Hepatitis (A/B/C)

Overview

Hepatitis is described as liver inflammation caused by a range of factors such as excessive alcohol use, autoimmune disease, medications, or pollutants. However, the most common cause of hepatitis is a viral infection, which is known as viral hepatitis.

Hepatitis A, B, and C are the most frequent kinds of viral hepatitis in the United States. Hepatitis D and E are the two kinds of viral hepatitis that are less common. The severity of hepatitis can range from moderate and self-limiting to severe sickness needing liver replacement, depending on the cause. 

What is Viral Hepatitis?

Viral hepatitis, a major health-care burden across the world, is defined as virally caused liver inflammation. Numerous viruses, including but not limited to Epstein-Barr virus, Herpes simplex virus, and Cytomegalovirus, are known to induce liver inflammation. The most prevalent causes, however, are the hepatotropic viruses A through E. Although types B, C, and E have the potential to become chronic, the majority of hepatotropic viruses are acute and self-limiting. There are several genotypes of the viruses, with some being more prevalent in certain geographical areas than others.

Furthermore, various genotypes have varied rates of seroconversion to chronic hepatitis and respond differently to different therapies. Chronic hepatitis can result in serious consequences such as cirrhosis and hepatocellular carcinoma. According to one estimate, viral hepatitis and its consequences cause 1 to 4 million deaths globally each year. Hepatitis B and C are responsible for the great majority of fatalities.

Acute hepatitis is distinguished from chronic hepatitis by the length of the inflammation/injury to the liver. If the liver inflammation lasts less than 6 months, it is called acute hepatitis; if it lasts more than 6 months, it is called chronic hepatitis. Acute hepatitis normally resolves on its own, but depending on the etiology, it might induce fulminant liver failure. Chronic hepatitis, on the other hand, can induce liver damage such as fibrosis, cirrhosis, hepatocellular carcinoma, and portal hypertension, resulting in severe morbidity and death.

Epidemiology

HAV develops intermittently and infrequently, generating outbreaks. Historically, endemic regions have been underdeveloped nations with low hygienic conditions. Natives are often infected as children and do not exhibit symptoms. They develop immunity and are able to prevent re-infection later in life. Individuals from industrialized nations with acceptable sanitary standards, on the other hand, are at risk while traveling to endemic areas due to a lack of exposure in childhood.

Because they are teens or adults with stronger immune systems, these populations have substantially more severe symptoms. In most cases, fulminant hepatitis does not occur. Africa, Asia, and South and Central America are among the endemic regions.

Sub-Saharan Africa and the Western Pacific have the highest rates of HBV infection. Transmission often occurs vertically or in early infancy in countries with high incidence of chronic HBV infection. This is the most likely moment for seroconversion to chronic illness. Due to the predominate genotypes of those regions, evidence shows that women of reproductive age are at peak infectivity in high-prevalence places. There is no high degree of infectivity in women of reproductive age in areas of moderate or low incidence where diverse genotypes exist.

As a result, the incidence of prenatal and childhood infection, as well as chronic illness, declines from high to low prevalence areas. The great majority of infections in low-prevalence locations are caused by sexual contact, intravenous drug use, and healthcare-related incidents in teenagers or adults.

The distribution of HCV infection among different age groups varies depending on the location studied. In the United States, for example, the prevalence of infection is greatest among people aged 30 to 49, owing mostly to injectable drug use. Individuals aged 50 and up, however, had the highest prevalence of illness in other countries. Africa and Asia have the greatest rates of HCV infection.

Those with persistent HBV infection are the most vulnerable to HDV infection. Surprisingly, HDV's geographic distribution differs from that of HBV. The Middle East, Asia, Africa, the Amazonian basin, and the Pacific islands are all endemic. According to recent studies, the largest frequency is among persons aged 20 to 39, notably in the Amazonian Basin.

Like hepatitis A, the majority of HEV-infected areas are in poorer countries with inadequate hygienic standards. The virus may be contracted by consuming raw or undercooked animal products, not just in resource-poor places but even in developed countries where these items are regarded delicacies. Infected moms can also spread the virus to their unborn children, though this is uncommon.

There has also been a report of a transfusion-related infection. Infection with the Hepatitis E virus is very dangerous in pregnant women. When compared to age-matched males and non-pregnant women, pregnant women had greater rates of illness and fulminant hepatic failure. Infection rates are highest in Asia, Africa, the Middle East, and Central America.

Viral Hepatitis causes 

Hepatitis is usually caused by hepatitis viruses A, B, C, D, and E. It is unknown if the Hepatitis G virus causes disease in people. Hepatitis A, B, C, and D are prevalent in the United States, with hepatitis A, B, and C viruses causing 90% of acute viral hepatitis and Hepatitis C being the most frequent chronic hepatitis cause. 

• Hepatitis A

Hepatitis A is caused by an RNA virus of the Picornaviridae family. It is most often seen in the feces of infected people, with the maximum viral load shedding happening at the end of the incubation period. The fecal-oral route is the most prevalent means of transmission of hepatitis A by contact with food, water, or items contaminated with fecal matter from an infected individual. It is more frequent in underdeveloped nations, where fecal-oral transmission is more likely due to poverty and a lack of cleanliness.

• Hepatitis B

Hepatitis B virus is a DNA virus that belongs to the Hepadnaviridae family. Hepatitis B virus can be identified at low levels in the blood, sperm, vaginal mucus, saliva, and tears but not in feces, urine, or perspiration. According to estimates, around 2.2 million persons in the United States have chronic hepatitis B virus infection. It is spread parenterally and sexually when people come into touch with infected people's mucosal membranes or bodily fluids.

 Parenteral and percutaneous exposures include transfusion of blood and blood products, injection drug use with shared needles, needlesticks or wounds caused by other instruments in healthcare workers, and hemodialysis, but parenteral mode remains the dominant mode of transmission both globally and in the United States.

Intravenous drug users, men who have sex with men, healthcare workers exposed to infected body fluids, patients requiring frequent and multiple blood transfusions, people with multiple sexual partners, prisoners, partners of hepatitis B virus carriers, and people born in endemic areas are all at high risk of hepatitis B virus infection.

• Hepatitis C

Hepatitis C virus is an RNA virus that belongs to the Flaviviridae family and has one serotype, at least six main genotypes, and over 80 subtypes. The high genetic heterogeneity makes developing a vaccination to prevent hepatitis C virus infection difficult. Parenteral, perinatal, and sexual transmission are all possible, with the most prevalent mechanism being the sharing of infected needles among IV drug users. People who require regular blood transfusions and organ transplants from contaminated donors are also high-risk categories. Sexual and perinatal transmission is uncommon.

• Hepatitis D

Hepatitis D is an RNA virus that belongs to the Deltavirus genus. Because it includes the hepatitis D antigen and RNA strand and uses HBsAg as its envelope protein, persons who have hepatitis D virus infection also get hepatitis B virus infection. Hepatitis D virus transmission is comparable to that of hepatitis B virus, however perinatal transmission is infrequent.

• Hepatitis E

Hepatitis E is an RNA virus that belongs to the Hepevirus genus. The fecal-oral pathway is the predominant method of transmission. The most prevalent way is by fecally contaminated water, but person-to-person transmission is uncommon. However, the maternal-neonatal transmission does occur on occasion.

Viruses such as cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and varicella-zoster virus are less common causes of hepatitis, although they do not predominantly affect the liver.

Pathophysiology

Whether a virus enters the body by the blood or the digestive tract, it ultimately makes its way to the liver, where it enters hepatocytes, multiplies, and releases virions. Replication is accomplished by either direct translation of viral RNA or reverse transcription of viral DNA. Hepatocyte injury can be rapid and self-limiting, or it can be subtle and persistent.

The host immunological response to viral antigens produced by infected hepatocytes, rather than the cytopathic effects of the viruses themselves, mediates the process of hepatocyte injury. The transition of HBV and HCV infection to chronic infection is related with a decrease in virus-specific T-cells. According to research, fatigue of these virus-specific T-cells results in an inability to remove the viruses, allowing the viruses to reside chronically in host hepatocytes.

Viral Hepatitis symptoms 

Recent travel to endemic locations, parenteral exposure (intravenous drug use, blood transfusion prior to 1992), and close or sexual interaction with persons known to have hepatitis or suffering from jaundice are all historical indicators of viral hepatitis infection. Patients should always be questioned about their immunosuppressive status, organ transplants, and exposure to raw meat.

Patients may have fever, anorexia, lethargy, nausea, vomiting, fullness or discomfort in the right upper quadrant, jaundice, dark urine, and pale stools. Some people are asymptomatic, while others may have severe liver failure. A physical examination may indicate scleral icterus or jaundice, hepatomegaly, and pain in the right upper quadrant.

Diagnosis

Elevated aminotransferases and bilirubin levels are frequently found in laboratory tests. Acute hepatitis is often characterized by aminotransferase levels in the thousands. Chronic hepatitis manifests differently, with aminotransferase levels often increased to 2 to 10 times the upper limit of normal.

In the diagnosis of acute and chronic viral hepatitis, enzyme-linked immunosorbent assays (ELISA) and polymerase chain reaction (PCR) are utilized.

• HAV: IgM antibody is used to diagnose acute infection. IgG positivity but IgM negativity implies previous exposure.
• HBV: The presence of surface antigen, IgM core antibody, envelope antigen, and viral load indicates acute infection. However, there is a "window time" during which the surface antigen fades before IgG antibody to the surface antigen emerges. The presence of surface antigen for more than 6 months, IgG core antibody, and HBV DNA, as well as the lack of surface antibody, all indicate chronic HBV infection.
• HCV: The presence of HCV RNA, with or without IgM antibodies, indicates acute infection. The presence of HCA RNA in conjunction with the presence of the IgG antibody indicates chronic infection. If a patient's infection is cleared, there will be no detectable HCV RNA, whether or not HCV antibodies are present.

Viral Hepatitis Management

HAV is handled in a supportive manner and usually resolves on its own. The treatment of acute HBV infection is mostly supportive; nevertheless, certain subpopulations require antiretroviral therapy. Individuals who are symptomatic, have increased bilirubin levels more than 3 mg/dl for more than four weeks, develop coagulopathy, or have acute liver failure are among these subpopulations. Monotherapy with tenofovir, entecavir, lamivudine, or telbivudine is one option for antiretroviral treatment. The decision to treat chronic infection is influenced by a number of circumstances, which are discussed in the HBV review issue.

Direct-acting antivirals (DAAs) are the preferred therapy for HCV infection. Different genotypes, however, respond better to particular DAAs than others. Another challenge is deciding whether to treat a patient at the onset of acute infection or to wait until the condition becomes chronic before treatment. This will be covered in the HCV review subject.

Acute HDV infection is mostly treated with supportive care. Furthermore, despite the absence of meaningful evidence, pegylated interferon alpha appears to be the therapy of choice in individuals with persistent HDV infection.

In immunocompetent people, HEV is generally self-limiting, with viremia lasting just approximately three weeks. In the case of acute and self-limiting sickness, supportive care with vitamin replacement and symptomatic cholestasis therapy is the mainstay. Ribavirin is most typically used to treat persistent HEV infection in solid organ transplant recipients.

Finally, viral hepatitis infections that result in fulminant hepatic failure necessitate prompt transfer to a liver transplant institution for liver transplant assessment.

Differential Diagnosis

Many different conditions can appear with symptoms and signs similar to those seen in hepatitis patients. Malaise, weariness, low-grade fever, anorexia, weight loss, nausea, vomiting, and other symptoms are common in patients with acute and chronic active viral hepatitis infections. Patients may appear perfectly normal on physical examination, or they may have right upper quadrant discomfort, hepatomegaly, an urticarial rash, and symptoms of dehydration.

Patients in the later phases of chronic viral hepatitis may present with hematemesis, ascites, pedal edema, encephalopathy, and other symptoms. Many additional acute or chronic viral or non-infectious illnesses have similar symptoms and indications.

Patients with viral or bacterial gastroenteritis, acute cholecystitis, acute cholelithiasis, TB, HIV, liver abscess, malignancies such as pancreatic cancer, lymphoma, and hepatocellular carcinoma, small intestinal obstruction, and peptic ulcer disease may exhibit signs and symptoms that overlap. Due to hepatic congestion, patients with severe congestive heart failure may appear with pedal edema, ascites, and hepatomegaly. Patients with gastrointestinal bleeding from other causes, such as cirrhosis from severe non-alcoholic steatohepatitis, can appear in the same way as patients with advanced liver disease from viral, autoimmune, or alcoholic hepatitis.

Patients in their 50s or 60s with hereditary hemochromatosis may appear with stomach discomfort, weariness, weakness, and symptoms and indications of liver failure. Hereditary hemochromatosis is an autosomal recessive condition in which the body's iron homeostasis is disrupted and excess iron accumulates in multiple organs, including the liver. Typically, serum iron, ferritin, and transferrin levels are used to make a diagnosis.

A liver biopsy may be required to determine the extent of fibrosis and to distinguish it from other liver illnesses such as viral or autoimmune hepatitis. Patients may complain of joint discomfort, and some may complain of pain in the knuckles of the first two fingers, known as the "iron fist" sign. This symptom is unique to hereditary hemochromatosis and does not appear in all individuals. Patients with drug-induced hepatitis and congenital hepatopathies might also present similarly, and a thorough history is essential when evaluating the patients.

Drug-induced liver damage has becoming increasingly widespread, and over a thousand medications have been discovered, with research underway to learn more about them. Drug-induced liver damage can be entirely asymptomatic, with just test abnormalities of increased aminotransferases to acute or chronic hepatitis or acute liver failure, and they continue to be one of the leading reasons of emergency liver transplants. The uncontrolled use of herbal and nutritional supplements has introduced a new barrier in identifying and treating patients as soon as possible.

Prognosis

HAV is a short-term disease. Only a small percentage of individuals with acute HAV infection progress to fulminant hepatic failure. Furthermore, the HAV vaccination provides nearly complete protection. There is a rare relapsing-remitting form of HAV that resolves spontaneously within a year and requires no intervention other than supportive care.

Acute HBV infection has less than a 1% probability of resulting in acute liver failure. Older persons, those with previous liver disease, and the immunocompromised are more likely to develop a serious infection than others. Furthermore, less than 5% of immunocompetent persons will become chronic carriers, lowering the risk of cirrhosis and hepatocellular cancer. Vaccination has resulted in a considerable reduction in disease burden.

The likelihood of seroconversion to chronic hepatitis C infection is estimated to be between 75% and 85%. As a result, there is a substantially increased chance of developing cirrhosis and hepatocellular cancer. However, with the introduction of DAAs, more than 90% of chronic HCV infected individuals can achieve persistent viral clearance.

In individuals with chronic hepatitis B, HDV coinfection and superinfection hastens the development to cirrhosis. Vaccination aids in the prevention of superinfection.

In immunocompetent people, HEV generally causes a brief sickness. Individual immunocompromised persons, including those with solid organ transplants, positive HIV status, and those with leukemia and lymphoma, can develop persistent viremia, chronic hepatitis, liver fibrosis, and cirrhosis.

Viral Hepatitis Complications

Chronic infection with chronic active hepatitis, acute or subacute hepatic necrosis, cirrhosis, liver failure, and hepatocellular cancer in people with hepatitis B or C infection are all complications of viral hepatitis. Patients infected with hepatitis B are at a significant risk of acquiring chronic infection. Patients are also at high risk of developing hepatocellular carcinoma, which accounts for 45 percent of all primary liver cancer cases globally.

Approximately 1% of patients may suffer fulminant hepatic failure, with a death rate of approximately 80%. About 75 to 85 percent of people who become infected with hepatitis C acquire chronic infection, and about 20 percent develop cirrhosis and, finally, hepatocellular cancer. Cirrhosis caused by hepatitis C is the major cause of liver transplantation in the United States.

Cirrhosis can lead to a variety of consequences, including hepatic encephalopathy, portal hypertension, ascites, spontaneous bacterial peritonitis, variceal hemorrhage, hepatorenal syndrome, and others. Patients with chronic hepatitis C are at a high risk of developing extrahepatic complications such as cryoglobulinemia, which can cause rash, vasculitis, and glomerulonephritis due to immune complex deposition in small vessels, non-Hodgkin lymphoma, focal lymphocytic sialadenitis, autoimmune thyroiditis, porphyria cutanea tarda, lichen planus, and others.

Conclusion 

Viral hepatitis is an illness that causes inflammation and damage to the liver. Inflammation is the swelling that happens when bodily tissues are harmed or diseased. Organs can be damaged by inflammation. The five unrelated hepatotropic viruses hepatitis A, B, C, D, and E are the most prevalent causes of viral hepatitis. Other viruses, such as cytomegalovirus, Epstein-Barr virus, and yellow fever, can also induce liver inflammation. There have also been several cases of viral hepatitis caused by the herpes simplex virus.