What Is Hepatitis?

Hepatitis is defined as the inflammation of the liver.² This inflammation can be caused by non-infectious agents such as drugs, alcohol, toxins, autoimmune diseases though the commonest cause are viral infection.¹ Viral hepatitis is further categorized based on the causative viral strains, with the five commonest being hepatitis A, B, C, D and E.⁶

The viruses can be transmitted through feces, blood and body fluids, and are spread when an unimmunized person comes in contact with the feces, blood and body fluids of an infected person. High risk groups include persons living in low- and middle-income countries (LMICs), healthcare workers who come in contact with body fluids or blood products, heavy alcohol drinkers, persons who inject drugs (PWID), people living with HIV/AIDS (as co-infection), individuals who engage in unprotected sex, homeless persons and men who have sex with men (MSM).^14,15 It is important to note that hepatitis B does not spread through sharing toilet seats, touching doorknobs, sneezing, coughing, hugging or eating meals with someone who is infected with hepatitis B.¹⁵

Viral hepatitis is termed as acute if the liver inflammation lasts for less than 6 months and chronic when it lasts longer than 6 months.¹ In an acute infection, symptoms can take between 2-6 weeks following exposure to appear, while in chronic infection, symptoms can take as long as decades to develop.³⁷ Hepatitis A and E usually cause acute infections while hepatitis B, C and D can cause both acute and chronic infection^44,54 In the UK, hepatitis C is the most common type of viral hepatitis though alcoholi hepatitis and hepatitis E are also common.^39,43

Overview

Viral hepatitis is a major public health burden, with Hepatitis B (HBV) and Hepatitis C (HCV) accounting for 96% of all hepatitis mortality.¹⁰ According to the World Health Organization (WHO), there are over 350 million people living with hepatitis worldwide.⁸ However, only 10% of people with chronic hepatitis B are aware, while for hepatitis C, about 21% know they are living with it.⁸ There are multiple reasons for low awareness and response. One, most infected people are asymptomatic, and where symptoms exist, these are usually nonspecific. By the time the patient reports to the health centre and the infection is detected, the disease is at an advanced stage.³⁷ Another reason is, some countries have policies that require only healthcare workers to carry out hepatitis tests.⁹ Thirdly, while very few people are aware they are living with HBV and HCV, even fewer people are receiving treatment. For example, less than 10% of babies in Africa have access to the HBV vaccine. Also, most countries lack a standard process for estimating the proportion of people diagnosed with HBV or HCV.^9,44 

With about 1.34 million deaths per year (an increase of 22% from the year 2000), viral hepatitis is considered a silent epidemic.¹⁰ There are currently different policies and guidelines being implemented to tackle this issue. The Global Health Sector Strategy (GHSS) on Viral Hepatitis 2022-2030 proposes strategies (interventions, equity, strategic information, financing and innovation) to eliminate viral hepatitis, especially HBV and HCV, as a public health threat by 2030 (reducing mortality by 65% and new infections by 90%).^7,8,10 The interventions include infant immunisation; preventing mother-to-child (vertical) transmission of HBV; safe blood transfusion and injection; harm reduction for high-risk populations (for example, those who inject drugs), and testing and treatment.¹³ The WHO also adopted a standard operating procedure to enhance the surveillance and case reporting of viral hepatitis. This SOP monitors three key indicators: incidence (new infections of acute hepatitis), prevalence (chronic hepatitis cases), and mortality.¹⁶ And the 2030 Agenda for Sustainable Development lists viral hepatitis prevention and control selected as Target 3 (indicator 3.3.4 aims to reduce acute HBV incidence per 100,000 population).^11,12 

Causes of hepatitis

The liver is the largest organ in the body (comprising roughly 2-3% body mass in the average 70 kg individual) and is involved in vital functions such as protein synthesis; nutrient production, metabolism and storage; filtering the blood for bacteria and poisonous substances immunity; bile secretion for digestion and intestinal absorption; and detoxification and excretion of drugs and metabolic waste products.^3,4,5 A decline in liver function occurs due to different factors which can lead to liver inflammation or damage.

• Viral diseases (hepatotropic viruses)^{1,17,18,19,20, 54}
  • Hepatitis A is caused by Hepatitis A virus (HAV), an RNA virus from the Picornaviridae family. HAV infection is usually acute. HAV virus is detected in the stool of infected people and is commonly spread via the faecal-oral route such as eating food, drinking water, or touching objects contaminated by faecal matter from an infected individual. Risk factors include poverty and poor hygiene
  • Hepatitis B is caused by Hepatitis B virus (HBV), a DNA virus from the Hepadnaviridae family. HBV can be detected in semen, vaginal mucus, saliva, serum though not in stool, urine, or sweat. The mode of transmission is via sexual contact with infected people (due to contact with their mucous membranes or body fluids), parenteral means (such as blood transfusion or sharing contaminated needles, syringes, medical instruments) or interpersonal contact (such as sharing razors and toothbrushes). HBV infection can be acute or chronic. High risk groups include certain occupations (like healthcare workers who are exposed to infected body fluids), intravenous drug users, babies of infected pregnant women, patients who require frequent and multiple blood transfusions, men who have sex with men (MSM), people who have multiple sexual partners (MSP), prisoners
  • Hepatitis C is caused by Hepatitis C virus (HCV), an RNA virus from the Flaviviridae family. The most common means of transmission is parenterally (such as blood transfusion or sharing contaminated needles, syringes, medical instruments) though it can also occur perinatally (babies of infected pregnant women) and sexually. HCV infection is usually chronic
  • Hepatitis D is caused by the Hepatitis D virus (HDV), an RNA virus from the Deltaviridae family. This virus shares some structural constituents as HBV hence usually occurs as a coinfection
  • Hepatitis E is caused by Hepatitis E virus (HEV), an RNA virus from the Hepeviridae family. It is mainly transmitted through the faecal-oral route though person-to-person and perinatal transmission can also occur. HEV infection is usually acute
  • Hepatitis G is caused by the Hepatitis G virus (HGV), an RNA virus from the Flaviviridae family. The primary mode of transmission is through infected blood and blood products. It is usually detected as a coinfection with chronic hepatitis B or hepatitis C infections
  • Other less common infectious causes are Varicella-zoster virus, Cytomegalovirus (CMV), Epstein-Barr virus (EBV), transfusion transmitted virus (TTV) and Herpes Simplex Virus (HSV)^{23, 24, 25, 26, 27} 

• Autoimmune hepatitis is a chronic condition in which an individual’s immune system attacks their healthy liver cells. It is not yet fully understood why this immune response happens, but this can be triggered by factors like drugs (like nitrofurantoin, minocycline, adalimumab, infliximab, or methyldopa), chemical toxins, certain nutritional supplements, viral infection (like the hepatitis viruses or Epstein-Barr virus) or genetic predisposition (positive family history).^21,22 High risk groups include females (4 times more common than in males), positive family history (hereditary) and persons with other autoimmune conditions (such as inflammatory bowel disease, celiac disease, vitiligo, type 1 diabetes)^28, 29,30
• Alcoholic hepatitis. The relationship between excessive alcohol intake and hepatitis is also not yet fully understood. Proposed mechanisms for this inflammation include toxic reactions triggered by alcohol and its metabolites on the liver; genetic predisposition, immunologic factors (such as free radicals, and oxidative injuries, stimulation of cytokines); and increasing gut permeability (penetration) thereby allowing infectious agents pass through to the liver.^31,32 Alcoholic liver disease is the leading cause of alcohol related deaths worldwide.³³ In the UK, alcohol accounts for 80% of all liver cirrhosis cases.³⁴ The recommended advice in the UK is to drink no more than 14 units of alcohol a week (around 6 medium (175ml) glasses of wine, or 6 pints of 4% beer) spread across 3 days or more^35,36

Signs and symptoms of hepatitis

Most people with hepatitis are asymptomatic and unaware of their disease.³⁷ Where symptoms exist, these are usually mild and nonspecific (vague) and can be mistaken for other conditions such as gastroenteritis or flu. The signs and symptoms of hepatitis are generally similar regardless of cause, and include jaundice (yellow tinge to the skin or eyes), feeling tired, muscle or joint aches and pains, abdominal discomfort (stomach discomfort), poor appetite, nausea (feeling sick), darker-coloured urine, pale-coloured stools, headache, fever (high temperature).^2,17,30 

Generally, hepatitis presents in 4 phases.¹

• Phase 1 (viral replication phase) – In this phase, patients are usually asymptomatic but show positive markers of hepatitis
• Phase 2 (prodromal phase) – In this phase, there are nonspecific symptoms like nausea, vomiting, malaise, rashes, itching and fatigue
• Phase 3 (icteric phase) – In this phase, patients may develop dark-coloured urine, pale-coloured stool, jaundice, or right upper abdominal quadrant pain with liver enlargement
• Phase 4 (convalescent phase) – In this phase, symptoms start resolving and liver enzymes return to normal levels 

Management and treatment for hepatitis

There are currently no specific treatments for hepatitis A, so the focus is on supportive therapy such as good nutrition, adequate fluid intake and immunisations (either hepatitis A vaccine or hepatitis A immune globulin).⁴⁹

Acute hepatitis B infection usually resolves spontaneously, with supportive therapy and behavioural changes.⁵⁰ Chronic infection can be treated with interferon-type drugs (that boost the immune system. Examples are Interferon alfa-2b and Peginterferon alfa-2a) and Antiviral Drugs (that arrest hepatitis B virus reproduction. Examples are Entecavir, Telbivudine and Tenofovir)^.52 However, these are more effective where there is an active liver disease.⁵² As treatment is usually lifelong, psychosocial support is important.

For hepatitis C, there is currently no effective vaccine but the direct-acting antivirals are curative in over 90% of infected persons.⁵⁴ In the UK, the choice of antiviral depends on the HCV genotype. There are 6 main genotype strains, of which type 1 and 3 are the most common in the UK.⁵³ The direct acting antivirals used by the NHS are sofosbuvir; a combination of ledipasvir and sofosbuvir; a combination of ombitasvir, paritaprevir and ritonavir, taken with or without dasabuvir; a combination of elbasvir and grazoprevir; a combination of sofosbuvir and velpatasvir; a combination of sofosbuvir, velpatasvir and voxilaprevir; a combination of glecaprevir and pibrentasvir; and ribavirin. These are taken for 8-12 weeks, again depending on the genotype strain.⁵³

Hepatitis D is treated with Pegylated interferon alpha for at least 48 weeks irrespective of the patient’s response.⁵⁵ There is no vaccine for hepatitis D though hepatitis B vaccine can prevent hepatitis D virus infection.⁵⁶

There is no specific treatment for hepatitis E as it usually resolves spontaneously.^57,58 Supportive treatment may be helpful.

For alcoholic hepatitis, supportive treatment (nutrition, fluid, psychotherapy, self-help groups) and behaviour changes (avoiding alcohol) are needed. In severe cases, hospitalisation, corticosteroids and liver transplant may be indicated.⁵⁹

Autoimmune hepatitis treatment is usually lifelong using immunosuppressants such as Prednisolone.³⁰

Analgesics (such as paracetamol) and anti-emetics (medication against vomiting) should be avoided when treating hepatitis.^49,51

FAQs

What are the types or forms of hepatitis?

Hepatitis can be caused by non-infectious agents or infectious agents. Non-infectious types could be autoimmune or alcoholic. Infectious agents are the common cause and are due to hepatotropic viruses. There are 6 types of hepatitis based on the corresponding causative virus. These types of hepatitis are A, B, C, D, E and G. 

How is hepatitis diagnosed?

As most people living with hepatitis are asymptomatic in the early stages, diagnosis of hepatitis is usually picked up during other routine tests. Therefore, regular testing is recommended for pregnant women, injection-drug users, people taking immunosuppressive drugs, men who have sex with other men and HIV-positive patients.^17, 47,48 If the individual is symptomatic, diagnosis is usually made following medical history taking, physical examination, and tests. Blood tests determine the presence and quantity of hepatitis virus antigens (foreign substance in the body) and antibodies (protective substance made by your body against foreign products).⁴⁷

The tests may be categorised as:⁴⁵

• General tests to detect liver inflammation and/or damage. These include alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin, albumin, total protein and prothrombin time (PT)⁴⁵ 
• Screening tests to detect viral hepatitis. Screening is done using enzyme immunoassay tests which detect hepatitis B surface antigen (HBsAg), anti-HBs antibodies, hepatitis B “e” antigen (HBeAg) and anti-HBe antibodies, anti-hepatitis B core (HBc) antibodies and anti-HBc IgM for hepatitis B infection; and total anti-HCV antibodies for hepatitis C infection, while confirmatory test is based on nucleic acid tests (NAT) which detect circulating viral genomes in serum or plasma, including HBV DNA or HCV RNA^{17, 46, 47,54}
• Diagnostic tests to detect underlying specific causes or if other tests are inconclusive. Examples are liver biopsy and abdominal ultrasound
• Follow-up tests to monitor progression of hepatitis and/or help guide treatment. For example, the type of HCV genotype determines the choice of antiviral therapy, while HBV DNA, HCV RNA and HCV core antigen are used to monitor the efficacy of antiviral therapy^.46

Autoimmune hepatitis is usually made as a diagnosis of exclusion, that is, after all other possible causes have been ruled out.³⁰

How can I prevent hepatitis?

Hepatitis is highly preventable. The approach taken will depend on the type of hepatitis and their mode of transmission. These include:

• Vaccination (against HAV and HBV infection). This is now administered to people of all ages and can also be given within 24 hours of exposure
• Screening of blood and blood products before transfusion (against HBV and HCV infection)
• Safe injection practices e.g. avoid sharing needles (against HBV and HCV infection)
• Safe sex practices e.g. use barrier methods (against HBV and HCV infection)
• Occupational safety prevents transmission to health care workers at high risk e.g. hand hygiene before touching a patient, before clean/aseptic procedures, after body fluid exposure/risk, after touching a patient and after touching patient surroundings,³⁸ (against HBV infection)
• Safe food and water (against HAV and HEV infection)
• Regular handwashing. You can watch a video of the correct way to wash your hands
• Safe alcohol drinking e.g. drink within limits, avoid binge drinking (against alcoholic hepatitis)

Who is at risk of hepatitis?

This also depends on the type of hepatitis but includes people living in low- and middle-income countries (LMICs), people who inject drugs (PWID), heavy alcohol drinkers, healthcare workers who come in contact with body fluids or blood products, people living with HIV/AIDS (as co-infection), individuals who engage in unprotected sex, homeless persons and men who have sex with men (MSM).

How common is hepatitis?

Viral hepatitis, especially HBV and HCV, is a huge public health burden. According to the World Health Organization, there are about 1.34 million deaths per year. In the UK, hepatitis C is the most common type of viral hepatitis and is usually spread through blood-to-blood contact with an infected person.³⁹ There are approximately 81,000 people living with chronic hepatitis due to HCV in England though, with treatments, deaths due to complications (advanced liver disease) from HCV have reduced from 482 (2015) to 314 (2020).⁴³ Alcoholic hepatitis is also common in the UK. Hepatitis E is now the most common cause of acute hepatitis and is mainly contracted through eating raw or undercooked pork meat^.17,39

In 2022, there was an outbreak of hepatitis in children worldwide, including the UK^17,41 This hepatitis was an acute infection, not caused by any of the known viruses. ^41, 42 There was also no association found between the hepatitis cases and the COVID-19 vaccine.⁴⁰

When should I see a doctor?

The NHS recommends seeing your GP if you develop symptoms you think may be caused by hepatitis.¹⁷

Summary

Hepatitis refers to the inflammation of the liver either from infectious or non-infectious causes. The most common causes are the hepatotropic viruses (A,B,C,D and E). Hepatitis is a huge public health burden. Hepatitis can be acute or chronic. Most people do not have symptoms or develop symptoms when complications arise. Hepatitis is highly preventable. Regular blood tests are recommended for high risk individuals and occupations. Some types of hepatitis have treatments that are curative while others require lifelong medications and supportive treatment.