Viral hepatitis

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Viral hepatitis
Ground glass hepatocytes high mag cropped 2.jpg
Micrograph showing ground glass hepatocytes, which are seen in chronic hepatitis B infections (a type of viral hepatitis), and represent accumulations of viral antigen in the endoplasmic reticulum. H&E stain.
Specialty Infectious diseases, gastroenterology   OOjs UI icon edit-ltr-progressive.svg

Viral hepatitis is liver inflammation due to a viral infection. [1] [2] It may present in acute form as a recent infection with relatively rapid onset, or in chronic form, typically progressing from a long-lasting asymptomatic condition up to a decompensated hepatic disease and hepatocellular carcinoma (HCC). [3]

Contents

The most common causes of viral hepatitis are the five unrelated hepatotropic viruses hepatitis A, B, C, D, and E. Other viruses can also cause liver inflammation, including cytomegalovirus, Epstein–Barr virus, and yellow fever. There also have been scores of recorded cases of viral hepatitis caused by herpes simplex virus. [4]

Mode of transmission

Viral hepatitis is either transmitted through contaminated food or water (A, E) or via blood and body fluids (B, C). The viruses transmitted through water and food are mostly self-limited, resulting in acute illness with full resolution. The blood borne viruses (B, C) can cause both acute and chronic liver disease and can be transmitted from mother to child during birth, through contact with body fluids during sex, unsafe injections and through unscreened blood transfusions. [5]

The most common types of hepatitis can be prevented or treated. [6] Hepatitis A and hepatitis B can be prevented by vaccination. Effective treatments for hepatitis C are available but costly. [6]

In 2013, about 1.5 million people died from viral hepatitis, most commonly due to hepatitis B and C. [6] East Asia, in particular Mongolia, is the region most affected. [6]

Hepatitis viruses

The most common cause of hepatitis is viral. Although the effects of various viruses are all classified under the disease hepatitis, these viruses are not all related.[ citation needed ]

Hepatitis viruses
Hepatitis A virus (HAV)Hepatitis B virus (HBV)Hepatitis C virus (HCV)Hepatitis D virus (HDV)Hepatitis E virus (HEV)
Viral species Hepatovirus A Hepatitis B virus Hepacivirus C Hepatitis delta virus Orthohepevirus A
Viral family Picornaviridae Hepadnaviridae Flaviviridae Incertae sedis Hepeviridae
Genome (+)ssRNA dsDNA-RT (+)ssRNA (−)ssRNA (+)ssRNA
AntigensHBsAg, HBeAgCore antigenDelta antigen
Transmission Enteral Parenteral ParenteralParenteralEnteral
Incubation period20–40 days45–160 days15–150 days30–60 days15–60 days
Severity/Chronicity [7] Mild; acuteOccasionally severe; 5–10% chronicSubclinical; 70% chronicExacerbates symptoms of HBV; chronic with HBVMild in normal patients; severe in pregnant women; acute
Vaccine2 injections; at least 20 years of protection [8] 3 injections; lifetime protectionNone availableNone available, but not considered necessary; Hep B vaccine provides protection [9] Investigational (approved in China)

Viral hepatitis types

Hepatitis A

Hepatitis A or infectious jaundice is caused by hepatitis A virus (HAV), a picornavirus transmitted by the fecal-oral route often associated with ingestion of contaminated food. It causes an acute form of hepatitis and does not have a chronic stage. A patient's immune system makes antibodies against HAV that confer immunity against future infection. People with hepatitis A are advised to rest, stay hydrated and avoid alcohol. A vaccine is available that will prevent HAV infection for up to 10 years. Hepatitis A can be spread through personal contact, consumption of raw sea food, or drinking contaminated water. This occurs primarily in third world countries. Strict personal hygiene and the avoidance of raw and unpeeled foods can help prevent an infection. Infected people excrete HAV with their feces two weeks before and one week after the appearance of jaundice. The time between the infection and the start of the illness averages 28 days. (ranging from 15 to 50 days), [10] Most patients recover fully within 2 months, although approximately 15% of affected people may experience continuous or relapsing symptoms from six months to a year following initial diagnosis. [11]

Hepatitis A [12]
MarkerDetection TimeDescriptionSignificance
Faecal HAV2–4 weeks or 28 days–Early detection
Ig M anti HAV4–12 weeksEnzyme immunoassay for antibodiesDuring acute Illness
Ig G anti HAV5 weeks–persistentEnzyme immunoassay for antibodiesOld infection or reinfection

Hepatitis B

Hepatitis B is caused by the hepatitis B virus, a hepadnavirus that can cause both acute and chronic hepatitis. Chronic hepatitis develops in the 15% of adults who are unable to eliminate the virus after an initial infection. Identified methods of transmission include contact with blood, blood transfusion (now rare), unsanitary tattoos, sex (through sexual intercourse or contact with bodily fluids), or mother-to-child by breast feeding;[ citation needed ] there is minimal evidence of transplacental crossing. However, in about half of cases the source of infection cannot be determined. Blood contact can occur by sharing syringes in intravenous drug use, shaving accessories such as razor blades, or touching wounds on infected persons. Needle-exchange programmes have been created in many countries as a form of prevention.[ citation needed ]

Patients with chronic hepatitis B have antibodies against the virus, but not enough to clear the infected liver cells. The continued production of virus and countervailing antibodies is a likely cause of the immune complex disease seen in these patients. A vaccine is available to prevent infection for life. Hepatitis B infections result in 500,000 to 1,200,000 deaths per year worldwide due to the complications of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Hepatitis B is endemic in a number of (mainly South-East Asian) countries, making cirrhosis and hepatocellular carcinoma big killers. There are eight treatment options approved by the U.S. Food and Drug Administration (FDA) available for persons with a chronic hepatitis B infection: alpha-interferon, pegylated interferon, adefovir, entecavir, telbivudine, lamivudine, tenofovir disoproxil and tenofovir alafenamide with a 65% rate of sustained response.[ citation needed ]

Hepatitis C

Hepatitis C (originally "non-A non-B hepatitis") is caused by hepatitis C virus (HCV), an RNA virus of the family Flaviviridae. HCV can be transmitted through contact with blood (including through sexual contact if the two parties' blood is mixed) and can also cross the placenta. Hepatitis C usually leads to chronic hepatitis, culminating in cirrhosis in some people. It usually remains asymptomatic for decades. Patients with hepatitis C are susceptible to severe hepatitis if they contract either hepatitis A or B, so all persons with hepatitis C should be immunized against hepatitis A and hepatitis B if they are not already immune, and avoid alcohol. HCV can lead to the development of hepatocellular carcinoma, however, only a minority of HCV-infected individuals develop cancer (1–4% annually), suggesting a complex interplay between viral gene expression and host and environmental factors to promote carcinogenesis. The risk is increased two-fold with active HBV coinfection and a 21% increase in mortality compared to those with latent HBV and HCV. [13] HCV viral levels can be reduced to undetectable levels by a combination of interferon and the antiviral drug ribavirin. The genotype of the virus is the primary determinant of the rate of response to this treatment regimen, with genotype 1 being the most resistant.[ citation needed ]

Hepatitis C is the most common chronic bloodborne infection in the United States, and the leading cause of liver tranplants. [14]

Hepatitis C [15]
MarkerDetection TimeDescriptionSignificanceNote
HCV-RNA1–3 weeks or 21 days PCR Demonstrates presence or absence of virusResults may be intermittent during course of infection. Negative result is not indicative of absence.
anti-HCV5–6 weeksEnzyme Immunoassay for antibodiesDemonstrates past or present infectionHigh false positive in those with autoimmune disorders and populations with low virus prevalence.
ALT5–6 weeks–Peak in ALT coincides with peak in anti-HCVFluctuating ALT levels is an indication of active liver disease.

Hepatitis D

Hepatitis D is caused by the hepatitis D virus (HDV), or hepatitis delta virus; it belongs to the genus Deltavirus. HDV is similar to a satellite virus as it can only propagate in the presence of the hepatitis B virus, depending on the helper function of HBV for its replication and expression. It has no independent life cycle, but can survive and replicate as long as HBV infection persists in the host body. It can only cause infection when encapsulated by hepatitis B virus surface antigens. The vaccine for hepatitis B protects against hepatitis D virus because of the latter's dependence on the presence of hepatitis B virus for it to replicate. [9] [16]

Hepatitis E

Hepatitis E is caused by the Hepatitis E virus (HEV), from the family Hepeviridae. It produces symptoms similar to hepatitis A, although it can take a fulminant course in some patients, particularly pregnant women (mortality rate about 20%); chronic infections may occur in immune-compromised patients. It is more prevalent in the Indian subcontinent. The virus is feco-orally transmitted and is usually self-limited.[ citation needed ]

Hepatitis F virus

Hepatitis F virus (HFV) is a hypothetical virus linked to certain cases of hepatitis. Several hepatitis F virus candidates emerged in the 1990s, but none of these reports have been substantiated. [17]

GB virus C

The GB virus C is a virus that is probably spread by blood and sexual contact. [18] It was initially identified as Hepatitis G virus. [19] There is very little evidence that this virus causes hepatitis, as it does not appear to replicate primarily in the liver. [20] It is now classified as GB virus C. [21]

2022 hepatitis of unknown origin

In 2022, several hundred cases of acute hepatitis of probable infectious origin were reported worldwide. [22] [23] As of May 2023, the virus causing these cases has not been identified, but an adenovirus is suspected. [24] [25]

Relationship between hepatitis C virus and liver cancer

Hepatitis C virus (HCV) can cause acute and chronic infections that are a major cause of hepatocellular carcinoma (HCC), advanced hepatic fibrosis and cirrhosis.[ citation needed ]

HCC is a major cause of death in patients with chronic HCV infection. Regarding the pathogenesis of HCC associated with HCV, that virus may play direct or indirect roles. [26]

A major risk for the development of HCC is persistent infection with HCV, and the highest risk for HCC development is associated with co-infection of HBV with HDV, HCV or HIV. [27]

Risk factors that can lead to the development of HCC in those with chronic HCV include synchronous liver diseases, viral genotype, diabetes mellitus, and obesity. Lifestyle factors such as liver steatosis, smoking, and alcohol use can accelerate progression to HCC and liver decompensation in patients with HCV. [3]

The purpose of HCV treatment is to eliminate the infection, reduce the transmission to other people and decrease the risk of HCC development. [3]

Other viruses

The virus first known to cause hepatitis was the yellow fever virus, a mosquito-borne flavivirus. Other viruses than can cause hepatitis include:

Additionally, a casual role between the virus KIs-V and hepatitis is suspected based on a 2011 study that isolated KIs-V from four patients with raised serum alanine transferases without other known cause. [36]

Related Research Articles

<span class="mw-page-title-main">Hepatitis</span> Inflammation of the liver

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.

<span class="mw-page-title-main">Hepatitis C</span> Human viral infection

Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include fever, dark urine, abdominal pain, and yellow tinged skin. The virus persists in the liver, becoming chronic, in about 70% of those initially infected. Early on, chronic infection typically has no symptoms. Over many years however, it often leads to liver disease and occasionally cirrhosis. In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach.

<span class="mw-page-title-main">Hepatocellular carcinoma</span> Medical condition

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.

<span class="mw-page-title-main">Liver disease</span> Medical condition

Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.

<span class="mw-page-title-main">Oncovirus</span> Viruses that can cause cancer

An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term oncornaviruses was used to denote their RNA virus origin. With the letters RNA removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with tumor virus or cancer virus. The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease of the liver which lasts over a period of six months. It consists of a wide range of liver pathologies which include inflammation, liver cirrhosis, and hepatocellular carcinoma. The entire spectrum need not be experienced.

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) co-infection is a multi-faceted, chronic condition that significantly impacts public health. According to the World Health Organization (WHO), 2 to 15% of those infected with HIV are also affected by HCV, increasing their risk of morbidity and mortality due to accelerated liver disease. The burden of co-infection is especially high in certain high-risk groups, such as intravenous drug users and men who have sex with men. These individuals who are HIV-positive are commonly co-infected with HCV due to shared routes of transmission including, but not limited to, exposure to HIV-positive blood, sexual intercourse, and passage of the Hepatitis C virus from mother to infant during childbirth.

Hepatitis B is endemic in China. Of the 350 million individuals worldwide infected with the hepatitis B virus (HBV), one-third reside in China. As of 2006 China has immunized 11.1 million children in its poorest provinces as part of several programs initiated by the Chinese government and as part of the Global Alliance for Vaccines and Immunization (GAVI). However, the effects of these programs have yet to reach levels of immunization that would limit the spread of hepatitis B effectively.

<span class="mw-page-title-main">Liver cancer</span> Medical condition

Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondary, in which the cancer spreads from elsewhere in the body to the liver. Liver metastasis is the more common of the two liver cancers. Instances of liver cancer are increasing globally.

Cancer immunoprevention is the prevention of cancer onset with immunological means such as vaccines, immunostimulators or antibodies. Cancer immunoprevention is conceptually different from cancer immunotherapy, which aims at stimulating immunity in patients only after tumor onset, however the same immunological means can be used both in immunoprevention and in immunotherapy.

<span class="mw-page-title-main">Hepatitis B</span> Human viral infection

Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.

<i>Hepatitis B virus</i> Species of the genus Orthohepadnavirus

Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B.

miR-122

miR-122 is a miRNA that is conserved among vertebrate species. miR-122 is not present in invertebrates, and no close paralogs of miR-122 have been detected. miR-122 is highly expressed in the liver, where it has been implicated as a regulator of fatty-acid metabolism in mouse studies. Reduced miR-122 levels are associated with hepatocellular carcinoma. miR-122 also plays an important positive role in the regulation of hepatitis C virus replication.

Patrizia Paterlini-Bréchot, born in the Italian city of Reggio Emilia, is an Italian scientist and a professor of cell biology and oncology working at the Faculté de Médecine Necker-Enfants Malades, Université Paris Descartes and at INSERM in Paris.

<span class="mw-page-title-main">Infectious causes of cancer</span> Pathogens as a cause of cancer

Estimates place the worldwide risk of cancers from infectious causes at 16.1%. Viral infections are risk factors for cervical cancer, 80% of liver cancers, and 15–20% of the other cancers. This proportion varies in different regions of the world from a high of 32.7% in Sub-Saharan Africa to 3.3% in Australia and New Zealand.

The transmission of hepadnaviruses between their natural hosts, humans, non-human primates, and birds, including intra-species host transmission and cross-species transmission, is a topic of study in virology.

<span class="mw-page-title-main">Neonatal infection</span> Human disease

Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or within the first four weeks of life. Neonatal infections may be contracted by mother to child transmission, in the birth canal during childbirth, or after birth. Neonatal infections may present soon after delivery, or take several weeks to show symptoms. Some neonatal infections such as HIV, hepatitis B, and malaria do not become apparent until much later. Signs and symptoms of infection may include respiratory distress, temperature instability, irritability, poor feeding, failure to thrive, persistent crying and skin rashes.

Christian Bréchot is a French physician and scientist who has been serving as president of the Global Virus Network (GVN) since 2017. He previously served as president of the Institut Pasteur from 2013 until 2017 and as chief executive officer of the French National Institute for Health and Medical Research (INSERM) from 2001 to 2007.

<i>Ground squirrel hepatitis virus</i> Species of virus

Ground squirrel hepatitis virus, abbreviated GSHV, is a partially double-stranded DNA virus that is closely related to human Hepatitis B virus (HBV) and Woodchuck hepatitis virus (WHV). It is a member of the family of viruses Hepadnaviridae and the genus Orthohepadnavirus. Like the other members of its family, GSHV has high degree of species and tissue specificity. It was discovered in Beechey ground squirrels, Spermophilus beecheyi, but also infects Arctic ground squirrels, Spermophilus parryi. Commonalities between GSHV and HBV include morphology, DNA polymerase activity in genome repair, cross-reacting viral antigens, and the resulting persistent infection with viral antigen in the blood (antigenemia). As a result, GSHV is used as an experimental model for HBV.

References

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