About hepatitis

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Hepatitis

Hepatitis refers to an inflammatory condition of the liver. It is commonly caused by a viral infection, but there are other possible causes of hepatitis. These include autoimmune hepatitis and hepatitis that occurs as a secondary result of medications, drugs, toxins and alcohol.

Types of viral hepatitis

Viral infections of the liver that are classified as hepatitis includes:

Causes of noninfectious hepatitis

Metabolic

Alcoholic hepatitis: Excessive alcohol consumption is a significant cause of hepatitis and is the most common cause of cirrhosis in the U.S. Alcoholic hepatitis is within the spectrum of alcoholic liver disease. This ranges in order of severity and reversibility from alcoholic steatosis (least severe, most reversible), alcoholic hepatitis, cirrhosis, and liver cancer (most severe, least reversible). Hepatitis usually develops over years-long exposure to alcohol, occurring in 10 to 20% of alcoholics. The most important risk factors for the development of alcoholic hepatitis are quantity and duration of alcohol intake. Long term alcohol intake in excess of 80 grams of alcohol a day in men and 40 grams a day in women is associated with development of alcoholic hepatitis (1 beer or 4 ounces of wine is equivalent to 12g of alcohol). Alcoholic hepatitis can vary from asymptomatic hepatomegaly (enlarged liver) to symptoms of acute or chronic hepatitis to liver failure.

Toxic and drug-induced hepatitis: Many chemical agents, including medications, industrial toxins, and herbal and dietary supplements, can cause hepatitis. The spectrum of drug-induced liver injury varies from acute hepatitis to chronic hepatitis to acute liver failure. Toxins and medications can cause liver injury through a variety of mechanisms, including direct cell damage, disruption of cell metabolism, and causing structural changes. Some drugs such as paracetamol exhibit predictable dose-dependent liver damage while others such as isoniazid cause idiosyncratic and unpredictable reactions that vary among individuals. There are wide variations in the mechanisms of liver injury and latency period from exposure to development of clinical illness.

Many types of drugs can cause liver injury, including the analgesicparacetamol; antibiotics such as isoniazid, nitrofurantoin, amoxicillin-clavulanate, erythromycin, and trimethoprim-sulfamethoxazole; anticonvulsants such as valproate and phenytoin; cholesterol-lowering statins; steroids such as oral contraceptives and anabolic steroids; and highly active anti-retroviral therapy used in the treatment of HIV/AIDS. Of these, amoxicillin-clavulanate is the most common cause of drug-induced liver injury, and paracetamol toxicity the most common cause of acute liver failure in the United States and Europe.

Non-alcoholic fatty liver disease: Non-alcoholic hepatitis is within the spectrum of non-alcoholic liver disease (NALD), which ranges in severity and reversibility from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) to cirrhosis to liver cancer, similar to the spectrum of alcoholic liver disease.

Non-alcoholic liver disease occurs in people with little or no history of alcohol use, and is instead strongly associated with metabolic syndrome, obesity, insulin resistance and diabetes, and hypertriglyceridemia. Over time, non-alcoholic fatty liver disease can progress to non-alcoholic steatohepatitis, which additionally involves liver cell death, liver inflammation and possible fibrosis. Factors accelerating progression from NAFLD to NASH are obesity, older age, non-African American ethnicity, female gender, diabetes mellitus, hypertension, higher ALT or AST level, higher AST/ALT ratio, low platelet count, and an ultrasound steatosis score.

In the early stages (as with NAFLD and early NASH), most patients are asymptomatic or have mild right upper quadrant pain, and diagnosis is suspected on the basis of abnormal liver function tests. As the disease progresses, symptoms typical of chronic hepatitis may develop. While imaging can show fatty liver, only liver biopsy can demonstrate inflammation and fibrosis characteristic of NASH. 9 to 25% of patients with NASH develop cirrhosis. NASH is recognized as the third most common cause of liver disease in the United States.

Autoimmune

Autoimmune hepatitis is a chronic disease caused by an abnormal immune response against liver cells. The disease is thought to have a genetic predisposition as it is associated with certain human leukocyte antigens involved in the immune response. As in other autoimmune diseases, circulating auto-antibodies may be present and are helpful in diagnosis. Auto-antibodies found in patients with autoimmune hepatitis include the sensitive but less specificanti-nuclear antibody (ANA), smooth muscle antibody (SMA), and atypical perinuclearantineutrophil cytoplasmic antibody (p-ANCA). Other autoantibodies that are less common but more specific to autoimmune hepatitis are the antibodies against liver kidney microsome 1 (LKM1) and soluble liver antigen (SLA). Autoimmune hepatitis can also be triggered by drugs (such as nitrofurantoin, hydralazine, and methyldopa), after liver transplant, or by viruses (such as hepatitis A, Epstein-Barr virus, or measles).

Autoimmune hepatitis can present anywhere within the spectrum from asymptomatic to acute or chronic hepatitis to fulminant liver failure. Patients are asymptomatic 25–34% of the time, and the diagnosis is suspected on the basis of abnormal liver function tests. Up to 40% of cases present with signs and symptoms of acute hepatitis. As with other autoimmune diseases, autoimmune hepatitis usually affects young women (though it can affect patients of either sex of any age), and patients can exhibit classic signs and symptoms of autoimmunity such as fatigue, anemia, anorexia, amenorrhea, acne, arthritis, pleurisy, thyroiditis, ulcerative colitis, nephritis, and maculopapular rash. Autoimmune hepatitis increases the risk for cirrhosis, and the risk for liver cancer is increased by about 1% for each year of the disease.

Many people with autoimmune hepatitis have other autoimmune diseases. Autoimmune hepatitis is distinct from the other autoimmune diseases of the liver: primary biliary cirrhosis and primary sclerosing cholangitis. However, all of these diseases can lead to scarring, fibrosis, and cirrhosis of the liver.

Genetic

Genetic causes of hepatitis include alpha-1-antitrypsin deficiency, hemochromatosis, and Wilson's disease. In alpha-1-antitrypsin deficiency, a co-dominant mutation in the gene for alpha-1-antitrypsin results in the abnormal accumulation of the protein within liver cells, leading to liver disease. Hemochromatosis and Wilson's disease are both autosomal recessive diseases involving abnormal storage of minerals. In hemochromatosis, excess amounts of iron accumulate in multiple body sites, including the liver, which can lead to cirrhosis. In Wilson's disease, excess amounts of copper accumulate in the liver and brain, causing cirrhosis and dementia.

When the liver is involved, alpha-1-antitrypsin deficiency and Wilson's disease tend to present as hepatitis in the neonatal period or in childhood. Hemochromatosis typically presents in adulthood, with the onset of clinical disease usually after age 50.

Ischemic hepatitis (also known as shock liver) results from reduced blood flow to the liver as in shock, heart failure, or vascular insufficiency. The condition is most often associated with heart failure but can also be caused by shock or sepsis. Blood testing of a person with ischemic hepatitis will show very high levels of transaminase enzymes (AST and ALT). The condition usually resolves if the underlying cause is treated successfully. Ischemic hepatitis rarely causes permanent liver damage.

Other

Hepatitis can also occur in neonates and is attributable to a variety of causes, some of which are not typically seen in adults. Congenital or perinatal infection with the hepatitis viruses, toxoplasma, rubella, cytomegalovirus, and syphilis can cause neonatal hepatitis. Structural abnormalities such as biliary atresia and choledochal cysts can lead to cholestatic liver injury leading to neonatal hepatitis. Metabolic diseases such as glycogen storage disorders and lysosomal storage disorders are also implicated. Neonatal hepatitis can be idiopathic, and in such cases, biopsy often shows large multinucleated cells in the liver tissue. This disease is termed giant cell hepatitis and may be associated with viral infection, autoimmune disorders, and drug toxicity.

Hepatitis A

Epidemiology

Hepatitis A virus (HAV) was first recognized in 1947, but it has been around for centuries. The two distinct forms of the virus were only identified in 1973, consisting of a RNA virus with four genotypes. It occurs worldwide but is highly prevalent in the developing countries and Greenland; however, the global incidence is decreasing because of improved sanitary and living conditions. In the United States, the incidence of hepatitis A has declined dramatically with the institution of the hepatitis A vaccine.

HAV is spread mainly by the fecal-oral route in low socioeconomic areas, but person to person spread has occurred in daycare centers, as have community epidemics from contaminated foods. Sexual intercourse, blood and intravenous drugs are minor routes of transmission of this virus as opposed to the other viral hepatitis disorders.

Clinical manifestations

HAV infection is usually an acute, self-limiting disease with no sequelae or chronic disease state. Its manifestations vary according to the age of the patient at presentation. Children usually have a silent or subclinical course as opposed to adults, who present with a wide range of symptoms, from an influenza like illness to fulminant hepatic failure.

Diagnosis

The diagnosis of HAV infection is made by the presence of antibodies against HAV in conjunction with the clinical picture. The incubation period is 30 days, with a range of 15 to 50 days. Hepatitis A virus (HAV) immunoglobulin M (IgM) is the gold standard for making the diagnosis; however HAV IgG appears early and remains positive for decades.

Treatment

Since HAV is usually a self-limiting disease, treatment is generally supportive. Eighty five percent (85%) of patients recover by three months, and nearly 100% will recover by six months. Death can occur in elderly patients or in those concomitantly infected with hepatitis C virus (HCV).

Prevention

Since HAV is predominately spread by the fecal-oral route, the mainstay of prevention is thorough hand washing, heating foods properly and avoiding water and raw foods in endemic areas. Household bleach (1:100 dilution) will adequately inactivate the virus. Passive immunity with intramuscular serum immune globulin given within two weeks of also provide protection against this virus.

Vaccinations

The current epidemic of hepatitis A could be avoided though a worldwide viral campaign. The vaccines are safe, efficacious and relatively inexpensive. The live attenuated vaccine is no longer in use because of the superiority of the inactivated vaccines. Therefore, the inactivated vaccines are the only Food and Drug Administration (FDA) approved vaccines that are used in the UnitedStates. The inactivated vaccine provides almost a 100% sero-conversion rate and a higher antibody response than even serum immune globulin.

Hepatitis B

Epidemiology

Hepatitis B virus (HBV) is a global problem, with > 350 million carriers worldwide and 1.25 million in the United States. An estimated 100,000 acute infections occur every year in the United States. The mortality is substantial; each year 5000 patients in the United States and > 1 million world-wide die. In high prevalence areas, the predominant mode of transmission is perinatal, while in low-prevalence areas it is by sexual transmission and intravenous drug use. Blood transfusions are another source of spread of HBV, which remains the number one transmitted blood borne virus in the health care environment.

Individuals with HBV are at risk of developing chronic infection, cirrhosis, hepatic decompensation and hepatocellular carcinoma. After the acute infection, 3% to 5% of adults and up to 95% of children fail to produce a sufficient immune response to clear the infection, thus going on to chronic hepatitis B.

Clinical manifestations

The clinical manifestations encompass a wide spectrum in the acute as well as the chronic state. The virus has an incubation period of two to six weeks. Up to 70% of the acute cases present as a subclinical anicteric state, and the remainder present with jaundice, nausea and vomiting, fevers, right upper quadrant pain and hepatomegaly or fulminant hepatic failure. Some of these can also present with extra hepatic manifestations.

If the LFTs are still elevated after six months, then the individual is considered to have a chronic HBV infection, but most patients with chronic hepatitis B are asymptomatic.

Diagnostic markers

The diagnosis of HBV is based on the clinical presentation (complete history and physical); serologic, virologic, and biochemical markers and occasionally histologic markers. Hepatitis B surface antigen (HBsAg) is the first serologic marker to appear after infection. Hepatitis B ‘‘e’’ antigen (HBeAg) indicates active viral replication, which makes a patient highly contagious. Hepatitis B core antibody (HBcAb) appears next and implies an acute or chronic state or early recovery period. Hepatitis B surface antibody (HBsAb) is the last to appear and implies recovery, immunity or the post-vaccine state.

Hepatitis B virus (HBV) DNA is a virologic marker that measures the level of viral replication. In the past, this was measured by non-amplified hybridization assays, which have been replaced by the current target amplification assays, such as polymerase chain reaction (PCR). Hepatitis B virus (HBV) has eight genotypes (A-H) based on DNA sequencing and geographic distribution. However, genotype testing is not used in clinical practice because its relevance remains uncertain and controversial.

Elevated LFTs are an indication of necroinflammation and represent the biochemical markers. An elevated PT, in conjunction with a low albumin, usually indicates a poor prognosis or chronicity. Histologic examination by liver biopsy is the most specific and accurate indicator of liver disease. Most individuals do not need a biopsy for diagnosis or prognosis. However, some individual with normal LFTs and elevated HBV DNA levels have substantial fibrosis on biopsy.

Hepatitis B serological markers

Hepatitis B surface antigen (HBsAg)

 Total hepatitis B core antibody (anti-HBc)

  IgM antibody to hepatitis B core antigen (IgM anti-HBc)

 Hepatitis B e antigen (HBeAg)

 Hepatitis B e antibody (HBeAb or anti-HBe)

  Hepatitis B surface antibody (anti-HBs)

 Treatment of HBV

The goals of HBV treatment are:

1) Prevent cirrhosis and its complications

2) Prevent hepatocellular carcinoma

3) Obtain undetectable HBV DNA levels

4) Normalize LFTs

5) Eradicate HBeAg

6) Improve histology.

The dilemma is that the above aims are difficult to achieve because no standard treatment algorithms, guidelines or treatment endpoints exist and because, patients usually present with conflicting data. Treatment should be considered for individuals who are HBsAg positive or DNA-positive by PCR. The care of the patient with normal ALT adds a further dilemma to the treatment options. With or without treatment, circulating HBsAg can disappear but HBV DNA can be found by PCR in the liver of many individuals. Regardless of the treatment, many experts believe that chronic HBV infection can be controlled but not cured.

Agents used to treat HBV include interferon, lamivudine, adefovir, entecavir and telbivudine. Tenofovir is approved to treat HIV and HBV co-infection only. The Asian-Pacific guide lines also include thymosin alpha, which is not an FDA-approved drug.

Interferon was the first drug used to treat HBV in most countries and has antiviral, antiproliferative, and immunomodulatory effects; in addition, it can achieve a durable response after a finite course of treatment (24-52 weeks). In general, elevated LFTs and low HBV DNA are the best predictors of treatment response. Interferon therapy, however, is costly, must be given by injection and has many side effects. The nucleoside or nucleotide analogues are more potent than interferon in suppressing the HBV DNA levels and can lead to undetectable levels by PCR; however, interferon has immunmoduatory effects and is the only drug associated with HBVsAg conversion. Interferon usually causes a flare in the ALT level because of immune mediated lyses of the hepatocytes. This response, coupled with a later normalization of LFTs and a decrease in inflammation.

Polyethylene glycol (PEG) is attached to the interferon molecule to decrease its rate of absorption and renal and cellular clearance, which increases its half-life. This characteristic has propelled PEG-interferon as the drug of choice over standard interferon. PEG-interferon is safe in compensated but not decompensated cirrhosis.

Lamivudine, a nucleoside analog, was originally used to treat HIV disease. For HBV, it is well tolerated, is given orally (100 mg/day), is relatively inexpensive, has minimal side effects, and can be used in decompensated cirrhosis; however, it is associated with a high rate of drug resistance.

Adefovir, a nucleotide analog of adenosine, can be used in HBeAg positive or HBeAg negative patients and with compensated or decompensated cirrhosis. Its route of administration is oral (10 mg/day). It has a low rate of drug resistance, but its duration of therapy is greater than one year and the dose needs to be adjusted in renal insuffiency. Adefovir can be added to lamivudine in case of lamivudine resistance; therefore, most physicians prefer adefovir.

Entecavir is a nucleoside analog that is given orally at 0.51mg/day that suppresses HBV DNA levels to a greater extent than lamivudine and adefovir. It is associated with a low rate of drug resistance, and the duration of therapy is greater than one year. Entecavir has few side effects, but like lamivudine, it has a black box warning as a potential cause of lactic acidosis, hepatomegaly and steatosis.

Tenofovir is a nucleotide analog similar to adefovir, but it is more potent. It is effective against HIV and HBV and should only be used in co-infection with both diseases. Telbivudine is a nucleoside analogue that was recently approved by the FDA. It is administered orally (600 mg/day) and might suppress HBV DNA levels to a greater extent than the previous medications.

HBV Prevention

There are more than 350 million carriers worldwide with HBV and almost one million deaths per year. The greatest hope to prevent this disease is through primary prevention: safe sexual practices, intravenous drug avoidance, and vaccination to increase herd immunity. The HBV vaccine is safe, is relatively inexpensive, has a high sero-conversion rate, and is given in three doses intramuscularly.

Hepatitis C

Epidemiology

Hepatitis C infection affects > 170 million people worldwide and > 4 million Americans, but most are asymptomatic and unaware of their disease. Most patients acquired HCV by injection drug use or through pre-1990 blood transfusions. In the 1980s, 230,000 new cases were diagnosed each year in the United States, but now only 36,000 cases are diagnosed year because of decreased injection drug use and increased awareness. The risk of transmission between monogamous partners is low but rises with multiple sexual partners. Rare forms of percutaneous transmissions are tattoos, body piercing and intranasal cocaine use.

HCV is a small RNA virus with six genotypes and was first identified in 1989. Genotype 1 accounts for 70% to 75% of all HCV infections in the United States. It is the most common blood borne infection in the United States, and the highest prevalence is in persons aged 30-49 years old. In this age group, the highest prevalence occurs in African Americans.

Most acutely infected patients are asymptomatic or have a subclinical infection without jaundice. Chronic HCV infection develops in 60% to 80% of infected persons, probably secondary to rapid mutations that cause a failure in T-cell immune recognition. Hepatitis C virus (HCV) is the number one cause of chronic liver disease, cirrhosis and liver transplantation in the United States.

Diagnostic tests

Hepatitis C virus (HCV) DNA in the serum or liver is the first sign of infection. The virus becomes positive in tests days to weeks after exposure. This test detects, quantifies and characterizes the viral particle components. This test is further broken down into a qualitative and a quantitative test. The qualitative test is more sensitive, 98% to 99% specific and is done by either PCR or by transcription mediated amplification (TMA). The quantitative test can detect < 50 copies of the virus and is done by either PCR, TMA or branched chain DNA (bDNA).

The indirect tests (HCV and geno-typing) detect antibodies. The third generation enzyme assay detects HCV proteins. It becomes positive eight weeks after exposure and detects 99% of immunocompetent individuals. HCV genotyping detects type-specific antibodies and predicts treatment response.

Liver function tests (LFTs) start to rise 6 to 12 weeks after exposure, with a range of 20 to 26 weeks. However, ALT level correlates poorly with disease activity and many individuals have normal levels despite having chronic HCV.

The National Institutes of Health (NIH) Consensus Development Conference in 1997 endorsed pretreatment liver biopsy as the gold standard for assessing inflammation (grade) and extent of fibrosis (stage) in anticipation of instituting antiviral therapy. It is also used to determine the urgency of treatment and prognosis and it can rule out other diseases, such as fatty liver, alcoholic liver disease and hemochromatosis. A liver biopsy is not necessarily needed with genotypes 2 and 3, since these are associated with an excellent prognosis. In untreated patients,a repeat liver biopsy is the only reliable means of assessing the progression of fibrosis and it is recommended every three to five years.

Several histologic classifications are used to standardize results and comparisons when assessing results in different clinical trials. The three common scoring systems are Knodell, Metavir and Ishak systems. The Knodell score, also known as the histologic activity index and the Metavir score have four scores, from normal to cirrhosis. The Metavir score was designed to address some of the shortcomings of the Knodell system; in addition, it was designed specifically to stage hepatitis C.

Factors affecting prognosis

The factors that affect the progression of fibrosis with a detrimental effect are external or host related. External factors are alcohol consumption, drug use and cigarette smoking. The host related factors are advanced age at infection, being African American, male sex, immunosuppression or co-infection (e.g., HIV, HBV and HAV) and comorbidities (e.g., hemochromatosis and obesity).

Therapy for Hepatitis C

The 2002 NIH consensus conference recommended that all patients with hepatitis C should be considered potential candidates for therapy. Once a patient is treated, the optimal end point of therapy is sustained virologic response (SVR). The factors associated with a SVR are: genotype, absence of fibrosis, etc.

Hepatitis C virus (HCV) RNA testing is done before therapy, 12 weeks into therapy and 24 weeks after the end of therapy and its absence is a surrogate marker for resolution of liver injury, reduction in fibrosis and a low likelihood of recurrent HCV infection.

The guidelines for therapy can be broken down into three areas: those in whom therapy is widely accepted, those whose therapy should be individualized and those in whom therapy is contraindicated. Indications for therapy are age > 18 years, abnormal LFTs, HCV RNA level elevation and acceptable hematologic and biochemical values (hemoglobin > 13 g/dl, lack of significant thrombocytopenia, creatinine < 1.5 mg/dl and liver biopsy without significant fibrosis).

Therapy needs to be individualized in those with normal LFTs, continuous alcohol or drug use, prior treatment failures with the older regimens, age < 18 years, minimal liver involvement, decompensated cirrhosis and HIV co-infection. Absolute contraindications to therapy are pregnancy, major uncontrolled psychiatric disorders, autoimmune disorders, hemoglobinopathies, transplant recipients, severe co-morbid conditions (coronary artery disease, cerebrovascular accident, end-stage renal disease and chronic obstructive pulmonary disease) and hypersensitivity to the components of therapy.

The use of PEG rather than standard interferon with ribavirin increases SVR to 54% to 56% with genotype 1 and 82% with genotype 2 or 3. Two different formulations of PEG-interferon are available: interferon alfa-2a is dosed at 180 µg subcutaneously every week and interferon alfa-2b is dosed at 1.5 µg/kg subcutaneously every week. Either drug plus oral ribavirin 800 to 1200 mg (weight based dosing) once a day is given for 48 weeks with genotype 1. The NIH consensus conference recommended that with genotypes 2 or 3, PEG-interferon plus ribavirin 800 mg be used for 24 weeks. Regardless of the regimen, therapy should be discontinued if HCV RNA has not decreased by > 2 logs at 12 weeks.

Treatment is associated with many side effects and approximately 20% of patients experience severe side effects that result in discontinuation of their therapy. Before starting therapy, patients should be thoroughly educated about the side effects and self-management techniques to help them get through their therapy. Many of the side effects can be easily managed with proper dose reductions, growth factors, epoetin for anemia, increased fluids and exercise, acetaminophen, dosing the medications at night, diphenhydramine, serotonin reuptake inhibitors for depression, and thyroid medications.

Milk thistle has been advocated by some to be beneficial in the treatment of HCV. It lowers LFTs but does not affect the virus itself. Viramidine, a ribavirin prodrug, produces less hemolysis, lasts longer in the liver, is less concentrated in peripheral blood and has fewer overall side effects but is not FDA approved. The protease inhibitor VX-950 has shown promise in early clinical trials.

Hepatocellular carcinoma

Patients with hepatitis B, hemochromatosis, environmental toxins and cirrhosis due to any cause are at increased risk for developing hepatocellular carcinoma (HCC). Hepatitis C in many parts of the world is the number one cause though. Screening for HCC should include: upper endoscopy in those with cirrhosis, ultrasound and serum alfa fetoprotein every six months.

Vaccines

Individuals with chronic liver disease should receive vaccines for hepatitis A and B, pneumococcus and influenza.

Hepatitis D

Hepatitis D virus, also known as delta virus, is a defective RNA virus that can replicate on its own, but it requires concurrent HBV for assembly and secretion; as a result, patients with HDV are always dually infected with HBV. There are three genotypes; all are spread percutaneously, through injection drug use and through unprotected intercourse. The virus is endemic in the Mediterranean region and Asia. Hepatitis D virus (HDV) presents as either a co-infection like an acute hepatitis B infection with its manifestations or as a super infection- a severe, acute infection in a previously stable chronic hepatitis B patient.

Diagnosis

Since HDV is dependent on HBV, HBsAg is a requirement for the diagnosis of HDV infection. In addition, antibodies to HDV (IgM and IgG) are required for the diagnosis. Serum assays for HDAg are short lived and are not clinically available in the United States. HDV RNA can be detected by molecular hybridization or by PCR.

Treatment

The primary aim and endpoint of treatment are undetectable HDV RNA levels, normalization of LFTs and a decrease of inflammation on liver biopsy. A secondary aim is suppression of HBV DNA levels and sero-conversion of HBsAg to HBsAb. Interferon alfa is the only FDA approved drug against HDV. Ribavirin, lamivudine and other drugs are ineffective against HDV infection.

Prevention

Hepatitis B affects > 350 million people worldwide. Thus, the only way to prevent HDV is through primary education about its risk factors or through vaccination against HBV.

Hepatitis E

Epidemiology

The hepatitis E virus (HEV) is an RNA virus with four genotypes that was first described in India in 1955. It is a self-limiting, enterically transmitted disease like hepatitis A but is more severe, easily transmitted and distributed worldwide. Its highest incidence is in developing countries, and it is the second most common cause of sporadic hepatitis in northern Africa and the Middle East. It is usually spread by fecally contaminated water, but it can also be spread by blood and blood products. There is a low incidence of person to person transmission.

Manifestations

Hepatitis E virus (HEV) infection has an incubation period of 15 to 60 days. It presents like other acute hepatitis illnesses but with prolonged cholestatis. There is a low rate of fulminant hepatic failure, except in pregnant women, who have a mortality of 15% to 25%. The acute state usually lasts for up to six weeks and for those that recover there is no chronic state.

Diagnosis, treatment and prevention

Hepatitis E virus (HEV) infection is diagnosed by detecting HEV in the serum or feces by PCR or by detecting IgM antibodies. A March 1, 2007 NEJM article featured a new recombinant HEV vaccine that showed promise in a phase two trial from Nepal. Therefore, treatment is generally supportive since there is no FDA approved vaccine. Therefore, prevention entails avoiding contaminated water and un-cooked foods in endemic areas. 

References:

Ethnicity & Disease, Volume 17, Spring 2007

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