hepatitis quiz
The USPSTF recommends hepatitis C screening once for all individuals born between ______ and _________.. Other populations deserving of screening include those with ____ , ______ , __________ .
1945 and 1965. HIV, dialysis patients, and incarcerated patients.
normal values for ALT and AST
ALT = normal range, 0-20 IU/L; AST = normal range 0-31 IU/L
You are asked to see a 30-year-old Korean man with chronic hepatitis B virus infection. He tested hepatitis B surface antigen (HBsAg) positive more than 6 months ago. He has no other significant medical problems and his physical examination is normal, except for mild right upper quadrant tenderness. Additional laboratories demonstrate: Hepatitis B e antigen (HBeAg): positive Antibody to hepatitis B e antigen (anti-HBe): negative HBV DNA: 260,000 IU/mL Albumin 4.1 g/dL Total bilirubin 0.8 mg/dL International Normalized Ratio (INR) 1.0 Platelet count: 190,000/µL Alanine aminotransferase (ALT): ranged between 90 to 110 U/L over the last 6 months. Which one of the following statements is true? A Current treatment guidelines suggest that treatment is indicated for this patient. B Liver biopsy is necessary before making a decision about initiating treatment C If the patient has compensated cirrhosis, antiviral treatment would not be indicated because it could precipitate hepatic decompensation. D The patient does not require treatment for hepatitis B at this point, but should periodically have testing to evaluate for spontaneous HBeAg seroconversion (loss of HBeAg and development of anti-HBe).
Answer A According to current guidelines for hepatitis B therapy, this patient should receive antiviral therapy for chronic hepatitis B. He has HBeAg-positive chronic hepatitis B infection in the immune active phase as suggested by the positive HBeAg, a high HBV DNA level, and persistently elevated ALT levels. His bilirubin, platelet count, and INR are all within normal limits, and he does not have a clinical history or laboratory findings consistent with decompensated cirrhosis. Case Summary The patient is HBeAg-positive with a high HBV DNA load and a persistently elevated serum ALT. Thus, according to published treatment guidelines, antiviral therapy should be initiated. Choice of anti-HBV therapy will be discussed in a subsequent case. The AASLD recommends treatment initiation for immune active chronic hepatitis B infection which is defined as an elevated ALT exceeding 2 times the upper limit of normal or evidence of significant inflammatory activity or fibrosis on biopsy AND an HBV DNA level above 2,000 IU/ml for HBeAg-negative patients or an HBV DNA level above 20,000 IU/mL for HBeAg-positive patients. The 2015 AASLD guidelines do not specify how many time points are necessary for this elevation to meet criteria for therapy but the general understanding is that the ALT and HBV viral level elevations should be considered persistent over 3 to 6 months [Ref: 2009 Guidelines]. Other clinical factors may be important to consider in the decision to initiate treatment including older age (greater than 40 years, which is associated with significant histologic disease), family history of liver cancer and extrahepatic complications of HBV such as renal disease or vasculitis.
A 36-year-old injection-drug user presents for follow-up management of cellulitis. As part of his general medical evaluation he undergoes serologic testing for hepatitis. His results show a positive antibody for hepatitis C (HCV) and negative hepatitis A (HAV) antibody. Results from his hepatitis B virus (HBV) serology panel show the following: Hepatitis B surface antigen (HBsAg): negative Hepatitis B surface antibody (anti-HBs): negative Hepatitis B core antibody (anti-HBc), total IgM and IgG: positive Hepatitis B core antibody, IgM (IgM anti-HBc): not performed The patient began injecting drugs at age 23 and he continues to regularly inject drugs. He does not recall ever having had acute HBV infection and he does not ever remember receiving HBV vaccine. Which one of the following most accurately describes the patient's HBV serology results? A finding of isolated anti-HBc may represent either acute or past infection with hepatitis B B The isolated anti-HBc test has a greater than 95% likelihood of representing a false positive result, and thus the patient should be considered negative for acute or prior HBV infection. C A finding of isolated anti-HBc most likely represents a weak response to hepatitis B vaccine, and the patient probably just doesn't remember that he's been vaccinated. D Persons with HIV and chronic HCV infection have the lowest prevalence of isolated anti-HBc because they generate enhanced levels of anti-HBs that remain elevated on a long-term basis.
Answer A Isolated anti-HBc is defined as the presence of anti-HBc in the absence of detectable HBsAg and anti-HBs. Isolated total anti-HBc may result from a false-positive result, acute HBV infection, or past HBV infection. A patient recently infected with HBV may develop isolated anti-HBc during the window period of acute infection when HBsAg has resolved prior to development of anti-HBs. With acute infection, anti-HBc primarily consists of IgM. Thus, the presence of IgM anti-HBc is the hallmark of acute HBV infection. Patients with remote infection most often have isolated anti-HBc in the scenario when anti-HBs levels gradually decline to an undetectable level, leaving detectable anti-HBc as the only evidence of previous infection. C:HBV vaccines consist of recombinant HBV surface antigen (HBsAg) and the HBsAg stimulates production of anti-HBs. The vaccine does not contain any hepatitis B core viral particles or hepatitis B core antigens (HBcAg) that might elicit anti-HBc responses. Thus, the measurable immune response to HBV vaccine consists of anti-HBs, not anti-HBc.
A 38-year-old Vietnamese woman with HBeAg-positive chronic hepatitis B presents for evaluation. Laboratory studies obtained 5 months prior showed a serum alanine aminotransferase (ALT) level of 115 U/L, HBV DNA level of 422,000 IU/ml, positive HBeAg. Repeat studies 1 month ago showed an ALT level of 112 u/L and positive HBeAg. She is asymptomatic and had a normal abdominal ultrasound 5 months prior. She has never received therapy for hepatitis B. Which one of the following statements is TRUE regarding the use of available therapeutic agents for patients with chronic hepatitis B infection? A Telbivudine (Tyzeka) and lamivudine (Epivir-HBV) are nucleoside analogues that share cross-resistance. B The major drawback for the use of peginterferon alfa-2a (Pegasys) is the rapid development of HBV resistance. C Tenofovir disoproxil fumarate (Viread) should not be considered an option for this patient because of the unacceptably high incidence of tenofovir-induced renal failure in Asian patients. D The same dose of entecavir (Baraclude) should be used for treatment-naïve patients and lamivudine-resistant patients.
Answer A Telbivudine and lamivudine are similar in their mechanism of action and resistance patterns. Indeed, telbivudine cross-resistance is observed (in vitro) with all major lamivudine resistance mutations. B:Peginterferon therapy, unlike the oral antiviral agents, has not been shown to be associated with the development of hepatitis B virus resistance. The major drawback for peginterferon alfa-2a therapy is the multiple side effects, such as fatigue, anorexia, influenza-like symptoms, and cytopenias. C. Although tenofovir disoproxil fumarate (TDF) can cause renal insufficiency, this adverse effect occurs infrequently, especially in persons without any co-morbid medical conditions. Further, there is no evidence that Asian patients have a higher incidence of TDF-induced renal insufficiency. he degree and durability of entecavir efficacy is diminished in patients who are refractory or resistant to lamivudine (Epivir) or telbivudine (Tyzeka). The recommended entecavir once daily 0.5 mg dose for treatment-naïve patients should be increased to 1.0 mg once daily in patients with prior resistance to lamivudine or telbivudine, or in those who experienced a refractory response to lamivudine or telbivudine.
A 32-year-old Chinese American woman whose mother was born in China presents to clinic. Her mother was recently informed she had chronic hepatitis B, so the patient asks to be tested for hepatitis B virus (HBV). Results from her hepatitis B testing and hepatic aminotransferase levels are as follows: Hepatitis B surface antigen (HBsAg): positive Hepatitis B core antibody (total anti-HBc): positive Hepatitis B core antibody (IgM anti-HBc): negative Hepatitis B surface antibody (anti-HBs): negative Hepatitis "e" antigen (HBeAg): positive Hepatitis "e" antibody (anti-HBe): negative HBV DNA: 1.1 x 107 IU/ml Alanine aminotransferase (ALT): 16 U/L (normal = less than 19 U/L in women) The provider elects to measure repeat aminotransferase levels in 3 months. At that point, both the ALT and the AST are within the normal range. Which one of the following describes the phase of this patient's hepatitis B infection and what should be done? A The patient has acute HBV infection and she should be followed closely to see if chronic infection develops. B The patient is in the immune tolerant phase and should be followed on a regular basis with ALT levels every 3 to 6 months (and more frequently if they become elevated). C The patient has evidence of hepatic inflammation and is in the immune active phase of chronic viral hepatitis; she should immediately start on therapy for HBV. D The patient is in the inactive chronic carrier phase of hepatitis B and she does not need evaluation again unless she develops an increase in hepatic transaminase levels (ALT and AST).
Answer B The patient is in the immune tolerant phase. This phase of chronic HBV infection most often develops when persons acquire HBV in the perinatal or early childhood period, as likely happened with this patient. There is no indication to initiate therapy at this point. In this phase, patients should have ALT levels followed every 3 to 6 months.
A 45-year-old Cambodian man with HBeAg-negative chronic hepatitis B presents for evaluation. He has had serum alanine aminotransferase (ALT) levels of 60 to 80 U/L and HBV DNA level of 30,000 IU/mL. He has no history of ascites or encephalopathy and laboratory studies are unremarkable, including a normal serum albumin and total bilirubin level. An abdominal ultrasound shows a nodular liver without signs of portal hypertension, findings consistent with compensated cirrhosis. He has never received therapy for hepatitis B. Which one of the following statements is TRUE regarding the choice of available therapeutic agents for patients with chronic hepatitis B infection? A Lamivudine (Epivir-HBV) would be the preferred choice of therapy in this patient given its good safety profile and superior efficacy in patients with advanced liver disease. B Adefovir (Hepsera) would be the preferred choice of therapy in this patient given its high potency. C Peginterferon alfa-2a (Pegasys) should be used with caution in this patient given the possibility of hepatic decompensation with an immune-mediated flare during therapy. D Initial combination therapy with three nucleoside/nucleotide analogue agents provides superior serologic and clinical outcomes when compared with monotherapy and thus triple nucleoside therapy would be the preferred treatment for this patient.
Answer C Peginterferon has been used safely in patients with compensated cirrhosis, but it should be used with caution and with close monitoring of liver function in patients with cirrhosis, given the possibility of immune-mediated hepatitis flares and hepatic decompensation on therapy. Lamivudine, while it has been shown to be safe in patients with cirrhosis, is not the preferred choice for initial therapy in any patient with chronic hepatitis B when long-term treatment is anticipated (as in this patient) given the high rates of cumulative resistance observed with this agent and reduced efficacy in head-to-head comparisons with newer agents. Adefovir is among the least potent antiviral agents against hepatitis B and is therefore not the preferred choice of therapy. Combination therapy with two or three oral agents has not been shown to improve serologic, biochemical, or histologic outcomes over single-agent therapy in patients with chronic hepatitis B.
A 24-year-old Asian man presents for evaluation of a positive blood test for hepatitis B surface antigen (HBsAg), detected when he went to donate blood during a college blood drive. Further tests show the patient has normal hepatic transaminase levels and a normal bilirubin. The patient was born in China and immigrated to the United States with his family when he was 15 years old. He is otherwise healthy and takes no medications. He has recently begun having sex with his girlfriend of 3 months. He has previously had one other sex partner. Which one of the following describes the most appropriate initial laboratory evaluation of this patient? A The next appropriate blood test is a hepatitis B core antibody (anti-HBc), which alone can determine if the patient has acute hepatitis B infection. B The most appropriate blood test is a hepatitis B e antigen (HBeAg), which alone can determine if the patient is an inactive carrier of hepatitis B or if he is actively infected. C No further blood work is necessary. The finding of positive HBsAg alone is enough to define the patient as a chronic hepatitis B carrier, and he should be screened for hepatocellular carcinoma with a serum alpha-fetoprotein measurement and abdominal ultrasound. D Appropriate laboratory studies should include a complete hepatitis B serologic evaluation, a serum HBV DNA level, and biochemical markers related to hepatic inflammation and function.
Answer is D The initial laboratory evaluation of a positive HBsAg includes a complete hepatitis B serologic evaluation, including IgM anti-HBc, HBeAg, and hepatitis B e antibody (anti-HBe). In addition, studies should be performed to measure serum HBV DNA level and biochemical markers related to hepatic inflammation and function. These tests are essential to accurately characterize the patient's HBV infection. B: HBeAg should be measured as part of the initial workup, but alone cannot determine if the patient has active hepatitis B infection. The presence of HBeAg indicates viral replication, and can be detected in persons with chronic active HBV infection as well as in those with acute infection. The exception is the some patients with immune reactive chronic hepatitis B will have elevated HBV DNA levels despite having a negative HBeAg test
which tx for hep B has lower potency? Which are the newer antiviral agents? Which drugs are currently the preferred oral antiviral agents for both HBeAg-negative and HBeAg-positive patients for initial therapy due to their greater potency and lower rate of HBV resistance?
Antiviral potency is notably lower for adefovir compared with the other agents and intermediate for lamivudine compared with the newer antiviral agents (entecavir, telbivudine, and tenofovir disoproxil fumarate). For patients with high HBV viral levels, the newer agents should be chosen over adefovir or lamivudine. The genetic barrier for drug resistance is one of the major distinguishing features among the antiviral agents and resistance is of particular importance considering prolonged therapy. The rates of HBV resistance observed over time with these different agents varies markedly, with high rates of resistance observed with lamivudine, moderate with adefovir and telbivudine, and low rates with entecavir and tenofovir disoproxil fumarate. Lamivudine is no longer recommended as initial therapy because of the high cumulative rate of resistance over time and although telbivudine is potent, the moderate rate of resistance with this agent argues against its use as first-line therapy. These different oral antiviral agents used for the treatment of hepatitis B have advantages and disadvantages. Tenofovir disoproxil fumarate and entecavir are currently the preferred oral antiviral agents for both HBeAg-negative and HBeAg-positive patients for initial therapy due to their greater potency and lower rate of HBV resistance. Both have a good long-term safety record. The risk of renal impairment or impact on bone mineral density with tenofovir disoproxil fumarate appears to be low in HBV-infected patients, but if there is a concern for this in a particular patient, entecavir may be a preferred choice. Tenofovir alafenamide is a nucleotide analogue that has been FDA-approved as a component of several fixed-dose combination HIV antiretroviral medications; this medication has a more favorable renal and bone mineral density profile than tenofovir disoproxil fumarate. Summary The choice between interferon-based versus oral antiviral therapy must be individualized and take into account efficacy, safety and tolerability, drug resistance and patient preference. Patient-specific baseline factors must also be weighed when considering interferon-based therapy. Elevated baseline serum ALT, low baseline HBV DNA levels, genotype A and younger age have been linked with a favorable treatment response with interferon-based preparations. Peginterferon should be used with caution patients who have cirrhosis given the possibility of hepatic decompensation with immune-mediated flares during therapy. Oral antiviral therapy may be preferred in patients with underlying clinical conditions that could be exacerbated by interferon-based therapy, such as significant psychiatric illness or an underlying leukopenia, anemia, or thrombocytopenia. In clinical practice, oral antiviral therapy is more often used than interferon-based therapy because of better patient tolerance and lower rates of adverse effects with oral antiviral agents. When oral antiviral therapy is used to treat hepatitis B, entecavir and tenofovir disoproxil fumarate are the preferred first-line agents given their good potency and low rates of resistance.
CHB
Chronic hepatitis B (CHB)
Which of the following medications has been used in the treatment of hepatitis B? (A) Ribavirin (Rebetol) (B) Interferon alpha (Intron-A) (C) Steroids (D) Plasmapheresis (E) Lamivudine (Epivir)
E. Choices (A) and (B), ribavirin and interferon alpha, are used in the treatment of hepatitis C. Choice (C), steroids, is used in the treatment of autoimmune hepatitis, a condition you see predominantly in young women. Choice (D), plasmapheresis, is used to treat thrombotic thrombocytopenic purpura (TTP). Choice (E), lamivudine, has been used in the treatment of hepatitis B, although it's primarily used to treat HIV.
antibody and antigen tests for hepatitis B: (know this)
Envelopes: There are two envelope tests: the hepatitis B envelope antigen and the hepatitis B envelope antibody. The hep B envelope antigen means that the virus is actively replicating and that the person is highly infective. The hep B envelope antibody means that the virus is replicating and the person is infective but to a lesser degree. Surface dudes: You again have two surface tests: the hepatitis B surface antigen and the hepatitis B surface antibody. The hep B surface antigen means that the person is still dealing with an active infection. The hep B surface antibody is what you test for after someone has been immunized against hep B. The surface antibody also means the person is immune to any infection. Core: In one special case, the hep B surface antigen isn't the first antigen positive in the setting of an infection. Sometimes the body does such a good job of clearing the virus initially that the only test that's positive is the hep B core antibody. Because the infection is acute, this is an IgM antibody, not an IgG antibody. In many people, hepatitis B resolves, and they develop antibodies against it. In some cases, someone develops a chronic hepatitis secondary to hep B. If the hepatitis B surface antigen stays elevated for 6 months or longer, that person is said to have a chronic hepatitis. Usually the ALT level stays elevated in that regard. Hep B is a DNA virus, so you can always order a quantitative hepatitis B DNA level to see how much the virus is replicating. Chronic hepatitis B is associated with the development of hepatocellular carcinoma; often you need to order a liver biopsy.
Fibrosis is scored from
F0 to F4, with F0 representing no fibrosis and F4 representing cirrhosis. In addition to elastography, another noninvasive method of determining the degree of fibrosis is the AST/platelet ratio index, abbreviated APRI. This is calculated as follows: APRI = [(patient AST - upper normal of lab AST)/ platelet count] × 100. Significant fibrosis (F2-F4) is present if the APRI is 0.7 or greater (77% sensitivity, specificity 72%) although some sources use 0.5 as the lower limit for "significant fibrosis." An APRI of 1 or greater represents cirrhosis. Finally, the FibroSure, Fibrotest, and ActiTest are proprietary methods of determining liver fibrosis—all of which have separate scoring systems for fibrosis. Note that a biopsy is not necessary for making a decision about who to treat: more on this below.
When applying treatment guidelines to patients with chronic hepatitis B, the following three clinical data are necessary:
HBeAg status, ALT level, and HBV DNA level.
The CDC recommends ordering the following three tests to screen for hepatitis B
Hepatitis B surface antigen (HBsAg): A protein on the surface of hepatitis B virus; it can be detected in high levels in serum during acute or chronic hepatitis B virus infection. The presence of HBsAg indicates that the person is infectious. The body normally produces antibodies to HBsAg as part of the normal immune response to infection. Hepatitis B surface antibody (anti-HBs): The presence of anti-HBs is generally interpreted as indicating recovery and immunity from hepatitis B virus infection. Anti-HBs also develops in a person who has been successfully vaccinated against hepatitis B. Total hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms in acute hepatitis B and persists for life. The presence of anti-HBc indicates previous or ongoing infection with hepatitis B virus in an undefined time frame.
hepatitis C
Hepatitis C is like hepatitis B in a couple of ways. First, the route of transmission is the same, and a primary way that hep C spreads is through blood transfusions. Like hep B, hep C can be an acute hepatitis that resolves, develops into a chronic hepatitis, or develops into fulminant liver failure. Unlike hep B, hep C is an RNA virus, not a DNA virus. And unlike hep B, you don't have six freakin' antibodies to worry about. If a person has hep C, the antibodies to hep C are positive. Hepatitis C antibodies don't show up until about 4 months after the initial exposure. You need to quantitate the hep C RNA to determine the viral load. If the viral load is significant, then the person has an ongoing infection. You can follow the viral load and the ALT levels over time. Sometimes, the liver can clear the viral load with resolution of the infection. Most people develop a chronic infection and thus is associated with development of liver cancer. The therapy for hep C involves pegylated interferon and ribavirin. Both of these can have serious side effects. The interferon can cause a flu-like illness as well as depression. Ribavirin can wreak havoc on the blood count and cause pancytopenia.
screening recommendations for hepatitis B
People born in regions where the prevalence of HBV infection is ≥2% US-born people not vaccinated as infants and whose parents were born in regions having an HBV prevalence of ≥8% Household and sexual contacts of persons with HBV infection All pregnant women Men who have sex with men Injection drug users Individuals infected with HIV People with certain medical conditions Needing immunosuppressive therapy Undergoing hemodialysis People with elevated ALT/AST Donors of blood/organ/tissue Healthcare providers People exposed to bodily fluids Inmates
REGIMENS FOR HEPATITIS C
Primary Regimens Genotype and Primary Regimens Response Rate (%) All Genotype 1 Harvoni (Ledipasvir/sofosbuvir) or Viekira Pak (ombitasvir/paritaprevir/ritonavir/ dasabuvir) 95 Without cirrhosis Duration of treatment differs based on cirrhosis vs. no cirrhosis, failure of prior treatment, etc. Note the oral only regimens: Harvoni for all genotype 1 and genotype 4 Genotype 1a and 1b Harvoni or Viekira Pak plus ribavirin 95 With cirrhosis Viekira pack for genotype 1 without cirrhosis. Genotype 2 Sofobufir (Sovaldi) plus ribavirin 97 Genotype 3 Harvoni plus ribavirin 98 Genotype 4 Viekira Pak plus ribavirin Harvoni Sovaldi plus ribavirin
Hepatitis B screening tests
The U.S. Preventive Services Task Force (USPSTF) and Centers for Disease Control and Prevention (CDC) recommend the following serologic tests: Hepatitis B surface antigen (HBsAg) Hepatitis B surface antibody (anti-HBs) Hepatitis B core antigen (anti-HBc)
the patient returns to discuss the results of her tests. Laboratory results show that she is positive for HBsAg and is anti-HBe positive. Her HBV DNA is undetectable using an unamplified assay, making her a carrier without evidence of viral replication (no chronic, active, hepatitis B). AFP is within limits and abdominal ultrasound is unremarkable. She continues to feel well. She also tells you that she will be getting married in 2 months. She asks you what can be done to prevent her fiancé and future children from becoming infected with HBV. All of the following are accurate responses to her question EXCEPT: A No special precautions need to be taken because she has undetectable HBV and is therefore not infectious. B If her fiancé has not been immunized against HBV, he should be tested and vaccinated if not immune. C If her fiancé is not immune to HBV, they should use barrier contraceptives (e.g., condoms) until he has completed his HBV vaccination series. D She should cover any open cuts or scratches with a bandage and clean up any blood spills with bleach. E Administration of hepatitis B immune globulin (HBIG) and HBV vaccination begun immediately after birth is 95% effective in preventing perinatal transmission of HBV.
The correct answer is "A." Although patients with higher levels of HBV DNA are more infectious than those with lower levels of viral DNA, the risk of transmission in the latter case is not zero. In the case of this patient, having "undetectable" HBV DNA simply indicates a level of HBV DNA that falls below the limit of detection of an unamplified assay (on the order of 105 copies/mL). Also, the positive HbsAg means she is still a carrier. Thus, precautions should be taken to prevent sexual or household transmission to her fiancé (use of condoms, immunization if required, etc.) and to her future children (HBIG and HBV vaccination).
The patient is concerned that he may transmit the virus to his wife or children. They are tested and are found to be negative for HCV antibody. He is relieved but asks for advice to prevent infecting them. You advise all of the following EXCEPT: A No change in sexual practices is recommended for couples in a long-term monogamous relationship in which one partner is HCV+ and the other HCV-. B The use of condoms is recommended for couples in a long-term monogamous relationship in which one partner is HCV+ and the other HCV-. C Hepatitis C is not spread by hugging, sneezing, or sharing a drinking glass. D Household members of persons infected with HCV should not share items that might be contaminated with small amounts of blood such as razors or nail clippers. E Parenteral exposure to infected blood is a major route of transmission of HCV.
The correct answer is "B." HCV is spread by parenteral contact with infected blood. In contrast to hepatitis B, sexual transmission of HCV is inefficient and appears to be a minor route of spread. In addition, the efficacy of latex condoms in preventing disease is not known. The NIH and the US Public Health Service do not recommend condom use for patients in a stable, long-term, and monogamous relationship. That said, using condoms will likely reduce an already low risk even further.
A 49-year-old man comes to your office, requesting testing for hepatitis C. He recently attended his 25-year college reunion where an old friend he had "partied" with during experimentation with injectable drugs related that he has cirrhosis due to hepatitis C. The patient is otherwise healthy and denies any symptoms except for occasional fatigue after a long day at work. Physical examination of the patient is unremarkable. There are no stigmata of chronic liver disease. Which of the following is the most appropriate course of action? A Check a quantitative Hepatitis C virus (HCV) PCR ("viral load"). B Order a recombinant immunoblot assay (RIBA). C Order HCV antibody test (enzyme immunoassay). D Order a qualitative HCV PCR. E Order ALT and AST.
The correct answer is "C." The sensitivity and specificity of the present-day HCV antibody test are excellent; thus, this is the best test to perform in this situation. Rarely, patients with immunologic impairment, such as HIV infection, have HCV viremia without detectable antibody, but this would not be a concern in this otherwise healthy patient. Quantitative HCV PCR is not a reliable means for diagnosing HCV infection because currently used methods are insensitive at low levels of viremia; thus, infection cannot be ruled out if the level of HCV viremia is below the lower limit of detection of the test. RIBA is an old test that is no longer used. Qualitative HCV PCR is the most sensitive test for the presence of HCV RNA, with a limit of detection that is lower than that of quantitative PCR. It is useful to establish the presence of viremia, but is more expensive than antibody testing and thus not a first-line test. Many patients with chronic HCV infection have normal liver enzymes and can still have progressive disease; therefore, in a high-risk patient, ALT and AST are not appropriate for screening for HCV.
Appropriate laboratory studies at this point include which of the following? A Quantitative HCV PCR. B Hepatitis B surface antigen (HBsAg). C Anti-hepatitis A antibodies (IgG and IgM). D B and C. E All of the above.
The correct answer is "D." As discussed previously, the quantitative HCV PCR is not a useful test for diagnosing HCV infection. HCV antibody testing would be a better choice. Both HBsAg and anti-HAV are useful tests in this patient. HBsAg is helpful to assess for HBV infection (acute and chronic) and anti-HAV antibodies will rule out acute hepatitis A infection. A positive total anti-HAV (positive IgG) with a negative IgM would indicate past infection, while a positive IgM would suggest acute HAV infection.
The patient returns several weeks later to discuss his test results. His HCV antibody test is positive. A liver panel obtained that day shows an ALT of 48 IU/L (normal range, 0-20) and an AST of 39 IU/L (0-31). His albumin and total bilirubin are within normal limits. He is extremely anxious about his liver. To most accurately assess the degree of liver disease, your next step is to: A Obtain a liver-spleen scan to assess for evidence of cirrhosis. B Reassure the patient that his mild liver test abnormalities rule out cirrhosis. C Order a right upper quadrant ultrasound with Doppler to assess for evidence of cirrhosis. D Order elastography for evidence of cirrhosis. E Obtain an abdominal CT to assess for evidence of cirrhosis.
The correct answer is "D." Having established that the patient has hepatitis C with elevated liver enzymes, the next step is to determine the severity of his liver disease. Although his liver function tests are reassuring, this does not exclude the possibility of advanced fibrosis or even well-compensated cirrhosis. While biopsy has been the definitive test for liver fibrosis in the past (and you would not be wrong to order a biopsy if it were an option in this question), ultrasound elastography, a noninvasive technique of determining liver fibrosis, is being used more and more. The idea is that a fibrotic liver is a stiff liver. Don't worry about the details; just know that elastography (for example FibroScan) is a noninvasive and accurate method for determining the degree of hepatic fibrosis. The "F" score, discussed below, should allow you do make decisions about your hepatitis C patients. You would not be incorrect to order ultrasound imaging as well.
You tell him which of the following? A Combination therapy with interferon and ribavirin results in sustained virologic responses (SVR) in 40% to 70% of patients treated. B Combination therapy with interferon and ribavirin can cause numerous side effects including cytopenias, flu-like symptoms, worsening of autoimmune conditions, depression, and hemolytic anemia. C The HCV genotype is a strong predictor of response to the treatment. D Newer treatment regimens including ledipasvir/sofosbuvir are much more effective than the tradition combination of interferon/ribavirin. E All of the above.
The correct answer is "E." Combination therapy with interferon and ribavirin is the traditional treatment of HCV and it is clearly not as effective at achieving a SVR as the newer drugs. The HCV genotype is a major factor determining the likelihood of achieving SVR, although not the likelihood of progression to end-stage liver disease. Genotype 1 is responsive to the newer drugs, such as the combination of ledipasvir/sofosbuvir (Harvoni); an entirely oral regimen with response rates of 93% or better for genotype 1. A second entirely oral treatment is ombitasvir/paritaprevir/ritonavir/dasabuvir (Viekira Pak [U.S.]). However, it must be combined with ribavirin for genotypes 1a and 1b if cirrhosis is present. Stage of fibrosis is also a factor, and patients with stages 3 and 4 (bridging fibrosis and cirrhosis) are less likely to achieve SVR. Higher baseline viral levels also tend to predict poorer response to the treatment. Combination therapy is expensive and is associated with significant toxicities. The major concerns with ribavirin are hemolytic anemia and teratogenicity, while the interferons (standard or the long-acting pegylated forms) have a long list of potential side effects, of which neuropsychiatric problems, such as depression and irritability, are often the most troublesome. Almost no treatment regimen still requires interferon. the new hepatitis C drugs and the genotype treated, For a more complete summary, see http://www.hepatitis.va.gov/pdf/treatment-considerations-2015-07.pdf. Side effects of the newer drugs are headache, GI upset, etc., and generally much less problematic than previous generations of hepatitis C treatment.
A 24-year-old female graduate student from China comes to your office complaining of fatigue for the past month. She has also had a poor appetite and has lost about 3 lb over this period. She reports that she was told that she had "hepatitis" when she was about 10 years old but does not recall what type. She is otherwise healthy and takes no medications. She has no history or percutaneous exposures or blood transfusion. Her grandfather died of liver cancer. Physical examination reveals a thin, tired-appearing woman. The liver edge is palpable 2 cm below the right costal margin and is slightly tender. There is no ascites, splenomegaly, or cutaneous stigmata of chronic liver disease. Laboratory studies are remarkable for anemia (hemoglobin 9.1 g/dL). Liver tests reveal elevated aminotransferases (ALT 289 IU/L, AST 158 IU/L), albumin 3.2 g/dL, and total bilirubin 1.5 mg/dL (normal 0.2-1.0 mg/dL). Diagnostic possibilities at this point include: A Hepatitis A. B Hepatitis B. C Hepatitis C. D Autoimmune hepatitis. E All of the above.
The correct answer is "E." Constitutional symptoms such as fatigue and anorexia can be seen with any form of acute or chronic liver disease; thus, they are not helpful in establishing a specific diagnosis. The first priority is to rule out infectious hepatitis including hepatitis A, B, and acute hepatitis C. Autoimmune hepatitis deserves consideration, particularly in female patients. While HCV infection is a worldwide problem, HBV infection is endemic in Asia and Africa, and the possibility of chronic hepatitis B also warrants special attention in this patient.
the patient's results show a positive HbsAg, indicating ongoing hepatitis B infection. She is immune to hepatitis A and is hepatitis C negative. After being out of contact for 4 months, she returns for a follow-up visit. She tells you that she took an herbal medicine her mother sent from China and has been feeling much better recently. Her HBsAg remains positive, but her liver enzymes, albumin, and total bilirubin are now completely normal. Appropriate actions at this time include: A Treatment with interferon-alpha 5 million units daily for 16 weeks. B Order hepatitis Be antigen, anti-HBe, and HBV DNA level. C Begin periodic screening for hepatocellular carcinoma (HCC) with ultrasound and alpha-fetoprotein (AFP). D A and C. E B and C.
The correct answer is "E." The HBe antigen reflects viral replication. Loss of HBeAg indicates decreased viral replication and less of a risk of progression to cirrhosis. Loss of HBeAg may occur spontaneously; it is also the therapeutic endpoint of the antiviral treatments of HBV infection (interferon, lamivudine, adefovir). If she is negative for HBeAg and is anti-HBe antibody positive (anti-HBe +) or has low or undetectable levels of HBV DNA, she has a low level of viral replication and will not benefit further from the antiviral treatment. Her liver panel should be monitored periodically as should the AFP (alpha-fetoprotein) and ultrasound. Ultrasound is recommended every 6 months +/- AFP. An AFP alone should not be done because of the poor sensitivity and specificity. Even asymptomatic HBV carriers with minimal liver disease are at risk for HCC. Screening for HCC in those who are carriers of hepatitis B is indicated in: Asians (men >40 years old, women >50 years old); those with family a history of HCC; cirrhotic patients; and those of African ancestry >20 years of age. Our patient had positive family history of HCC, so monitoring for HCC is indicated.
A 45-year-old woman was diagnosed 6 months ago with acute hepatitis B infection. She is unaware of how she contracted the virus. She takes no medications and since the diagnosis, she has started taking a multivitamin and has started exercising. She now has the following serologies: HBsAg negative; anti-HBsAg positive; HBeAg negative; anti-HBcAg positive. Which of the following is the correct diagnosis? A Chronic active infection with low infectivity B Chronic active infection with high infectivity C Resolved acute infection D Resolved acute infection but contagious to sexual contacts E Resolved infection but at risk for reinfection in the future
The correct answer is C. Explanation: These serologies are consistent with resolved hepatitis B infection and ongoing immunity; the HBsAg antibodies indicate immunity. This patient has both negative surface and e antigens, so is not at risk to spread the disease to others.
A 60-year-old retired Navy captain comes to the doctor after a 15-lb unintentional weight gain over the past 4 months. His medical history is significant for osteoarthritis and his only complaint is fatigue. He has smoked a pack of cigarettes daily since his early 20s and consumes two to three alcoholic beverages several times per week. On examination, he is slightly jaundiced, with no hepatomegaly or RUQ tenderness to palpation. He has mild shifting dullness in his abdomen, and significant lower extremity edema. His skin is noted to have several faded tattoos. Which of the following antibodies would most likely be present in this patient? A Anti-HAV IgG B Anti-HBc IgM C Anti-HBs IgG D Anti-HBe IgM E Anti-HCV IgG
The correct answer is E. You answered B. Explanation: The patient has chronic hepatitis C that has progressed to cirrhosis causing the edema, weight gain, and ascites. Hepatitis A does not proceed to cirrhosis. Anti-HBs is present in people immunized to hepatitis B. Anti-HBe IgM reflects viral infectivity of hepatitis B. Anti-HBc IgM reflects exposure to hepatitis B 4 to 36 weeks after exposure.
ALT and AST can be elevated secondary to:
Viral agents: Hepatitis (A, B, C, D, E), CMV, Epstein-Barr virus, and other viruses. Drugs and chemicals: Acetaminophen overdose, the "glitazones," HMG-CoA reductase inhibitors, INH, griseofulvin, anticonvulsants, NSAIDs, chemicals (carbon tetrachloride, etc.), alcohol, and many other agents. Primary liver diseases: Primary sclerosing cholangitis, primary biliary cirrhosis (positive antimitochondrial antibody [AMA]). Metabolic diseases: Wilson disease (decreased ceruloplasmin), hemochromatosis, alpha1 antitrypsin deficiency, and cystic fibrosis. Mechanical difficulties: Ductal obstruction secondary to common duct stone or carcinoma (especially pancreatic, hepatoma, metastatic), Budd-Chiari syndrome (thrombosis of the hepatic vein). Cholestasis from central venous nutrition (CVN), pregnancy, or ceftriaxone therapy. Infiltrative processes: Fatty liver (especially those with diabetes, hypothyroidism, obesity; determine by U/S), amyloid, granulomatous hepatitis, liver abscess (including amebic or echinococcal; diagnosis by U/S or CT; may have eosinophilia), AIDS-related lymphoma, or other neoplasm. Other: Congestive heart failure, celiac sprue, muscle diseases (e.g., polymyositis). Alkaline phosphatase may be elevated secondary to: Pregnancy, after a fatty meal in persons with type O or B blood. Liver: Cholestasis, partial obstruction of the biliary ducts, primary sclerosing cholangitis, adult bile ductopenia, primary biliary cirrhosis, sarcoidosis, and other granulomatous disease. Bone diseases such as Paget disease and metastatic disease. For elevated liver tests, workup should include (in approximate order, which may vary depending on patient presentation): Rule out toxin exposure (alcohol, drugs). Hepatitis A, B, and C serology. Serum ferritin, iron, TIBC, transferrin saturation (hemochromatosis). Ultrasound or CT imaging (ultrasound first). ANA and antismooth muscle antibody (autoimmune hepatitis but only 28-40% sensitive). Serum alpha1 antitrypsin. Serum protein electrophoresis (elevated levels in autoimmune hepatitis, 80% sensitive). Antiendomysial antibodies or tissue transglutaminase (gluten-sensitive sprue). Serum ceruloplasmin (Wilson disease).
The AASLD recommends treatment initiation for immune active chronic hepatitis B infection which is defined as
an elevated ALT exceeding 2 times the upper limit of normal or evidence of significant inflammatory activity or fibrosis on biopsy AND an HBV DNA level above 2,000 IU/mL for HBeAg-negative patients or an HBV DNA level above 20,000 IU/mL for HBeAg-positive patients. the general understanding is that the ALT and HBV viral level elevations should be considered persistent over 3 to 6 months.[17] Other clinical factors may be important to consider in the decision to initiate treatment including older age (greater than 40 years, which is associated with significant histologic disease), family history of liver cancer and extrahepatic complications of HBV such as renal disease or vasculitis. The AASLD currently recommends that all patients with compensated cirrhosis be treated with antiviral therapy to reduce the risk of decompensation and death, regardless of ALT or HBV DNA level. Entecavir or tenofovir disoproxil fumarate (Viread) should be chosen above other oral antivirals because of the lower risk of resistance (and virologic breakthrough) with these agents. Because antiviral therapy has been shown to improve transplant-free survival in patients with decompensated cirrhosis, they should also be started on oral antiviral therapy (with either entecavir or tenofovir) regardless of ALT or HBV DNA levels. Peginterferon is contraindicated in decompensated disease due to the risk of further hepatic decompensation.
A 27-year-old woman presents to the urgent care clinic with the new onset of nausea and jaundice. During the past 3 years, she has experienced major problems with drug addiction and has been regularly injecting crystal methamphetamine. She almost always uses clean needles, but 6 weeks ago she shared needles with a man she later found out has hepatitis B virus infection. She has never received HBV vaccine. Two years ago, she had negative antibody tests for hepatitis A, B, and C, but did not return for follow-up and vaccinations. Her physical examination is normal except for track marks on her arms and visible jaundice. Laboratory studies show a total bilirubin of 6.8 mg/dl, aspartate aminotransferase (AST) level of 1906 U/L, and an alanine aminotransferase (ALT) level of 2086 U/L. Serology tests for hepatitis A, B, and C viruses are ordered. The panel ordered for hepatitis B includes hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), total hepatitis B core antibody (total anti-HBc), hepatitis e antigen (HBeAg), and antibody to hepatitis B e antigen (anti-HBe). Which of the following serologic profiles would be most consistent with acute HBV infection? A HBsAg (-), anti-HBs (+), Total anti-HBc (+), HBeAg (-), anti-HBe (+). B HBsAg (+), anti-HBs (-), Total anti-HBc (-), HBeAg (-), anti-HBe (+). C HBsAg (+), anti-HBs (-), Total anti-HBc (+), HBeAg (+), anti-HBe (-). D HBsAg (-), anti-HBs (+), Total anti-HBc (-), HBeAg (-), anti-HBe (-).
answer C This serologic profile is consistent with acute HBV infection, but it is also consistent with chronic HBV infection. In the case presented here, several factors—the recent epidemiologic exposure, the negative hepatitis B serologic test 2 years prior, and the markedly elevated hepatic aminotransferase levels—suggest that this woman has acute HBV infection. Patients with acute HBV infection typically have high titers of viral antigens (HBsAg and HBeAg) and absence of anti-HBs and anti-HBe. Patients with chronic infection usually have a similar profile, but may have negative HBeAg with positive anti-HBe. A positive total anti-HBc is present with both acute and chronic HBV infection. To differentiate acute versus chronic infection, an IgM anti-HBc should be ordered, since this test is positive with acute HBV infection, but not chronic HBV infection. A: This serologic profile is most consistent with resolved self-limited infection. Self-limited infection is characterized by the disappearance of viral antigens (HBsAg and HBeAg) and the appearance of host antibodies (anti-HBs and anti-HBe). With self-limited infection, patients may still have low levels of HBV DNA in blood, but it remains unclear whether these patients can transmit HBV to others. D: This serologic profile is most consistent with an appropriate immune response to HBV vaccine. Patients who receive HBV vaccine are exposed only to HBsAg, not to any other components of HBV. Thus, serologic markers in persons who have never been infected with HBV, but have received HBV vaccine should exclusively show anti-HBs antibodies.
A 48-year-old executive of a construction company is referred to you for further evaluation of a positive hepatitis C virus (HCV) antibody test. The HCV testing was done because routine laboratory studies showed an alanine aminotransferase (ALT) level of 55 IU/L (range 8 to 35 IU/ml). The patient brings a printout of the lab result to his appointment with you and it states "HCV antibody is positive by enzyme immunoassay—confirmation is suggested". He denies ever injecting drugs or receiving a blood transfusion and he has does not have any tattoos. He does, however, acknowledge some non-injection use of illicit drugs years earlier. He is married with two children. The patient has not been previously tested for HCV infection. His medical history is otherwise unremarkable, except for an appendectomy about 30 years ago. His review of systems is negative and his physical examination is normal. Which of the following tests would best determine whether the patient has chronic HCV infection? A Repeat of the enzyme immunoassay (EIA) test for HCV antibody B Recombinant immunoblot assay (RIBA) for HCV antibody C Alpha-fetoprotein level D HCV RNA test
answer D A positive HCV RNA test result (preferably performed as a quantitative assay) confirms that the patient has chronic HCV infection, and provides the basis for prompt initiation of counseling and pre-treatment evaluation. A: Repeating the enzyme immunoassay test for HCV antibody is not likely to be very helpful in this situation. If the test was falsely positive in the first place, it is usually positive when repeated. In addition, although a true positive enzyme immunoassay for HCV establishes infection with HCV at some point in the past, it does not determine whether the patient has developed chronic HCV infection. B: In a person with a positive screening test (in this case, EIA for HCV antibody), a positive recombinant immunoblot assay (RIBA) result proves this person had HCV infection at some point in the past. A negative result means that the screening test was falsely positive. A positive RIBA does not tell us if the patient has active HCV infection, and is probably unnecessary in this patient since we already know he has an elevated ALT. C: Alpha fetoprotein levels are used to screen for hepatocellular carcinoma. This test is not used to determine whether a patient has active hepatitis C virus infection.
(FDA) had approved seven agents for the treatment of chronic hepatitis B virus (HBV) infection
interferon alpha-2b (Intron A) [not used much anymore due to improved response rates and easier dosing schedule of pegylated interferon], peginterferon alpha-2a (Pegasys), adefovir dipivoxil (Hepsera), entecavir (Baraclude), lamivudine (Epivir-HBV), telbivudine (Tyzeka), and tenofovir disoproxil fumarate (TDF) (Viread). These agents are broadly classified as either interferons (interferon-alpha 2b and peginterferon-alpha 2a), nucleoside analogue reverse transcriptase inhibitors (entecavir, lamivudine, and telbivudine) or nucleotide analogue reverse transcriptase inhibitors (adefovir and TDF). The generic and trade medication names, along with recommended dosing are listed in (Figure 2); common side effects and cautionary notes are outlined in (Figure 3). Among these seven FDA-approved agents, most experts now consider peginterferon-alpha 2a, entecavir, or TDF as the preferred first-line therapeutic options for treatment-naïve individuals with chronic hepatitis B.[4] This discussion will review key studies for each agent, including a review of the virologic, biochemical, serologic, and histologic responses of each agent. Agents that have activity against HBV, but are not FDA-approved for the treatment of HBV, specifically emtricitabine (Emtriva) or tenofovir alafenamide (TAF), will not be discussed; in January 2016, tenofovir alafenamide was submitted to FDA for approval to treat chronic HBV.
decompensated cirrhosis
progressing cirrhosis; very pronounced symptoms indicate liver failure. liver function is impaired with obvious manifestations of liver failure.
The patient's liver biopsy shows mild-to-moderate inflammatory activity and portal and periportal fibrosis (stage 2). He is relieved to find out that he does not have cirrhosis, but remains very concerned about his hepatitis and wants to do everything possible to "get rid of" the hepatitis C. He asks about the treatment of his HCV. Which of the following is NOT an indication for the treatment of hepatitis C? A Elastography showing cirrhosis. B APRI of 0.25 (pre-cirrhosis). C Liver biopsy showing bridging fibrosis. D Ability to pay for the treatment.
the correct answer (and not an indication for hepatitis C treatment) is "B." The cutoff APRI for the treatment is 0.5 to 0.7, representing F2 fibrosis. F2 fibrosis diagnosed by any method, including biopsy or elastography (e.g., FibroSure), is an indication for the treatment. You may be wondering about "D." Starting in 2014, a wave of new and more tolerable hepatitis C treatments started to become commercially available. However, the cost of these new drugs—at least, in the United States—is immorally high, costing up to $100,000 for a complete 12-week treatment. Public and private insurers have been forced into outright rationing.
After a few phone calls, you find that elastography is not available anywhere nearby. The patient agrees to a liver biopsy to diagnosis cirrhosis and you make the referral. He is still very concerned about his situation and asks what you think the chances are that he already has cirrhosis. Regarding the development of progressive liver disease in hepatitis C, all of the following are true EXCEPT: A Approximately 20% of patients with chronic HCV infection will develop serious liver disease. B Heavy alcohol use is a risk factor for development of serious liver disease. C Acquisition of HCV infection after the age of 40 is associated with increased risk of developing serious liver disease. D HCV genotype affects the probability of developing end-stage liver disease. E Males are more likely than females to develop serious liver disease.
the correct answer is "D." While only a minority of persons infected with HCV develop serious liver disease (20%), the likelihood of progression is difficult to predict in an individual patient. Nonetheless, male gender, heavy alcohol use, and acquisition of HCV infection after the age of 40 are associated with increased risk of progressive liver disease, while genotype is not. In addition, Japanese ancestry, smoking (both cigarettes and marijuana), and acquiring hepatitis C from a blood transfusion, have been associated with an increased risk of progression. The genotype of the hepatitis C certainly makes a difference when it comes to treatment but not with progression to cirrhosis.
Patients who have a persistently normal ALT, acquired hepatitis C before the age of 35, are female, do not drink alcohol, and have minimal or no fibrosis on liver biopsy are likely or unlikely to progress to end-stage liver disease?
unlikely to progress to end-stage liver disease.
