Hepatitis

Hepatitis refers to inflammation of the liver.

Hepatitis is a general term that refers to inflammation of the liver parenchyma. It may be caused a variety of insults to the liver and characteristically causes a rise in the liver transaminases (e.g. ALT/AST). Worldwide, the most common cause is viral hepatitis (e.g. hepatitis B/C).

There are several infectious and non-infectious causes of hepatitis.

Hepatitis may be caused by both infectious and non-infectious aetiologies, which include:

• Hepatitis A
• Hepatitis B
• Hepatitis C
• Hepatitis D
• Hepatitis E
• Other viruses (e.g. cytomegalovirus, Epstein-Barr virus)
• Autoimmune hepatitis
• Alcoholic hepatitis
• Ischaemic hepatitis
• Non-alcoholic steatohepatitis
• Drug-induced hepatitis (often referred to as drug-induced liver injury)

The inflammation may be acute and transient (e.g. acute hepatitis A) or chronic (e.g. chronic hepatitis B) leading to fibrosis and features of chronic liver disease. Continued inflammation can ultimately result in advanced, irreversible scarring known as cirrhosis. For more information see our Chronic liver disease note.

Patients with hepatitis may be completely asymptomatic.

The clinical features of hepatitis depend on the severity of the insult and the absence or presence of underlying liver disease. Many patients may have an asymptomatic or ‘subclinical’ episode that does not come to medical attention. If the insult is removed (e.g. clearance of viral hepatitis or alcohol cessation) then the hepatitis may completely settle. If the insult remains (e.g. chronic hepatitis B, continued alcohol consumption) then chronic liver disease may develop.

Symptoms

• Asymptomatic
• Myalgia
• Fever
• Nausea and/or vomiting
• Anorexia
• Abdominal pain
• Fatigue
• Jaundice

Signs

• Right upper quadrant pain
• Hepatomegaly
• Jaundice
• Fever

Features of acute liver failure

Patients who develop severe hepatitis may rarely develop acute liver failure (ALF). This refers to a syndrome of acute liver dysfunction without underlying chronic liver disease. It is broadly defined as severe acute liver injury (abnormal transaminases) with the development of coagulopathy (INR >1.5) and hepatic encephalopathy within 28 weeks of disease onset.

ALF is characterised by the development of:

• Confusion (i.e. encephalopathy)
• Jaundice
• Asterixis (flapping tremor; a sign of encephalopathy)
• GI bleeding
• Ascites
• Bruising (high INR)

For more information see our Acute liver failure note.

Features of chronic liver disease

Patients with chronic inflammation in the liver are at risk of developing progressive fibrosis. Severe, irreversible fibrosis is known as cirrhosis and it is associated with significant complications (e.g. hepatocellular carcinoma, GI bleeding, encephalopathy, spontaneous bacterial peritonitis, etc).

Chronic liver disease is characterised by:

• Caput medusa
• Splenomegaly
• Palmar erythema
• Dupuytren’s contracture
• Leuconychia
• Gynaecomastia
• Spider naevi

Many patients with cirrhosis remain undiagnosed. The liver retains a small amount of residual function to enable patients to carry out their normal daily activities. This is known as ‘compensated cirrhosis’. With ongoing insults (e.g. hepatitis B, alcohol) or a concurrent illness (e.g. infection, trauma) the liver may lose its ability to function adequately and ‘decompensate’. This state of decompensation is characterised by GI bleeding, encephalopathy, ascites, jaundice and coagulopathy.

For more information including why these clinical features occur, see our Chronic liver disease note.

Hepatitis is characterised by a derangement in liver function tests.

Patients who are at risk, or have suspected, hepatitis should undergo liver function tests (LFTs). LFTs refer to a series of blood tests that can help to investigate abnormalities within the hepatobiliary system. Theses include:

• Alanine transaminase (ALT)
• Asparate transaminase (AST)
• Alkaline phosphatase (ALP)
• γ-glutamyl transpeptidase (gGT)
• Bilirubin
• Albumin

Hepatic enzymes

ALT, AST, gGT, and ALP are enzymes found within the liver that are released when the liver is injured and thus act as markers for hepatitis. The pattern of enzyme elevation helps to determine whether the problem is an injury with the liver parenchyma or with the bile ducts and biliary system.

• Hepatic (liver parenchyma): a predominant rise in ALT/AST
• Cholestatic (biliary system): a predominant rise in gGT/ALP

In hepatitis, there is usually a significant elevation in ALT/AST that are known as transaminases. Certain conditions can cause a profound elevation >1000 U/L, which include acute viral hepatitis, autoimmune hepatitis, paracetamol overdose, and ischaemic hepatitis.

Synthetic function

While the liver enzymes are a reflection of injury, they do not act as markers of how well the liver is actually functioning. Bilirubin, albumin, and INR are all markers of liver function. This is because hepatocytes are important in the conjugation of bilirubin and transport into the biliary system, synthesis of albumin, and synthesis of clotting factors.

Therefore, a rise in INR, fall in albumin, or rise in bilirubin are features that the liver is not working or functioning properly. Confusingly, bilirubin may be seen to rise in biliary obstruction (e.g. stone blocking the common bile duct). In this situation, there would be a cholestatic pattern in the liver function tests (i.e. High ALP/gGT) and elevated bilirubin.

Non-invasive liver screen

The cause of hepatitis may be known from the history (e.g. heavy alcohol consumption, known hepatitis B carrier). However, it can be difficult to determine the cause of hepatitis just based on the history, examination, and basic blood tests. Therefore, when patients present with abnormal liver function tests they undergo a non-invasive liver screen to try and identify the cause.

A non-invasive liver screen refers to screening questions, biochemical tests, and imaging to assess patients with suspected liver disease (e.g. hepatitis). This screen includes tests for viruses, autoimmune diseases, and other rare causes of inflammation. For more information see our Chronic liver disease note.

The management of hepatitis depends on the underlying cause.

Causes of hepatitis may be transient and resolve without treatment (e.g. drug-induced, hepatitis A), whereas others may require long-term treatment to prevent progression to cirrhosis (e.g. autoimmune hepatitis). Therefore, it is important to determine the underlying cause of hepatitis and then target treatment appropriately.