الجوهرة المصونة
*****
المشاركات : 17164
العمـر : 36
تعاليق : مشرفة الطب والصحة
المزاج : 
الدولة : 
المهنة : 
الهواية : 
التسجيل : 10/10/2008
النقاط : 18248
التقييم : 501
 
توفيقك يارب
 |  موضوع: Hepatitis C الأربعاء سبتمبر 07, 2011 10:03 am | |
| Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV).[1] The infection is often asymptomatic, but once established, chronic infection can progress to scarring of the liver (fibrosis), and advanced scarring (cirrhosis), which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure or other complications of cirrhosis, including liver cancer[1] or life-threatening esophageal varices and gastric varices.
The hepatitis C virus is spread by blood-to-blood contact. Most people have few, if any symptoms after the initial infection, yet the virus persists in the liver in about 85% of those infected. Persistent infection can be treated with medication, peginterferon and ribavirin being the standard-of-care therapy. Overall, 51% are cured. Those who develop cirrhosis or liver cancer may require a liver transplant, and the virus universally recurs after the transplant takes place.
An estimated 180 million people worldwide are infected with hepatitis C. Hepatitis C is not known to cause disease in other animals. No vaccine against hepatitis C is currently available. The existence of hepatitis C (originally "non-A non-B hepatitis") was postulated in the 1970s and proven in 1989.[2] It is one of five known hepatitis viruses: A, B, C, D, and E
Signs and symptoms
Acute
Acute hepatitis C refers to the first 6 months after infection with HCV. Most people suffer no symptoms upon infection but for those who do the main symptoms are generally mild and nonspecific, and rarely lead to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominal pain, jaundice, itching, and flu-like symptoms.
The hepatitis C virus is usually detectable in the blood by PCR within one to three weeks after infection, and antibodies to the virus are generally detectable within three to 15 weeks. Spontaneous viral clearance rates are highly variable; between 10 and 60%[3] of persons infected with HCV clear the virus from their bodies during the acute phase, as shown by normalization of the liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST), and plasma HCV-RNA clearance (this is known as spontaneous viral clearance). However, persistent infections are common[4] and most patients develop chronic hepatitis C, i.e., infection lasting more than 6 months.[5][6][7]
Previous practice was to not treat acute infections to see if the person would spontaneously clear; recent studies have shown that treatment during the acute phase of genotype 1 infections has a greater than 90% success rate, with half the treatment time required for chronic infections.[8]
Chronic
Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months. Clinically, it is often asymptomatic, and it is mostly discovered accidentally (e.g., usual checkup).
The natural course of chronic hepatitis C varies considerably from one person to another. Although almost all people infected with HCV have evidence of inflammation on liver biopsy, the rate of progression of liver scarring (fibrosis) shows significant variability among individuals. Accurate estimates of the risk over time are difficult to establish because of the limited time that tests for this virus have been available.
Recent data suggest that among untreated patients, roughly one-third progress to liver cirrhosis in less than 20 years. Another third progress to cirrhosis within 30 years. The remainder of patients appear to progress so slowly that they are unlikely to develop cirrhosis within their lifetimes. In contrast, the NIH consensus guidelines state the risk of progression to cirrhosis over a 20-year period is 3-20 percent.[9]
Factors that have been reported to influence the rate of HCV disease progression include age (increasing age associated with more rapid progression), gender (males have more rapid disease progression than females), alcohol consumption (associated with an increased rate of disease progression), HIV coinfection (associated with a markedly increased rate of disease progression), and fatty liver (the presence of fat in liver cells has been associated with an increased rate of disease progression).
Symptoms specifically suggestive of liver disease are typically absent until substantial scarring of the liver has occurred. However, hepatitis C is a systemic disease and patients may experience a wide spectrum of clinical manifestations ranging from an absence of symptoms to a more symptomatic illness prior to the development of advanced liver disease. Generalized signs and symptoms associated with chronic hepatitis C include fatigue, flu-like symptoms, joint pains, itching, sleep disturbances, appetite changes, nausea, and depression.
Once chronic hepatitis C has progressed to cirrhosis, signs and symptoms may appear that are generally caused by either decreased liver function or increased pressure in the liver circulation, a condition known as portal hypertension. Possible signs and symptoms of liver cirrhosis include ascites (accumulation of fluid in the abdomen), bruising and bleeding tendency, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy. Hepatic encephalopathy is due to the accumulation of ammonia and other substances normally cleared by a healthy liver.
Liver enzyme tests show variable elevation of ALT and AST. Periodically, they might show normal results. Usually prothrombin and albumin results are normal, but may become abnormal, once cirrhosis has developed. The levels of elevation of liver tests do not correlate well with the amount of liver injury on biopsy. Viral genotype and viral load also do not correlate with the amount of liver injury. Liver biopsy is the best test to determine the amount of scarring and inflammation. Radiographic studies, such as ultrasound or CT scan, do not always show liver injury until it is fairly advanced. However, noninvasive tests (blood sample) are coming, with FibroTest[10] and ActiTest, respectively estimating liver fibrosis and necrotic inflammation. These tests are validated[11] and recommended in Europe (FDA procedures initiated in USA).
Chronic hepatitis C, more than other forms of hepatitis, can be associated with extrahepatic manifestations associated with the presence of HCV, such as porphyria cutanea tarda, cryoglobulinemia (a form of small-vessel vasculitis)[12] and glomerulonephritis (inflammation of the kidney), specifically membranoproliferative glomerulonephritis (MPGN).[13] Hepatitis C is also rarely associated with sicca syndrome (an autoimmune disorder), thrombocytopenia, lichen planus, diabetes mellitus and with B-cell lymphoproliferative disorders.[14]
Virology
The hepatitis C virus is a small (50 nm in size), enveloped, single-stranded, positive sense RNA virus. It is the only known member of the hepacivirus genus in the family Flaviviridae. There are six major genotypes of the hepatitis C virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.). Based on the NS5 gene there are three major and eleven minor genotypes. The major genotypes diverged about 300-400 years ago from the ancestor virus. The minor genotypes diverged about 200 years ago from their major genotypes. All of the extant genotypes appear to have evolved from genotype 1 subtype 1b.[15]
The hepatitis C virus is transmitted by blood-to-blood contact. In developed countries, it is estimated that 90% of persons with chronic HCV infection were infected through transfusion of unscreened blood or blood products or via injecting drug use or sexual exposure. In developing countries, the primary sources of HCV infection are unsterilized injection equipment and infusion of inadequately screened blood and blood products. There has not been a documented transfusion-related case of hepatitis C in the United States for over a decade, as the blood supply is vigorously screened with both EIA and PCR technologies.[citation needed]
Although injection drug use is the most common route of HCV infection, any practice, activity, or situation that involves blood-to-blood exposure can potentially be a source of HCV infection. The virus may be sexually transmitted, although this is rare, and usually only occurs when an STD that causes open sores and bleeding is also present and makes blood contact more likely.[16]
Transmission
Sexual activities and practices were initially identified as potential sources of exposure to the hepatitis C virus. More recent studies question this route of transmission.[17] Currently, heterosexual vaginal intercourse is thought to be a rare means of transmission of hepatitis C infection. The following are the currently known modes of transmission. There may be other, as yet unknown, means of transmission. In a 2006 study, 30 percent of chronic hepatitis patients tested positive for traces of the virus in their saliva before brushing their teeth, while 38 percent tested positive in their saliva after brushing.
The diagnosis
The diagnosis of hepatitis C is rarely made during the acute phase of the disease, because the majority of people infected experience no symptoms during this phase. Those who do experience acute phase symptoms are rarely ill enough to seek medical attention. The diagnosis of chronic phase hepatitis C is also challenging due to the absence or lack of specificity of symptoms until advanced liver disease develops, which may not occur until decades into the disease.
Chronic hepatitis C may be suspected on the basis of the medical history (particularly if there is any history of IV drug abuse or inhaled substance usage such as cocaine), a history of piercings or tattoos, unexplained symptoms, or abnormal liver enzymes or liver function tests found during routine blood testing. Occasionally, hepatitis C is diagnosed as a result of targeted screening, such as blood donation (blood donors are screened for numerous blood-borne diseases including hepatitis C) or contact tracing.
Hepatitis C testing begins with serological blood tests used to detect antibodies to HCV. Anti-HCV antibodies can be detected in 80% of patients within 15 weeks after exposure, in >90% within 5 months after exposure, and in >97% by 6 months after exposure. Overall, HCV antibody tests have a strong positive predictive value for exposure to the hepatitis C virus, but may miss patients who have not yet developed antibodies (seroconversion), or have an insufficient level of antibodies to detect. Immunocompromised individuals infected with HCV may never develop antibodies to the virus and therefore, never test positive using HCV antibody screening. Because of this possibility, RNA testing (see nucleic acid testing methods below) should be considered when antibody testing is negative but suspicion of hepatitis C is high (e.g. because of elevated transaminases in someone with risk factors for hepatitis C). However, liver function tests alone are not useful in predicting the severity of infection and normal results do not exclude the possibility of liver disease.[30]
Anti-HCV antibodies indicate exposure to the virus, but cannot determine if ongoing infection is present. All persons with positive anti-HCV antibody tests must undergo additional testing for the presence of the hepatitis C virus itself to determine whether current infection is present. The presence of the virus is tested for using molecular nucleic acid testing methods, such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), or branched DNA (b-DNA). All HCV nucleic acid molecular tests have the capacity to detect not only whether the virus is present, but also to measure the amount of virus present in the blood (the HCV viral load). The HCV viral load is an important factor in determining the probability of response to interferon-based therapy, but does not indicate disease severity nor the likelihood of disease progression.
In people with confirmed HCV infection, genotype testing is generally recommended. HCV genotype testing is used to determine the required length and potential response to interferon-based thera
Prevention
According to Centers for Disease Control, hepatitis C virus is spread by exposure to large quantities of blood, either through the skin or by injection:[31]
Injection drug use (currently the most common means of HCV transmission in the United States)
Receipt of donated blood, blood products, and organs (once a common means of transmission, but now rare in the United States since blood screening became available in 1992)
Needle stick injuries in healthcare settings
Birth to an HCV-infected mother
HCV can also be spread infrequently through
Sex with an HCV-infected person (an inefficient means of transmission)
Sharing personal items contaminated with infectious blood, such as razors or toothbrushes (also inefficient vectors of transmission)
Other healthcare procedures that involve invasive procedures, such as injections (usually recognized in the context of outbreaks)
Sharing drug products via insufflation
Strategies such as the provision of new needles and syringes, and education about safer drug injection procedures, greatly decrease the risk of hepatitis C spreading between injecting drug users.
No vaccine protects against contracting hepatitis C, or helps to treat it. Vaccines are under development and some have shown encouraging results.ed]Treatment
The hepatitis C virus induces chronic infection in 50%-80% of infected persons. Approximately 50% of these do not respond to therapy. There is a very small chance of clearing the virus spontaneously in chronic HCV carriers (0.5% to 0.74% per year).[33][34] However, the majority of patients with chronic hepatitis C will not clear it without treatment.
In May 2011, the Food and Drug Administration approved 2 drugs for Hepatitis C. The first one is boceprevir and the other is telaprevir (Incivek). Both drugs block an enzyme that helps the virus reproduce. The drugs are intended to improve on standard treatments using the injected drug pegylated interferon alpha and the pill ribavirin.[35]
[edit]
Medications (interferon and ribavirin)
Current treatment is a combination of pegylated interferon-alpha-2a or pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) and the antiviral drug ribavirin for a period of 24 or 48 weeks, depending on hepatitis C virus genotype. In a large multicenter randomized control study among genotype 2 or 3 infected patients (NORDymanIC),[36] patients achieving HCV RNA below 1000 IU/mL by day 7 who were treated for 12 weeks demonstrated similar cure rates as those treated for 24 weeks.[37][38]
Pegylated interferon-alpha-2a plus ribavirin may increase sustained virological response among patients with chronic hepatitis C as compared to pegylated interferon-alpha-2b plus ribavirin according to a systematic review of randomized controlled trials .[39] The relative benefit increase was 14.6%. For patients at similar risk to those in this study (41.0% had sustained virological response when not treated with pegylated interferon alpha 2a plus ribavirin), this leads to an absolute benefit increase of 6%. About 16.7 patients must be treated for one to benefit (number needed to treat = 16.7; click here [40] to adjust these results for patients at higher or lower risk of sustained virological response). However, this study's results may be biased due to uncertain temporality of association, selective dose response.
Treatment is generally recommended for patients with proven hepatitis C virus infection and persistently abnormal liver function tests.
Treatment during the acute infection phase has much higher success rates (greater than 90%) with a shorter duration of treatment; however, this must be balanced against the 15-40% chance of spontaneous clearance without treatment (see Acute Hepatitis C section above).
Those with low initial viral loads respond much better to treatment than those with higher viral loads (greater than 400,000 IU/mL). Current combination therapy is usually supervised by physicians in the fields of gastroenterology, hepatology or infectious disease.
The treatment may be physically demanding, particularly for those with a prior history of drug or alcohol abuse. It can qualify for temporary disability in some cases. A substantial proportion of patients will experience a panoply of side effects ranging from a 'flu-like' syndrome (the most common, experienced for a few days after the weekly injection of interferon) to severe adverse events including anemia, cardiovascular events and psychiatric problems such as suicide or suicidal ideation. The latter are exacerbated by the general physiological stress experienced by the patient.
دعواتكم لي بالنجاح والتوفيق في حياتي
| |
|
