2. Objectives:
• To Describe the etiology, epidemiology, pathophysiology of hepatitis.
• To Summarize sign and symptoms of hepatitis.
• To Outline prognosis, treatment and vaccines of hepatitis.
3. Introduction:
Hepatitis is an inflammation and swelling of the liver that is caused by a variety of infectious viruses and
noninfectious agent leading to range of health problems, some of which can be fatal. Some hepatitis factors
might include chemical toxins, poisons, drugs, and alcohol. There are different types of hepatitis, depending
on their modes of transmission, severity of illness, geographical distribution and prevention methods. These
types are classified as: A, B, C, D and E. Some types of hepatitis are preventable through vaccination.
Alcoholic hepatitis is caused by heavy alcohol use. Autoimmune hepatitis is a chronic type in which your
body's immune system attacks your liver [1]
. The cause is not known, but genetics and your environment
may play a role. Hepatitis can be further classified into acute and chronic based on the duration of the
inflammation/insult to the liver. If inflammation of the liver lasts for less than 6 months, then it is termed
as acute hepatitis and if it lasts longer than 6 months it is termed as chronic hepatitis. Acute hepatitis is
usually self-resolving but can cause fulminant liver failure depending on the etiology. In contrast, chronic
hepatitis can cause liver damage that includes liver fibrosis, cirrhosis, hepatocellular carcinoma, and
features of portal hypertension leading to significant morbidity and mortality [2,3]
. In particular , types B
and C lead to chronic disease in hundreds of millions of people and together are the most common cause
of liver cirrhosis, liver cancer and viral hepatitis-related deaths [4].
4. Etiology:
Viral hepatitis
Viral hepatitis results from infection with viruses A, B, C, D, and E. Hepatitis A is a picornavirus most
commonly transmitted through the oral-fecal route via exposure to contaminated food with greater viral load
shedding occurring during the end of the incubation period. According to the World Health Organization
(WHO),
infection rates in developed countries are low. However, high-risk groups include injection-drug users, men
who have sex with men, people traveling to endemic areas, and isolated communities[4]
. Hepatitis B on the
other hand is
[5]
.
a
member
of
the hepadnavirus
family
Unlike
type
A
the
virus
particle
(virion)
consists
of
an
outer lipid envelope and an icosahedral nucleocapsid core composed of core protein. Hepatitis B virus is
known to have eight genotype variants of no practical use to determine severity. Hepatitis B virus can be
detected in serum, semen, vaginal mucus, saliva, and tears even at a lower level but not found in the stool,
urine, or sweat. The virus can be transmitted parenterally and to less extent sexually. Intravenous drug
users, healthcare workers with exposure to infected body fluids, patients who require frequent and multiple
blood transfusions, prisoners, partners of hepatitis B virus carriers, and persons born in endemic areas are
all at high risk for hepatitis B virus infection. The virus can be transmitted perinatal also, and it occurs in
infants of HBeAg positive women where the infants would have a 70% to 90% chance of infection and may
end up having cirrhosis[5]
. The hepatitis C virus (HCV) is a small, enveloped, single-stranded, positive-sense
RNA virus [6]
. It is a member of the genus Hepacivirus in the family Flaviviridae. There are seven major
genotypes of HCV. Transmission Percutaneous contact with contaminated blood is responsible for most
infections [7]
.
5. Autoimmune Hepatitis
The exact etiology of autoimmune hepatitis is unknown. Various factors like drugs, environmental agents, or viral
infection with hepatitis C viruses or Epstein-Barr virus may trigger an autoimmune response. Drugs like nitrofurantoin,
minocycline, adalimumab, infliximab, or methyldopa can trigger autoimmune hepatitis [9]
.
Alcoholic Hepatitis
The exact mechanism of how alcoholic hepatitis is not well defined; many factors play a role that includes genetic
factors, metabolism of ethanol and its metabolite acetaldehyde causing damage to hepatocyte cell membranes [10]
.
Epidemiology:
Viral Hepatitis
Viral Hepatitis is considered a major public health issue. starting with type A virus affects 90% of children in high
endemic regions[11]
. and are commonly associated with poor sanitary conditions like water contamination and inadequate
sewage disposal in both developing and developed countries [12]
. Children who get infected at an early age with
asymptomatic exposure end up acquiring lifelong immunity in highly endemic countries [13]
. In the US, approximately
24,900 new infections are diagnosed each year. Chronic Hepatitis B and C infection can cause liver damage that includes
liver fibrosis, cirrhosis, hepatocellular carcinoma, and features of portal hypertension. The World Health Organization
(WHO) estimated that 1.3 million people have died due to hepatitis in 2015, and 1 in 3
6. people in the world have had infections with either hepatitis B or hepatitis C virus. Reportedly, infection
rates show that 2 billion people infected with the hepatitis B virus, 185 million with the hepatitis C virus
(most commonly being affected are IV drug users and hemophiliacs), and 20 million with the hepatitis E
virus [11,12,13]
. Viral hepatitis ends up causing 1.4 million deaths annually, and hepatitis B and C viruses are
responsible for about 90% of those deaths. Despite high rates of HBV infection, there are very low rates of
HDV co-infection in other Asian countries, including China [13]
. Regardless of geography, the populations at
highest risk for HDV include people who inject drugs and those with human immunodeficiency virus (HIV)
or HCV [14]
. HDV is even more prevalent in patients with HBV associated cirrhosis and HCV. according to
type E it occur for the same cause as type A but unlike type A hepatitis E virus genotypes 1 and 2 are only
known to infect humans and are highly endemic in developing countries throughout the world[15]
.
Autoimmune Hepatitis
The prevalence of autoimmune hepatitis is estimated to be 0.1 to 1.2 cases per 100000 people in Western
Europe. Autoimmune hepatitis accounts for about 6% of liver transplantation in the United States, while it
accounts for about 3% in Europe. Prevalence in Japan is estimated to be 0.08 to 0.015 cases per 100000
persons and causes 1.9% of cases of liver cirrhosis [16]
.
7. Alcoholic Hepatitis
The precise prevalence of alcoholic hepatitis is unknown, but it is known to be high, with a rising rate of mortality.
It is difficult to assess the correct prevalence as alcoholic hepatitis may remain undiagnosed and completely
asymptomatic [17]
. The prevalence of alcohol use disorder is about 8% of the population of the United States or 16
million people. However, approximately 35% of those with the diagnosis have changes consistent with alcoholic
hepatitis, which means that around 5 million patients may have alcoholic hepatitis[18].
Pathophysiology:
Viral Hepatitis
The incubation period differs according to hepatitis type ranging from 2-6 weeks for type A to 12 weeks for type
B and D while it takes 8 weeks for type C and E [19]
. The time to onset of symptoms may be dose-related. Acute
infections are more severe with higher mortality in adults than children. Relapses are not common. only less than
1% of cases result in fulminant hepatic failure[20]
. Chronic hepatitis is more common (75%) with type C and to less
extent with B type. 30% of hepatitis C even may end up developing cirrhosis with high risk of developing
hepatocellular carcinoma[21]
. D virus results in hepatitis only in persons already having acute or chronic hepatitis
B. Superinfection can result in fulminant hepatic failure [22]
.
8. Autoimmune Hepatitis
Autoimmune hepatitis typically results in high levels of gammaglobulin and circulating autoantibodies. Many
patients have a family history of other autoimmune disorders or had history of immunosuppressive therapy
intake. genetic predisposition may be claimed [23]
.
Alcoholic Hepatitis
The pathogenetic mechanism of alcoholic hepatitis is complex and multifactorial. It results from interactions
between ethanol metabolism, inflammation mediators like cytokines and tumor necrosis factors , and innate
immunity, which end up causing hepatocyte death by necrosis or apoptosis from oxidative stress [24]
.
9. Sign and Symptoms:
Hepatitis has a broad spectrum of presentations that range from a complete lack of symptoms to severe liver
failure [25,26]
. The acute form of hepatitis, generally caused by viral infection, is characterized by constitutional
symptoms that are typically self-limiting[27]
. Chronic hepatitis presents similarly, but can manifest signs and
symptoms specific to liver dysfunction with long-standing inflammation and damage to the organ[28,29]
. The most
common symptoms for viral hepatitis are malaise, fatigue, low-grade fever, anorexia, loss of weight, nausea,
vomiting, etc. Patients can be completely normal on physical exam or may have right upper quadrant pain with
hepatomegaly, urticarial rash and may show signs of dehydration. In advanced stages of liver disease from
chronic viral hepatitis, patients may present with hematemesis, ascites, pedal edema, encephalopathy, etc. [30]
.
These symptoms and signs are observable with many other acute or chronic infectious or non-infectious
conditions. Patients with autoimmune hepatitis and alcoholic hepatitis can also have similar symptoms as in viral
hepatitis, especially when the disease is advanced, and patients experience severe liver dysfunction. A careful
history, laboratory studies, and liver biopsy, when necessary, should be obtained to differentiate them [31]
.
In advanced stages of liver disease from chronic viral hepatitis, patients may present with hematemesis, ascites,
pedal edema, encephalopathy, etc. These symptoms and signs are observable with many other acute or chronic
infectious or non-infectious conditions like viral or bacterial gastroenteritis, acute cholecystitis, acute
cholelithiasis, tuberculosis, HIV, liver abscess, malignancies and peptic ulcer diseases [32]
.
10.
11. Prognosis:
Prognosis of viral hepatitis depends on the virus, causing the infection. with type A infection is usually a mild
self- limiting illness. Patients who infect with this type will develop lifelong immunity against
subsequent infection from hepatitis A and its of low mortality rate. Moving to type B and C patients
will be at risk of developing chronic hepatitis and liver cirrhosis as well as hepatocellular carcinoma as a
consequence [38]
. both type B and C are responsible for a high rate of mortality. type D usually end up with
end stage liver disease and cirrhosis [39]
. Lastly type E unlike type A it causes a high mortality rate in
pregnant patients even though its mechanism still not clear [40]
. On the other hand, the prognosis of
autoimmune hepatitis is directly related to the severity of liver inflammation. Patients who frequently
relapse or do not respond to treatment also have a worse prognosis. 70% of the children diagnosed with
autoimmune hepatitis end up requiring treatment during adulthood. And about 10% of patients require
liver transplantation with low possibility of developing hepatocellular Carcinoma [9]
. for patients who have
alcoholic hepatitis, the prognosis depends on whether they abstain from alcohol and the degree of liver
injury. Various prognostic scoring methods have been developed in the last two decades and include the
discriminant function (DF) model for end-stage liver disease (MELD) score, Glasgow alcoholic hepatitis
score (GAHS), and asymmetric dimethylarginine (ADMA) score [37]
.
12. Treatment:
The treatment of hepatitis varies according to the type, whether it is acute or chronic, and the severity of
the disease. Hepatitis can lead to serious complications if left untreated. There are several treatments
available for hepatitis, depending on the cause and severity of the disease [41]
. One common treatment for
viral hepatitis is antiviral therapy such as interferon and ribavirin these can help to reduce the amount of
virus in the body and improve liver function. In some cases, a combination of antiviral drugs may be used
to treat chronic hepatitis such as with type B and C [42]
. Another approach of treating hepatitis is to focus on
managing the symptoms and complications of the disease. For example, patients with hepatitis may need to
avoid alcohol and certain medications that can further damage the liver. They may also need to make
dietary changes and get regular exercise to improve their overall health. In some cases, more aggressive
treatments may be necessary [43]
. For example, patients with advanced liver disease may require a liver
transplant to replace the damaged liver with a healthy one. However, this is a complex and risky procedure
that is typically reserved for patients with very severe liver damage It is important for patients with
hepatitis to work closely with their healthcare provider to develop a treatment plan that tailored their
individual needs [44]
.
Viral Hepatitis
Here is an overview of the treatment options for different types of hepatitis. according to type A , D and E
Treatment mainly involves supportive care, such as rest, fluids, and pain relievers [45]
. There is no specific
treatment for this type. Moving to type B and C treatment may involve antiviral medications, such as
entecavir ,
13. tenofovir , interferon or direct-acting antivirals (DAAs) which are the main treatment for hepatitis C and can
cure the infection in most cases. In some cases, a liver transplant may be necessary [46]
.
Autoimmune hepatitis
Autoimmune hepatitis is commonly treated by immunosuppressants such as the corticosteroids prednisone
or prednisolone. Treatment of autoimmune hepatitis consists of two phases; an initial and maintenance
phase. The initial phase consists of higher doses of corticosteroids which are tapered down over a number of
weeks to a lower dose [47]
. If used in combination, azathioprine is given during the initial phase as well. Once
the initial phase has been completed, a maintenance phase that consists of lower dose corticosteroids, and in
combination therapy,
Alcoholic hepatitis
First-line treatment of alcoholic hepatitis is treatment of alcoholism.[32]
For those who abstain completely
from alcohol, reversal of liver disease and a longer life are possible [13]
. In addition to referral to
psychotherapy and other treatment programs, treatment should include nutritional and psychosocial
evaluation [49,50]
. Patients should also be treated appropriately for related signs and symptoms, such as
ascites, hepatic encephalopathy, and infection. Severe alcoholic hepatitis has a poor prognosis and is
notoriously difficult to treat [51]
. Without any treatment, 20-50% of patients may die within a month, but
evidence shows treatment may extend life beyond one
[52,53]
.
month
Available treatment options include pentoxifylline, which is a nonspecific TNF inhibitor,
corticosteroids, such as prednisone, corticosteroids with N-acetylcysteine , and corticosteroids with pentoxifylline
14. Vaccines:
Vaccines are available for hepatitis A, B, and E. Hepatitis
A vaccine is highly effective and provides long-term
immunity with one or two doses. Combination vaccines
for hepatitis A and B are available, and are
recommended for individuals at risk of both infections
[53]
. Hepatitis E vaccine is available in some countries, but
its efficacy and long-term protection is still under
investigation. Vaccination is the most effective way to
prevent hepatitis and its complications [54]
. Hepatitis
vaccination is recommended for individuals at high risk
of infection, such as healthcare workers, travelers to
endemic areas, individuals with chronic liver disease, and
people who engage in high-risk behaviors. Vaccine safety
and efficacy are continually monitored through post-
marketing surveillance and clinical trials [55]
.
15. Conclusions:
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms,
whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite,
vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and
chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis,
or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis),
liver failure, and liver cancer. Hepatitis is most commonly caused by the viruses hepatitis A, B, C, D, and E.
Other causes include heavy alcohol use, certain medications, toxins, other infections, autoimmune diseases,
and non-alcoholic steatohepatitis (NASH). 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 and spread through infected blood. Hepatitis C is 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 viral hepatitis. Antiviral medications are recommended in all with
chronic hepatitis C, except those with conditions that limit their life expectancy. There is no specific
treatment for NASH; however, physical activity, a healthy diet, and weight loss are recommended.
Autoimmune hepatitis may be treated with medications to suppress the immune system. A liver transplant
may be an option in both acute and chronic liver failure.
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