What Is Hepatitis C; Symptoms, Treatment

What Is Hepatitis C/Hepatitis C is a liver infection caused by the Hepatitis C virus (HCV). Hepatitis C is a blood-borne virus. Today, most people become infected with the Hepatitis C virus by sharing needles or other equipment to inject drugs. For some people, hepatitis C is a short-term illness but for 70%–85% of people who become infected with Hepatitis C, it becomes a long-term, chronic infection. Chronic Hepatitis C is a serious disease that can result in long-term health problems, even death. The majority of infected persons might not be aware of their infection because they are not clinically ill. There is no vaccine for Hepatitis C. The best way to prevent Hepatitis C is by avoiding behaviors that can spread the disease, especially injecting drugs.

Hepatitis C is a viral infection that causes liver inflammation and damage. Inflammation is swelling that occurs when tissues of the body become injured or infected. Inflammation can damage organs.

Types of Hepatitis C

• Acute hepatitis C – Acute hepatitis C is a short-term infection. Symptoms can last up to 6 months. Sometimes your body is able to fight off the infection and the virus goes away.
• Chronic hepatitis C – Chronic hepatitis C is a long-lasting infection. Chronic hepatitis C occurs when your body isn’t able to fight off the virus. About 75 to 85 percent of people with acute hepatitis C will develop chronic hepatitis C.

Pathophysiology

The Hepatitis C RNA virus enters the hepatocyte via endocytosis mediated by at least four co-receptor molecules. Following internalization in the cytoplasm, its positive-stranded RNA is uncoated and translated into ten mature peptides. These are then cleaved by both host proteases and virally encoded proteases known as NS3-4a serine proteases. These mature peptides then go on to reside in the endoplasmic reticulum, forming a replication complex that contains an important enzyme, the NS5B RNA dependent RNA polymerase. This enzyme catalyzes the positive RNA strand into its negative-strand intermediate which in turn serves as the template for new positive-strand synthesis. These are then packaged with core and envelop glycoprotein into mature virions which then exit the cell via exocytosis. HCV has no ability to integrate into the host’s genome. The virus can be detected in plasma within days of exposure, often 1 to 4 weeks. Viremia peaks in the first 8 to 12 weeks of infection, and then plateaus or drops to undetectable levels (viral clearance); in the majority, 50% to 85% it persists. Persistent infection appears to be due to weak CD4+ and CD8+ T-cell responses which fail to control viral replication. When the chronic infection is established, HCV does not appear to be cytopathic; it is the local inflammatory response that triggers fibrogenesis. Multiple external factors including alcohol consumption, HIV/HBV coinfections, Genotype 3 infection, insulin resistance, obesity, and non-alcoholic fatty liver disease are linked to accelerated fibrosis progression and cirrhosis. The severity of liver fibrosis is tightly correlated with the increased risk of hepatocellular carcinoma via facilitating genetic aberrations and promoting neoplastic clones.[rx]

Stages of Hepatitis C

The hepatitis C virus affects people in different ways and has several stages:

• Incubation period – This is the time between first exposure to the start of the disease. It can last anywhere from 14 to 80 days, but the average is 45
• Acute hepatitis C – This is a short-term illness that lasts for the first 6 months after the virus enters your body. After that, some people who have it will get rid of, or clear, the virus on their own.
• Chronic hepatitis C – If your body doesn’t clear the virus on its own after 6 months, it becomes a long-term infection. This can lead to serious health problems like liver cancer or cirrhosis.
• Cirrhosis – This disease leads to inflammation that, over time, replaces your healthy liver cells with scar tissue. It usually takes about 20 to 30 years for this to happen, though it can be faster if you drink alcohol or have HIV.
• Liver cancer – Cirrhosis makes liver cancer more likely. Your doctor will make sure you get regular screenings because there are usually no symptoms in the early stages.

Causes and Transmission of Hepatitis C

Although infrequent, HCV can also be spread through

• Sex with an HCV-infected person (an inefficient means of transmission, although HIV-infected men who have sex with men [MSM] have increased risk of sexual transmission)
• Sharing personal items contaminated with infectious blood, such as razors or toothbrushes (also inefficient vectors of transmission)
• Other health care procedures that involve invasive procedures, such as injections (usually recognized in the context of outbreaks)
• Unregulated tattooing

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 outcomes 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.

Hepatitis C cannot be transmitted by

• Kissing
• Sharing food, cups or cutlery
• Shaking hands or day-to-day physical contact

Symptoms of Hepatitis C

Symptoms of acute HCV infection

The incubation period for hepatitis C ranges from 2 weeks to 6 months. Following initial infection, approximately 80% of people do not exhibit any symptoms.

• Those who are acutely symptomatic may exhibit fever, fatigue, decreased appetite, nausea, vomiting,
• Abdominal pain, dark urine, grey-colored feces,
• Joint pain with jaundice (yellowing of the skin and the whites of the eyes).
• Fever
• Fatigue
• Dark urine
• Clay-colored stool
• Loss of appetite
• Joint pain
• Jaundice (yellowing of the skin and eyes)
• Nausea and vomiting
• Loss of appetite
• Fatigue (feeling tired all the time)
• Fluid buildup in your abdomen (ascites)
• Swelling in your legs
• Weight loss
• Confusion, drowsiness and slurred speech (hepatic encephalopathy)
• Spiderlike blood vessels on your skin (spider angiomas)
• Bleeding easily
• Bruising easily

Diagnosis of Hepatitis C

CDC recommends HCV testing for

• Current or former injection drug users, including those who injected only once many years ago
• Everyone born from 1945 through 1965 [rx]
• Recipients of clotting factor concentrates made before 1987 when less advanced methods for manufacturing those products were used
• Recipients of blood transfusions or solid organ transplants prior to July 1992, before better testing of blood donations, became available
• Chronic hemodialysis patients
• People with known exposures to HCV, such as health care workers after needlesticks involving HCV-positive blood recipients of blood or organs from a donor who tested HCV-positive
• People with HIV infection
• Children born to HCV-positive mothers

U.S. Preventive Services Task Force (USPSTF) also recommends HCV testing external icon for

• Incarcerated persons
• People who use intranasal drugs,
• People who get an unregulated tattoo

Several blood tests are performed to test for HCV infection, including

• Magnetic resonance elastography (MRE) – A noninvasive alternative to a liver biopsy (see below), MRE combines magnetic resonance imaging technology with patterns formed by sound waves bouncing off the liver to create a visual map showing gradients of stiffness throughout the liver. Stiff liver tissue indicates the presence of scarring of the liver (fibrosis) as a result of chronic hepatitis C.
• Transient elastography – Another noninvasive test, transient elastography is a type of ultrasound that transmits vibrations into the liver and measures the speed of their dispersal through liver tissue to estimate its stiffness.
• Liver biopsy – Typically done using ultrasound guidance, this test involves inserting a thin needle through the abdominal wall to remove a small sample of liver tissue for laboratory testing.
• Blood tests – A series of blood tests can indicate the extent of fibrosis in your liver.
• Transient elastography – A member of the care team performs transient elastography — a painless alternative to liver biopsy — to assess liver damage.
• The hepatitis C PCR test – is recommended for anyone who has positive hepatitis C antibodies unless they have recently completed hepatitis C treatment. If you have had treatment, antibodies will persist whether you have cleared the hepatitis C virus or not.

Screening Tests

Anti–HCV antibody testing followed by polymerase chain reaction testing for viremia is accurate for identifying patients with chronic HCV infection. Various noninvasive tests with good diagnostic accuracy are possible alternatives to liver biopsy for diagnosing fibrosis or cirrhosis.

• Screening tests for antibody to HCV (anti-HCV) and enzyme immunoassay (EIA), enhanced chemiluminescence immunoassay (CIA)
• Qualitative tests to detect the presence or absence of virus (HCV RNA polymerase chain reaction [PCR])
• Quantitative tests to detect amount (titer) of virus (HCV RNA PCR)

Biopsy – Liver biopsies are used to determine the degree of liver damage present; however, there are risks from the procedure.^[rx] The typical changes seen are lymphocytes within the parenchyma, lymphoid follicles in portal triad, and changes to the bile ducts.^[rx] There are a number of blood tests available that try to determine the degree of hepatic fibrosis and alleviate the need for biopsy.^[rx]

Genotype test – Your doctor can use this test to find out what strain, or form, of hepatitis C virus you have. At least six specific strains—called genotypes—of hepatitis C exist. Genotype 1 is the most common hepatitis C genotype in the United States.¹ Your doctor will recommend treatment based on which hepatitis C genotype you have.

Treatment of Hepatitis C

• Get plenty of rest
• Maintain a cool, well-ventilated environment, wear loose clothing, and avoid hot baths or showers if itching is a problem
• Those with chronic hepatitis C – are advised to avoid alcohol and medications toxic to the liver.^[rx] They should also be vaccinated against hepatitis A and hepatitis B due to the increased risk if also infected.^[rx]
• The use of acetaminophen – is generally considered safe at reduced doses.^[rx]
• Nonsteroidal anti-inflammatory drugs (NSAIDs) – are not recommended in those with advanced liver disease due to an increased risk of bleeding.^[rx] Take over-the-counter painkillers, such as paracetamol or ibuprofen, for tummy pain. 
• Ultrasound surveillance for hepatocellular carcinoma – is recommended in those with accompanying cirrhosis.^[rx] Coffee consumption has been associated with a slower rate of liver scarring in those infected with HCV.^[rx]

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No Prior Treatment

• HCV genotype 1a (no cirrhosis) – 8 weeks of glecaprevir/pibrentasvir or ledipasvir/sofosbuvir (the latter for people who do not have HIV/AIDS, are not African-American, and have less than 6 million HCV viral copies per milliliter of blood) or 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir.^[rx] Sofosbuvir with either daclatasvir or simeprevir may also be used.^[rx]
• HCV genotype 1a (with compensated cirrhosis) – 12 weeks of elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. An alternative treatment regimen of elbasvir/grazoprevir with weight-based ribavirin for 16 weeks can be used if the HCV is found to have antiviral resistance mutations against NS5A protease inhibitors.^[rx]
• HCV genotype 1b (no cirrhosis) – 8 weeks of glecaprevir/pibrentasvir or ledipasvir/sofosbuvir (with the aforementioned limitations for the latter as above) or 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. Alternative regimens include 12 weeks of ombitasvir/paritaprevir/ritonavir with dasabuvir or 12 weeks of sofosbuvir with either daclatasvir or simeprevir.^[rx]
• HCV genotype 1b (with compensated cirrhosis) – 12 weeks of elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. A 12-week course of paritaprevir/ritonavir/ombitasvir with dasabuvir may also be used.^[rx]
• HCV genotype 2 (no cirrhosis) – 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir. Alternatively, 12 weeks of sofosbuvir/daclatasvir can be used.^[rx]
• HCV genotype 2 (with compensated cirrhosis) – 12 weeks of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir. An alternative regimen of sofosbuvir/daclatasvir can be used for 16–24 weeks.^[rx]
• HCV genotype 3 (no cirrhosis) – 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir or sofosbuvir and daclatasvir.^[rx]
• HCV genotype 3 (with compensated cirrhosis) – 12 weeks of glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, or if certain antiviral mutations are present, 12 weeks of sofosbuvir/velpatasvir/voxilaprevir (when certain antiviral mutations are present), or 24 weeks of sofosbuvir and daclatasvir.^[rx]
• HCV genotype 4 (no cirrhosis) – 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir, elbasvir/grazoprevir, or ledipasvir/sofosbuvir. A 12-week regimen of ombitasvir/paritaprevir/ritonavir is also acceptable in combination with weight-based ribavirin.^[rx]
• HCV genotype 4 (with compensated cirrhosis) – A 12-week regimen of sofosbuvir/velpatasvir, glecaprevir/pibrentasavir, elbasvir/grazoprevir, or ledipasvir/sofosbuvir is recommended. A 12-week course of ombitasvir/paritaprevir/ritonavir with weight-based ribavirin is an acceptable alternative.^[rx]
• HCV genotype 5 or 6 (with or without compensated cirrhosis) – If no cirrhosis is present, then 8 weeks of glecaprevir/pibrentasvir is recommended. If cirrhosis is present, then a 12-week course of glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, or ledipasvir/sofosbuvir is warranted.^[rx]

Chronic infection can be cured in more than 90% of people with medications.^[rx] Getting access to these treatments however can be expensive.^[rx] The combination of sofosbuvir, velpatasvir, and voxilaprevir may be used in those who have previously been treated with sofosbuvir or other drugs that inhibit NS5A and were not cured.^[rx]

Surgery

• Cirrhosis due to hepatitis C is a common reason for liver transplantation though the virus usually (80–90% of cases) recurs afterward. Infection of the graft leads to 10–30% of people developing cirrhosis within five years. Treatment with pegylated interferon and ribavirin post-transplant decreases the risk of recurrence to 70%.^[rx] A 2013 review found unclear evidence regarding if the antiviral medication was useful if the graft became reinfected.^[rx]

Alternative medicine

• Several alternative therapies are claimed by their proponents to be helpful for hepatitis C including milk thistle, ginseng, and colloidal silver.^[rx] However, no alternative therapy has been shown to improve outcomes in hepatitis C, and no evidence exists that alternative therapies have any effect on the virus at all.^[rx][rx]
  

Counseling Patients

What topics should be discussed with patients who have HCV infection?

• First and foremost, patients should be informed about the effectiveness and benefits of new direct acting antivirals (DAAs) and referred for prompt assessment and treatment, if indicated.
• Patients should be informed about the low but present risk for transmission with sex partners.
• Sharing personal items that might have blood on them, such as toothbrushes or razors, can pose a risk to others.
• Cuts and sores on the skin should be covered to keep from spreading infectious blood or secretions.
• Donating blood, organs, tissue, or semen can spread HCV to others.
• HCV is not spread by sneezing, hugging, holding hands, coughing, sharing eating utensils or drinking glasses, or through food or water.

What should HCV-infected persons be advised to do to protect their livers from further harm?

• Patients should be informed about the effectiveness and benefits of new direct-acting antivirals (DAAs) and referred for prompt assessment and treatment if indicated.
• HCV-positive patients should be advised to avoid alcohol because it can accelerate cirrhosis and end-stage liver disease.
• Viral hepatitis patients should also check with a health professional before taking any new prescription pills, over-the-counter drugs (such as non-aspirin pain relievers), or supplements, like these, can potentially damage the liver.
• Clinicians may wish to consider vaccinating HCV-positive patients against hepatitis A and hepatitis B even in the absence of liver disease.

Prevention

Primary prevention

• There is no effective vaccine against 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 and men who have sex with men, particularly those infected with HIV or those who are taking pre-exposure prophylaxis against HIV.

The following list provides a limited example of primary prevention interventions recommended by WHO

• Safe and appropriate use of health care injections;
• Safe handling and disposal of sharps and waste;
• Provision of comprehensive harm-reduction services to people who inject drugs including sterile injecting equipment and effective treatment of dependence;
• Testing of donated blood for HBV and HCV (as well as HIV and syphilis);
• Training of health personnel;
• Prevention of exposure to blood during sex;
• Hand hygiene, including surgical hand preparation, hand washing and use of gloves; and
• Promotion of correct and consistent use of condoms.

Secondary prevention

For people infected with the hepatitis C virus, WHO recommends:

• Education and counseling on options for care and treatment;
• Immunization with the hepatitis A and B vaccines to prevent coinfection from these hepatitis viruses and to protect their liver;
• Early and appropriate medical management including antiviral therapy; and
• Regular monitoring for early diagnosis of chronic liver disease.

Screening, care, and treatment of persons with hepatitis C infection

In July 2018, WHO updated its “Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection“.

These guidelines are intended for government officials to use as the basis for developing national hepatitis policies, plans, and treatment guidelines. These include country program managers and health-care providers responsible for planning and implementing hepatitis care and treatment programs, particularly in low- and middle-income countries.

WHO Response

In May 2016, The World Health Assembly adopted the first “Global Health Sector Strategy on Viral Hepatitis, 2016-2021”. The strategy highlights the critical role of universal health coverage and sets targets that align with those of the Sustainable Development Goals. The strategy has the vision to eliminate viral hepatitis as a public health problem. This is encapsulated in the global targets to reduce new viral hepatitis infections by 90% and reduce deaths due to viral hepatitis by 65% by 2030. Actions to be taken by countries and the WHO Secretariat to reach these targets are outlined in the strategy.

WHO is working in the following areas to support countries in moving towards achieving the global hepatitis goals under the Sustainable Development Agenda 2030:

• Raising awareness, promoting partnerships and mobilizing resources;
• Formulating evidence-based policy and data for action;
• Preventing transmission; and
• Scaling up screening, care and treatment services.

Since 2011, together with national governments, civil society and partners, WHO have organized annual World Hepatitis Day campaigns (as 1 of its 9 flagship annual health campaigns) to increase awareness and understanding of viral hepatitis. The date of 28 July was chosen because it is the birthday of Nobel-prize winning scientist Dr Baruch Bloomberg, who discovered the hepatitis B virus and developed a diagnostic test and vaccine for the virus.

For World Hepatitis Day 2019, WHO is focusing on the theme “Invest in eliminating hepatitis” to highlight the need for increased domestic and international funding to scale up hepatitis prevention, testing and treatment services, in order to achieve the 2030 elimination targets.

References

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