• Hepatitis C

    What is Hepatitis C Virus (HCV)?

    Hepatitis C virus (HCV) damages the liver, one of the body's most important organs. More than 180 million people worldwide-including nearly 4 million Americans-have antibodies to HCV (anti-HCV), indicating ongoing or previous infection with the virus. Each year, hepatitis C results in approximately 8,000 to 10,000 deaths in the United States.

    HCV is one of the primary causes of chronic liver disease and is also one of the most common reasons for liver transplant surgery in the United States. In this country, HCV accounts for 15 percent of acute viral hepatitis, 60 to 70 percent of chronic hepatitis, and as much as 50 percent of the cases of cirrhosis and end-stage liver disease.

    In comparison to other types of viral hepatitis (hepatitis A through E), HCV has the greatest tendency to cause chronic liver disease. Approximately 75 percent of patients with acute hepatitis C ultimately develop chronic liver disease, and 20 percent of these patients will eventually develop cirrhosis over a period of 10 to 20 years. A small proportion of patients with HCV-related cirrhosis will also develop liver cancer.

    Learn more about Hepatitis C

    To learn more about the Hepatitis C virus (HCV), consult the related sections below:

    Risk Factors and Transmission

    HCV is spread primarily by contact with blood and blood products. In fact, blood transfusions and the use of shared or nonsterile needles are the main causes of HCV spread in the United States. An effort to remove HCV from public blood supplies began in 1991 with the introduction of routine screening of the blood supply for the hepatitis C antibody, and continued with improvements to this test made shortly thereafter. Thanks to these efforts, transfusion-related hepatitis C has virtually disappeared in the United States. Currently, injection drug use is the most common risk factor for contracting HCV, though many patients acquire the disease without known exposure to blood or drug use.

    Click here to view a diagram explaining the sources of Hepatitis C infection

    Major high-risk groups for hepatitis C infection include:  

    • Individuals who received blood transfusions before July 1992.
    • People who have frequent exposure to blood products, including those from hemophiliacs; patients who have undergone organ transplants; and those with chronic renal failure or cancer who require chemotherapy.
    • Health care workers who sustain accidental needle sticks contaminated with blood from an HCV patient.
    •  Injection drug users who share drug paraphernalia.
    • Infants born to HCV-infected mothers. Maternal-infant transmission is uncommon, and occurs in less than 5 percent of infants born to infected woman. In addition, breastfeeding does not appear to be linked to the spread of HCV.
    • People who are involved in sexual activities with multiple partners, those who engage in rectal sex or individuals with other sexually transmitted diseases.
    • People who use cocaine, particularly through intranasal administration.
    • Individuals with tattoos or body piercings.
    • Transmission of hepatitis C between monogamous sexual partners appears to be uncommon, with recent data involving spouses indicating that the disease occurs in less than 5 percent of partners. On the other hand, people with multiple sexual partners should protect themselves against hepatitis C, hepatitis B, HIV and other sexually transmitted diseases by practicing safe sex (e.g., using condoms).

    Clinical Symptoms and Signs

    Many individuals with chronic hepatitis C have no symptoms of liver disease and therefore are unaware that they are infected and are capable of transmitting the virus. Generally, symptoms that do appear are mild, nonspecific and intermittent and may include:

    • Fatigue
    • Pain or discomfort on the upper right side of the belly
    • Nausea
    • Loss of appetite
    • Myalgia or joint pain

    If the patient develops advanced liver disease (cirrhosis), additional symptoms may develop. These include:  

    • Jaundice
    • Muscle weakness
    • Anorexia
    • Itching
    • Dark urine
    • Fluid retention (edema)
    • Abdominal swelling
    • Confusion

    Some patients with hepatitis C may exhibit additional symptoms, including skin rashes, joint pain, kidney disease, neuropathy or arthritis.  

    Stages of HCV

    Acute HCV disease

    Acute hepatitis C is diagnosed on the basis of symptoms such as jaundice, fatigue and nausea, along with marked increases-usually tenfold or greater-in the level of certain liver enzymes called ALT or AST. Patients with acute disease may not have anti-HCV, so a PCR test is the best determinant of early HCV infection.

    Chronic HCV disease

    Patients with chronic hepatitis C usually have a positive anti-HCV test and an elevation (two to fivefold) in their ALT or AST levels. These patients also have a positive HCV-RNA level, confirming the presence of active infection. Liver biopsy is used to grade and stage the severity of their liver disease.

    In general, HCV-infected individuals have a good prognosis, and few develop clinical manifestations of chronic liver disease. However, persons with moderate to severe chronic HCV may be symptomatic, regularly exhibit the presence of HCV-RNA in their serum and experience inflammation in the liver. These patients are more likely to progress to cirrhosis and end-stage liver disease. Risk factors for progression to cirrhosis include increased alcohol intake, age greater than 40 years at the time of infection, the presence of HIV disease, routine use of hepatotoxic drugs and co-infection with other hepatitis viruses.

    It is estimated that approximately 20 percent of patients with chronic HCV will develop cirrhosis-severe fibrosis and scarring—but the progression to this disease is long, often taking 10 to 20 years. In this group of patients with HCV-related cirrhosis, 3 to 4 percent of the individuals typically progress to liver cancer each year. Liver transplant may be a treatment option for such patients.

    Other causes of hepatitis C include autoimmune hepatitis, chronic hepatitis B and D, alcoholic hepatitis, nonalcoholic steatohepatitis, drug-induced liver disease, Wilson's disease, and liver damage due to sclerosing cholangitis (bile accumulation in the liver). 

    Diagnosing HCV

    Enzyme immunoassay (EIA) screening test

    Antibody to hepatitis C (anti-HCV) by EIA is often used as a screening test for the disease. Current EIA tests are very sensitive and specific, but each positive test is still confirmed by a second test. Antibody to hepatitis C is usually present in patients four to six weeks following acute illness.

    Polymerase chain reaction (PCR) test

    The PCR test, which is even more sensitive than the EIA test, is used to detect HCV-RNA, a marker of active HCV infection. Quantitative PCR levels indicate the extent of active infection and the amount of HCV viral load or replication. Patients who are co-infected with HIV are more likely to have a high HCV-RNA level.

    HCV-RNA is helpful in monitoring a patient's response to HCV treatment. Individuals with very high levels of HCV-RNA (> 2 million copies/ml) may be less likely to respond to combination therapy with the drugs interferon and ribavirin.

    HCV genotyping

    There are six known genotypes of HCV and more than 50 subtypes. Genotypes of HCV vary by geographic area, with genotype 1 present in approximately 75 percent of infected individuals in the United States.

    HCV genotyping is helpful for making treatment and counseling recommendations regarding HCV therapy. Patients with genotypes 2 and 3 are approximately three times more likely to respond to therapy with interferon and ribavirin therapy when compared to patients with genotype 1. In addition, patients with genotypes 2 and 3 may also respond to a shorter course of therapy (24 weeks) compared to patients with genotype 1 (48 weeks).

    Biochemical indicators of HCV

    Patients with chronic HCV infection also exhibit elevated levels of the serum liver enzyme alanine (ALT) or aspartate aminotransferases (AST). These changes are non-specific for HCV and usually indicate inflammation of the liver. Alkaline phosphatase, another liver enzyme, also may be elevated in some patients with hepatitis C disease.

    Liver biopsy

    Minimal Inflammation, No FibrosisLiver biopsy is helpful in grading the severity of the disease and staging the scarring (fibrosis) due to chronic inflammation in the liver. Appropriate assessment of the stage of liver disease, as determined by the amount of inflammation and scarring, cannot be reasonably estimated by blood tests and therefore requires a liver biopsy. Special stains performed on the liver biopsy tissue are helpful in grading inflammation and staging the degree of fibrosis. 

    HCV Treatment

    Severe Inflammation and FibrosisThe treatment of chronic HCV has evolved steadily over the past five years. At the present time, the optimal therapy typically includes a 24- to 48-week course of pegylated alpha interferon (pIFN) and ribavirin (RBV). Variations in combination therapy and its duration may vary by HCV genotype.

    Responses to HCV therapy are measured by the elimination of or decrease in HCV-RNA, biochemical reduction in ALT levels, and histologic improvement in inflammation and fibrosis. Patients started on combination therapy with pIFN and RBV often experience improvements in their ALT levels, and the HCV-RNA disappears in up to 50 to 70 percent of patients. However, HCV is considered cured only if the HCV-RNA level that disappears with therapy remains undetectable once therapy is discontinued.

    Although patients with chronic HCV and fibrosis may not be cured by pIFN and RBV therapy, the therapy may reduce symptoms and delay the progression of cirrhosis to end-stage liver disease. Therapy recommendations may be reviewed at the Web sites for the CDC's National Center for Infectious Diseases and the National Digestive Diseases Information Clearinghouse (NDDIC). 

    Side effects of HCV treatment

    Interferon (IFN): Common side effects of IFN—those that occur in more than 10 percent of patients—include:  

    • Fatigue and headache
    • Flu-like symptoms, including muscle aches, headaches, nausea and vomiting
    • Skin irritation
    • Low-grade fever
    • Weight loss
    • Irritability
    • Depression
    • Insomnia
    • Bone marrow suppression
    • Hair loss
    • Neutropenia (abnormally low number of neutrophils, a type of white blood cell)
    • Thrombocytopenia (abnormally low number of platelets, resulting in abnormal bleeding due to the inability of blood to clot)
    • Diabetes
    • Thyroid disease

    Most of these side effects are mild to moderate and can be managed with prophylaxis. However, all patients started on IFN—with or without RBV therapy—need frequent monitoring for side effects and toxicity. Side effects are usually worse during the first few weeks of treatment and tend to diminish thereafter. Depression and personality changes can occur with interferon therapy and need to be monitored closely, particularly with patients who have a history of depression or social circumstances that may lead to depression.

    Ribavirin (RBV)
    RBV has side effects that include:  

    • Anemia
    • Teratogenicity (disturbance of the development of the embryo and fetus, which can lead to birth defects)
    • Fatigue
    • Irritability
    • Itching
    • Skin rash
    • Nasal stuffiness
    • Sinusitis
    • Cough and shortness of breath
    • Insomnia
    • Anorexia

    Ribavirin's main side effect is the breakdown of red blood cells, resulting in anemia. Patients such as those with cardiac disease or those co-infected with HIV may be at particularly high risk for developing low red blood cell levels.

    New anti-HCV agents in development
    A variety of new antiviral agents for hepatitis C are in development. These include protease inhibitors, helicases and prelimerase inhibitors. It is likely that these drugs or a combination thereof may be the treatment of the future, as there have been various side effects and complications with the use of IFN and RBV therapy.

    Liver transplantation For patients with advanced liver disease who cannot tolerate IFN-RBV therapy, or for any patients with end-stage liver disease, consideration should be given to undergoing a living donor liver transplant. Lahey's Department of Hepatobiliary Surgery and Liver Transplantation will be able to coordinate a complete and thorough medical evaluation to determine whether you are an appropriate candidate for surgery.  

    Preventing HCV

    At the present time, there is no vaccine or immunoglobulin product that can be used to treat patients or health care workers who have been exposed to HCV. Current means of preventing HCV include the following:

    Continued screening of the blood supply
    Encouraging health professionals to remain cautious when handling blood and body fluids
    Promotion of needle exchange programs to reduce the sharing of contaminated paraphernalia among injection drug users
    Avoiding the sharing of razors and toothbrushes
    Practicing safe sex, particularly if you have multiple sexual partners  

    HCV and HIV

    Patients with HCV may be co-infected with HIV disease, and in fact this combination is seen in 50 to 70 percent of injection drug users and persons with hemophilia. It is estimated that 15 to 30 percent of patients with HIV, many of whom have substance abuse problems or a history of unprotected sex with multiple partners, are co-infected with HCV. According to a number of studies, HCV is the major cause of death in patients with HIV infection.

    HIV infection appears to increase the persistence of the HCV virus, the levels of HCV-RNA, and in most studies the progression of HCV-related liver disease. Clearly, these patients should avoid alcohol, receive vaccinations against other hepatitis viruses (A and B) and undergo careful evaluation and follow-up.  

    Recommended Links 

    Lahey's Department of Hepatobiliary Surgery and Liver Transplantation
    Centers for Disease Control and Prevention
    National Digestive Diseases Information Clearinghouse (NDDIC) 

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