection with almost no chronic sequelae, even in the absence of treatment. Patients exposed to HCV will subsequently develop [[anti-HCV antibodies]] but will demonstrate undetectable viral levels and negative HCV RNA. | ||
In the majority of cases, however, HCV persists beyond 6 months and individuals | In the majority of cases, however, HCV persists beyond 6 months and individuals become chronic carriers of HCV. Chronic [[HCV]] occurs in approximately 55-85% of patients. These patients will have positive [[anti-HCV antibodies]] and positive [[nucleic acid test]] (NAT) for HCV RNA, demonstrating the persistence of HCV and the inability of the body to appropriately clear the infection.<ref name="pmid21139063">{{cite journal| author=Thomson EC, Fleming VM, Main J, Klenerman P, Weber J, Eliahoo J et al.| title=Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men. | journal=Gut | year= 2011 | volume= 60 | issue= 6 | pages= 837-45 | pmid=21139063 | doi=10.1136/gut.2010.217166 | pmc=PMC3095479 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21139063 }} </ref><ref name="pmid12851873">{{cite journal| author=Gerlach JT, Diepolder HM, Zachoval R, Gruener NH, Jung MC, Ulsenheimer A et al.| title=Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. | journal=Gastroenterology | year= 2003 | volume= 125 | issue= 1 | pages= 80-8 | pmid=12851873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12851873 }} </ref> | ||
[[Image:HCV_NH.png|thumb|600px|center|Natural History of HCV | [[Image:HCV_NH.png|thumb|600px|center|Natural History of HCV - Source: http://www.who.int/en/]] | ||
<br> | <br> | ||
==Complications== | ==Complications== | ||
===Hepatic Manifestations=== | |||
A major complication of chronic HCV infection is [[cirrhosis]], which ultimately leads to a decompensated state or transforms into a malignant [[hepatocellular carcinoma]] (HCC).<ref name=WHO>{{cite web |url=http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1&ua=1 |title=Guidelines for the screening, care, and treatment of persons with HCV infection|date=April 2014 |website=WHO |publisher=WHO |accessdate=July 27, 2014}}</ref> Not all patients develop cirrhosis at the same rate; exposure to other risk factors of cirrhosis, such as [[alcohol]], [[HBV]], or [[HIV infection]], or [[immunocompromise|immunocompromised status]] may hasten [[fibrosis]] of the liver and the development of HCC.<ref name="pmid12823595">{{cite journal| author=Freeman AJ, Law MG, Kaldor JM, Dore GJ| title=Predicting progression to cirrhosis in chronic hepatitis C virus infection. | journal=J Viral Hepat | year= 2003 | volume= 10 | issue= 4 | pages= 285-93 | pmid=12823595 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12823595 }} </ref> | |||
Chronic HCV eventually progresses to cause | Chronic HCV often eventually progresses to cause [[cirrhosis]] of the liver due to persistence of tissue [[inflammation]] and [[necrosis]], along with [[fibrogenesis]] and deposition of components in the [[extracellular matrix]]. In the absence of treatment, '''15-30% of patients with chronic HCV develop cirrhosis within 20 years.'''<ref name=WHO>{{cite web |url=http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1&ua=1 |title=Guidelines for the screening, care, and treatment of persons with HCV infection|date=April 2014 |website=WHO |publisher=WHO |accessdate=July 27, 2014}}</ref> | ||
Similarly, HCC is a known complication of chronic HCV infection. Patients with HCV develop HCC when the liver reaches its cirrhotic stage. The annual risk of | Similarly, [[hepatocellular carcinoma]] ([[HCC]]) is a known complication of chronic HCV infection. Patients with HCV develop HCC when the liver reaches its cirrhotic stage. The annual risk of developing [[hepatocellular carcinoma]] in a patient with cirrhosis is approximately 2-4%. | ||
====Extrahepatic complications of HCV infection<ref name="pmid22497808">{{cite journal| author=Fletcher NF, McKeating JA| title=Hepatitis C virus and the brain. | journal=J Viral Hepat | year= 2012 | volume= 19 | issue= 5 | pages= 301-6 | pmid=22497808 | doi=10.1111/j.1365-2893.2012.01591.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22497808 }} </ref><ref name=WHO>{{cite web |url=http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1&ua=1 |title=Guidelines for the screening, care, and treatment of persons with HCV infection|date=April 2014 |website=WHO |publisher=WHO |accessdate= | ===Extrahepatic complications of HCV infection=== | ||
Extrahepatic complications of HCV infection include:<ref name="pmid22497808">{{cite journal| author=Fletcher NF, McKeating JA| title=Hepatitis C virus and the brain. | journal=J Viral Hepat | year= 2012 | volume= 19 | issue= 5 | pages= 301-6 | pmid=22497808 | doi=10.1111/j.1365-2893.2012.01591.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22497808 }} </ref><ref name=WHO>{{cite web |url=http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1&ua=1 |title=Guidelines for the screening, care, and treatment of persons with HCV infection|date=April 2014 |website=WHO |publisher=WHO |accessdate=July 27, 2014}}</ref> | |||
* | *[[Lymphopriliferative disorders]] | ||
* | ** [[Benign]]:[[Cryoglobulinemia]]: Divided into Type I, and mixed types; Type II, and III [[cryoglobulinemia]]. Mixed [[Cryoglobulinemia|cryoglobulinemic]] [[vasculitis]] is usually mildly symptomatic, which include palpable [[purpura]], [[arthralgia]], and [[fatigue]]. [[Peripheral nervous system]] involvement demonstrating as asymmetric, [[pain|painful]] [[paresthesia]] subsequently becoming symmetric is not uncommon. Motor deficit affecting legs in the later stages of the diseases is also seen. Rarely, the disease may progress to a life-threatening widespread vasculitis with involvement of the [[central nervous system|CNS]], [[heart]], or [[gastrointestinal tract]].<ref name="CacoubLongo2021">{{cite journal|last1=Cacoub|first1=Patrice|last2=Longo|first2=Dan L.|last3=Saadoun|first3=David|title=Extrahepatic Manifestations of Chronic HCV Infection|journal=New England Journal of Medicine|volume=384|issue=11|year=2021|pages=1038–1052|issn=0028-4793|doi=10.1056/NEJMra2033539}}</ref> | ||
* | **[[Malignant]]: [[Hodgkin's lymphoma]] and [[non-Hodgkin's lymphoma]]<ref name="CacoubLongo2021">{{cite journal|last1=Cacoub|first1=Patrice|last2=Longo|first2=Dan L.|last3=Saadoun|first3=David|title=Extrahepatic Manifestations of Chronic HCV Infection|journal=New England Journal of Medicine|volume=384|issue=11|year=2021|pages=1038–1052|issn=0028-4793|doi=10.1056/NEJMra2033539}}</ref> | ||
*Sjogren syndrome | *[[Membranoproliferative glomerulonephritis]]<ref name="CacoubLongo2021">{{cite journal|last1=Cacoub|first1=Patrice|last2=Longo|first2=Dan L.|last3=Saadoun|first3=David|title=Extrahepatic Manifestations of Chronic HCV Infection|journal=New England Journal of Medicine|volume=384|issue=11|year=2021|pages=1038–1052|issn=0028-4793|doi=10.1056/NEJMra2033539}}</ref> | ||
*Insulin resistance and type-2 diabetes mellitus | *[[Autoimmune thyroiditis]] | ||
*Porphyria cutanea tarda | *[[Sjogren syndrome]] | ||
*Lichen Planus | *[[Insulin resistance]] and [[type-2 diabetes mellitus]] | ||
* | *[[Porphyria cutanea tarda]] | ||
*[[Lichen Planus]] | |||
*Cognitive dysfunction | *[[Seronegative arthritis]] | ||
*Depression | *[[Cognitive dysfunction]] | ||
*[[Depression]] | |||
* [[Autoimmune hemolytic anemia]] (AIHA)<ref name="CacoubLongo2021">{{cite journal|last1=Cacoub|first1=Patrice|last2=Longo|first2=Dan L.|last3=Saadoun|first3=David|title=Extrahepatic Manifestations of Chronic HCV Infection|journal=New England Journal of Medicine|volume=384|issue=11|year=2021|pages=1038–1052|issn=0028-4793|doi=10.1056/NEJMra2033539}}</ref> | |||
* [[ITP| immune thrombocytopenia]]<ref name="CacoubLongo2021">{{cite journal|last1=Cacoub|first1=Patrice|last2=Longo|first2=Dan L.|last3=Saadoun|first3=David|title=Extrahepatic Manifestations of Chronic HCV Infection|journal=New England Journal of Medicine|volume=384|issue=11|year=2021|pages=1038–1052|issn=0028-4793|doi=10.1056/NEJMra2033539}}</ref> | |||
*[[Monoclonal gammopathy of undetermined significance]] (MGUS)<ref name="CacoubLongo2021">{{cite journal|last1=Cacoub|first1=Patrice|last2=Longo|first2=Dan L.|last3=Saadoun|first3=David|title=Extrahepatic Manifestations of Chronic HCV Infection|journal=New England Journal of Medicine|volume=384|issue=11|year=2021|pages=1038–1052|issn=0028-4793|doi=10.1056/NEJMra2033539}}</ref> | |||
==Prognosis== | ==Prognosis== | ||
===Acute HCV Infection<ref name="pmid16614742">{{cite journal| author=Chen SL, Morgan TR| title=The natural history of hepatitis C virus (HCV) infection. | journal=Int J Med Sci | year= 2006 | volume= 3 | issue= 2 | pages= 47-52 | pmid=16614742 | doi= | pmc=PMC1415841 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16614742 }} </ref>=== | |||
*Spontaneous clearance of [[HCV RNA]]: 15-45% | |||
*Progression to chronic infection: 55-85% | |||
*[[Fulminant hepatitis]]: Rare | |||
===Chronic HCV Infection<ref name="pmid16614742">{{cite journal| author=Chen SL, Morgan TR| title=The natural history of hepatitis C virus (HCV) infection. | journal=Int J Med Sci | year= 2006 | volume= 3 | issue= 2 | pages= 47-52 | pmid=16614742 | doi= | pmc=PMC1415841 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16614742 }} </ref>=== | |||
*: | *[[Cirrhosis]] after 20 years: 10-20% | ||
*: | *[[Decompensated cirrhosis]]: 50% survival rate at 5 years | ||
*: | *[[Hepatocellular carcinoma]]: 1-4% per year | ||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Gastroenterology]] | [[Category:Gastroenterology]] | ||
[[Category:FinalQCRequired]] | |||
[[Category:Emergency mdicine]] | |||
[[Category:Disease]] | |||
[[Category:Up-To-Date]] | |||
[[Category:Infectious disease]] | [[Category:Infectious disease]] | ||
[[Category: | [[Category:Hepatology]] | ||
Latest revision as of 23:14, 12 June 2021
Hepatitis C |
Diagnosis |
Treatment |
Hepatitis C natural history On the Web |
American Roentgen Ray Society Images of Hepatitis C natural history |
Risk calculators and risk factors for Hepatitis C natural history |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Yazan Daaboul, Serge Korjian, Javaria Anwer M.D.[2]
Overview
The majority of individuals infected with HCV will become chronic carriers. The primary and most severe complications of HCV are hepatic, namely liver cirrhosis years after the onset of infection and the consequent development of hepatocellular carcinoma. Other classical extra-hepatic manifestations (e.g., cryoglobulinemia, lichen planus, membranoproliferative glomerulonephritis, and porphyria cutanea tarda) are also complications of chronic HCV infection. Treatment is necessary for patients with chronic stable HCV infection; otherwise, the prognosis is poor and progression of the disease is potentially fatal.
Natural History
Upon exposure, HCV causes an acute phase that is asymptomatic in approximately 80% of cases. Acute HCV persists for less than 6 months. In 15-45% of cases, HCV is an isolated acute infection with almost no chronic sequelae, even in the absence of treatment. Patients exposed to HCV will subsequently develop anti-HCV antibodies but will demonstrate undetectable viral levels and negative HCV RNA.
In the majority of cases, however, HCV persists beyond 6 months and individuals become chronic carriers of HCV. Chronic HCV occurs in approximately 55-85% of patients. These patients will have positive anti-HCV antibodies and positive nucleic acid test (NAT) for HCV RNA, demonstrating the persistence of HCV and the inability of the body to appropriately clear the infection.[1][2]
![](/images/2/28/HCV_NH.png)
Complications
Hepatic Manifestations
A major complication of chronic HCV infection is cirrhosis, which ultimately leads to a decompensated state or transforms into a malignant hepatocellular carcinoma (HCC).[3] Not all patients develop cirrhosis at the same rate; exposure to other risk factors of cirrhosis, such as alcohol, HBV, or HIV infection, or immunocompromised status may hasten fibrosis of the liver and the development of HCC.[4]
Chronic HCV often eventually progresses to cause cirrhosis of the liver due to persistence of tissue inflammation and necrosis, along with fibrogenesis and deposition of components in the extracellular matrix. In the absence of treatment, 15-30% of patients with chronic HCV develop cirrhosis within 20 years.[3]
Similarly, hepatocellular carcinoma (HCC) is a known complication of chronic HCV infection. Patients with HCV develop HCC when the liver reaches its cirrhotic stage. The annual risk of developing hepatocellular carcinoma in a patient with cirrhosis is approximately 2-4%.
Extrahepatic complications of HCV infection
Extrahepatic complications of HCV infection include:[5][3]
- Lymphopriliferative disorders
- Benign:Cryoglobulinemia: Divided into Type I, and mixed types; Type II, and III cryoglobulinemia. Mixed cryoglobulinemic vasculitis is usually mildly symptomatic, which include palpable purpura, arthralgia, and fatigue. Peripheral nervous system involvement demonstrating as asymmetric, painful paresthesia subsequently becoming symmetric is not uncommon. Motor deficit affecting legs in the later stages of the diseases is also seen. Rarely, the disease may progress to a life-threatening widespread vasculitis with involvement of the CNS, heart, or gastrointestinal tract.[6]
- Malignant: Hodgkin's lymphoma and non-Hodgkin's lymphoma[6]
- Membranoproliferative glomerulonephritis[6]
- Autoimmune thyroiditis
- Sjogren syndrome
- Insulin resistance and type-2 diabetes mellitus
- Porphyria cutanea tarda
- Lichen Planus
- Seronegative arthritis
- Cognitive dysfunction
- Depression
- Autoimmune hemolytic anemia (AIHA)[6]
- immune thrombocytopenia[6]
- Monoclonal gammopathy of undetermined significance (MGUS)[6]
Prognosis
Acute HCV Infection[7]
- Spontaneous clearance of HCV RNA: 15-45%
- Progression to chronic infection: 55-85%
- Fulminant hepatitis: Rare
Chronic HCV Infection[7]
- Cirrhosis after 20 years: 10-20%
- Decompensated cirrhosis: 50% survival rate at 5 years
- Hepatocellular carcinoma: 1-4% per year
References
- ↑ Thomson EC, Fleming VM, Main J, Klenerman P, Weber J, Eliahoo J; et al. (2011). "Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men". Gut. 60 (6): 837–45. doi:10.1136/gut.2010.217166. PMC 3095479. PMID 21139063.
- ↑ Gerlach JT, Diepolder HM, Zachoval R, Gruener NH, Jung MC, Ulsenheimer A; et al. (2003). "Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance". Gastroenterology. 125 (1): 80–8. PMID 12851873.
- ↑ 3.0 3.1 3.2 "Guidelines for the screening, care, and treatment of persons with HCV infection" (PDF). WHO. WHO. April 2014. Retrieved July 27, 2014.
- ↑ Freeman AJ, Law MG, Kaldor JM, Dore GJ (2003). "Predicting progression to cirrhosis in chronic hepatitis C virus infection". J Viral Hepat. 10 (4): 285–93. PMID 12823595.
- ↑ Fletcher NF, McKeating JA (2012). "Hepatitis C virus and the brain". J Viral Hepat. 19 (5): 301–6. doi:10.1111/j.1365-2893.2012.01591.x. PMID 22497808.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Cacoub, Patrice; Longo, Dan L.; Saadoun, David (2021). "Extrahepatic Manifestations of Chronic HCV Infection". New England Journal of Medicine. 384 (11): 1038–1052. doi:10.1056/NEJMra2033539. ISSN 0028-4793.
- ↑ 7.0 7.1 Chen SL, Morgan TR (2006). "The natural history of hepatitis C virus (HCV) infection". Int J Med Sci. 3 (2): 47–52. PMC 1415841. PMID 16614742.