Hepatitis is inflammation of the liver tissue. Some people have no symptoms whereas others develop yellow discoloration of the skin and whites of the eyes, poor appetite, vomiting, tiredness, abdominal pain, or diarrhea. Hepatitis may be temporary (acute) or long term (chronic) depending on whether it lasts for less than or more than six months. Acute hepatitis can sometimes resolve on its own, progress to chronic hepatitis, or rarely result in acute liver failure. Over time the chronic form may progress to scarring of the liver, liver failure, or liver cancer.
The most common cause of hepatitis worldwide is viruses. Other causes include heavy alcohol use, certain medications, toxins, other infections, autoimmune diseases, and non-alcoholic steatohepatitis (NASH). There are five main types of viral hepatitis: type A, B, C, D, and E. Hepatitis A and E are mainly spread by contaminated food and water. Hepatitis B is mainly sexually transmitted, but may also be passed from mother to baby during pregnancy or childbirth. Both hepatitis B and C are commonly spread through infected blood such as may occur during needle sharing by intravenous drug users. Hepatitis D can only infect people already infected with hepatitis B.
Hepatitis A, B, and D are preventable with immunization. Medications may be used to treat chronic cases of viral hepatitis. There is no specific treatment for NASH; however, a healthy lifestyle, including physical activity, a healthy diet, and weight loss, is important. Autoimmune hepatitis may be treated with medications to suppress the immune system. A liver transplant may also be an option in certain cases.
Worldwide in 2015, hepatitis A occurred in about 114 million people, chronic hepatitis B affected about 343 million people and chronic hepatitis C about 142 million people. In the United States, NASH affects about 11 million people and alcoholic hepatitis affects about 5 million people. Hepatitis results in more than a million deaths a year, most of which occur indirectly from liver scarring or liver cancer. In the United States, hepatitis A is estimated to occur in about 2,500 people a year and results in about 75 deaths. The word is derived from the Greek hêpar (?pa?), meaning “liver”, and -itis (-?t??), meaning “inflammation”.
Signs and symptoms
Hepatitis has a broad spectrum of presentations that range from a complete lack of symptoms to severe liver failure. The acute form of hepatitis, generally caused by viral infection, is characterized by constitutional symptoms that are typically self-limiting. Chronic hepatitis presents similarly, but can manifest signs and symptoms specific to liver dysfunction with long-standing inflammation and damage to the organ.
Acute viral hepatitis follows three distinct phases:
The initial prodromal phase (preceding symptoms) involves non-specific and flu-like symptoms common to many acute viral infections. These include fatigue, nausea, vomiting, poor appetite, joint pain, and headaches. Fever, when present, is most common in cases of hepatitis A and E. Late in this phase, people can experience liver-specific symptoms, including choluria (dark urine) and clay-colored stools.
Yellowing of the skin and whites of the eyes follow the prodrome after about 1–2 weeks and can last for up to 4 weeks. The non-specific symptoms seen in the prodromal typically resolve by this time, but people will develop an enlarged liver and right upper abdominal pain or discomfort. 10–20% of people will also experience an enlarged spleen, while some people will also experience a mild unintentional weight loss.
The recovery phase is characterized by resolution of the clinical symptoms of hepatitis with persistent elevations in liver lab values and potentially a persistently enlarged liver. All cases of hepatitis A and E are expected to fully resolve after 1–2 months. Most hepatitis B cases are also self-limiting and will resolve in 3–4 months. Few cases of hepatitis C will resolve completely.
Both drug-induced hepatitis and autoimmune hepatitis can present very similarly to acute viral hepatitis, with slight variations in symptoms depending on the cause. Cases of drug-induced hepatitis can manifest with systemic signs of an allergic reaction including rash, fever, serositis (inflammation of membranes lining certain organs), elevated eosinophils (a type of white blood cell), and suppression of bone marrow activity.
Fulminant hepatitis, or massive hepatic cell death, is a rare and life-threatening complication of acute hepatitis that can occur in cases of hepatitis B, D, and E, in addition to drug-induced and autoimmune hepatitis. The complication more frequently occurs in instances of hepatitis B and D co-infection at a rate of 2–20% and in pregnant women with hepatitis E at rate of 15–20% of cases. In addition to the signs of acute hepatitis, people can also demonstrate signs of coagulopathy (abnormal coagulation studies with easy bruising and bleeding) and encephalopathy (confusion, disorientation, and sleepiness). Mortality due to fulminant hepatitis is typically the result of various complications including cerebral edema, gastrointestinal bleeding, sepsis, respiratory failure, or kidney failure.
Acute cases of hepatitis are seen to be resolved well within a six-month period. When hepatitis is continued for more than six months it is termed chronic hepatitis. Chronic hepatitis is often asymptomatic early in its course and is detected only by liver laboratory studies for screening purposes or to evaluate non-specific symptoms. As the inflammation progresses, patients can develop constitutional symptoms similar to acute hepatitis, including fatigue, nausea, vomiting, poor appetite, and joint pain. Jaundice can occur as well, but much later in the disease process and is typically a sign of advanced disease. Chronic hepatitis interferes with hormonal functions of the liver which can result in acne, hirsutism (abnormal hair growth), and amenorrhea (lack of menstrual period) in women. Extensive damage and scarring of the liver over time defines cirrhosis, a condition in which the liver’s ability to function is permanently impeded. This results in jaundice, weight loss, coagulopathy, ascites (abdominal fluid collection), and peripheral edema (leg swelling). Cirrhosis can lead to other life-threatening complications such as hepatic encephalopathy, esophageal varices, hepatorenal syndrome, and liver cancer.
Causes of hepatitis can be divided into the following major categories: infectious, metabolic, ischemic, autoimmune, genetic, and other. Infectious agents include viruses, bacteria, and parasites. Toxins, drugs, alcohol, and non-alcoholic fatty liver disease are metabolic causes of liver injury and inflammation. Autoimmune and genetic causes of hepatitis involve genetic predispositions and tend to affect characteristic populations.
Viral hepatitis is the most common type of hepatitis worldwide. Viral hepatitis is caused by five different viruses (hepatitis A, B, C, D, and E). Hepatitis A and hepatitis E behave similarly: they are both transmitted by the fecal–oral route, are more common in developing countries, and are self-limiting illnesses that do not lead to chronic hepatitis.
Hepatitis B, hepatitis C, and hepatitis D are transmitted when blood or mucous membranes are exposed to infected blood and body fluids, such as semen and vaginal secretions. Viral particles have also been found in saliva and breastmilk. However, kissing, sharing utensils, and breastfeeding do not lead to transmission unless these fluids are introduced into open sores or cuts.
Hepatitis B and C can present either acutely or chronically. Hepatitis D is a defective virus that requires hepatitis B to replicate and is only found with hepatitis B co-infection. In adults, hepatitis B infection is most commonly self-limiting, with less than 5% progressing to chronic state, and 20 to 30% of those chronically infected developing cirrhosis or liver cancer. However, infection in infants and children frequently leads to chronic infection.
Unlike hepatitis B, most cases of hepatitis C lead to chronic infection. Hepatitis C is the second most common cause of cirrhosis in the US (second to alcoholic hepatitis). In the 1970s and 1980s, blood transfusions were a major factor in spreading hepatitis C virus. Since widespread screening of blood products for hepatitis C began in 1992, the risk of acquiring hepatitis C from a blood transfusion has decreased from approximately 10% in the 1970s to 1 in 2 million currently.
The purpose of screening for viral hepatitis is to identify people infected with the disease as early as possible. This allows for early treatment, which can prevent disease progression, and decreases transmission to others.
Hepatitis A causes an acute illness that does not progress to chronic liver disease. Therefore, the role of screening is to assess immune status in people who are at high risk of contracting the virus, as well as in people with known liver disease for whom hepatitis A infection could lead to liver failure. People in these groups who are not already immune can receive the hepatitis A vaccine.
Those at high risk and in need of screening include:
People with poor sanitary habits such as not washing hands after using the restroom or changing diapers
People who do not have access to clean water
People in close contact (either living with or having sexual contact) with someone who has hepatitis A
Illicit drug users
People with liver disease
People traveling to an area with endemic hepatitis A
The presence of anti-hepatitis A IgG in the blood indicates past infection with the virus or prior vaccination.
The CDC, WHO, USPSTF, and ACOG recommend routine hepatitis B screening for certain high-risk populations. Specifically, these populations include people who are:
Born in countries where the prevalence of hepatitis B is high (defined as =2% of the population), whether or not they have been vaccinated
Born in the United States whose parents are from countries where the prevalence of hepatitis B is very high (defined as =8% of the population), and who were not vaccinated
Intravenous drug users
Men who have sex with men
In close contact with (i.e. live or have sex with) people known to have hepatitis B
Beginning immunosuppressive or cytotoxic therapy
Found to have elevated liver enzymes without a known cause
Blood, organ, or tissue donors
Screening consists of a blood test that detects hepatitis B surface antigen (HBsAg). If HBsAg is present, a second test – usually done on the same blood sample – that detects the antibody for the hepatitis B core antigen (anti-HBcAg) can differentiate between acute and chronic infection. People who are high-risk whose blood tests negative for HBsAg can receive the hepatitis B vaccine to prevent future infection.
The CDC, WHO, USPSTF, AASLD, and ACOG recommend screening people at high risk for hepatitis C infection. These populations include people who are:
Intravenous drug users (past or current)
Intranasal illicit drug users
Men who have sex with men
Incarcerated, or who have been in the past
On long-term hemodialysis, or who have been in the past
Recipients of tattoos in an “unregulated setting”
Recipients of blood products or organs prior to 1992 in the United States
Adults in the United States born between 1945-1965
Born to HCV-positive mothers
Pregnant, and engaging in high-risk behaviors.
Workers in a healthcare setting who have had a needlestick injury
Blood or organ donors.
For people in the groups above whose exposure is ongoing, screening should be “periodic,” though according to the USPSTF, research has not defined the optimal screening interval. The AASLD recommends screening men who have sex with men who are HIV-positive annually. People born in the US between 1945-1965 should be screened once (unless they have other exposure risks).
Screening consists of a blood test that detects anti-hepatitis C virus antibody. If anti-hepatitis C virus antibody is present, a confirmatory test to detect HCV RNA indicates chronic disease.
Recommended immunization schedules in the United States for ages 0 through 18 years as of 2016
The CDC recommends the hepatitis A vaccine for all children beginning at age one, as well as for those who have not been previously immunized and are at high risk for contracting the disease.
For children 12 months of age or older, the vaccination is given as a shot into the muscle in two doses 6–18 months apart and should be started before the age 24 months. The dosing is slightly different for adults depending on the type of the vaccine. If the vaccine is for hepatitis A only, two doses are given 6–18 months apart depending on the manufacturer. If the vaccine is combined hepatitis A and hepatitis B, up to 4 doses may be required.
The CDC recommends the routine vaccination of all children under the age of 19 with the hepatitis B vaccine. They also recommend it for those who desire it or are at high risk.
Routine vaccination for hepatitis B starts with the first dose administered as a shot into the muscle before the newborn is discharged from the hospital. An additional two doses should be administered before the child is 18 months.
For babies born to a mother with hepatitis B surface antigen positivity, the first dose is unique – in addition to the vaccine, the hepatitis immune globulin should also be administered, both within 12 hours of birth. These newborns should also be regularly tested for infection for at least the first year of life.
There is also a combination formulation that includes both hepatitis A and B vaccines.
There are currently no vaccines available in the United States for hepatitis C or E.
Because hepatitis A is transmitted primarily through the oral-fecal route, the mainstay of prevention aside from vaccination is good hygiene, access to clean water and proper handling of sewage.
Hepatitis B and C
As hepatitis B and C are transmitted through blood and multiple bodily fluids, prevention is aimed at screening blood prior to transfusion, abstaining from the use of injection drugs, safe needle and sharps practices in healthcare settings, and safe sex practices.
The hepatitis D virus requires that a person first be infected with hepatitis B virus, so prevention efforts should focus on limiting the spread of hepatitis B. In people who have chronic hepatitis B infection and are at risk for superinfection with the hepatitis D virus, the preventive strategies are the same as for hepatitis B.
Hepatitis E is spread primarily through the oral-fecal route but may also be spread by blood and from mother to fetus. The mainstay of hepatitis E prevention is similar to that for hepatitis A (namely, good hygiene and clean water practices).
As excessive alcohol consumption can lead to hepatitis and cirrhosis, the following are maximal recommendations for alcohol consumption:
Women – = 3 drinks on any given day and = 7 drinks per week
Men – = 4 drinks on any given day and = 14 drinks per week
In the United States, universal immunization has led to a two-thirds decrease in hospital admissions and medical expenses due to hepatitis A.
In the United States new cases of hepatitis B decreased 75% from 1990–2004. The group that saw the greatest decrease was children and adolescents, likely reflecting the implementation of the 1999 guidelines.
Hepatitis C infections each year had been declining since the 1980s, but began to increase again in 2006. The data are unclear as to whether the decline can be attributed to needle exchange programmes.
Because people with alcoholic hepatitis may have no symptoms, it can be difficult to diagnose and the number of people with the disease is probably higher than many estimates. Programs such as Alcoholics Anonymous have been successful in decreasing death due to cirrhosis, but it is difficult to evaluate their success in decreasing the incidence of alcoholic hepatitis.
Nearly all patients with hepatitis A infections recover completely without complications if they were healthy prior to the infection. Similarly, acute hepatitis B infections have a favorable course towards complete recovery in 95–99% of patients. However, certain factors may portend a poorer outcome, such as co-morbid medical conditions or initial presenting symptoms of ascites, edema, or encephalopathy. Overall, the mortality rate for acute hepatitis is low: ~0.1% in total for cases of hepatitis A and B, but rates can be higher in certain populations (super infection with both hepatitis B and D, pregnant women, etc.).
In contrast to hepatitis A & B, hepatitis C carries a much higher risk of progressing to chronic hepatitis, approaching 85–90%. Cirrhosis has been reported to develop in 20–50% of patients with chronic hepatitis C.
Other rare complications of acute hepatitis include pancreatitis, aplastic anemia, peripheral neuropathy, and myocarditis.
Despite the relatively benign course of most viral cases of hepatitis, fulminant hepatitis represents a rare but feared complication. Fulminant hepatitis most commonly occurs in hepatitis B, D, and E. About 1–2% of cases of hepatitis E can lead to fulminant hepatitis, but pregnant women are particularly susceptible, occurring in up to 20% of cases. Mortality rates in cases of fulminant hepatitis rise over 80%, but those patients that do survive often make a complete recovery. Liver transplantation can be life-saving in patients with fulminant liver failure.
Hepatitis D infections can transform benign cases of hepatitis B into severe, progressive hepatitis, a phenomenon known as superinfection.
Acute hepatitis B infections become less likely to progress to chronic forms as the age of the patient increases, with rates of progression approaching 90% in vertically transmitted cases of infants compared to 1% risk in young adults. Overall, the 5-year survival rate for chronic hepatitis B ranges from 97% in mild cases to 55% in severe cases with cirrhosis.
Most patients who acquire hepatitis D at the same time as hepatitis B (co-infection) recover without developing a chronic infection; however, in people with hepatitis B who later acquire hepatitis D (superinfection), chronic infection is much more common at 80-90%, and liver disease progression is accelerated.
Chronic hepatitis C progresses towards cirrhosis, with estimates of cirrhosis prevalence of 16% at 20 years after infection. While the major causes of mortality in hepatitis C is end stage liver disease, hepatocellular carcinoma is an important additional long term complication and cause of death in chronic hepatitis.
Rates of mortality increase with progression of the underlying liver disease. Series of patients with compensated cirrhosis due to HCV have shown 3,5, and 10-year survival rates of 96, 91, and 79% respectively. The 5-year survival rate drops to 50% upon if the cirrhosis becomes decompensated.
Hepatitis A is found throughout the world and manifests as large outbreaks and epidemics associated with fecal contamination of water and food sources. Hepatitis A viral infection is predominant in children ages 5–14 with rare infection of infants. Infected children have little to no apparent clinical illness, in contrast to adults in whom greater than 80% are symptomatic if infected. Infection rates are highest in low resource countries with inadequate public sanitation and large concentrated populations. In such regions, as much as 90% of children younger than 10 years old have been infected and are immune, corresponding both to lower rates of clinically symptomatic disease and outbreaks. The availability of a childhood vaccine has significantly reduced infections in the United States, with incidence declining by more than 95% as of 2013. Paradoxically, the highest rates of new infection now occur in young adults and adults who present with worse clinical illness. Specific populations at greatest risk include: travelers to endemic regions, men who have sex with men, those with occupational exposure to non-human primates, individuals with clotting disorders who have received clotting factors, individuals with a history of chronic liver disease where co-infection with hepatitis A can lead to fulminant hepatitis, and intravenous drug users (rare).
Hepatitis B is the most common cause of viral hepatitis in the world with more than 240 million chronic carriers of the virus, 1 million of whom are in the United States. In approximately two-thirds of patients who develop acute hepatitis B infection, no identifiable exposure is evident. Of those acutely infected, 25% become lifetime carriers of the virus. Risk of infection is highest among intravenous drug users, individuals with high-risk sexual behaviors, healthcare workers, individuals with a history of multiple transfusions, organ transplant patients, dialysis patients and newborns infected during the birthing process. Close to 780,000 deaths in the world are attributed to hepatitis B. The most endemic regions are in sub-Saharan Africa and East Asia, where as many as 10% of adults are chronic carriers. Carrier rates in developed nations are significantly lower, encompassing less than 1% of the population. In endemic regions, transmission is thought to be associated with exposure during birth and close contact between young infants.
Chronic hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma. It is a common medical reason for liver transplantation due to its severe complications. It is estimated that 130–180 million people in the world are affected by this disease representing a little more than 3% of the world population. In the developing regions of Africa, Asia and South America, prevalence can be as high as 10% of the population. In Egypt, rates of hepatitis C infection as high as 20% have been documented and are associated with iatrogenic contamination related to schistosomiasis treatment in the 1950s–1980s. Currently in the United States, approximately 3.5 million adults are estimated to be infected. Hepatitis C is particularly prevalent among people born between 1945–1965, a group of about 800,000 people, with prevalence as high as 3.2% versus 1.6% in the general U.S. population. Most chronic carriers of hepatitis C are unaware of their infection status. The most common mode of transmission of hepatitis C virus is exposure to blood products via blood transfusions (prior to 1992) and intravenous drug injection. A history of intravenous drug injection is the most important risk factor for chronic hepatitis C. Other susceptible populations include individuals with high-risk sexual behavior, infants of infected mothers, and healthcare workers.
The hepatitis D virus causes chronic and fulminant hepatitis in the context of co-infection with the hepatitis B virus. It is primarily transmitted via non-sexual contact and via needles. Susceptibility to hepatitis D differs by geographic region. In the United States and Northern Europe, populations at risk are intravenous drug users and individuals who receive multiple transfusions. In the Mediterranean, hepatitis D is predominant among hepatitis B virus co-infected individuals.
Similar to Hepatitis A, hepatitis E manifests as large outbreaks and epidemics associated with fecal contamination of water sources. It accounts for more than 55,000 deaths annually with approximately 20 million people worldwide thought to be infected with the virus. It affects predominantly young adults, causing acute hepatitis. In infected pregnant women, Hepatitis E infection can lead to fulminant hepatitis with third trimester mortality rates as high as 30%. Individuals with weakened immune systems, such as organ transplant recipients, are also susceptible. Infection is rare in the United States but rates are high in the developing world (Africa, Asia, Central America, Middle East). Many genotypes exist and are differentially distributed around the world. There is some evidence of hepatitis E infection of animals, serving as a reservoir for human infection.
Alcoholic hepatitis (AH) in its severe form has a one-month mortality as high as 50%. Most people who develop AH are men but women are at higher risk of developing AH and its complications likely secondary to high body fat and differences in alcohol metabolism. Other contributing factors include younger age <60, binge pattern drinking, poor nutritional status, obesity and hepatitis C co-infection. It is estimated that as much as 20% of people with AH are also infected with hepatitis C. In this population, the presence of hepatitis C virus leads to more severe disease with faster progression to cirrhosis, hepatocellular carcinoma and increased mortality. Obesity increases the likelihood of progression to cirrhosis in individuals with alcoholic hepatitis. It is estimated that a high proportion of individuals (70%) who have AH will progress to cirrhosis.
Non-alcoholic steatohepatitis (NASH) is projected to become the top reason for liver transplantation in the United States by the year 2020, supplanting chronic liver disease due to hepatitis C. About 20–45% of the U.S. population have NAFLD and 6% have NASH. The estimated prevalence of NASH in the world is 3–5%. Of NASH patients who develop cirrhosis, about 2% per year will likely progress to hepatocellular carcinoma. Worldwide, the estimated prevalence of hepatocellular carcinoma related to NAFLD is 15–30%. NASH is thought to be the primary cause of cirrhosis in approximately 25% of patients in the United States, representing 1–2% of the general population.