Pathologist’s Corner – Dr. Simpal Gill on Hepatitis ABCs

Published: June 8, 2015 – Simpal Gill MD FCAP


What is “Hepatitis”?

Hepatitis is derived from the Greek hêpar, meaning “liver”, and the suffix -itis, meaning “inflammation”. Liver performs important functions such as processing nutrients, clearing the blood of harmful substances and resisting infections by producing immune factors and removing bacteria from the bloodstream.

When the liver is inflamed or damaged, its function can be affected. The inflammation can be self-limiting or progress to cirrhosis or liver cancer. Heavy alcohol intake, toxins, certain medications, and some medical conditions can cause hepatitis.  Viral hepatitis is the most common cause of hepatitis in the world. In the United States, the most common types of virus-induced hepatitis include Hepatitis A, Hepatitis B, and Hepatitis C.

Three different types of viruses cause Hepatitis A, Hepatitis B, and Hepatitis C. Although the symptoms are similar, they vary in their mode of transmission and affect the liver differently. Vaccines are available to prevent Hepatitis A and B but not for Hepatitis C. If infected with one type of viral hepatitis in the past, it is still possible to get the other types.

Hepatitis A

Hepatitis A infection is caused by Hepatitis A virus (HAV) and is highly contagious. The virus is present in the feces of infected individuals and commonly acquired by consumption of contaminated water or food. Certain sex practices can also spread HAV.

Symptoms may appear anytime 2-7 weeks after exposure and include jaundice, fatigue, abdominal pain, nausea and diarrhea. Infected people are most at risk to spread the virus in the 2 weeks before onset of symptoms and the week after.

Symptoms may appear anytime 2-7 weeks after exposure and include jaundice, fatigue, abdominal pain, nausea and diarrhea. Infected people are most at risk to spread the virus in the 2 weeks before onset of symptoms and the week after.

Majority of adults (more than 80%) with Hepatitis A are symptomatic unlike children who do not have symptoms or have unrecognized infection. Antibodies produced in response to Hepatitis A are life long and protect against re-infection. Hepatitis A is a self-limited disease that does not result in chronic infection. Safe and effective vaccines are available to prevent HAV. Hepatitis A is rarely fatal (less than 1% of cases). Treatment is supportive with rest and avoiding alcohol.

Hepatitis B

Hepatitis B caused by the hepatitis B virus (HBV) is a contagious liver disease that varies in severity from a mild illness that lasts a few weeks to a lifelong disease. Hepatitis B infection can be acute or chronic. Acute infection occurs within the first 6 months of exposure to the virus. Acute infection can but does not always lead to chronic infection. Chronic hepatitis B virus infection is a persistent illness that occurs when the virus remains in a person’s body.

Hepatitis B virus (HBV) is transmitted through exposure to contaminated blood, semen, and other body fluids, from infected mothers to infants at the time of birth. Transmission can also occur through transfusions of HBV-contaminated blood, blood products and organ transplants, contaminated injections during medical procedures, and intravenous drug use (sharing needles). Health care workers are at risk through accidental needle stick injuries while caring for infected patients. The virus can survive for a long time outside the body (sharing toys, toothbrush etc).

Symptoms of hepatitis B vary from flu like illness (fever, abdominal pain, fatigue, poor appetite, nausea and sometimes jaundice) early in the disease to liver failure in severe cases. Many patients are asymptomatic especially children, most of which are diagnosed when their liver disease is late stage. Those with chronic infection are at increased risk for cirrhosis and liver cancer.

There are a number of tests that are used to diagnose or monitor hepatitis B infection:

–  Hepatitis B surface antigen (HBsAg) shows up in the blood 1-10 weeks after exposure. It disappears after 4-6 months if the patient recovers or persists if chronic infection has developed.

–  Hepatitis B surface antibody (anti-HBs) is present in recovered patients or those vaccinated. People with this protein are usually immune.

–  Hepatitis B core antibody (anti-HBc) is present throughout infection and persists after recovery. It is absent in those vaccinated against hepatitis B.

–  Hepatitis B e antigen (HBeAg) indicates that the virus is making copies of itself. It is a sign of a high level of viral load and a high risk of transmission of infection.

–  Hepatitis B e antibody (anti-HBe) is present if virus replication has slowed down.

–  Hepatitis B DNA (HBV DNA) is genetic material found in the virus that usually disappears from the blood after recovery. HBV DNA (viral load) is a measure of the concentration of virus in the circulating blood. Doctors use the levels of HBV DNA to decide who is a candidate for treatment with antiviral medicines and track progress.

–  Other tests monitor the liver status and include liver enzyme tests, bilirubin level, alkaline phosphatase, albumin, prothrombin time, and platelet count.

Specific treatment for acute hepatitis B is usually not needed. Several antiviral drugs are available. Liver transplantation may be the only option for people who develop advanced cirrhosis. In people who develop chronic hepatitis, antiviral drugs can reduce or reverse liver damage and prevent long-term complications of hepatitis B. Safe and effective vaccines are available to prevent HBV.

Hepatitis C

The Hepatitis C virus (HCV) causes hepatitis C infection. Many people with hepatitis C infection do now know how they were infected. The hepatitis virus is spread through injection drug use (needle sharing), blood transfusion before 1990, having sex with an infected person, improperly sanitized equipment for body piercings or tattoos done, sharing toothbrushes, razors, or other objects with blood on them, needle stick injuries and rarely pregnant women can spread the virus to their fetus.

Persons with recently acquired HCV infection are usually asymptomatic or have mild symptoms (20-30%) such as fever, dark urine, clay-colored stool, abdominal pain, loss of appetite, nausea, vomiting, joint pain and jaundice. In those who develop symptoms, the average time period from exposure to onset of symptoms is 4–12 weeks.

Acute Hepatitis C infection occurs in the first several months after someone is infected and can range in severity from a mild illness with few or no symptoms to a serious condition requiring hospitalization. Approximately 15%–25% of persons clear the virus from their bodies in the first 6 months without treatment and do not develop chronic infection; the reasons for this are not well known. Unfortunately, most people who get infected are not able to clear the Hepatitis C virus and develop a chronic infection.

HCV-positive persons should be evaluated for presence of chronic liver disease, including assessment of liver function tests, evaluation for severity of liver disease and possible treatment, and determination of the need for Hepatitis A and Hepatitis B vaccination. Several effective medications are available for the treatment for chronic hepatitis C infection.

Of every 100 persons infected with HCV, approximately 75–85% will go on to develop chronic infection, 60–70% develop chronic liver disease, 5–20% develop cirrhosis over a period of 20–30 years and 1–5% will die from the consequences of chronic infection (liver disease, liver failure, cirrhosis, and liver cancer).

Prior infection with HCV does not protect against later infection with the same or different genotypes of the virus. For the same reason, no effective pre- or post exposure vaccines are available.

Role of liver biopsy in viral hepatitis

Histopathologic evaluation of liver tissue by needle biopsy is an integral part of the management of liver diseases despite development in diagnosis and management.

Proper interpretation of liver biopsy requires adequate clinical information, clinical signs and symptoms, medications used and serologic test results. Acute hepatitis is not an indication for liver biopsy, unless there is doubt of the clinical diagnosis. Biopsy is utilized to monitor liver damage in people with known chronic hepatitis, help decide if treatment is needed, and find signs of cirrhosis or liver cancer.

Assessment of the liver architecture is the first step in the assessment of a liver biopsy specimen.  Normal liver is composed of sheets of liver cells (hepatocytes) interrupted at discrete intervals by portal tracts and central veins. Fibrous tissue is scant in normal liver.

Histologic examination should include all tissue fragments and structures.  Viral hepatitis is defined by the death of hepatocytes and increased white blood cells infiltration, which leads to a constellation of clinical and morphological findings.

In acute hepatitis, the liver cells are destroyed by white blood cells, are lost and regenerated during the acute phase, a pattern referred to as lobular disarray.

Chronic hepatitis on biopsy is a combination of inflammation in the portal tracts, in periportal areas, damage of liver cells, and in many cases, fibrosis.  Several classification systems for scoring liver damage by inflammation and scarring have been developed, including Ishak Modified hepatitis Activity score (HAI) and Batts-Ludwig grading and staging of chronic hepatitis.  The latter system uses five categories (0 through 4) for grade (inflammation) and stage (scarring).

Evaluation of liver biopsy remains the gold standard for determination of the degree of fibrosis, despite limitations such as inadequate sampling and observer variability.


  6. Odze and Goldblum, Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas, 3rd Edition

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