Diseases

Transmission of hepatitis C can be prevented in several ways.Prevention programs aim at needle sharing among drug addicts. Needle exchange programs and education have reduced transmission of hepatitis C infection. However IV drug users are a difficult to reach population, and rates of hepatitis C remain high among them. Among healthcare workers, safe needle-usage techniques have been developed to reduce accidental needle-sticks. Newer needle systems prevent manual recapping of needles after use of syringes, which is a frequent cause of accidental needle-sticks There is no clear way to prevent transmission of hepatitis C from mother to fetus at this time. People with multiple sexual partners should use barrier precautions such as condoms to limit the risk of hepatitis C and other sexually transmitted diseases, including HIV. If one partner is infected, monogamous couples may want to consider the low risk of transmission of hepatitis C infection when deciding whether to use condoms during sex. Some couples may decide to use them and some may not. Screening of the blood supply has almost eliminated the risk of transmission of hepatitis C infection through transfusion. People with hepatitis C infection should not share razors or toothbrushes with others because of the possibility that these items may be contaminated with blood. People who want to get a body piercing(s) or tattoo(s) are encouraged to do so only at licensed piercing and tattoo shops (facilities), and verify that the body piercing or tattoo shop uses infection-control practices.It is critical that physicians and clinics follow manufacturers and regulatory agency directions for sterilizing/cleaning instruments and that disposable instruments be discarded properly. There is no need to use special isolation procedures when dealing with hepatitis C infected patients.

Most of the signs and symptoms of hepatitis C infection relate to the liver. Less often, hepatitis C infection can affect organs other than the liver.Hepatitis C infection can cause the body to produce abnormal antibodies called cryoglobulins. Cryoglobulins cause inflammation of arteries (vasculitis). This may damage skin, joints, and kidneys. Patients with cryoglobulinemia (cryoglobulins in the blood) may have

• joint pain,
• arthritis,
• a raised purple rash on the legs, and
• generalized pain or swelling of their bodies.

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.

Blood tests for hepatitis CThere are several blood tests for the diagnosis of hepatitis C infection. Blood can be tested for antibody to hepatitis C (anti-HCV antibody). It takes up to six months for antibodies to develop after the initial infection with hepatitis C, so screening for antibodies may miss a few newly-infected individuals. Having antibodies is not an absolute indication of active, multiplying hepatitis C virus, but if the antibody test is positive (antibody is present), the statistical probability of active infection is greater than 99%.Several tests are available to measure the amount of hepatitis C virus in a person's blood (the viral load). The hepatitis C virus's RNA can be identified by a type of test called polymerase chain reaction (PCR) that detects circulating virus in the blood as early as 2-3 weeks after infection, so it can be used to detect suspected acute infection with hepatitis C early infection. It also is used to determine whether active hepatitis is present in someone who has antibodies to hepatitis C, and to follow the viral load during treatment.Blood tests are also performed to identify the genotypes of HCV. Genotypes respond differently to different treatment, so this information is important in selection of the most appropriate treatment regimen.Estimation of liver fibrosis using blood tests also is quite reliable in diagnosing clinically significant scarring; these include FIB-4, FibroSure, Fibrotest, and aspartate aminotransferase-to-platelet ratio index (APRI).

• Like HIV and hepatitis B, hepatitis C (hepatitis C virus, or HCV) is spread by exposure to infected blood (blood-borne pathogen).
• The most common way of getting hepatitis C is from contaminated blood on needles shared by IV drug users.
• Accidental needle-sticks in healthcare workers also have transmitted the virus. The average risk of getting hepatitis C infection from a stick with a contaminated needle is 1.8%.
• Before 1992, some people acquired the hepatitis C infection from blood transfusions or blood products. Since 1992, all blood products have been screened for hepatitis C, and cases of hepatitis C due to blood transfusion now are extremely rare.
• Hepatitis C infection also can be passed from mother to unborn child. Approximately 4% of children born to mothers infected with hepatitis C become infected.
• Hepatitis C is not transmitted by breast-milk. However, nipples may crack and bleed during the first few weeks until the nipples are adapted to nursing, and the infant may be exposed to infected blood. If this occurs, breastfeeding should stop, and milk production can be maintained by pumping the milk and discarding it until healed.
• A very small number of cases of hepatitis C are transmitted through sexual intercourse. The risk of transmission of hepatitis C from an infected individual to a non-infected spouse or sexual partner without the use of condoms over a lifetime has been estimated to be between 1% and 4%.
• Hepatitis C is not transmitted by casual contact, kissing, coughing, sneezing, or sharing eating utensils. There is no transmission by bug bites. However, because of the potential for blood exposure, members of the household are advised not to share shaving razors, nail clippers, or toothbrushes.
• Poor infection control practices during tattooing and body piercing potentially can lead to spread of infection. This may occur in prison or nonprofessional situations, but it has not been reported in licensed, commercial tattooing facilities where it has been studied.
• There have been some outbreaks of hepatitis C when instruments exposed to blood have been re-used without adequate cleaning and sterilization between patients.
• Hepatitis C can be transmitted from an organ donor to an organ recipient. Donors of organs are tested for hepatitis C.
  • If the donor who provides the organ is infected with hepatitis C, it is offered to a recipient who also is infected with hepatitis C.
  • For kidney transplant recipients, however, this does not seem to affect long-term outcome after transplantation.
  • For liver transplant recipients who have hepatitis C and receive an organ from a person who is not infected with hepatitis C, the transplanted organ is expected to become infected within a few weeks. Fortunately newer medications are allowing successful treatment of hepatitis C after transplants, and this area of medicine continues to evolve.

Once patients successfully complete treatment, the viral load after treatment determines if there is an SVR or cure. If cure is achieved (undetectable viral load after treatment), no further additional testing is recommended unless the patient has cirrhosis. Those who are not cured will need continued monitoring for progression of liver disease and its complications.While cure eliminates worsening of fibrosis by hepatitis C, complications may still affect those with cirrhosis. These individuals still need regular screening for liver cancer as well as monitoring for esophageal varices that may bleed.Because hepatitis B co-infection may reactivate or worsen even after treatment for HCV, monitoring for hepatitis symptoms may be needed after the end of therapy.

This is hard to say for certain because most people who are infected with hepatitis C do not have symptoms early in the course of the infection. Those who develop symptoms early after getting infected (6 to 10 weeks) experience mild gastrointestinal symptoms that may not prompt a visit to the doctor.

Hepatitis C is the leading reason for 40% to 45% of liver transplants in the U.S. Hepatitis C usually recurs after transplantation and infects the new liver. Approximately 25% of these patients with recurrent hepatitis will develop cirrhosis within five years of transplantation. Despite this, the five-year survival rate for patients with hepatitis C is similar to that of patients who are transplanted for other types of liver disease.Most transplant centers delay therapy until recurrent hepatitis C in the transplanted liver is confirmed. Oral, highly effective, direct-acting antivirals have shown encouraging results in patients who have undergone liver transplantation for hepatitis C infection and have recurrent hepatitis C. The choice of therapy needs to be individualized and is rapidly evolving.

• Hepatitis C is known to be associated with two skin conditions, lichen planus and porphyria cutanea tarda.
• Diabetes, heart disease, and arterial blockage are more common among patients with chronic hepatitis C infection than in the general population. It may be that liver damage and chronic inflammation caused by hepatitis C may affect the levels of blood fats (lipids) and blood sugar.
• Low platelet counts may occur as a result of the destruction of platelets by antibodies.
• Hepatitis C also is associated with B-cell lymphoma, a cancer of the blood.

End-stage liver diseaseOver several years or decades, chronic inflammation may cause death of liver cells and cirrhosis (scaring, fibrosis). When the liver becomes cirrhotic, it becomes stiff, and it cannot perform its normal functions of clearing waste products from the blood. As fibrosis worsens, symptoms of liver failure begin to appear. This is called "decompensated cirrhosis" or "end-stage liver disease." Symptoms of end-stage liver disease include:

• Small spider veins begin to appear on the skin as the stiff, scarred liver obstructs the forward flow of blood.
• Body fluids back up and accumulate in the abdomen (ascites).
• The spleen enlarges because of back-pressure.
• Yellowing of eyes and skin (jaundice) occur because the liver is not clearing bilirubin (a yellow pigment from breakdown of red blood cells) from the blood.
• A serious complication is severe bleeding from varicose veins that develop in the swallowing tube or esophagus (esophageal varices).

Cirrhosis-associated immune dysfunction syndromeThe liver and spleen have an important function of clearing bacteria from the blood stream. Cirrhosis affects many areas of immune function, including attraction of white blood cells to bacteria, reduced killing of bacteria, reduced production of proteins involved in immune defenses, and decreased life span of white blood cells involved in immune defenses. This may be referred to as having cirrhosis-associated immune dysfunction syndrome or CAIDS.

• Fluid in the abdomen often becomes infected (spontaneous bacterial peritonitis), and preventive antibiotics may be given for this type of infection.
• Bacteria also may enter the bloodstream easily (bacterial translocation), referred to as sepsis, especially when esophageal varices bleed.
• Individuals may succumb to many types of bacterial infections more easily than normal, but some are specific to cirrhosis.
  • Vibrio species of bacteria are a serious risk from eating raw oysters or exposure to sea water.
  • Listeria species may cause sepsis and meningitis, and are a risk from unpasteurized dairy products and salty processed meats.
  • Yersinia species may be picked up from raw or undercooked pork, especially intestines (chitterlings).
  • People with chronic hepatitis C and fibrosis should avoid being exposed to these bacteria.

Side effects of interferon or pegylated interferon

• The most common side effects of interferon or pegylated interferon include fever, flu-like symptoms, and depression. Patients must be monitored closely for depression. Risk of suicide is a reason to avoid interferons.
• Interferons also reduce white blood cell and/or red blood cell counts (leucopenia and anemia, respectively). This may cause increased susceptibility to infection. Interferons also increase the risk of certain cancers. Death rarely occurs as a result of therapy, but may occur from progression of liver failure in patients with advanced cirrhosis.

Side effects of ribavirin

• Ribavirin most commonly causes anemia due to destruction of red blood cells (hemolysis). This can be severe enough that people with heart disease may suffer a heart attack from insufficient blood flow, so people with heart disease should not receive this drug. Anemia improves with a reduction in the dose of ribavirin. Injected growth factor (erythropoietin) that stimulates the production of red blood cells often is used to improve the anemia associated with ribavirin. Ribavirin also accumulates in the testicles and ovaries and causes birth defects in animals. Although no birth defects have been reported in humans, both men and women should use contraceptive measures to avoid pregnancy during and for at least six months after ribavirin treatment.

Side effects of DAAsCompared to these drugs, the side effects of DAAs are far fewer and more tolerable. These side effects usually do not require discontinuation of therapy and are self-limiting after completion of therapy.

• The most common and significant side effects of boceprevir (Victrelis), sofosbuvir (Sovaldi), and ledipasvir/sofosbuvir (Harvoni) include
  • fatigue (feeling tired),
  • headache, and
  • trouble sleeping (insomnia).
• The most common side effects of simeprevir (Olysio) include
  • itching,
  • skin rash, and
  • photosensitivity (tendency to get sunburns).
• Simeprevir has significant drug interactions with other medications. Certain medications can affect levels of simeprevir in the body and make simeprevir less effective or more toxic.
• The combination of ombitasvir, paritaprevir, and ritonavir tablets with dasabuvir tablets (Viekira Pak) is very well tolerated, and the most commonly reported side effects are
  • fatigue,
  • trouble sleeping, and
  • itching.
• The combination of elbasvir and grazoprevir (Zepatier) is well-tolerated. Most common side effects include
  • fatigue,
  • headache, and
  • nausea.
  • It may be used with ribavirin, which adds the side effect of anemia.
  • About 1% of people in studies may develop elevated liver enzyme blood tests last into treatment or afterward, so these tests are closely monitored.
• Use of milk thistle should be discussed with the treating doctor, because it interacts with several DAAs.

Patients with hepatitis B co-infection should be monitored for symptoms of reactivation of hepatitis, which are the same as the symptoms of acute hepatitis. The treating doctor may perform blood screening for this as well.

About 75% of people have no symptoms when they first get HCV infection. The remaining 25% may have

1. fatigue,
2. loss of appetite,
3. muscle aches, or
4. fever.

Very few people experience hepatitis symptoms or signs such as dark urine, yellow eyes, or clay colored stools in acute or early infection. Over time, people with chronic HCV infection may develop signs of liver inflammation that suggests that the infection may be present. Infected individuals may become easily fatigued or complain of nonspecific symptoms.As cirrhosis develops, symptoms and signs increase and may include:

1. Elevated liver enzymes in the blood
2. Weakness
3. Loss of appetite
4. Weight loss
5. Breast enlargement in men (gynecomastia)
6. Redness of the palms of the hands
7. Difficulty with the clotting of blood
8. Spider-like blood vessels on the skin
9. Abdominal pain
10. Clay colored stools
11. Bleeding from the esophagus
12. Fluid in the abdomen
13. Yellow skin and eyes (jaundice)
14. Confusion
15. Coma

The treatment of hepatitis C is best discussed with a doctor or specialist familiar with current and developing options as this field is changing, and even major guidelines may become outdated quickly.The latest treatment guidelines by the American Association for the Study of Liver Disease (AASLD) and Infectious Disease Society of America (IDSA) recommends use of DAAs as first-line treatment for hepatitis C infection. The choice of DAA varies by specific virus genotype, and the presence or absence of cirrhosis. In the U.S., specific insurance providers also might influence the choice due to the high cost of DAAs. Although the individual, public health, and cost benefits of treating all patients with hepatitis C is clear, the most difficult barrier to treating all people with HCV is the very high cost of the drug regimens.Patients are encouraged to discuss options with their health-care professional.Treatment is recommended in all patients with chronic hepatitis C unless they have a short life expectancy that is not related to liver disease. Severe life-threatening liver disease may require liver transplantation. Newer therapies with DAAs have allowed more and more patients to be treated.What are the goals of therapy for hepatitis C infection?The ultimate goals of antiviral therapy are to

• prevent transmission of hepatitis C,
• normalize liver tests,
• reduce inflammation and scarring,
• prevent progression to cirrhosis and liver cancer, and
• improve survival and quality of life.

A side goal is preventing co-infections with other hepatitis viruses, such as A and B, which can cause more liver disease than HCV alone. These can be prevented by vaccines and treatment.

At this time there are no effective home or over-the-counter treatments for hepatitis C.

Hepatitis C virus infection is an infection of the liver caused by the hepatitis C virus (also referred to as HCV). It is difficult for the human immune system to eliminate hepatitis C from the body, and infection with hepatitis C usually becomes chronic. Over decades, chronic infection with hepatitis C damages the liver and can cause liver failure. In the U.S., the CDC has estimated that approximately 29,718 new cases occurred in 2013. When the virus first enters the body there usually are no symptoms, so this number is an estimate. Up to 85% of newly-infected people fail to eliminate the virus and become chronically infected. In the U.S., more than three million people are chronically infected with hepatitis C. Infection is most commonly detected among people who are 40 to 60 years of age, reflecting the high rates of infection in the 1970s and 1980s. There are 8,000 to 10,000 deaths each year in the U.S. related to hepatitis C infection. HCV infection is the leading cause of liver transplantation in the U.S. and is a risk factor for liver cancer.

Because hepatitis C is transmitted by exposure to blood, there is no specific period of contagiousness. If a person develops chronic hepatitis C, their blood carries the virus and is contagious to others for their entire life, unless the person is cured of their hepatitis C.

As our knowledge of hepatitis C increases, more and more patients are being diagnosed with chronic infection. Current research is very active and includes diagnosis, natural history, treatment, and vaccine development. Thus the field is constantly changing, with new guidelines being added frequently.

Hepatitis means inflammation of the liver. Hepatitis C is one of several viruses that can cause viral hepatitis. It is unrelated to the other common hepatitis viruses (for example, hepatitis A or hepatitis B). Hepatitis C is a member of the Flaviviridae family of viruses. Other members of this family of viruses include those that cause yellow fever and dengue fever.There are at least six different genotypes (strains) of the virus which have different genetic profiles (genotypes 1 to 6). In the U. S., genotype 1 is the most common strain of hepatitis C. Even within a single genotype there may be some variations (genotype 1a and 1b, for example). Genotyping is used to guide treatment because some viral genotypes respond better to some therapies than to others.Like human immunodeficiency virus (HIV), hepatitis C multiplies very fast and attains very high levels in the body. The genes that make the surface proteins of the virus also mutate (change) quickly, and thousands of genetic variations of the virus ("quasi-species") are produced daily. It is impossible for the body to keep up with making anti-HCV antibodies against all of the quasi-species circulating at one time. It has not been possible yet to develop an effective vaccine because the vaccine must protect against all genotypes.Hepatitis C infection in the liver triggers the immune system, which leads to inflammation. Very few people experience typical hepatitis symptoms such as dark urine or clay colored stools in acute or early infection. Chronic hepatitis C usually causes no symptoms until very late in the disease, and hepatitis C has been referred to by sufferers as the "sleeping dragon." Over several years or decades, chronic inflammation may cause death of liver cells and scarring ("fibrosis"). Extensive scarring in the liver is called cirrhosis. This progressively impairs vital functions of the liver. Cirrhotic livers are more prone to liver cancer (hepatoma). Drinking alcohol speeds up liver damage with hepatitis C. Concurrent HIV infection also accelerates progression to cirrhosis.

This is hard to say for certain what the incubation period for hepatitis C is because most people who are infected with hepatitis C do not have symptoms early in the course of the infection. Those who develop symptoms early after getting infected (6 to 10 weeks) experience mild gastrointestinal symptoms that may not prompt a visit to the doctor.

In general, among patients with untreated hepatitis C:

• 75% to 85% become chronically infected,
• 60% to 70% develop liver disease,
• 5% to 20% develop cirrhosis, and
• 1% to 5% will die from complications such as cirrhosis or liver cancer.

Drinking alcohol and acquiring other hepatitis viruses are risk factors for worse liver disease. People with chronic hepatitis C should avoid drinking alcohol and should be screened for antibodies to hepatitis A and B. If they do not have antibodies, they should be vaccinated against these other hepatitis viruses.People with hepatitis C should be educated about preventing HIV infection. Infection with both HIV and hepatitis C speeds up and worsens liver damage caused by the hepatitis C. Hepatitis C also can affect the HIV infection and how it is treated. About 25% of people with HIV infection are co-infected (also infected) with hepatitis C, and up to 90% of IV drug users with HIV are co-infected with hepatitis C. Screening for hepatitis viruses is important in all people infected with HIV, just as screening for HIV is important in people who have hepatitis C.Liver cancer (hepatocellular carcinoma, or hepatoma) is associated with cirrhosis from chronic hepatitis C. Some experts recommend screening patients with hepatitis C infection and cirrhosis for liver cancer periodically.

When people first get hepatitis C, the infection is said to be acute. Most people with acute hepatitis C do not have symptoms so they are not recognized as being infected. However, some have low-grade fever, fatigue or other symptoms that lead to an early diagnosis. Others who become infected and have a known exposure to an infected source, such as a needle-stick injury, are monitored closely.Treatment decisions should be made on a case-by-case basis. Response to treatment is higher in acute hepatitis infection than chronic infection. However, many experts prefer to hold off treatment for 8-12 weeks to see whether the patient naturally eliminates the virus without treatment. Approaches to treatment is evolving. Patients with acute hepatitis C infection should discuss treatment options with a health-care professional who is experienced in treating the disease. There is no established treatment regimen at this time.How effective is hepatitis C treatment?If the hepatitis C RNA remains undetectable at the end of the treatment and follow-up period, this is called a sustained virologic response (SVR) and is considered a cure. Over 90% of people treated with DAAs are cured. These people have significantly reduced liver inflammation, and liver scarring may even be reversed.About 5% of people who are treated for HCV infection are not cured by some of the older regimens. These people may still have options for cure with the newer regimens.Who should not receive treatment with antiviral therapy?Few people with hepatitis C are at risk for problems if they are treated, however there are some factors that affect treatment regimens, such as concurrent HIV medications and kidney dysfunction. Some drugs are not safe for people with cirrhosis. Individuals who are unable to comply with the treatment schedule for psychological reasons or ongoing drug or alcohol abuse may not be good candidates for treatment because the drugs are very costly and require adherence to the pill regimen and regular follow-up visits. There are some important drug interactions with some of the medications that should be considered by the health-care professional.People with past hepatitis B or who have chronic active hepatitis B should not be treated for HCV without treating for HBV as well. As highly effective treatment for HCV has emerged, reports of serious hepatitis B have come to light. Similar to HCV, hepatitis B usually does not clear from the liver after acute infection, even though it is far less likely to cause chronic active hepatitis than hepatitis C infection. It remains dormant in most people, but it can reactivate with changes in the immune system. It is not clear why eliminating the HCV can allow the HBV infection to flare up. Hepatitis B screening is an important part of the hepatitis C evaluation.

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Interferons, for example, Roferon-A and Infergen, and pegylated interferons such as Peg-IntronT, Pegasys, were mainstays of treatment for years. Interferons produced sustained viral response (SVR, or cure) of up to 15%. Later, peglatedll forms produced SVR of 50%-80%. These drugs were injected, had many adverse effects, required frequent monitoring, and were often combined with oral ribavirin, which caused anemia. Treatment durations ranged up to 48 weeks.Direct-acting agents (DAA) are antiviral drugs that act directly on hepatitis C multiplication.

• They are taken by mouth, are well-tolerated, and cure over 90% of patients.
• Treatment time is much shorter, often 12 weeks, depending on drug and genotype.
• Similar to treatments for HIV, treatment of HCV is most effective if the drugs are given in combination.
• The earliest options were sofosbuvir (Sovaldi) and simeprevir (Olysio). These were approved by the Food and Drug Administration (FDA) in 2013.
• Ledipasvir and sofosbuvir (Harvoni) followed as a once-a-day combination pill, in 2014.
• With this combination of DAAs, about 94%-99% of people achieve an SVR (cure) in 12 weeks with few side effects.
• Ombitasvir, paritaprevir and ritonavir co-packaged with dasabuvir tablets (Viekira Pak), is a combination approved in 2014. SVR with this combination is 91%-100%. The combination of elbasvir and grazoprevir (Zepatier) was approved in 2016. SVR with this combination depends on the HCV genotype and whether individual patient factors require the addition of ribavirin. Genotype 1 has a 94%-97% SVR, and SVR is 97%-100% in genotype 4.
• In August 2017, FDA approved an 8-week regimen of glecaprevir and pibrentasvir (Mavryet) for all HCV genotypes. Unlike some of the earlier regimens, this combination is effective whether or not the patient has cirrhosis. It also can be given to people on kidney dialysis, whose kidney function limits treatment options. Moreover, this regimen is effective in people with genotype 1 who have failed treatment with some of the other regimens.

Hepatitis C is treated by either a gastroenterologist, a hepatologist (a gastroenterologist with additional training in liver disease), or an infectious disease specialist. The treatment team may include more than one specialist, depending on the extent of liver damage.Surgeons who specialize in surgery of the liver, including liver ransplantation, are part of the medical team and should see patients with advanced disease (liver failure or cirrhosis) early, before the patient needs a liver transplant. They may be able to identify issues that need to be addressed before surgery can be considered. Other persons that can be helpful in managing patients include dieticians to consult on nutritional issues and pharmacists to assist with management of drugs.

The U.S Preventive Health Services task force recommends that all adults born between 1945 and 1965 be tested once routinely for hepatitis C, regardless of whether risk factors for hepatitis C are present. One-time testing also is recommended for:

• People who currently inject drugs or snort drugs, or ever did so, even once many years previously
• People with persistently elevated alanine aminotransferase (ALT) level, a liver enzyme found in blood
• People who have HIV infection
• Children born to HCV- or HIV-infected mothers
• People who were ever on long-term hemodialysis
• People who got a tattoo in an unregulated setting, such as prison or by an unlicensed person
• People who received clotting factor produced before 1987
• People who received transfusions or organ transplants before July 1992, or who were notified that they received blood from a donor who later tested positive for hepatitis C infection
• Healthcare, emergency medical, and public safety workers after a needle-stick, eye or mouth exposure to hepatitis C-infected blood

People who may have been exposed to hepatitis C in the previous 6 months should be tested for viral RNA load rather than anti-HCV antibody because antibody may not be present early in hepatitis C infection.In general, yearly screening may be appropriate for people with ongoing risk factors such as repeated sexually transmitted diseases (STDs) or many sex partners, ongoing IV drug use, or long-term sex partners of people with hepatitis C. Whether or not to test these people is determined on a case-by-case decision.