ACUTE HEPATITIS

D R M O H A M M A D A RI F
 Objectives

• Identify the common etiologies and epidemiology of

acute hepatitis.
• Review the physical findings in patients presenting with
acute hepatitis.
• Describe laboratory testing and how results relate to the
treatment and disposition decisions for acute hepatitis.
 Definition and classification

Acute hepatitis is a term used to describe a wide variety

of conditions characterized by acute inflammation of the
hepatic parenchyma or injury to hepatocytes resulting in
elevated liver function indices
 In general, hepatitis is classified as acute or chronic
based on the duration of the inflammation and insult to
the hepatic parenchyma. If the period of inflammation or
hepatocellular injury lasts for less than six months,
characterized by normalization of the liver function tests,
it is called acute hepatitis.
 Etiology

Acute hepatic inflammation can be caused by many

infectious and noninfectious causes, of which the most
common causes are secondary to a viral infection or drug-
induced liver injury.
 Infectious causes

• Hepatotropic viruses:
• Hepatitis A Virus(HAV)
• Hepatitis B Virus (HBV)

• Hepatitis C Virus (HCV)

• Hepatitis D Virus (HDV)

• Hepatitis E Virus (HEV)

• Non hepatotropic virus:
• Epstein-Barr virus (EBV)
• Cytomegalovirus (CMV)

• Herpes simplex virus (HSV)

• Coxsackievirus
• Adenovirus
• Dengue virus

• Coronavirus-19(COVID-19)

• Bacteria, fungi, and parasites

 Toxin or substance-related causes include

• Alcohol-related: fatty liver disease, acute alcoholic

hepatitis, or alcoholic cirrhosis
• Drugs and toxins
• Dose-dependent, e.g. acetaminophen (paracetamol)
• Non-dose-dependent, e.g., idiosyncratic drug reaction most
commonly related to antibiotics and anticonvulsants but also statins,
NSAIDs, herbal/nutritional supplements
• Other toxins, e.g., mushroom (Amanita phalloides), herbal and
dietary supplements, carbon tetrachloride, sea anemone sting  
 Immunologic or inflammatory conditions

• Autoimmune hepatitis
• Biliary disease such as primary biliary cholangitis or
primary sclerosing cholangitis.
 Metabolic or hereditary

• Nonalcoholic fatty liver disease

• Hemochromatosis
• Wilson's disease
 Pregnancy-related 

• Preeclampsia
• Acute fatty liver of pregnancy
• HELLP syndrome
 Ischemic and Vascular

• Cardiogenic/Distributive shock
• Hypotension
• Heatstroke
• Cocaine, methamphetamine, ephedrine
• Acute Budd-Chiari syndrome
• Sinusoidal obstruction syndrome
 Miscellaneous

• Acute fatty liver of pregnancy

• Malignancy
• Eclampsia
• HELLP syndrome
• Reye' syndrome
• Primary graft non-function after liver transplantation
 Epidemiology

Based on reported data, viral and drug-induced liver

injury are the most common causes of acute hepatitis and
acute liver failure
Generally, the rates of viral hepatitis are low in high-
income regions and high in resource-poor areas
The incidence of Hepatitis A virus (HAV) has
significantly decreased by approximately 95% since the
introduction of the hepatitis A vaccine in 1995
cases of acute HBV have decreased significantly since the
introduction of the vaccine in 1990
Hepatitis C has been steadily increasing since 2010,
particularly in the 20 to 40 age group, thought to be
secondary to injection drug use related to the opioid crisis
and improved surveillance
Worldwide, the World Health Organization estimates that
1 in 3 people have been infected with either HBV or HCV
In high endemic areas, HAV has affected more than 90%
of children by age 10 , the majority of cases are in low-
income regions
 Histopathology

ACETAMINOPHEN---- Central lobular necrosis and

minimal cell infiltrates
VIRAL----Intranuclear viral inclusions and surrounding
neutrophils
AUTOIMMUNE----portal inflammation and interface
hepatitis formally known as piecemeal necrosis 
HEMOCHROMATOSIS---Iron accumulation with
hepatocellular hemosiderin pigment
WILSON----Increase hepatic copper concentrations 
 History and Physical

 Duration of the presenting illness,

Travel history,
High-risk activities like IV drug use
 Alcohol consumption
Sexual history
Prior blood-product transfusion history, or recent food
intake
Drug history
 Evaluation

It is very important to distinguish between acute hepatitis

and chronic hepatitis. 
 The biochemical tests such as AST, ALT, alkaline
phosphatase, GGT, lactate dehydrogenase, bilirubin,
PT/INR, and albumin determine the normal functioning of
the liver and any abnormalities in these tests is indicative
of injury to the hepatocytes from infectious and
noninfectious causes.
 Markers of hepatocyte metabolic/catabolic activities

• Elevated serum bilirubin: Synthesized primarily in the

reticuloendothelial cells from the breakdown of heme-
containing proteins. It can be abnormally increased in
liver diseases secondary to impaired uptake, impaired
conjugation, or secondary to leak from damaged
hepatocytes or bile ducts.
• Elevated ammonia: increase because the liver fails to
metabolize ammonia. 
 Markers suggestive hepatocellular injury

Elevation of serum transaminases

Marked elevations greater than five times the upper limit of
normal or greater than 500 IU/L is suggestive of extensive
hepatocellular injury(acute hepatitis, drug-induced, ischemia,
autoimmune hepatitis)
Milder elevations are considered less than five times the
upper limit of normal or less than 500 IU/L and can result
from a variety of liver injuries or disorders(chronic hepatitis,
autoimmune disorders, hemochromatosis, Wilson disease,
alpha-1 antitrypsin deficiency, alcoholic liver disease, drug-
induced liver injury)
 Markers of liver injury secondary to cholestasis 

Elevation in alkaline phosphatase (AP) and gamma-

glutamyl transferase (GGT) reflect underlying cholestasis
secondary to the liver's impaired ability to secrete bile
Common causes include choledocholithiasis, malignancy,
primary biliary cirrhosis, or primary sclerosing
cholangitis.
 Markers of synthetic function 

Elevated Prothrombin time (PT

This occurs when liver injury results in decreased synthetic
function of the vitamin K-dependent coagulation factors (II,
VII, IX, X)
Prolongation of the international normalized ratio (INR)
more than 1.5 is considered a poor prognostic sign
Decreased albumin
This is not specific to liver injury, and its utility in the
diagnosis of acute hepatitis is limited.
 American College of Gastroenterology Guidelines

Mild elevation in serum transaminases ( <5 times the

upper limit of normal)
complete blood count, AST, ALT, alkaline phosphatase,
total bilirubin, albumin, PT/INR, comprehensive hepatitis
panel that includes Hepatitis A IgM Antibody, Hepatitis B
Surface Antigen, Hepatitis B Core Antibody (IgM),
Hepatitis B Surface Antibody and Hepatitis C Antibody,
and iron panel
Severe elevation in serum transaminases (>15 times the
upper limit of normal) or massive (ALT over 10000 U/L)
elevations
checking for Ebstein-Barr virus(EBV),
cytomegalovirus(CMV), ceruloplasmin, autoimmune markers
drug panel test that includes acetaminophen, and urine
toxicology
Doppler study of the hepatic vein, portal vein,
and hepatic artery to rule out vascular occlusion, eg. Budd-
Chiari syndrome.  
 Imaging

Abdominal ultrasound examination is the best initial

choice of imaging study in patient's presenting with lab
abnormalities suggestive of cholestasis
Findings of biliary dilatation are suggestive of
extrahepatic causes of cholestasis (gallstones or masses)
absence of biliary ductal dilatation suggests intrahepatic
causes of cholestasis such as drug-induced liver injury,
PBC and PSC
 Treatment / Management

The management of acute hepatitis depends on the

specific etiological factor implicated in the acute injury to
the hepatocytes
Acute acetaminophen ingestion is a common
noninfectious cause of acute hepatitis leading to acute
liver failure and needs to be considered in all patients
presenting with signs and symptoms of acute liver failure
 N-acetylcysteine

• 72-hour oral protocol -  N-acetylcysteine oral: 140 mg/kg

orally as a loading dose, followed by 70 mg/kg every 4
hours for a total of 17 doses
• 20 hour IV protocol - N-acetylcysteine IV: 150 mg/kg
intravenously over 60 minutes as a loading dose, followed
by 50 mg/kg over 4 hours (12.5 mg/k/ per hour for 4 hrs),
then 100 mg/kg over 16 hours (6.25 mg/kg per hour for
16 hours)
 Complications

1% of patients with acute hepatitis A and about 1% of

patients with acute hepatitis B will progress to ALF.
In contrast, 20 to 40% of patients with acute hepatitis E
progress to ALF in developing countries
About 69% of patients with acute, severe autoimmune
hepatitis progress to ALF, and about 2% of ALF results
from Wilson disease
 Deterrence and patient education

Vaccinations for both hepatitis A virus and hepatitis B virus

have been available since the 1990s and have
significantly decreased the incidence of these infections
Hepatitis A virus gets transferred by fecal-oral
contamination, and improved food handling, water
purification, and improved hygiene will reduce the risk of
spreading infection.
Accidently toxic ingestion of acetaminophen by children can
be reduced with safe storage practices out of reach from
children and utilizing packaging that utilize childproof safety
precautions
 Conclusion

• Get a complete history including all medications, herbal or

nutritional supplements,  travel history, and social history, including
alcohol use, IV drug use, and sexual history. 
• Consider acetaminophen (paracetamol) toxic ingestion, either
intentional or unintentional/accidental. 
• Consider extrahepatic or non-hepatitic causes of elevated liver
biochemical tests.
• If the patient appears ill, consider acute liver failure looking for
encephalopathy and coagulopathy.
• If the patient does not appear ill with no encephalopathy, normal
INR, and able to maintain oral fluid intake and nutrition, outpatient
follow-up is appropriate. 
 MCQ 1

 
Which of these things can cause hepatitis?
A. Viruses
B. Medicines and alcohol
C. Immune system that's not working as it should
D. All of the above 
 MCQ 2

Hepatitis exists in short-term (acute) and long-term

(chronic) forms. How long does acute hepatitis last?
A. Less than 6 months
B. Less than 3 months
C. About 6 weeks
D. 1 month
 MCQ 3

How many forms of viral hepatitis have been found so

far?
A. 3
B. 4
C. 5
D. 8
 MCQ4

Which form of hepatitis can be passed on through

contaminated food or water?
A. B
B. C
C. A and E
D. All of the above
 MCQ5

Which form can exist for years without symptoms?

A. Hepatitis B
B. Hepatitis C
C. Hepatitis D
D. All of the above
 MCQ6

A . Acetaminophen overdosage 
B  . Viral hepatitis 
C . Autoimmune hepatitis
D . Hemochromatosis 
E . Wilson Disease 
 SAQ

A 10 year old boy brought by his mother with complaints of fever , loss of
appetite and mild abdominal discomfort for the past few days . He was
seen by his doctor and prescribed oral antipyretics and antibiotics for sore
throat two days ago .

On examination he is febrile but well appearing . He is not dehydrated and

apart from mild tenderness in epigastrium abdominal examination is
unremarkable. Other system examination revealed no abnormality

Q1 . What is your working diagnosis

Q 2 . Give 4 investigations to help you in the diagnosis .

Q3,. What specific test would you like to do to confirm the diagnosis .

Q4 . Give briefly your management plan