An Overview of Hepatitis

Hepatitis is a disease characterized by the inflammation of the liver. While we tend to associate it with viral infections, such as hepatitis B or C, there are also non-viral forms of the disease, including autoimmune hepatitis and alcoholic hepatitis.

Hepatitis can occur with or without symptoms and can often resolve on its own without any medical intervention. When symptoms do occur, there can be tell-tale signs such as the yellowing of the skin and eyes (jaundice), a loss of appetite, and feelings of extreme exhaustion, which can last for weeks at a time.

Acute and Chronic Hepatitis

Depending on the cause, hepatitis can present as either an acute or chronic condition.

Acute hepatitis tends to be viral in nature and is often self-limiting, presenting initially with generalized, flu-like symptoms (fever, headache, joint pain, nausea) before manifesting with jaundice, darkened urine (choluria), and clay-colored stools. An enlarged liver and abdominal pain or discomfort (typically in the right upper quadrant beneath the ribs) are also common.

Recovery tends to take around a month or so, although in some cases—particularly with hepatitis B—it can take up to four months for symptoms to fully resolve.

Chronic hepatitis, by contrast, is a progressive disease. It can be symptom-free in the early stages and detectable only by lab tests. However, as the inflammation gradually progresses, it can cause a build-up of scar tissue (called fibrosis), which can impede the blood flow in and out of the liver. If scarring continues to mount, the liver’s ability to function can become severely hindered, resulting in a condition called cirrhosis. It is during this time that jaundice and other clinical symptoms may appear, typically as signs of advanced liver disease.

The causes of hepatitis are diverse, ranging from viral infections to genetic disorders and excessive alcohol use. The three most common causes can be broadly categorized as infectious, metabolic, and autoimmune.

Infectious Causes of Hepatitis

While viral hepatitis is the most common form of hepatitis worldwide, there are also bacterial and parasitic causes of the disease. These include liver infections caused by everything from Salmonella and E. coli bacteria to protozoan organisms that directly attack the liver.

In terms of disease prevalence, we tend to focus on viral forms of hepatitis, given that more than 1.5 million people die from the disease each year. The five most common forms are only marginally related and can vary by modes of transmission, disease progression, and methods of prevention.

  • Hepatitis A is caused by the hepatitis A virus (HAV) and is most commonly transmitted through food or water that has been contaminated with HAV-infected feces. It presents acutely with no progression to a chronic stage. The average incubation period is between 14 and 48 days, with a full recovery from the acute symptoms taking around two months. A vaccine is available that can prevent HAV infection for up to 10 years.
  • Hepatitis B is caused by the hepatitis B virus (HBV). It is spread through contact with HBV-infected blood, semen, or saliva, either during sex or as a result of injecting drug use. Sharing razors, unsanitary tattooing, or breastfeeding can also transmit the virus. Hepatitis B can present both acutely and chronically, with an average incubation period of 45 to 160 days. In addition to two HBV vaccines, there are seven FDA-approved drugs used in the treatment of HBV infection. While none of the drugs can clear the virus, they can effectively prevent replication of the virus and damage to the liver.
  • Hepatitis C is caused by the hepatitis C virus (HCV). Hepatitis C is spread predominantly through injecting drug use, but can also be transmitted through sexual contact and from mother to child during pregnancy. The incubation time can range from 14 to 150 days. While anywhere from 20 to 40 percent of HBV-infected individual will spontaneously clear the virus without treatment or symptoms, the remaining will advance to a chronic infection. While there is no vaccine to prevent HBV infection, newer generation drugs are now able to affect cure rates of up to 99 percent in some groups.
  • Hepatitis D is caused by the hepatitis D virus (HDV) and can only occur when a person is co-infected with the hepatitis B virus (HBV). It is primarily spread through injecting drug use and has the highest fatality rate of all viral types (20 percent). Rare in the U.S., hepatitis D is seen predominantly in developing countries, such as those in sub-Saharan Africa, the Middle East, and the northern section of South America. While the HBV vaccine is known to prevent infection (since HDV cannot manifest on its own), treatment options are poor, with only 20 percent of those on therapy able to achieve sustained viral remission.
  • Hepatitis E is caused by the hepatitis E virus (HEV) and is spread primarily through contaminated water in areas with poor sanitation. Hepatitis E is most prevalent in India, Southeast Asia, Central America, and northern and central Africa. The incubation period is between 14-60 days, with most acute infections resolving on their own. However, in persons with compromised immune systems, the disease can progress to a chronic infection. No vaccine is yet available to prevent HEV infection. Treatment options are limited, although there has been success in achieving viral clearance with the use of the drug ribavirin.

    Metabolic Causes of Hepatitis

    Metabolic causes of hepatitis are those related to substances we either take or are exposed to, or those associated with obesity, insulin resistance, and diabetes. It doesn’t mean to suggest that a person "causes" their hepatitis, but that there are changeable factors that put an individual at greater risk of liver inflammation and injury.

    The metabolic causes of hepatitis can be broadly classified as:

    • Alcoholic hepatitis, an extension of alcoholic liver disease, is the greatest cause of cirrhosis in the United States. It tends to develop over a long period of time and is known to affect around 10 to 20 percent of alcoholics. The risk of hepatitis seems to be directly related to the quantity and duration of alcohol abuse, with excessive intake defined as more than 80 grams of alcohol per day in men and 40 grams per day in women. Excessive alcohol use is also known to exacerbate complications of viral hepatitis, particularly hepatitis B and C.
    • Drug-induced hepatitis is that caused by any number of toxins or medications a person may be exposed to. It can include the excessive use of acetaminophen (Tylenol, paracetamol), as well as a number of herbal and dietary supplements available over the counter. Anti-tuberculosis drugs, anti-epileptics, HIV medications, statin drugs, oral contraceptives, and anabolic steroids are among the classes of drug for which liver injury can occur as a result of regular use.
    • Non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic syndrome, a cluster of medical conditions which include abdominal obesity, high blood pressure, and elevated lipid, glucose, and cholesterol levels. As NAFLD progresses, symptoms of chronic hepatitis may develop, presenting with increased rates of liver inflammation and fibrosis. NAFLD is today the third most common cause of liver disease in the U.S.

    Autoimmune Hepatitis

    Autoimmune hepatitis, a form of autoimmune disease, is a disorder in which the body’s own immune system acts against its liver cells. The condition is believed to be genetic in nature, with some individuals predisposed to liver inflammation with no infectious or metabolic causes. Autoimmune hepatitis is most frequently seen in women, generally between the ages of 15 and 40.

    Symptoms can range from mild to severe, with some individuals presenting with acute hepatitis (jaundice, upper right abdominal pain), while others exhibit chronic symptoms (such as fatigue, aches, abnormal liver function tests).

    A definitive diagnosis of autoimmune hepatitis requires a liver biopsy. Treatment options include the use of the corticosteroid drugs, prednisone or budesonide, both of which can achieve remission rates of between 60 and 80 percent.

    Sources:

    Basra G, Basra S, and Parudupi S. Signs and symptoms of acute alcoholic hepatitis.”World Journal of Hepatology. 2011; 35(5):118-120.

    Centers for Disease Control and Prevention (CDC). Viral Hepatitis. Atlanta, Georgia. 

    Kaplowitz N. Drug-Induced Liver InjuryClinical Infectious Diseases. 2004; 38(Suppl 2):S44-S48.

    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Autoimmune Hepatitis. Bethesda, Maryland. 

    Rinella M. Nonalcoholic fatty liver disease: a systematic review. Journal of the American Medical Association. 2015; 313(22): 2263-2273.

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