Pathophys Review Exam 2 -- Hepatitis PDF

Hepatitis Disease Summary Definition → Viral Hepatitis refers to a group of inflammatory conditions of the liver that are caused by at least 6 different strains of viruses Viral hepatitis is characterized primarily by: ○ A low grade fever ○ Fatigue...

Hepatitis Disease Summary Definition → Viral Hepatitis refers to a group of inflammatory conditions of the liver that are caused by at least 6 different strains of viruses Viral hepatitis is characterized primarily by: ○ A low grade fever ○ Fatigue ○ Jaundice ○ Hepatomegaly ○ Anorexia (poor appetite) ○ Abdominal discomfort ○ Abnormal liver function ○ Light colored stools ○ Dark urine Each type of VH differs from the others in modes of transmission: ○ Incubation period ○ Clinical manifestations ○ Degree and persistence of liver injury ○ Ability to evolve to a carrier state Despite this significant variation among types of VH, it is often clinically impossible to distinguish a specific type in a given patient without blood testing Viral hepatitis can either be acute (i.e, short term and lasting 6 months) or chronic (i.e, prolonged, lasting 6 months and often a lifelong) Significance: VH is considered a preventable illness However, it is a serious disease because it can: ○ Cause fatigue ○ Headache ○ Muscle aches ○ Nausea ○ Vomiting ○ Diarrhea ○ Destroy liver tissue and cause the liver to fail ○ Spread from person to person – including mother to infant ○ Weaken the body’s immune system ○ Increase the risk for liver cancer ○ Progress from an acute disease to a chronic, often lifelong, condition. Chronic VH:  ○ Is the principle cause of chronic liver disease, cirrhosis, hepatocellular cancer worldwide, now ranks as the leading reason for liver transplantation among adults. Causes and risk factors: Many viruses including: ○ Adenovirus, cytomegalovirus, epstein-barr virus, herpes simplex virus. All can infect the liver and cause inflammation The clinical presentation ranges form self-limited mild transaminitis and malaise to fulminant hepatitis The term viral hepatitis is often reserved for disease caused by one of the 5 hepatitis viruses: Hepatitis A (HAV) B virus (HBV) C virus (HCV) D virus (HDV) E virus (HEV) A 6th hepatitis virus – hepatitis G virus (HGV) – has been discovered, but it has not yet been clearly determined if this virus causes disease in humans. Collectively, HAV, HBV, HCV,HDV, and HEV cause 95% of all cases of acute VH in the US today A related virus known as SEN-V has been found in approximately 2% of blood donors in the United states, is transmitted by blood transfusion and may account for some cases of transfusion- associated non-ABCDE hepatitis. HAV, HBV, and HCV are the most common causes of VH in the US today HAV and HCV each account for approximately 150,000 cases or 25-30% of the total number of cases of VH that occur each year HBV accounts for approximately 200,000-300,000 cases of 40-50% of the total number of cases of VH that occur each year. A large outbreak of Hepatitis A among patrons of a restaurant in Monaca, Pennsylvania, in 2003 was traced to contaminated green onions from Mexico In the United States, approximately 30% of the population has serologic evidence of a periove infection with HAV HBV is a DNA hepadnavirus with 8 different genotypes (designated A-H) that may impact both clinical course of the disease and the response of the microorganism to therapy HBV is usually transmitted by inoculation of infected blood or blood products or by sexual contact and is present in saliva, semen and vaginal secretions The virus has not been detected in urine, sweat or stool The risk of infection to an infant born to an HBV positive mother is as high as 85%, depending on the viral genotype  HBV is prevalent in homosexual and bisexual men and in IV drug users, but the greatest number of cases will result from heterosexual transmission – the incidence of which has decreased by 75% in the last 25 years. HCV HCV is an RNA hepacivirus that belongs to the flavivirus family. At least 6 major genotypes of HCV have been identified ○ Genotype 1, which causes more severe liver disease, accounts for 70-75% of all cases of hepatitis C in the US Today, more than half of all the cases of hepatitis C are transmitted by IV drug use HCV also remains an important occupational risk for healthcare workers with the probability of infection after accidental needlestick at 2-3% There is also concern that transmission of small amounts of blood during tattooing, acupuncture and body piercing may facilitate transmission of HCV and constitute potential risk factors In addition, transmission from bloody fisticuffs, hemodialysis and intranasal cocaine/heroin use has been reported The risk of sexual or maternal neonatal transmission is low and greatest when circulating levels of HCV are high. Having multiple sexual partners also increases risk as approximately 1 in 5 cases of HCV infection is due to sexual contact An outbreak of Hepatitis C in patients with immune deficiency disorders occurred in some recipients of IV immune globulin In addition, transmission via multidose vials of saline used to flush catheters and between hospitalized patients in a liver unit has been reported. Testing donated blood for HCV has helped reduce the risk of transfusion-associated hepatitis C from 10% in 1990 to approximately 1 case/2 million units today. There are more than 2.7 million carriers of HCV in the United states who serve as a source of infection to others Worldwide, approximately 3% of the population is chronically infected HDV HDV is an RNA virus that replicates and causes hepatitis only in association with HBV infection HDV can only occur as a coinfection alongside active/infectious Hepatitis B HDV is believed to infect approximately 5% of the world’s 400 million HBV carriers HDV may co-infect or may superinfect a patient with chronic hepatitis B, usually be percutaneous exposure New cases of hepatitis D in the US are rare today, and currently diagnosed cases are usually in people infected years ago by IV drug use or who were exposed to infected blood or blood products HEV  HEV is an RNA virus similar to calicivirus Hepatitis E is rare in the US today byt should be considered in patients after a trip to an endemic area of the world, especially where they have been waterborne VH outbreaks Parental transmission is possible but also very rare HGV HGV, detected in blood of 1.5% of blood donors, 50% of IV drug users, 30% of hemodialysis patients, and 20% of hemophiliacs, has not yet shown an ability to cause significant liver disease Necrosis of hepatocytes, scarring, proliferation of Kupffer cells, and infiltration of the liver with macrophages and lymphocytes occur with varying severity Cellular injury is promoted by cell-mediated immunologic mechanisms (i.e., cytotoxic T lymphocytes and natural killer cells) Regeneration of hepatocytes begins within 48 hours of initial injury and may provide a source of development of liver cancer Because inflammation is a non-specific protective mechanism, bile canaliculi can be damaged, resulting in obstruction to the flow of bile and clinical jaundice Damage to the liver tends to be the most severe when HBV or HCV is the causative agent Hepatitis B is also associated with a rare form of hepatitis known as acute fulminant hepatitis in which there is an exaggerated immune response, massive hepatic necrosis and profound liver failure. Liver failure results in a number of typical clinical manifestations in addition to jaundice: Including bleeding Low serum concentrations of albumin and other proteins Edema Glucose intolerance Bone disease (i.e., osteomalacia) characterized by brittle bones and fractures ○ Ricketts is a condition that affects bone development in children. ○ It causes bone pain, poor growth and soft, weak bones that can lead to bone deformities. ○ Adults can experience a similar condition which is known as osteomalacia or soft bone) In males, feminization Reduced protein synthesis leads to decreased production of clotting factors and low levels of serum albumin Decreased serum albumin, in turn, leads to widespread edema as a result of low systemic intravascular osmotic pressure Impaired glycogenolysis and gluconeogenesis may cause hypoglycemia Reduced production of bile salts by a severely injured liver impairs the absorption of fats and fat soluable vitamins (i.e., A, D, E and K) in the gastrointestinal tract Lack of vitamin D may lead to osteomalacia  A deficiency of vitamin K contributes to reduced synthesis of blood clotting factors Abnormal processing of lipoproteins by the liver may lead to dyslipidemia (i.e., abnormal serum lipid profile), especially hypertriglyceridemia (i.e., high serum levels of triglycerides) Liver failure is also associated with impaired processing of endogenous steroid hormones and byproducts of protein metabolism, as well as decreased elimination of drugs and toxins Impaired metabolism of estrogen leads to feminization in men: (i.e., gynecomastia) Impotence Testicular atrophy Distribution of body hair in a female pattern Irregular menses in women Redness of the palms (palmar erythema) Development of “spider veins” in the skin Reduced metabolism of cortisol and aldosterone may lead to cushing syndrome and hyperaldosteronism, respectively Impaired conversion of ammonia to urea may have a profound effect on brain function – a condition known as hepatic encephalopathy: which is manifested initially by confusion followed by stupor, later coma. Symptoms i guess? Fever is generally present but is low grade, except for occasional cases of Hepatitis A In fact, HAV infection is the only type of VH that presents with a high-grade fever (i.e., 102*F) Fever often breaks with the onset of jaundice Mild to severe pruritus (i.e., itching) often accompanies jaundice Abdominal pain is usually mild and constant in the RUQ and is often aggravated by sudden movement or physical exertion A weight loss of 5-10 pounds is not unusual Hepatomegaly –rarely marked– is present in more than half of all cases of VH Splenomegaly is reported in approximately 15% of patients and soft, enlarged lymph nodes – especially in the cervical area – may be palpated. A unique feature of HBV infection is the onset of a variety of immune complex related phenomena – including hives, arthritis, localized edema, and glomerulonephritis (i.e., inflammation of the glomeruli) that may cause a mild proteinuria Unique features of HCV infection include polyarteritis Nodosa (inflammation of medium sized blood vessels) and glomerulonephritis The white blood cell count is normal to low Large, atypical lymphocytes may occasionally be seen with a peripheral blood smear Bilirubin often precedes the appearance of jaundice Light-colored stools from the absence of bile pigments are often present  Strikingly increased serum AST (i.e., aminotransferase) and ALT (i.e., alanine aminotransferase) concentrations occur early in the disease, followed by elevations in serum bilirubin and alkaline phosphatase The first antibody to appear in the blood is IgM anti-HBcAg (i.e., core antigen of HBV), which is diagnostic for acute HBV infection Weeks later, IgM anti-HBcAg disappears and IgG anti-HBcAg is detected and may be present for life Blood studies in patients who recovered from Hepatitis B will show positive Hepatitis B core Antibody (HBcAb) and Hepatitis B surface Antibody(HBsAb) HBeAg is a cleavage product of the core antigen of HBV and a serum marker for viral replication When viral replication shows, HBeAg disappears and anti-HBeAg is detected and may persist for years HCV RNA (i.e., ribonucleic acid) testing (e.g., with polymerase chain reaction) is currently the best clinical tool available to confirm the presence of active HCV infection The test is especially beneficial in early cases of infection, prior to the presence of IgG anti-HCV or an elevation of the serum ALT level and for assessing the HCV genotype and viral load Serious complications and prognosis: Clearly, the most serious complications of acute VH are: ○ Persistence of the disease as chronic hepatitis ○ The development of acute fulminating hepatitis with hepatic failure ○ Cirrhosis ○ Hepatocellular cancer ○ In most patients, recovery from VH is complete within 6 weeks ○ Lab evidence of liver dysfunction (e.g., high serum ALT and AST levels) may persist longer, but most patient ultimately recover completely Appropriate therapy: Spontaneous clearance of hepatitis viruses is much more likely in symptomatic than in asymptomatic patient Bedrest is recommended only when symptoms are severe If nausea and vomiting are pronounced or if oral intake is poor, IV.45% saline solution with 20 meg/L potassium chloride is often given to maintain hydration Signs of encephalopathy or bleeding indicate impending hepatic failure and hospitalization is mandatory Dietary management consists of meals as tolerated without overeating Breakfast is usually best tolerated A low-fat, high-carb diet is beneficial when the patient is jaundiced Strenuous physical exertion, alcohol and potentially hepatotoxic agents are avoided No current antiviral therapy changes the course of acute HAV infection Long-term pharmacotherapy often is necessary Even with prolonged treatment, success rates (defined as complete and lasting eradication of the virus) are often 80% and most often approximately 50% of patients with HBV who develop acute fulminating hepatitis may require aggressive treatment for coagulopathy (i.e., a blood clotting disorder), encephalopathy or cerebral edema Antiviral therapy for HCV infection has 6 major goals that include: 1. Decreasing viral replication or eradicating HCV 2. Preventing progression of the illness 3. Decreasing the frequency of cirrhosis 4. Decreasing the frequency of liver cancer as a complication of cirrhosis 5. Ameliorating symptoms such as fatigue and joint pain 6. When necessary, relieving extrahepatic complications of HCV infection, such as glomerulonephritis Although most patients with HCV infections are candidates for treatment, many have other health problems that contraindicate pharmacotherapy. Interferons are currently the mainstay of antiviral strategies used against HCV infection Treatment with peginterferon and ribavirin is costly (approximately $15,000 per year), insurance coverage is inconsistent, and adverse effects—which include flu-like symptoms and severe depression—are extremely common. Treatment for acute hepatitis D is supportive and chronic hepatitis D is best treated with interferon-α. However, patients co-infected with HBV and HDV are less responsive to interferon therapy than patients infected only with HBV. Lamivudine is ineffective against HBV/HDV co-infection. Treatment for acute hepatitis E is supportive and the illness usually resolves within several months without pharmacotherapy. Liver transplantation is a treatment option for acute fulminant hepatitis with hepatic failure. Transplantation has been more successful in patients with hepatitis C than with hepatitis B. Although the transplanted liver often is re-infected, hepatitis seems to progress more slowly