What is Hepatitis C?
First identified in 1989, the Hepatitis C virus, or HCV, is a major global health issue that affects 58 million people all over the world. From 1990 to 2005, the percentage of people who tested positive for HCV antibodies globally has risen from 2.3% to 2.8%. Roughly 80% to 85% of patients who get the virus can’t get rid of it, leading to a long-term infection. The long-term infection can result in serious health conditions like liver scarring (cirrhosis), high blood pressure in the liver (portal hypertension), liver failure, brain problems (encephalopathy), and liver cancer (hepatocellular carcinoma).
HCV is the most common virus transmitted through blood and a major cause of illness and death. However, treatment has improved significantly since 2011, with the invention of highly effective antiviral drugs known as Direct-Acting Antivirals (DAAs). The purpose of these treatments is to eliminate the virus, slow down the progression of liver fibrosis (tissue scarring), ease symptoms, prevent health complications, reduce the risk of death from any cause, and ultimately enhance quality of life.
What Causes Hepatitis C?
The Hepatitis C virus (HCV) is a small, round virus that is surrounded by shell. It carries its genetic information in a molecule called RNA. This virus is part of the Flaviviridae family, but it’s unique enough to fall under its own category, or genus, called Hepacivirus.
The virus’s genetic material is about 9.6 thousand units long. It carries instructions to make a large protein. This protein is then cut up into at least ten smaller proteins. Among these, there are three that form the structure of the virus, including two that make up the virus’s outer shell and one that makes up its inner core. There are two more proteins that are necessary for the virus to multiply and five others that are important for the virus to copy its genetic material.
One particular feature about the HCV is that it makes a lot of copies of itself but without a proper ‘spell-check’, causing to create many different versions of itself, known as “quasispecies”. This happens due to an imperfection in one of its proteins called the NS5B RNA polymerase.
Risk Factors and Frequency for Hepatitis C
Over 58 million individuals all around the world are thought to be living with Hepatitis C (HCV). In developed nations, around 1 to 2% of the population have HCV. The number of sudden (acute) cases reported in the US has gone up each year from 2009 through to 2013. In fact, in 2013, it’s estimated there were around 29,718 acute cases of HCV. Out of all the types of viral hepatitis (including A, B, and C), HCV was found to cause the most deaths with a mortality rate of 5.0 deaths per 100,000 people in 2013.
HCV can only infect a person if the virus is able to enter the body and make contact with specific types of cells that can be infected. The virus can be found in several body fluids including blood, saliva, tears, seminal fluid, and fluids in the brain and abdominal cavity.
Although it is possible to acquire HCV through sexual intercourse, this is rare. The chances of a baby being born with HCV from a mother with the virus range from 0 to 4%. In the US and Europe, most people with HCV acquire the virus through intravenous drug use or unsafe medical practices in areas with limited resources.
- Type 1 of the HCV virus is the most widespread globally. In the US, 60 to 70% of virus samples are subtype 1a or 1b
- Type 2 is widely distributed but most diverse in central and west Africa
- Type 3 is commonly found but most diverse in Asia, and often associated with illegal drug use
- Type 4 is prevalent in Northern Africa and the Middle East
- Type 5 is common in South Africa
- Type 6 is prevalent in Southeast Asia
- Type 7 is found in Central Africa, specifically the Congo
Signs and Symptoms of Hepatitis C
Acute Hepatitis C virus (HCV) infection often doesn’t come with noticeable symptoms. However, some people may experience general discomfort, feeling nauseous, and discomfort in the upper right portion of their belly. These symptoms could also be followed by dark-colored urine and jaundice (a yellowing of the skin or eyes). These features make it difficult to distinguish from other types of acute viral hepatitis. Those with chronic HCV infection often don’t show any symptoms. When symptoms do appear, they can be vague, including feelings of fatigue, discomfort in the upper right part of the abdomen, joint pain, and a general feeling of unwellness. These symptoms, however, could be caused by several factors, including the psychological stress of knowing they have a chronic disease.
About 10% to 20% of people with HCV who develop cirrhosis (scarring of the liver) will show signs within five years. These signs can include high blood pressure in the portal vein (the vein that supplies the liver), varicose veins in the esophagus, fluid accumulation in the abdomen (ascites), clotting abnormalities, confusion or changes in behavior (encephalopathy), or liver cancer. At this stage, they might have physical signs of chronic liver disease. In addition to the liver disease, they may also show signs of other conditions that can occur with HCV, such as mixed cryoglobulinemia (a type of vasculitis), glomerulonephritis (a type of kidney disease), porphyria cutanea tarda (a group of rare genetic disorders that affect the nervous system and skin), lichen planus (a rash), changes in cognitive abilities, insulin resistance, and disorders affecting B cells (a type of white blood cell).
The physical examination may reveal signs of severe liver disease, such as :
- Muscle wasting around the temples, bluish discoloration of the skin, yellowing of the skin or eyes, swelling of the parotid gland (the major salivary gland)
- Redness of the palms, tremor of the hand when stretched out, finger clubbing, a condition affecting the hands and fingers causing them to thicken and stiffen (Dupuytren’s contracture)
- Breast enlargement in men, small testicles
- Musty breath (fetor hepaticus)
- Swelling of the ankles, red spots on the skin shaped like a spider, small red spots on the skin, scanty body hair
- Appearance of varicose veins around the navel, umbilical hernia, enlarged liver and spleen
Testing for Hepatitis C
Diagnosing Hepatitis C virus (HCV) infection is primarily done through two techniques. The first involves detecting antibodies that fight against HCV, and the second is assessing for HCV RNA or genetic material. These tests measure antibodies that are directed against different parts of the virus but can’t tell if the infection is current or something you’ve had in the past. To make this distinction, doctors test directly for HCV RNA. A quick HCV antibody test can also be a useful tool in settings where immediate results are needed.
In some cases, the HCV RNA test should be done right away. These scenarios include if you’ve been exposed to HCV within the past six months, if you have a weakened immune system, or if there’s a suspicion of reinfection.
Further tests involve checking the viral type, as this can guide treatment choice and predict treatment response. Other recommended tests include tests for HIV, hepatitis B, susceptibility to hepatitis A and B, and tests for other potential causes of liver disease such as autoimmune disease, iron overload, and Wilson’s disease. Once all this is done, the disease is staged, or its severity assessed – usually through a liver biopsy or specific imaging or blood tests. Screening for varices (swollen veins) and liver cancer should also be done.
Other tests could include:
- A test to measure how your blood clots (INR, prothrombin time)
- A complete blood count
- Liver function tests
- Test for kidney function (GFR)
- Tests for other liver viruses
- Checks for thyroid function
- Screening for drug abuse and alcohol consumption
- Mental health assessment
While a liver biopsy isn’t routinely done, it can be informative in assessing the disease’s severity. It might be necessary if the diagnosis isn’t clear, if it looks like another liver disease might be present, or if the patient has a weakened immune system.
Treatment Options for Hepatitis C
Acute Hepatitis C virus (HCV) infection can either clear up on its own or turn into a long-term condition called chronic HCV infection. The goal of treating chronic HCV is to eliminate the virus from the body completely by getting rid of HCV RNA, a molecule linked with the virus. This is achieved through a process called a sustained virologic response (SVR). SVR occurs when HCV RNA can’t be detected in the blood after 12 weeks of treatment. This leads to a decrease in the level of antibodies in the body related to the virus and can result in improvements to liver health.
Before we had oral drugs specifically for treating HCV, the main form of treatment was injections with drugs called pegylated interferon and ribavirin. However, this form of treatment could only cure 40% to 60% of patients, and it led to a number of negative side effects including flu-like symptoms, a drop in certain types of blood cells, severe anemia and effects on brain function. But today, we have drugs known as Direct-Acting Antivirals (DAAs) specifically for treating HCV, which have caused significant improvements in treatment. They’ve shortened the length of treatment from 48 weeks to 12 weeks, reduced the side effects, increased cure rates to between 90% and 97% and gotten rid of the need for injections.
There are three types of DAAs today. The first type, second-generation protease inhibitors, stop a certain enzyme linked with HCV. The second type, NS5A inhibitors, interfere with a structural protein known as NS5A that helps the virus reproduce. The third type, NS5B polymerase inhibitors, stop an enzyme linked with the replication of the virus. Different combinations of these three types of DAAs make up a strong treatment plan against the different variations of Hepatitis C.
The typical treatment plans can last from 12 weeks to 24 weeks with or without ribavirin, another antiviral drug. The specifics can depend on the particular variation of HCV, whether the patient has had treatment before, and whether there is damage to the liver. With the current DAAs, the type of HCV that is least responsive is Genotype 3 infection, which leads to faster liver damage and a higher chance of liver cancer. Genotype 1, which is the most common type in the United States, has four approved treatments, two of which only require a single pill per day. For instance, there are single-pill combinations of sofosbuvir and ledipasvir, and grazoprevir and elbasvir. There are also many more drugs under evaluation in clinical trials that have the potential to get rid of the need to even check the type of Hepatitis C. However, discussing each of these treatment plans for the different variations of Hepatitis C is beyond the scope of this summary.
What else can Hepatitis C be?
- Autoimmune hepatitis (a disease where the body’s immune system attacks the liver)
- Alcoholic liver disease (damage to the liver caused by alcohol abuse)
- Abdominal aneurysm (a bulging, weak spot in the main artery of the stomach)
- Bowel obstruction (a blockage that prevents food or liquid from passing through your small or large intestine)
- Cholangitis (an infection of the bile ducts, tubes that carry bile from the liver to the gallbladder and intestines)
- Cholecystitis (inflammation of the gallbladder often caused by gallstones)
- Cholelithiasis (the medical term for gallstones)
- Drug-induced liver injury (damage to the liver caused by a medication or drug overdose)
- Gastritis (inflammation of the stomach lining)
- Gastroenteritis (an intestinal infection commonly known as the “stomach flu”)
- Hepatocellular carcinoma (a type of liver cancer)
- Liver abscess (a pocket of pus that forms in the liver)
- Peptic ulcer disease (painful sores in the lining of the stomach, lower esophagus, or small intestine)
- Viral hepatitis (inflamed liver caused by a virus)
What to expect with Hepatitis C
Only 10-15% of people infected with Hepatitis C virus (HCV) are able to self-limit the infection; in the majority of cases, the infection keeps progressing. Statistics show that about 20% of these patients will develop a severe liver condition called cirrhosis within 20 years, and another 1 to 5% will develop liver cancer within 30 years.
The disease tends to progress faster in those who frequently consume alcohol, people already suffering from cirrhosis, and individuals who also have Hepatitis B. However, those who can’t detect the virus in their system generally have a lowered risk of both developing cirrhosis and dying from the disease.
Possible Complications When Diagnosed with Hepatitis C
End-stage liver disease and liver cancer are two major health conditions related to the liver.
