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Hepatitis C

Type C Viral Hepatitis

Hepatitis C is a viral infection caused by the hepatitis C virus. A mildly symptomatic chronic illness is observed in the majority of cases. But because of its risk of progression to cirrhosis and hepatocellular carcinoma which can both be life-threatening, timely detection is necessary. Detection of specific antibodies and viral RNA in serum is required to confirm the diagnosis.

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Presentation

With over 170 million infections caused by hepatitis C virus (HCV) worldwide, hepatitis C infection remains one of the largest public health concerns due to its rather important place in the etiology of chronic liver disease [1] [2]. HCV is transmitted through blood products (through intravenous drug use and needle-sharing) and via the sexual route, while blood transfusions have been an important source of HCV until the introduction of routine screening of blood [1] [2] [3] [4]. Vertical transmission, on the other hand, is the principal mode of virus acquisition in children, and approximately 8000 new cases of hepatitis C infection are reported in the United States every year [3]. The primary reason for such a high number of cases globally is the insidious nature of the infection, as up to 85% of infected individuals develop a stable chronic infection [5] [6]. The incubation period of hepatitis C infection ranges from 14-180 days, after which one of the following clinical scenarios can be observed [5] [6] [7]:

  • Acute hepatitis C infection - In about 15% of cases, a non-specific clinical presentation comprised of nausea, fatigue, malaise, myalgia and right upper quadrant pain is characteristic [4] [5] [6]. More specific signs of liver injury, however, are jaundice and dark urine, and their presence should immediately point toward viral hepatitis as the underlying cause. Patients usually recover from acute infection without sequelae.
  • Chronic hepatitis C infection - More than 70% of patients who acquire hepatitis C develop a persistent infection and chronic fatigue is the principal symptom, which may last for decades [5]. Diabetes mellitus type 2, insulin resistance, and hepatic steatosis have all been associated with chronic HCV infection [1] [5]. Most importantly, however, is the progression to liver cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC), seen in about 5-20% of chronically infected patients [1] [5]. In these individuals, the typical presentation includes palmar erythema, spider nevi, hepatosplenomegaly, ascites, enlargement of parotid glands and wasting of the temporal muscles, as well as gynecomastia and testicular atrophy [4].
  • Fulminant hepatitis C - A rapid progression of acute hepatitis to fulminant hepatic failure is observed in a minority of cases.
Fatigue
  • In clinical trials , the most common side effects in both drugs were fatigue and headache .[webmd.com]
  • Acute HCV can cause abdominal discomfort, nausea, fatigue , and fever . Chronic HCV can lead to more severe scarring of the liver and liver cancers .[medicalnewstoday.com]
  • When signs and symptoms are present, they may include jaundice, along with fatigue, nausea, fever and muscle aches. Acute symptoms appear one to three months after exposure to the virus and last two weeks to three months.[mayoclinic.org]
  • Chronic hepatitis C infection - More than 70% of patients who acquire hepatitis C develop a persistent infection and chronic fatigue is the principal symptom, which may last for decades.[symptoma.com]
Weakness
  • The initial symptoms of chronic hepatitis C are: Weakness and fatigue Nausea Loss of appetite Muscle and joint aching Weight loss As chronic hepatitis C progresses to liver failure (hepatic decompensation), additional symptoms develop including: Dark[emedicinehealth.com]
  • Crocock, a Hepatitis C survivor who began using drugs in 1967 before quitting in 1993, only found out about his diagnosis in 2008 after he was forced into the hospital from chronic fatigue and weakness.[news.vice.com]
  • As cirrhosis develops, symptoms and signs increase and may include: Elevated liver enzymes in the blood Weakness Loss of appetite Weight loss Breast enlargement in men ( gynecomastia ) Redness of the palms of the hands Difficulty with the clotting of[medicinenet.com]
Malaise
  • […] incubation period of hepatitis C infection ranges from 14-180 days, after which one of the following clinical scenarios can be observed: Acute hepatitis C infection - In about 15% of cases, a non-specific clinical presentation comprised of nausea, fatigue, malaise[symptoma.com]
  • Other complaints include weight loss, muscle or joint pain, irritability, nausea, malaise, anorexia, depression, abdominal discomfort, difficulty concentrating, and jaundice.[clevelandclinicmeded.com]
Raynaud Phenomenon
  • In addition, infected individuals with cryoglobulinemia may develop Raynaud's phenomenon in which the fingers and toes turn color (white, then purple, then red), and become painful at cold temperatures.[medicinenet.com]
Ankle Edema
  • edema and abdominal distention ( ascites ) Physical findings usually are not abnormal until portal hypertension or decompensated liver disease develops.[emedicine.medscape.com]
Nausea
  • They can have side effects like fatigue , flu -like symptoms, anemia , skin rash , mild anxiety , depression , nausea , and diarrhea . Your treatment will depend on many things including what type of hepatitis C virus you have.[webmd.com]
  • If symptoms of liver problems do appear, they may include: fatigue nausea vomiting loss of appetite jaundice (yellowing of the skin and the whites of the eyes) low-grade fever (fever up to 102 F).[familydoctor.org]
  • Symptoms may be very mild and flu-like: nausea, fatigue, loss of appetite, fever, headaches, and abdominal pain. Most people do not have jaundice although jaundice can sometimes occur along with dark urine.[hepfi.org]
  • Acute HCV can cause abdominal discomfort, nausea, fatigue , and fever . Chronic HCV can lead to more severe scarring of the liver and liver cancers .[medicalnewstoday.com]
  • When symptoms do occur, they can develop within a few weeks up to about six months (the average is six weeks) and might include: Jaundice (yellowing of the skin and eyes) Nausea and vomiting Abdominal pain Dark urine Joint pain (arthritis) Loss of appetite[hhs.gov]
Loss of Appetite
  • Symptoms may be very mild and flu-like: nausea, fatigue, loss of appetite, fever, headaches, and abdominal pain. Most people do not have jaundice although jaundice can sometimes occur along with dark urine.[hepfi.org]
  • When symptoms do occur, they can develop within a few weeks up to about six months (the average is six weeks) and might include: Jaundice (yellowing of the skin and eyes) Nausea and vomiting Abdominal pain Dark urine Joint pain (arthritis) Loss of appetite[hhs.gov]
  • Symptoms can include: flu-like symptoms , such as muscle aches and a high temperature (fever) feeling tired all the time loss of appetite tummy (abdominal) pain feeling and being sick The only way to know for certain if these symptoms are caused by hepatitis[nhs.uk]
  • But you could notice these: Jaundice (a condition that causes yellow eyes and skin , as well as dark urine) Stomach pain Loss of appetite Nausea Fatigue How Do You Get It? The virus spreads through the blood or body fluids of an infected person.[webmd.com]
  • If symptoms of liver problems do appear, they may include: fatigue nausea vomiting loss of appetite jaundice (yellowing of the skin and the whites of the eyes) low-grade fever (fever up to 102 F).[familydoctor.org]
Abdominal Bruit
  • bruit Ankle edema Scant body hair Skin signs: Spider nevi, petechiae, excoriations due to pruritus Other common extrahepatic manifestations include the following: Cryoglobulinemia Membranoproliferative glomerulonephritis Lichen planus Keratoconjunctivitis[emedicine.medscape.com]
Right Upper Quadrant Pain
Hypertension
  • , such as the following: Ankle edema and abdominal distention ( ascites ) Physical findings usually are not abnormal until portal hypertension or decompensated liver disease develops.[emedicine.medscape.com]
  • It also can be defined clinically by the development of liver decompensation, such as jaundice, or complications of portal hypertension, such as ascites, variceal hemorrhage, or hepatic encephalopathy Treatment decisions for people with decompensated[clevelandclinicmeded.com]
  • This transformation occurs at a rate of 1–3% per year. [5] [15] Being infected with hepatitis B in addition to hepatitis C increases this risk further. [27] Liver cirrhosis may lead to portal hypertension , ascites (accumulation of fluid in the abdomen[en.wikipedia.org]
Cyanosis
  • Signs in patients with decompensated liver disease include the following: Head signs: Icteric sclera, temporal muscle wasting, enlarged parotid gland, cyanosis Fetor hepaticus Gynecomastia, small testes Abdominal signs: Paraumbilical hernia, ascites,[emedicine.medscape.com]
Jaundice
  • Most people do not have jaundice although jaundice can sometimes occur along with dark urine. Those infected with hepatitis C should not drink alcohol, as it accelerates the liver damage. The incubation period varies from 2-26 weeks.[hepfi.org]
  • When signs and symptoms are present, they may include jaundice, along with fatigue, nausea, fever and muscle aches. Acute symptoms appear one to three months after exposure to the virus and last two weeks to three months.[mayoclinic.org]
  • Signs of severe liver scarring (cirrhosis) may include: Ascites (accumulation of fluid and swelling of the abdominal cavity) Star-shaped vein pattern developing on the swollen belly Jaundice Itching Easy bruising and bleeding Because symptoms of hepatitis[sfcdcp.org]
  • Signs and symptoms of hepatitis C include: fatigue , muscle aches, tenderness in the upper abdomen, yellow tinge to the skin and eyes, dark urine ( jaundice ), and light colored bowel movements.[emedicinehealth.com]
Hepatosplenomegaly
  • In these individuals, the typical presentation includes palmar erythema, spider nevi, hepatosplenomegaly, ascites, enlargement of parotid glands and wasting of the temporal muscles, as well as gynecomastia and testicular atrophy.[symptoma.com]
  • […] patients with decompensated liver disease include the following: Head signs: Icteric sclera, temporal muscle wasting, enlarged parotid gland, cyanosis Fetor hepaticus Gynecomastia, small testes Abdominal signs: Paraumbilical hernia, ascites, caput medusae, hepatosplenomegaly[emedicine.medscape.com]
Fetor Hepaticus
  • Signs in patients with decompensated liver disease include the following: Head signs: Icteric sclera, temporal muscle wasting, enlarged parotid gland, cyanosis Fetor hepaticus Gynecomastia, small testes Abdominal signs: Paraumbilical hernia, ascites,[emedicine.medscape.com]
Pruritus
  • Examples include the following: Arthralgias Paresthesias Myalgias Pruritus Sicca syndrome Sensory neuropathy Symptoms characteristic of complications from advanced or decompensated liver disease are related to synthetic dysfunction and portal hypertension[emedicine.medscape.com]
Petechiae
  • […] temporal muscle wasting, enlarged parotid gland, cyanosis Fetor hepaticus Gynecomastia, small testes Abdominal signs: Paraumbilical hernia, ascites, caput medusae, hepatosplenomegaly, abdominal bruit Ankle edema Scant body hair Skin signs: Spider nevi, petechiae[emedicine.medscape.com]
Palmar Erythema
  • In these individuals, the typical presentation includes palmar erythema, spider nevi, hepatosplenomegaly, ascites, enlargement of parotid glands and wasting of the temporal muscles, as well as gynecomastia and testicular atrophy.[symptoma.com]
Myalgia
  • […] period of hepatitis C infection ranges from 14-180 days, after which one of the following clinical scenarios can be observed: Acute hepatitis C infection - In about 15% of cases, a non-specific clinical presentation comprised of nausea, fatigue, malaise, myalgia[symptoma.com]
  • Examples include the following: Arthralgias Paresthesias Myalgias Pruritus Sicca syndrome Sensory neuropathy Symptoms characteristic of complications from advanced or decompensated liver disease are related to synthetic dysfunction and portal hypertension[emedicine.medscape.com]
Arthralgia
  • Associated extrahepatic manifestations of HCV infection may include mixed cryoglobulinemia, arthralgias, porphyria cutanea tarda, and membranoproliferative glomerulonephritis (Figure 3) . 20, 21 Back to Top Diagnosis Diagnosis of HCV infection is usually[clevelandclinicmeded.com]
  • Examples include the following: Arthralgias Paresthesias Myalgias Pruritus Sicca syndrome Sensory neuropathy Symptoms characteristic of complications from advanced or decompensated liver disease are related to synthetic dysfunction and portal hypertension[emedicine.medscape.com]
Dark Urine
  • Most people do not have jaundice although jaundice can sometimes occur along with dark urine. Those infected with hepatitis C should not drink alcohol, as it accelerates the liver damage. The incubation period varies from 2-26 weeks.[hepfi.org]
  • When symptoms do occur, they can develop within a few weeks up to about six months (the average is six weeks) and might include: Jaundice (yellowing of the skin and eyes) Nausea and vomiting Abdominal pain Dark urine Joint pain (arthritis) Loss of appetite[hhs.gov]
  • Signs and symptoms of hepatitis C include: fatigue , muscle aches, tenderness in the upper abdomen, yellow tinge to the skin and eyes, dark urine ( jaundice ), and light colored bowel movements.[emedicinehealth.com]
  • But you could notice these: Jaundice (a condition that causes yellow eyes and skin , as well as dark urine) Stomach pain Loss of appetite Nausea Fatigue How Do You Get It? The virus spreads through the blood or body fluids of an infected person.[webmd.com]
  • More specific signs of liver injury, however, are jaundice and dark urine, and their presence should immediately point toward viral hepatitis as the underlying cause. Patients usually recover from acute infection without sequelae.[symptoma.com]
Paresthesia
  • Examples include the following: Arthralgias Paresthesias Myalgias Pruritus Sicca syndrome Sensory neuropathy Symptoms characteristic of complications from advanced or decompensated liver disease are related to synthetic dysfunction and portal hypertension[emedicine.medscape.com]

Workup

The diagnosis of a hepatitis C infection based solely on clinical criteria is difficult, especially in mildly symptomatic chronic carriers. For this reason, a detailed patient history is mandatory during the workup, as physicians can assess risk factors - risky sexual intercourse, intravenous drug abuse or even recent tattooing, as well as the onset and progression of symptoms. When clinical suspicion of viral hepatitis is supported by data obtained during history and a physical examination, an extensive laboratory workup is necessary. Firstly, a complete biochemical profile is drawn, comprised of serum electrolytes, a complete blood count, liver function tests (alanine and aspartate aminotransferases, or ALT and AST), renal parameters (blood urea nitrogen and creatinine), and bilirubin levels. Liver enzymes are usually elevated up to 10 times the normal values, in which case, testing for viral hepatitis should be carried out [5] [6]. In the setting of hepatitis C, serology testing for anti-HCV IgM and IgG antibodies is the cornerstone of the diagnosis of both acute as well as chronic infections, and IgM titers can be quite high even in chronic carriers [1] [2] [3] [4]. Antibodies cannot be detected for at least 7 weeks after viral acquisition, until the process of seroconverision occurs [6]. However, detection of viral RNA in blood can be made through polymerase chain reaction (PCR) testing much earlier, which is also one of the most important tools for long-term monitoring and response of individuals to therapy [1] [2] [3] [5] [6]. If PCR detects viral RNA in blood, the diagnosis can be made with certainty. It must be noted that coinfections with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are rather common in HCV patients, which is why testing for both of these infections through appropriate serological (anti-HIV antibodies and HBsAg/HBeAg/anti-HBc antibodies) and molecular (isolation of viral RNA through PCR) methods is imperative [1] [5] [6] [7].

Hepatocellular Carcinoma
  • Most importantly, however, is the progression to liver cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC), seen in about 5-20% of chronically infected patients.[symptoma.com]
  • carcinoma (HCC) in the CheckMate 040 study, according to a report at the 2017 AASLD Liver Meeting last month in Washington, DC.[hivandhepatitis.com]
  • As cirrhosis is the primary risk factor for hepatocellular carcinoma, alcohol use is associated with this cancer risk through its cirrhosis effect.[clevelandclinicmeded.com]
  • The estimate comes from ... 01 November 2017 Keith Alcorn Curing hepatitis C with DAAs linked to 71% reduction in liver cancer People who achieved a sustained response to hepatitis C treatment lowered their risk of hepatocellular carcinoma by around 70%[aidsmap.com]
  • The World Health Organization (WHO) estimates about 71 million people globally have chronic hepatitis C, with approximately 399,000 dying from this infection as primarily due to cirrhosis and hepatocellular carcinoma.[emedicine.medscape.com]

Treatment

  • […] for the treatment of chronic hepatitis C (CHC) genotype 1 infection as a component of a combination antiviral treatment regimen Pegasys pegylated interferon Roche treatment of adults with chronic hepatitis C virus infection who have compensated liver[fda.gov]
  • Recommendations on hepatitis C treatment 5. Assessing for HCV treatment All adults and children with chronic HCV infection should be assessed for antiviral treatment. 6.[who.int]
  • It has one of the shortest treatment cycles. Treatment dosage and length of treatment cycle depends on stage of disease.[familydoctor.org]
  • From: HIV treatment update Combinations and conundrums: the challenges of hepatitis C treatment A multiplicity of new drugs for hepatitis C are being researched.[aidsmap.com]
  • Goals of HCV treatment Predicting the response to treatment Treating acute HCV HIV and HCV treatment for people with coinfection DAAs and HBV reactivation Retreating HCV Drug interactions between HCV and HIV meds HCV treatment and people who inject drugs[i-base.info]

Prognosis

  • With early diagnosis and treatment, the current prognosis is excellent for those who are chronically infected.[emedicinehealth.com]
  • Those who acquire the infection at a younger age have a somewhat better prognosis than those who are infected later in life.[emedicine.medscape.com]
  • EASL–ALEH Clinical Practice Guidelines: non–invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63:237–264. Gara N Zhao X, Kleiner DE, et al.[clevelandclinicmeded.com]
  • The prognosis can be bleak. *** It is not surprising, given the profile of the virus, that Orkin included it in her Going Viral test.[theguardian.com]

Etiology

  • With over 170 million infections caused by hepatitis C virus (HCV) worldwide, hepatitis C infection remains one of the largest public health concerns due to its rather important place in the etiology of chronic liver disease.[symptoma.com]
  • "An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis". Science . 244 (4902): 362–4. doi : 10.1126/science.2496467 . PMID 2496467 . "2000 Winners Albert Lasker Award for Clinical Medical Research" .[en.wikipedia.org]
  • Etiology Transmission Transfusion of blood contaminated with hepatitis C virus (HCV) was once a leading means of HCV transmission.[emedicine.medscape.com]

Epidemiology

  • Publication EU/EEA capacity for the surveillance of hepatitis B and C using molecular methods Publication Hepatitis C - Annual Epidemiological Report for 2015 News ECDC-EMCDDA review: Can active case finding help reduce communicable diseases in prisons[ecdc.europa.eu]
  • […] features of hepatitis C to guide prevention activities and HCV-related services Local epidemiology: Twenty-one cases of acute HCV infection were reported in 2015.[kingcounty.gov]
  • Hepatitis B ECHO-TV Program Videos available in seven languages with information on hepatitis B awareness and prevention If you have questions or comments about this page, use our IDEPC Comment Form or call 651-201-5414 for the MDH Infectious Disease Epidemiology[health.state.mn.us]
  • […] following hepatitis C cure Hepatitis C resources Hepatitis C in Canada (infographic) Laying out the changing landscape of hepatitis C: Potential programming implications in prevention, testing, treatment and care (CATIE webinar series): Surveillance and epidemiology[catie.ca]
  • "Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews" . Lancet . 378 (9791): 571–83. doi : 10.1016/S0140-6736(11)61097-0 . PMC 3285467 .[en.wikipedia.org]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology Hepatitis C virus (HCV) is a spherical, enveloped, single-stranded RNA virus belonging to the family Flaviviridae, genus Flavivirus .[emedicine.medscape.com]

Prevention

  • (July 8, 2008) Centers for Disease Control and Prevention. Hepatitis C Information for Professionals. Available online at . Accessed July 2013. (July 21, 2008) Centers for Disease Control and Prevention. Hepatitis C FAQs for Professionals.[labtestsonline.org]
  • You can help prevent potential liver damage by starting treatment right away.[healthline.com]
  • Prevention Primary prevention There is no vaccine for hepatitis C, therefore prevention of HCV infection depends upon reducing the risk of exposure to the virus in health-care settings and in higher risk populations, for example, people who inject drugs[who.int]
  • Testing for hepatitis C Prevention and harm reduction Treatment for hepatitis C Living with hepatitis C Frequently asked questions Hep C mobile CATIE has collected its core information on hepatitis C into an app for mobile devices.[catie.ca]
  • Prevention Preventing HCV involves limiting exposure to the virus in the first instance.[medicalnewstoday.com]

References

Article

  1. Li H-C, Lo S-Y. Hepatitis C virus: Virology, diagnosis and treatment. World J Hepatol. 2015;7(10):1377-1389.
  2. Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335-1374.
  3. Khaderi S, Shepherd R, Goss JA, Leung DH. Hepatitis C in the pediatric population: Transmission, natural history, treatment and liver transplantation. World J Gastroenterol. 2014;20(32):11281-11286.
  4. Modi A, Liang T. Hepatitis C: a clinical review. Oral dis. 2008;14(1):10-14.
  5. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
  6. Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. Seventh edition. Philadelphia: Elsevier/Saunders; 2013.
  7. Blackard JT, Shata MT, Shire NJ, Sherman KE. Acute Hepatitis C Virus Infection: A Chronic Problem. Hepatology. 2008;47(1):321-331.

Symptoms

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