Viral hepatitis: Pathology Review

at your clinic 44 year old colin comes to the office because of abdominal pain for the past three months he has not been to a physician in 10 years and has been using iv drugs since he was 17. he does not drink alcohol and has no significant family history his temperature is 38.2 degrees celsius or 100.76 degrees fahrenheit pulse is 98 per minute respirations are 19 per minute and blood pressure is 126 over 84 millimeter of mercury physical examination shows a large distended abdomen yellow sclera palmer erythema and spider angioma on his abdomen and extremities lab results reveal the following hepatitis a igm antibody negative hepatitis b surface antigen negative hepatitis b surface antibody positive hepatitis b core antibody negative and hcv antibody positive at the same time a 32 year old pregnant individual named megan comes to the emergency department because of vomiting and fever the patient worked as a global health nurse and her medical history is relevant for recent traveling to nepal physical examination shows yellowing of the skin and sclera right upper quadrant tenderness and hepatomegaly her temperature is 38.5 degrees celsius or 101.3 degrees fahrenheit pulse is 97 per minute respirations are 15 per minute and blood pressure is 120 over 75 millimeters mercury both colin and megan have viral hepatitis which is inflammation of the liver parenchyma caused by hepatitis viruses a b c d or e based on the duration of symptoms hepatitis c can be acute which lasts less than six months or chronic which lasts more than six months individuals with acute viral hepatitis typically present with fatigue malaise nausea vomiting anorexia low-grade fever jaundice dark urine and right upper quadrant tenderness whereas individuals with chronic viral hepatitis can be asymptomatic or they can present with non-specific symptoms such as malaise and fatigue regardless of the virus that's causing it histopathology of viral hepatitis is characterized by two main findings first there's hepatocyte injury where the damaged hepatocytes swell up this is called ballooning degeneration second there's hepatocyte death and necrosis the dead cells are replaced by scar tissue which disrupts the normal architecture of hepatic lobules if the damage is severe enough dead hepatocytes can become confluent and form stripes that connect zones of adjacent lobules which is called bridging necrosis other histopathological findings include councilmen or apoptotic bodies lastly there's pan-lobular mononuclear infiltration where macrophages and lymphocytes move into the lobules in order to contain the infection and clear out the debris okay so each lobule can be divided into three zones zone one is closest to the portal triad so it's also called the periportal zone if we move towards the center we have zone two or the transitional zone and closest to the central vein we have zone 3 or the paracentral zone a high-yield concept to remember is that viral hepatitis affects zone 1 first ischemic injury and metabolic toxins like those from alcohol and acetaminophen metabolism affect zone 3 first as far as laboratory findings go viral hepatitis is associated with increased levels of serum aspartate transaminase or ast and alanine aminotransferase or alt it's important to note that in viral hepatitis drug-induced liver injury and ischemic hepatitis levels of serum alt are higher than ast in contrast to alcoholic hepatitis where serum asd is higher than alt and the ratio is usually 1 to greater than 1.5 so remember in viral hepatitis alt is higher the exception is when there's progression to advanced hepatic fibrosis and cirrhosis the ast will then become higher than alt okay now let's focus on the specific viruses starting with hepatitis a and hepatitis e viruses these viruses are naked viruses that do not rely on an envelope hepatitis a virus or hav is an rna picornovirus which is transmitted by the fecal oral root through ingestion of contaminated water or food such as shellfish it's the most common cause of acute viral hepatitis and populations at risk include travelers and those in day care centers the incubation period which typically lasts for 30 days can be followed by a silent or subclinical course which is characterized by the absence of symptoms or by the classic presentation of acute viral hepatitis along with hepatomegaly and aversion to smoking also keep in mind that hepatitis a infection is a self-limiting disease that does not progress to chronic hepatitis therefore the prognosis is usually good and there's no risk of cirrhosis or hepatocellular carcinoma a high-yield concept to know is that the anti-hav igm antibody is produced early in the infection so if detected it means there's an active infection the anti-hav igg antibody is the protective antibody produced later on or even after the infection has passed and it suggests prior infection or vaccination also hepatitis a virus does not have a carrier state where infected individuals do not have symptoms but can spread the infection to others treatment is supportive and generally there's a complete recovery within three to six weeks finally hepatitis a vaccine made from killed or inactivated hiv is indicated for people traveling to living or working in endemic areas individuals with chronic liver disease or clotting factor disorders and men who have sex with other men on the other hand passive immunization with immune globulin against hav should be given to individuals who were in close contact with an infected person the second type is hepatitis e virus or hev hepatitis e virus is a single stranded rna virus that belongs to the hepa virus family it's transmitted by the fecal oral root such as undercooked seafood or contaminated water and it can cause waterborne epidemics that are especially common in asia africa and the middle east hepatitis e virus is characterized by its short incubation period and usually lasts for six weeks after the incubation period individuals with hepatitis e virus infection typically present with a classic presentation of acute viral hepatitis and during this period they shed the virus in the stool just like hepatitis a hepatitis e infection is also a self-limiting disease that does not progress to chronic hepatitis therefore there's no risk of hepatocellular carcinoma also you have to know that in pregnant individuals this virus can cause fulminant hepatitis which is a life-threatening condition with severe liver function impairment as far as serology markers go at the early stages of infection while the person is still asymptomatic there's increased hev antigen or hev rna when symptoms appear there's an increase in serum levels of alt and ast because the liver gets damaged and this is the stage when anti-hev igm can be detected remember that igm indicate an active hepatitis infection on the other hand anti-hev igg are produced during the latest stage and they signal recovery from the infection finally the treatment for hepatitis e infection is supportive and there is currently no commonly used vaccine moving on to the third type which is hepatitis b virus or hbv this virus belongs to the dna hep adenovirus family on the surface of the mature virion there's a lipid envelope with hepatitis b surface antigen within the envelope there's a hexagonal protein capsid which consists of proteins called hepatitis b core antigen or just core antigen between the lipid envelope and capsid is a secretory hepatitis b e antigen within the capsid there's a partially double stranded viral dna and dna polymerase enzyme which has dna and rna-dependent activity now once the virion enters the cell the viral dna is transferred into the nucleus of the hepatocyte where dna polymerase turns the partially double-stranded dna into a fully double-stranded circular dna next the host rna polymerase transcribes the newly formed dna to make viral rna which is sent to the cytoplasm of the cell where it's used to synthesize viral proteins but that's not all you have to know that the dna polymerase then reverse transcribes the viral rna into a new partially double-stranded dna molecule and this will be packaged together with the newly synthesized viral proteins to make a new virus now hepatitis b virus has several modes of transmission first there's parenteral transmission or via blood and individuals who are at risk include intravenous drug users health care workers exposed to blood and needle stick accidents patients on dialysis and blood transfusion recipients but remember even though blood is the primary mode of transmission hepatitis b virus can also be detected in other bodily fluids such as saliva tears sweat semen and breast milk so the second route is sexual transmission and together with parenteral they are categorized as horizontal transmission the third type is perinatal transmission which is categorized as vertical transmission and this is when a mother transmits the infection to her infant either right before the birth via the placenta or during and after birth via blood body fluids or breast milk so once a person is infected they will go through a long incubation period that can last from 30 to 180 days the incubation period is usually followed by a prodrome period which is characterized by malaise fever arthralgias lymphadenopathy paritis and rash now after the prodrome the individual can develop acute hepatitis with complete resolution on the other hand some people will develop chronic hepatitis with or without cirrhosis in this case they might be in the carrier state where damage to the liver stops but they can still spread the infection to others finally they can also develop fulminant hepatitis which is characterized by rapid and massive necrosis of liver parenchyma and subsequent liver atrophy okay so a high yield concept is that in adults the possibility to progress to chronic hepatitis is less than five percent in children it is 20 to 30 percent while in neonates this number goes up to 90 percent therefore a baby born to a mother with active hepatitis b infection has to receive anti-hepatitis b immunoglobulin and the initial dose of the hepatitis b vaccine hepatitis b vaccine is a subunit vaccine meaning that it contains a hepatitis b surface antigen which stimulates the production of antibodies against this antigen interferon alpha is used in the treatment of chronic hepatitis b infection hepatitis b virus can also cause extra hepatic manifestations which can be subdivided into hematologic such as aplastic anemia renal which includes membranous glomerulonephritis which is more common and membranoproliferative glomerulonephritis which is less common and vascular such as polyarteritis nodosa now histopathology of an individual with chronic hepatitis b infection shows a granular eosinophilic ground glass appearance which is the hallmark of chronic hepatitis b infection this ground glass appearance occurs when the cytoplasm of hepatocytes gets filled with bits and pieces of hepatitis b viral proteins it's important to note that the virus itself is not cytotoxic instead the liver is damaged by the response of cytotoxic t cells to antigens that are presented on infected hepatocytes such as hepatitis b surface antigen and hepatitis b core antigen now let's move on to serological markers which are super high yield let's start with a hepatitis b surface antigen which indicates active hepatitis b infection and hepatitis b surface antibody which suggests recovery from infection or immunity due to vaccination next there's hepatitis b core antigen which can only be detected after liver biopsy and if positive indicates active viral replication on the other hand hepatitis b core antibody can be igm which is associated with recent hepatitis b infection typically in the last six months or igg which suggests resolved or chronic infection finally the hepatitis b e antigen also suggests active viral replication elevated levels of this antigen are closely linked to poor prognosis and high transmissibility a high yield fact to remember is that this is especially true for vertical transmission on the other hand antibody to hepatitis b e antigen is present after recovery from acute infection and is associated with low transmissibility now let's draw a graph of the serological markers in acute hepatitis b infection the vertical axis of the graph is the relative concentrations of serological markers the horizontal axis of the graph is time after exposure measured in months and on the top are phases of infection first there's the incubation period that lasts two months which is followed by prodrome and acute infection that lasts for three months the last phase is the recovery phase one month after exposure to the virus hepatitis b surface antigen starts to rise and peaks when the symptoms are most severe soon after hepatitis b surface antigen rises hepatitis b e antigen and viral dna appear and they indicate that the person is highly infectious these markers are further followed by the appearance of igm antibody to hepatitis b core antigen in the next few months these will go down and get replaced by igg antibody for your exam you have to know that the hepatitis b e antigen and viral dna disappear before the hepatitis b surface antigen shortly after hepatitis b e antigen disappears antibody to hepatitis b e antigen can be detected and at this stage the person is no longer highly infectious after that hepatitis b surface antigen will also disappear and the acute infection has passed antibodies to hepatitis b surface antigen will go up some time after these antibodies remain undetectable for several weeks and this period of infection without detectable hepatitis b surface antigen and antibodies to hepatitis b surface antigen is referred to as the window period this is high yield because it's possible to miss the infection based on serological markers during this period once detectable antibody to hepatitis b surface antigen rises and persists providing lifelong immunity finally we need to mention that at the end of the incubation period and during the acute phase of the infection a person will have elevated liver enzymes especially alt also you should not forget that if hepatitis b surface antigen persists after six months the person has progressed to chronic hepatitis b infection okay let's summarize the serological markers during the phases of infection an individual with an acute hepatitis b infection has the following serological markers hepatitis b surface antigen and igm antibody to hepatitis b core antigen next during the window period of hepatitis b infection an individual is positive for hepatitis b e antibody and igm antibody to hepatitis b core antigen an individual with chronic hepatitis b infection who is highly infectious will have hepatitis b surface antigen hepatitis b e antigen and igg antibody to hepatitis b core antigen on the other hand if an individual has chronic hepatitis b infection and a low infectivity he will have hepatitis b surface antigen and igg antibody to hepatitis b core antigen so remember only individuals who have been infected with hepatitis b virus will be positive for igg to hepatitis b core antigen after clearing the infection or transitioning to chronic infection finally during the recovery period of hepatitis b infection a person has the following serologic markers antibody to hepatitis b surface antigen hepatitis b e antibody and igg antibody to hepatitis b core antigen while immunized individuals have only igg antibody to hepatitis b surface antigen since the other components are not in the vaccine moving on to hepatitis d virus or hdv this virus is a single stranded rna virus and is most commonly transmitted parentally less common modes of transmission include sexual and perinatal transmission for your exam you have to know that hepatitis d virus requires the hepatitis b surface antigen to enter and infect hepatocytes therefore the virus can be acquired either as a co-infection with hepatitis b virus where both infections happen at the same time or as a super infection of a chronic hbv carrier where the person is infected with hbv first and then later with hdv it's important to note that the super infection of a chronic hbv carrier is associated with a worse prognosis and increased risk of liver cirrhosis the incubation period is short and the clinical presentation of hepatitis d infection is similar to hepatitis b infection also hepatitis d virus is associated with an increased risk of hepatocellular carcinoma liver biopsy is similar to hepatitis b infection but if serology reveals either igm or igg hdv antibodies this suggests that a person has an active infection since igg is not considered to be a protective antibody in hepatitis d infection finally vaccination against hepatitis b virus also protects against hepatitis d virus since it needs hepatitis b surface antigen to infect hepatocytes the next one is hepatitis c virus or hcv this virus belongs to the flaviviridae family of viruses and it's an enveloped single-stranded rna virus with icosahedral capsid symmetry a very high-yield fact to remember is that it lacks the three prime five prime exonuclease enzyme activity in other words this virus is not capable of proofreading to correct errors made during viral replication eventually this leads to variations in the antigenic structure of its envelope proteins now there are six or more genotypes and multiple sub-genotypes of hepatitis c virus due to genetic mutations of the region that codes envelope proteins as a result individuals with hepatitis c infection typically have several different subspecies of the hepatitis c virus in their blood and due to the continuous formation of new mutant strains of the virus the host's immune system lags in the production of antibodies as a result these individuals fail to develop an effective immune response against hepatitis c virus now this virus is mainly transmitted parentally and individuals who are at risk include intravenous drug users health care workers exposed to blood and needle stick accidents patients on dialysis and blood transfusion recipients hepatitis c virus can also be transmitted sexually and perinatally but these modes of transmission are less common the long incubation period that lasts from two weeks to six months is followed by an acute or chronic hepatitis c infection acute infection can present as asymptomatic infection or mild hepatitis that typically resolves within a few weeks but for your exam you have to know that the virus more commonly causes stable chronic infection which can further progress to cirrhosis or hepatocellular carcinoma hepatitis c virus can also cause extra hepatic manifestations which can be subdivided into hematologic which include essential mixed cryoglobulinemia immune thrombocytopenia autoimmune hemolytic anemia and increased risk of b-cell non-hodgkin lymphoma renal like membranoproliferative glomerulonephritis which is more common and membranous glomerulonephritis which is less common vascular which include leukocytoclastic vasculitis dermatologic such as sporadic porphyria cutanea tarda and lichen planus and finally endocrine which include increased risk of diabetes mellitus and autoimmune hypothyroidism just like in hepatitis b hepatitis c does have a carrier state now the best screening test for hepatitis c infection is the hcv antibody test which detects antibodies to the hepatitis c virus while the gold standard test for hepatitis c infection is the hcv rna test which reveals the level of circulating virus individuals with resolved hepatitis c infection are anti-hcv positive and hcv rna negative in contrast to individuals with a chronic infection who are anti-hcv positive and hcv rna positive also individuals with a chronic infection have persistently elevated liver enzymes as far as histopathology goes hepatitis c infection is associated with lymphoid aggregates and focal areas of macrovesicular steatosis which is characterized by one or more lipid droplets within the cytoplasm that displace the nucleus to the periphery of the hepatocyte another high yield topic is the treatment of hcv which includes several medications but for your exam you have to know that none of them is approved as a monotherapy based on their mechanism of action these medications are subdivided into several groups first we have non-structural protein 5a inhibitors which include ledipisphere and ambitosphere these medications inhibit the viral non-structural 5a phosphoprotein thereby preventing the replication of the viral rna their main side effects include headaches and diarrhea moving on to non-structural protein 5b inhibitors which include sofosbuvir and desabovir these medications act as chain terminators and inhibit the viral rna-dependent rna polymerase thereby preventing the replication of the viral rna common side effects of these medications include fatigue and headache next we have the non-structural protein 3-4-a inhibitors which include cement prevere and grazoprevir these medications inhibit non-structural 34a protease and subsequently prevent viral replication for your exam you have to know that grazo pervere can cause photosensitivity reactions and rash while cemepervere can cause headaches and fatigue the last medication you should know for your exam is ribavirin which works by inhibiting the synthesis of guanine nucleotides by competitively inhibiting innocene monophosphate dehydrogenase ribavirin is typically used as a supplementary medication of the therapy rather than the essential medication finally hepatitis b and c infections can be treated with interferon alpha alright as a quick recap viral hepatitis is defined as inflammation of the liver parenchyma and it's most commonly caused by hepatitis viruses a b c d and e now let's use this hepatitis worm to present the most common roots of transmission of each virus we write the letter a at the head then b c d and finally e at the tail the two ends where the mouth and butt are have fecal oral root so that's hav and hev everything else in between so hbv hcv and hdv are most commonly transmitted parentally but also sexually and perinatally now hepatitis a virus is an rna picornovirus that has a short incubation period that typically lasts for 30 days it can cause subclinical infection or acute hepatitis but the overall prognosis is good and there's no risk for hepatocellular carcinoma hepatitis b virus is a dna hepatin virus that has a long incubation period from 30 to 180 days which is followed by a prodrome and serum sickness-like symptoms it can cause one of three syndromes acute hepatitis with complete resolution which is the most common outcome chronic hepatitis with or without cirrhosis and hepatocellular carcinoma or fulminant hepatitis hepatitis c virus is an rna flavivirus with a long incubation period from two weeks to six months it can cause acute hepatitis which can present as asymptomatic infection or mild hepatitis or stable chronic hepatitis which is more common and can progress to cirrhosis or hepatocellular carcinoma hepatitis d virus is an rna delta virus that requires the hepatitis b surface antigen to be infectious therefore the virus can be acquired either as a co-infection with hepatitis b virus or as a more dangerous super infection in a chronic hpv carrier also it's associated with an increased risk of hepatocellular carcinoma finally the hepatitis e virus is an rna hepa virus with a short incubation period that usually lasts for six weeks in most individuals it causes self-limiting acute viral hepatitis and there's no risk for hepatocellular carcinoma however in pregnant individuals this virus can cause life-threatening fulminant hepatitis now let's go back to our case colin who came to the office because of abdominal pain for three months presented with a large distended abdomen yellow sclera palmer erythema and spider angioma on his abdomen and extremities the key to the diagnosis is in the lab results which revealed the following hepatitis a igm antibody negative hepatitis b surface antigen negative hepatitis b surface antibody positive hepatitis b core antibody negative and hcv antibody positive now since he has symptoms we can narrow it down to either hcv or hbv infection or maybe both his history of iv drug use is a risk factor for both so that's no help however the lack of hepatitis b surface antigen means he doesn't have an active infection and the hepatitis b surface antibody could be from a previous hbv infection that's resolved or he's been vaccinated against the virus so hcv infection is the most likely diagnosis on the other hand megan who came to the emergency department because of vomiting and fever presented with yellowing of the skin and sclera right upper quadrant tenderness and hepatomegaly she worked as a global health nurse and she recently traveled to nepal which is an endemic area of hev infections although hepatitis e infection is primarily a self-limiting disease pregnant individuals like megan can develop fulminant hepatitis we can confirm the diagnosis by testing for igm and igg hev antibodies in the serum helping current and future clinicians focus learn retain and thrive learn more

Channel: Osmosis from Elsevier

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Keywords: Health (Industry), Medicine (Field of Study), Disease (Cause of Death), Osmosis, Pathology (Medical Specialty), what is, nursing (field of study), Nursing school (organization)

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Length: 29min 25sec (1765 seconds)

Published: Tue Feb 22 2022