Hepatitis is an inflammation of the liver. The word comes from a combination of two Greek words: "Hepatos-" ("liver"), and "-itis" ("inflammation"). The inflammation of the liver (hepatitis) can be caused by several factors:
- viruses - viral hepatitis is caused by several viruses that attack mainly the liver. The viruses identified until now have been named as A, B, C, D, E, and G, from which A and E are contagious.
- toxic agents - alcohol, drugs or other chemicals.
- auto-immune disorders.
If inflammation and necrosis of hepatocytes persist for more than 6 months we are dealing with chronic hepatitis.
Based on histological criteria, chronic hepatitis classification is as follows:
chronic persistent;
chronic lobular and
chronic active hepatitis.
A)
Chronic Persistent Hepatitis and
Chronic Lobular Hepatitis
They usually follow acute hepatitis B or C. These disorders may persist for years, but are mild and rarely progress to chronic active hepatitis or cirrhosis. Clinical features for both are :
Liver biopsy shows:
Treatment is not necessary and natural recovery is usual. However, periodic controls are recommended. |
B) Chronic Active Hepatitis
It's a serious disorder that has a general tendency to progress to hepatic cirrhosis and possibly even primary liver cancer. Histologically it's characterized by: a) Inflammation - Initially a lymphocytic portal reaction is present and lymphocytes infiltrate progressively the acini, causing considerable necrosis of hepatocytes (spotty and confluent necrosis). b) Fibrosis - Necrosis of hepatocytes causes collapse of the reticular strome that supports liver cells. Then an irreversible deposition of collagen (fibrosis) occurs. Zones of collapse, fibrosis and abnormal hepatocellular regeneration (nodular regeneration) lead to distortion of the acinar architecture, which is characteristic for liver cirrhosis. The histological activity of Chronic Active Hepatitis is a concept that takes into account both inflammatory infiltration and hepatocellular damage that lead to fibrosis. Inflammatory activity defines grade (mild, moderate or severe) of Chronic Active Hepatitis, and therefore its prognosis (probability of evolution into cirrhosis), and is to a great extent reversible with therapy. The degrees of fibrosis express the stage reached by Chronic Active Hepatitis into its evolution to cirrhosis. It is irreversible, but therapy, reducing inflammation, can lessen or stop its progression. Patients are usually asymptomatic for a long time. Signs and symptoms often occur when an advanced histological disease is present. Sometimes symptoms are vague and may be mistaken for other disease or simply consequences of aging. The main symptoms are:
Clinical signs are:
In about 20% of cases other organs are affected:
and sometimes:
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Hepatitis B Virus (HBV) infection becomes chronic in about 10% of cases. In the natural evolution of chronic hepatitis B can be distinguished three phases:
Immune Tolerance
Immune Clearance
Non Replicative Infection
1) Phase of Immune
Tolerance - Is characterized by a high level of viral replication (HBV DNA is
present in high concentration, HBeAg and HBsAg are positive), but low liver histological
injury (serum transaminases are near normal). It's asymptomatic.
This phase is more evident in infant acquired chronic hepatitis B. Evolution into phase of
immune clearance occurs when tolerance to HBV breaks down (usually between the ages of
15-35 years). In adult acquired chronic hepatitis B this phase evolves rapidly into phase
of immune clearance.
2) Phase of Immune
Clearance - Is characterized by low levels of viral replication, but increasing
liver injury (serum transaminases are elevated) that can lead to liver cirrhosis (active
liver cirrhosis), and is symptomatic.
Blood tests show: increased transaminases values (usually), low levels of HBV DNA
and HBeAg positive.
Liver biopsy shows: chronic hepatitis of varying activity (HAI Score), often with
lobular inflammation.
3) Phase of Non
Replicative Infection - Is characterized by cessation of viral replication.
Inflammation and necrosis decrease and cirrhosis, if present, becomes inactive (there is
no further evolution). HBV DNA (viral genome) is integrated into the host hepatocytes'
genome (there is increased risk of developing primary liver cancer) and produces HBsAg
(patient is HBsAg positive). Often a brief episode of significant elevation of
transaminases values precedes this phase.
Blood tests show : HBV DNA, DNA polymerase and HBeAg negative (HBeAb is positive); HBsAg
is positive.
Transition from replicative to non replicative infection may be rapid (less injury, low probability of developing cirrhosis), or prolonged and marked by recurrent exacerbations. Those exacerbation occur because of :
HBV reactivation (spontaneous or after treatment)
super infection with HDV (most commonly it can become chronic and prognosis of patient worsen)
mutant HBV variant
Hepatitis C is a form of hepatitis caused by an RNA (Ribo Nucleic Acid) virus, and accounts for most of the hepatitis cases previously referred to as non-A, non-B hepatitis. The Hepatitis C Virus (HCV) was first identified in 1988 and a hepatitis C antibody test (anti-HCV) to identify individuals exposed to HCV became commercially available in 1990. In 1995 the hepatitis C virus was seen for the first time by using an electron microscope.
The hepatitis C virus has a high mutation rate. These ongoing changes in the virus make it difficult for the body's own immune system to fight it off, as by the time the immune system figures out the virus, it has changed to look different. For the same reason it is very difficult to develop a vaccine.
Hepatitis C is considered a bloodborn disease, and it is thought that many people with hepatitis C contracted it either through a blood transfusion or by receiving blood products (gammaglobulin, plasma, etc.) that were contaminated with hepatitis C, or by sharing needles with intravenous drug users that were infected with hepatitis C. Prior to 1990 blood could not be screened for HCV due to the absence of a reliable test, and therefore people who received blood products before that year are considered as having been at risk. Thanks to HCV testing after 1990 the risk of acquiring hepatitis C from blood transfusion has been reduced to well under 1%.
There are cases of hepatitis C with no evidence of blood to blood exposure (receiving blood transfusions or products, needle sticks or needle sharing), where it is unknown how these individuals became infected.
Chronic Hepatitis C
Hepatitis C Virus (HCV) infection becomes chronic in about 50-80% of cases, therefore HCV is known to cause the most cases of Chronic Active Hepatitis.
Chronic hepatitis C behaves differently from hepatitis B. The disease is generally milder and most people are asymptomatic or have vague (mild asthenia) or no symptoms. Nevertheless, 10-15 years (and even more) from the infection, the complications of cirrhosis appear in about 20-30% of patients, sometimes unexpectedly. The percentage of patients who develop cirrhosis is much greater than in chronic hepatitis B, while primary liver cancer appears to be much less common.
About 80% of patients have abnormal aminotrasferase values. A characteristic feature of chronic hepatitis C is the fluctuation in aminotrasferase values seen in approximately 50% of cases. Fluctuations seem to represent effects of mutations in the virus or episodic immune reactions. Transaminase values don't correlate well with histological features of disease.
About 20% of patients with positive diagnostic tests for HCV (anti-HCV positive) have persistently normal liver enzymes. Some of them progress to more advanced disease, in others infection appears to remain quiescent.
HCV has the property to involve bile duct epithelial cells, causing a significant cholestatic component (stoppage or obstacle of the flow of bile), with abnormalities of serum Alkaline Phosphatase and Gamma Glutamyl Transferase (GGT) levels. However, pure cholestasis has not been described.
Clinical consequences of Chronic Active Hepatitis
Chronic liver injury caused by Chronic Active Hepatitis can lead to cirrhosis and hepatocellular carcinoma.
1) Cirrhosis
About 20% of patients with chronic hepatitis C and 25% of those with chronic hepatitis B progress to cirrhosis after 15-20 years from onset of the infection. Rapid progress to cirrhosis (evolution within 5-10 years from infection) is associated to:
The scar tissue that forms in cirrhosis replaces the normal liver cells, making the flow of blood through the liver increasingly difficult. The loss of normal liver tissue slows the processing of nutrients, hormones, drugs, and toxins by the liver, as well as the production of proteins and other substances made by the liver. |
2) Hepatocellular carcinoma (HCC)
Liver cirrhosis is associated with development of HCC and therefore it can be considered a pre-cancerous lesion. Approximately 5% of chronic HBV and 10% of chronic HCV carriers develop HCC (about 50% of patients with cirrhosis). HCC can also be found in patients with chronic hepatitis but without cirrhosis. This situation is more frequent in patients with chronic hepatitis B (HBV becomes integrated into hepatocytes' genome) than in chronic hepatitis C. |
Chronic hepatitis is frequently asymptomatic, therefore it is often discovered casually, during routine blood tests. The first element of suspicion is the elevation of transaminase levels, sign of liver injury. Positivity for HBsAg and/or anti-HCV confirms the suspicion. Chronic hepatitis can be distinguished from an acute form because it persists and gives no sign of recovery (blood tests are persistently abnormal). In chronic hepatitis B antibody of IgM class against antigen c (HBcAb IgM) are negative (it's positive only in acute infection).
Positivity for anti-HCV does not necessary mean presence of chronic hepatitis C, because this antibody persists for some months after recovery from an acute form. Diagnosis of chronic hepatitis C can be posed only after the detection of HCV in patient's blood with PCR, which can detect minute amounts of viral genome (RNA).
If chronic hepatitis is present a liver biopsy should be performed to assess the degree of liver inflammation and extent of fibrosis (hepatitis staging and grading). In fact, if cirrhosis is present, treatment requires caution and, in some cases, cannot be applied.