Hepatitis and HBV Tutorial

Hepatitis
Hepatitis is inflammation of the liver, and although it could have various causes such as abuse of alcohol and certain drugs, its most common cause is one of the five types of hepatitis viruses, denoted by the first five letters of the alphabet, A through E. Hepatitis A is usually spread by poor hygiene (fecal-oral route and contaminated water) as well as by sexual contact. Usually, there are no symptoms; the patient recovers and does not become a carrier. Hepatitis B, a more serious condition than hepatitis A, is usually transmitted by body fluids and, in case of drug addicts, by the sharing of needles. Patients can become carriers of the virus, and in 10% of the patients, the condition may become chronic, leading to cirrhosis and cancer of the liver. In the past, hepatitis C was transmitted by blood transfusions, but screening has almost completely eradicated that route and now it is transmitted mostly by shared needles among drug addicts. About three-quarters of people who have the hepatitis C virus will reach the chronic stage, and of these, 20% to 25% will develop cirrhosis and then liver cancer. Hepatitis D is also transmitted by the sharing of needles and is always accompanied by hepatitis B. The double infection is a more severe condition. Hepatitis E is spread by the fecal-oral route and is responsible for epidemics but mostly in underdeveloped countries. Neither chronic nor carrier states are present with this form of the hepatitis virus. Universal vaccination is recommended to protect the population from hepatitis B, and this has the added benefit t of protection against hepatitis D; it is recommended that travelers to underdeveloped countries where hepatitis A is prevalent be vaccinated against hepatitis A. There are no vaccines currently available against hepatitis C or E.

Serologic testing in HBV| See HBV Antibody-Viral Test Surface antigen: The outer coating of the virus is made up of the surface antigen or HBsAg. It surrounds the core of the virus. Core antigen: The inner shell contains the core antigen (HBcAg). E antigen: Another antigen found in the cores interior is the e antigen (HBeAg). Also, within the core of the virus are the viral DNA genetic material and the DNA polymerase enzyme, which contains the key genetic replication instructions.

Hepatitis and HBV Tutorial| mic 08-13

FIRST AID 2013 (pgs. 162-65)

Hepatitis and HBV Tutorial| mic 08-13

Hepatitis and HBV Tutorial| mic 08-13

VIRAL HEPATITIS: The Big Picture| Pathology In the acute phase of HBV infection, HBV surface antigen (HBsAg) and antibodies to HBV core antigen (anti-HBc) are detected in the serum. HBsAg disappears within 35 months, and antibodies to HBV surface antigen(HbsAb) do not appear until 6 months after infection. During this variable length window period, anti-HBc antibody is the only serologic marker of infection. Immunity to HBV is conferred by anti-HBV surface antibodies (HBsAb) and is seen in resolved acute infection (Table 15-4).

Outcomes of viral hepatitis Carrier state: Patients have no symptoms but can transmit the disease; a carrier state is not seen with HAV. HBe antigen is associated with a highly infectious state. Asymptomatic infection: No symptoms. Important clinical points Hepatitis A (HAV) and hepatitis E (HEV): Have no chronic carrier state so there is no risk of cirrhosis; rarely can HAV cause fulminant hepatic failure. When HEV causes fulminant hepatic failure, it is most commonly associated with Southeast Asian pregnant females. Of the forms of viral hepatitis, acute hepatitis B (HBV) is most likely to cause fulminant hepatic failure, especially if the patient is co-infected with hepatitis D (HDV). Immune response is critical in the pathogenesis of acute hepatitis. A vigorous immune response on exposure to HBV increases the risk of acute hepatitis and fulminant hepatic failure but decreases the risk of subsequent development of the chronic carrier state.
Hepatitis and HBV Tutorial| mic 08-13 4

 The immune response to chronic viral hepatitis (e.g., TGF- ) is responsible for most of the damage to the liver. HAV is transmitted by the fecal-oral route. HBV is transmitted by exposure to blood or body fluid, sexual contact, or congenital transmission. Transmission of hepatitis C (HCV) requires exposure to blood, and conclusive evidence of routine sexual or congenital transmission is lacking.

Formative Exam (From First Aid Q & A for the USMLE Step 1) Micro2. A hepatitis panel is ordered for a 27-year-old woman as part of a routine workup for abdominal pain. Results of serologic testing are negative for HBeAg and HBsAg, but positive for HBsAb and IgG HBcAb. Which of the following is the appropriate conclusion? (A) The patient has been exposed to hepatitis B and has completely recovered (B) The patient has been exposed to hepatitis B and is in the acute disease phase (C) The patient has been exposed to hepatitis B and is in the window phase (D) The patient has been exposed to hepatitis B and is now chronically infected (E) The patient has been exposed to hepatitis B but was never infected Micro10. Oncogenic viruses act through a variety of mechanisms. Some introduce oncogenes directly into host cells, while others force cells to repeatedly undergo cycles of proliferation that eventually become unregulated. Still others introduce oncogenic potential by manipulating chromosomal structure through deletions or translocations. Which of the following viruses causes neoplasia by inactivating tumor suppressor genes such as p53 and Rb? (A) Epstein-Barr virus (B) Hepatitis C virus (C) HIV (D) Human papillomavirus (E) Human T-cell lymphotropic virus type 1

Hepatitis and HBV Tutorial| mic 08-13

Micro27. A 31-year-old pregnant woman comes to the physician because of painful vesicular lesions that have recently appeared on her genitalia. A positive result on which of the following diagnostic tests would mean that her baby is at risk for congenital anomalies? (A) Anti-hepatitis B surface antibody test (B) Giemsa stain for cytoplasmic inclusions (C) Monospot test (D) Tzanck smear for multinucleated giant cells (E) Weil-Felix test Micro32. A 54-year-old man presents to the clinic with scleral icterus, hepatosplenomegaly, ascites, and a history of episodes of jaundice over the past 3 years. He was involved in an auto accident when he was 21 years old, for which he required surgery and blood transfusions. Laboratory tests show: Aspartate aminotransferase: 734 U/L Alanine aminotransferase: 846 U/L Direct bilirubin: 0.1 mg/dL Indirect bilirubin: 7.6 mg/dL Assuming a viral etiology, which of the following is the most likely cause of this patients illness? (A) Hepatitis A (B) Hepatitis C (C) Hepatitis D (D) Hepatitis E (E) Hepatitis G

Hepatitis and HBV Tutorial| mic 08-13

1.GI A 35-year-old woman who is HIV-positive presents to the physician with jaundice and right upper quadrant abdominal pain. The patient reports having had multiple episodes of jaundice over the past 10 years. A hepatitis panel is positive for HBsAg and anti-HBc IgM, but negative for HBsAb and anti-HAV IgM. Which of the following would most likely be lower thannormal in this patient? (A) Albumin (B) Alkaline phosphatase (C) Bilirubin (D) Prothrombin time (E) Transaminases

12GI. Which of the following types of hepatocellular injury is commonly seen after acetaminophen overdose? (A) Acute hepatitis (B) Centrilobular necrosis (C) Fibrosis (D) Granuloma formation (E) Microvesicular fatty change

Hepatitis and HBV Tutorial| mic 08-13

20.GI A 37-year-old woman is found by police in a confused state and is brought to the emergency department for evaluation. The patient is unable to answer any of the physicians questions. Physical examination reveals jaundice. Despite aggressive therapy the patient dies. An autopsy is performed and a microscopic view of the patients liver is shown in the image.

Which of the following conditions is most consistent with these fi ndings? (A) 1-Antitrypsin defi ciency (B) Acute viral hepatitis (C) Alcoholic hepatitis (D) Fatty liver of pregnancy (E) Neonatal hepatitis

Hepatitis and HBV Tutorial| mic 08-13

47FLE. A major problem in hospitals is the risk of needle sticks and the accidental transmission of hepatitis C, hepatitis B, and HIV to health care personnel. Although different circumstances can make the likelihood of infection higher or lower, it is well known that the chance of infection transmission from a needle is not the same for each of these diseases. From greatest chance of infection to least, which of the following is the order of infection among these three diseases? (A) Hepatitis B, hepatitis C, HIV (B) Hepatitis C, hepatitis B, HIV (C) Hepatitis B, HIV, hepatitis C (D) Hepatitis C, HIV, hepatitis B (E) HIV, hepatitis B, hepatitis C

Further Study: HBV Antibody-Viral Test HBV Wikipedia A Clinical Trial Treatment of Hepatitis B e AntigenPositive Chronic Hepatitis with Telbivudine or Adefovir: A Randomized Trial http://annals.org/article.aspx?articleid=737735

Editors' Notes Context

Optimal regimens for suppressing virus in chronic hepatitis B infection are unclear.

Contribution

In this 52-week open label trial, 135 adults with hepatitis B e antigenpositive chronic hepatitis B were randomly assigned to telbuvidine, adefovir, or adefovir for 24 weeks followed by telbivudine for 28 weeks. The telbivudine and the adefovir-to-telbivudine groups experienced similar reductions in viral levels that were greater than those in the adefovir group.
9

Hepatitis and HBV Tutorial| mic 08-13

Caution

The small trial did not establish long-term drug resistance or effects on clinical outcomes.

Implication

Telbivudine and switching from adefovir to telbivudine suppressed viral levels more than adefovir in adults with chronic hepatitis B.

The Editors In chronic hepatitis B virus (HBV) carriers, elevated serum HBV DNA levels have been associated with increased risk for end-stage complications, such as cirrhosis and hepatocellular carcinoma (14). Corresponding evidence supports the concept that antiviral therapy can ameliorate liver injury and reduce or delay the progression of cirrhosis and the incidence of hepatocellular carcinoma (59). Effectively maintained viral suppression has been correlated with these effects (5, 10). Recent studies further suggest that, with direct-acting anti-HBV nucleosides and nucleotides, therapeutic efficacy and the emergence of resistance are related to the degree of viral suppression achieved early in the course of treatment (1118). Specifically, achieving low serum HBV DNA levels in the first 6 to 12 monthspreferably levels undetectable by polymerase chain reaction (PCR) assayhas been associated with greater subsequent efficacy and less resistance, with observations now extending to treatment periods beyond 2 years. Maximizing early viral suppression is therefore emerging as an important therapeutic goal for patients with hepatitis B. Telbivudine and adefovir are approved for use in the United States and elsewhere (8, 1922). Telbivudine, a thymidine nucleoside analogue, had greater antiviral efficacy than lamivudine in phase IIb and III trials (2223). Adefovir, an adenosine nucleotide analogue, had greater efficacy than placebo in phase III trials (8, 21). Telbivudine and adefovir have not been compared directly, although HBV DNA reductions after 1 year of telbivudine in phase III trials seemed greater than those reported with adefovir in similar patient populations (8, 2122). We compared the degree of telbivudine- and adefovir-induced viral suppression after 24 and 52 weeks of treatment to assess the relative antiviral efficacy and safety of these agents. Because trial data (8, 22) suggest that the clinical antiviral effects of telbivudine may be greater than those of adefovir, we also assessed antiviral efficacy and safety in patients switched to telbivudine after receiving adefovir treatment for 24 weeks. Finally, we evaluated potential relationships between the degree of viral suppression achieved after 6 months of therapy and subsequent efficacy outcomes at 1 year.

Hepatitis and HBV Tutorial| mic 08-13

10