Sections

Workup

Approach Considerations

A simple screening test for the nonicteric patient with suspected viral hepatitis involves checking the urine for the presence of bilirubin. As an alternative, a liver enzyme panel (generally a costly test) could be obtained. Bedside fingerstick glucose testing is important to evaluate for hypoglycemia in patients with an altered or questionable mental status.

Total bilirubin levels may be elevated in infectious hepatitis. Bilirubin levels higher than 30 mg/dL indicate more severe disease. Levels of alkaline phosphatase (ALP) are usually in the reference range but may elevate to no higher than twice the normal level. If ALP is elevated significantly, consider liver abscess or biliary obstruction.

A prolonged prothrombin time (PT), if present, is a grave finding indicating impaired synthetic function of the liver. Blood urea nitrogen (BUN) and serum creatinine levels should be assessed to look for evidence of renal impairment. Decreased renal function suggests fulminant hepatic disease. Serum ammonia should be measured in patients with altered mental status or other evidence of hepatic encephalopathy.

Detection of immunoglobulin M (IgM) for hepatitis A virus (HAV) is the standard test for diagnosing acute infection with HAV.

Detection of IgM for hepatitis B core antigen (HBcAg) in serum is required to make the diagnosis of acute hepatitis B virus (HBV) infection. Hepatitis B surface antigen (HBsAg) may be present in acute infection or in patients who are chronic carriers. Its presence in patients with symptoms of acute hepatitis strongly suggests acute HBV infection but does not rule out chronic HBV with acute superinfection by another hepatitis virus. The presence of HBsAg in the serum for 6 months or longer indicates chronic infection.

Hepatitis C virus (HCV) infection can be confirmed with serologic assays to detect antibody to HCV (anti-HCV) or with molecular tests for the presence of viral particles. Third-generation assays for anti-HCV are sensitive and specific and can detect such antibodies within 4-10 weeks of infection. A rapid antibody test strip is available. Qualitative polymerase chain reaction (PCR) assay for the presence of viral particles is the most specific test of HCV infection and may be helpful in diagnosing acute HCV infection before antibodies have developed.

Assays to detect IgM antibody to hepatitis D virus (HDV) do not need to be routinely performed in all patients with suspected hepatitis.

No specific imaging studies are required to make the diagnosis of hepatitis. However, obtain the appropriate diagnostic imaging studies (eg, ultrasonography or computed tomography [CT]) if the differential diagnosis favors gallbladder disease, biliary obstruction, or liver abscess.

Liver biopsy may be recommended for the initial assessment of disease severity in patients with chronic hepatitis B or chronic hepatitis C infection.

Hepatitis A

Acute infection is documented by the presence of immunoglobulin M (IgM) antibody to hepatitis A virus (HAV) (anti-HAV), which disappears several months after the initial infection. The presence of immunoglobulin G (IgG) anti-HAV merely demonstrates that an individual has been infected with HAV at some point in the past, from 2 months ago to decades ago. IgG anti-HAV appears to offer patients lifelong immunity against recurrent HAV infection.

Acute self-limited infection

Hepatitis B surface antigen (HBsAg) is the first serum marker seen in persons with acute infection. It represents the presence of hepatitis B virus (HBV) virions (Dane particles) in the blood. Hepatitis B e antigen (HBeAg), a marker of viral replication, is also present. When viral replication slows, HBeAg disappears, and antibody to HBeAg (anti-HBe) is detected. Anti-HBe may persist for years.

The first antibody to appear is antibody to hepatitis B core antigen (HBcAg) (anti-HBc). Initially, it is of the immunoglobulin M (IgM) class. Indeed, the presence of IgM anti-HBc is diagnostic for acute HBV infection. Weeks later, IgM anti-HBc disappears, and IgG anti-HBc is detected. Anti-HBc may be present for life. The anti-HBc (total) assay detects both IgM and IgG antibodies. The presence of anti-HBc (total) demonstrates that the patient has had a history of infection with HBV at some point in the past.

In patients who clear HBV, HBsAg usually disappears 4-6 months after infection, as titers of antibody to HBsAg (anti-HBs) become detectable. Anti-HBs is believed to be a neutralizing antibody, offering immunity to subsequent exposures to HBV. Anti-HBs may persist for the life of the patient.

Several key points should be kept in mind in interpreting serology findings from patients with acute HBV infection. The presence of HBsAg does not indicate whether the infection is acute or chronic. The presence of anti-HBc (IgM) is the sine qua non of acute HBV infection. The presence of anti-HBc (total) indicates that a patient has been infected with HBV at some point. The anti-HBc (total) remains positive both in patients who clear the virus and in patients with persistent infection.

The presence of anti-HBc (total) with a negative HBsAg and a negative anti-HBs indicates one of the following:

The test result is a false positive
The patient is in a window of acute hepatitis between the elimination of HBsAg and the appearance of anti-HBs; this scenario is not observed in patients with chronic HBV infection
The patient has cleared HBV but has lost anti-HBs over the years
The patient is one of the uncommon individuals with active HBV replication who is negative for HBsAg; this situation is diagnosed when either a positive HBeAg or a positive HBV DNA result is found

In some clinicians’ opinions, the discovery of a lone positive anti-HBc (total) finding in the setting of negative HBsAg and negative anti-HBs findings mandates the performance of a polymerase chain reaction (PCR) assay for HBV DNA.

Chronic infection

HBsAg may remain detectable for life in many patients. Individuals who have positive findings for HBsAg are termed carriers of HBV. They may be inactive carriers or they may have chronic hepatitis. Anti-HBc is present in all patients with chronic HBV infections. HBeAg and HBV DNA may or may not be present. They reflect a state of active viral replication. HBV DNA levels are typically low or absent in inactive carriers. HBV DNA levels are higher in patients with chronic hepatitis B. High HBV DNA levels are associated with increased infectivity.

Anti-HBs is usually absent in patients with chronic infection. If anti-HBs is present in a patient who has positive HBsAg findings, it reflects the presence of a low level of antibody that was unsuccessful at inducing viral clearance.

Table 1 (below) summarizes diagnostic tests for HBV.^{[10, 13]}

Table 1. Diagnostic Tests for Hepatitis B (Open Table in a new window)

Test	CHB HBeAg Positive	CHB HBeAg Negative	Inactive Carrier
HBsAg	+	+	+
Anti-HBs	-	-	-
HBeAg	+	-	-
Anti-HBe	-	+	+
Anti-HBc	+	+	+
IgM anti-HBc	-	-	-
HBV DNA	>2 × 10⁴ IU/mL* (>10⁵ copies/mL)	>2 × 10³ IU/mL (>10⁴ copies/mL)	< 2 × 10³ IU/mL (< 10⁴ copies/mL)
ALT level	Elevated	Elevated	Normal
ALT = alanine aminotransferase; anti-HBc = antibody to hepatitis B core antigen; anti-HBe = antibody to HBeAg; anti-HBs = antibody to HBsAg; CHB = chronic hepatitis B; HBV = hepatitis B virus; HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; IgM = immunoglobulin M. *Increasingly, experts in the field use IU/mL rather than copies/mL.

Markers after vaccination for HBV

The HBV vaccine delivers recombinant HBsAg to the patient without HBV DNA or other HBV-associated proteins. More than 90% of recipients develop protective anti-HBs. Vaccine recipients are not positive for anti-HBc unless they were previously infected with HBV.

Hepatitis C

The tests most commonly used in the diagnosis of hepatitis C are liver chemistry, serology, hepatitis C virus (HCV) RNA testing, and liver biopsy.

In August 2012, the Centers for Disease Control and Prevention (CDC) expanded their existing, risk-based testing guidelines to recommend a one-time blood test for HCV infection in baby boomers—the generation born between 1945 and 1965, who account for approximately 75% of all chronic HCV infections in the United States—without prior ascertainment of HCV risk (see Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965).^[56]One-time HCV testing in this population could identify nearly 808,600 additional people with chronic infection. All individuals identified with HCV should be screened and/or managed for alcohol abuse, followed by referral to preventative and/or treatment services, as appropriate.

Liver chemistry

Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels merely indicate the presence of liver injury. Patients with chronically elevated aminotransferase values should undergo a workup to exclude the possibility of chronic liver disease.

Measuring aminotransferase levels is an imperfect test in patients with documented HCV infection. The values do not predict the severity of clinical findings, the degree of histologic abnormalities, the patient’s prognosis, or the therapeutic response. Indeed, patients can have HCV-induced cirrhosis while still having normal liver chemistry values.

Although increases and decreases in aminotransferase levels do not appear to correlate with clinical changes, normalization of AST and ALT levels after acute infection may signal clearance of HCV. Normalization of AST and ALT levels while a patient is undergoing treatment with interferon predicts a virologic response to treatment. Similarly, an increase in AST and ALT values may signal a relapse after apparently successful drug therapy.

Serology

Structural and nonstructural regions of the HCV genome have been synthesized. These can be recognized by human immunoglobulin G (IgG) antibody to HCV (anti-HCV). Recombinant HCV antigens are used in enzyme-linked immunosorbent assay (ELISA) to detect anti-HCV in patients’ sera.

Anti-HCV test results remain negative for several months after acute HCV infection. Once anti-HCV appears, it usually remains present for the life of the patient—even in the 15% of cases in which the patient clears the virus and does not develop chronic hepatitis. Anti-HCV is not a protective antibody and does not guard against future exposures to HCV.

In 2010, the US Food and Drug Administration (FDA) approved the OraQuick HCV Rapid Antibody Test.^[57]It can be used for persons at risk for hepatitis or for those with signs or symptoms of hepatitis. The test strip can be used with a sample collected from oral fluid, whole blood, serum, or plasma.

Recombinant immunoblot assays (RIBAs) use recombinant HCV antigens that are fixed to a solid substrate. They are more specific than ELISA testing and have been used to confirm positive ELISA results. However, their use is being abandoned in favor of HCV RNA testing.

A positive HCV result with ELISA or RIBA has one of three potential interpretations, as follows:

The test result is a true positive, and the patient is infected with HCV.
The test result is a true positive, but the patient is no longer viremic for HCV and does not have chronic hepatitis; the results from neither ELISA nor RIBA distinguish resolved infection from active infection
The test result is a false positive

ELISA testing has a positive predictive value (PPV) of more than 95% when used in patients at high risk for hepatitis C (eg, intravenous [IV] drug users and those with abnormal liver chemistry findings). However, its PPV is only 50-61% in patients at low risk for HCV infection. Furthermore, patients with autoimmune hepatitis or hypergammaglobulinemia frequently have false-positive ELISA results. Thus, a positive HCV ELISA or RIBA result does not prove that HCV infection is present. Positive serologic tests require confirmation with HCV RNA testing.

Other limitations of ELISA testing are that it fails to detect anti-HCV in 2-5% of infected patients and that it fails to detect anti-HCV in immunosuppressed patients (eg, patients with end-stage renal disease [ESRD], human immunodeficiency virus [HIV] infection, or concomitant immunosuppressant therapy). The possibility of HCV infection in this patient population should prompt HCV RNA testing.

HCV RNA testing

Since the early 1990s, polymerase chain reaction (PCR) assays and branched DNA assays have been used to detect HCV RNA in serum. In contrast to ELISA and RIBA testing, HCV RNA testing can confirm the presence of an active HCV infection.

HCV RNA testing aids in the diagnosis of early cases of HCV infection (before the development of HCV antibody positivity or an elevated ALT level), seronegative cases (as in the setting of ESRD), and cases of perinatal transmission. It is also useful for confirming false-positive cases (eg, autoimmune hepatitis), assessing the HCV genotype and viral load, predicting the response to interferon therapy, guiding the duration and dose of interferon therapy, and determining the likelihood of relapse after a response to interferon therapy.

Liver biopsy

Liver biopsy is an important diagnostic test in possible cases of chronic hepatitis C. Biopsy results can help confirm the diagnosis, as well as help exclude other diseases that might have an impact on the antiviral therapy, such as autoimmune hepatitis or hemochromatosis. Furthermore, liver biopsy offers the most reliable assessment of the severity of the disease.

Assessment of the degree of hepatic fibrosis is important for several reasons. The presence of advanced fibrosis (ie, stage 3 or 4) might trigger a decision to initiate screening to rule out the development of hepatocellular carcinoma (HCC) as a complication of advanced liver disease. Patients with previously unsuspected cirrhosis on biopsy should be monitored to ensure that they do not develop large esophageal varices. Some clinicians consider that patients with stage 3 fibrosis should be regarded as “cirrhotic until proven otherwise.”

Knowledge of the severity of histologic changes may influence the patient and the physician to be either more or less aggressive in the pursuit of an effective antiviral therapy. The presence of significant fibrosis (ie, stage 2, 3, or 4) might lead to a decision to initiate antiviral therapy in the hope that eradication of HCV would help to improve the patient’s long-term outcome. Patients with advanced histologic findings may seek experimental therapies should their condition not respond to standard antiviral therapy.

Patients with minimal fibrosis on biopsy (ie, stage 1 disease) might elect either to receive antiviral therapy or to postpone therapy. Indeed, the patient with stage 1 disease might be considered to be at low risk for complications of HCV infection. Furthermore, the risks of therapy might exceed the benefits in such a patient (eg, a patient with HCV infection, stage 1 fibrosis and major depression).

In some clinicians&rsquo9; practices, before patients with stage 1 fibrosis elect to undergo a course of watchful waiting, they are advised that only virologic eradication of HCV can ensure that none of the extrahepatic complications of hepatitis C will develop. Patients are also advised to return for a repeat biopsy in 3-4 years to rule out progression of liver disease.

Liver biopsy has a number of noteworthy limitations. First, as an invasive procedure, it may be accompanied by significant complications (eg, bleeding) in approximately 1 in 1000 patients. Second, a sampling error may occur. Indeed, in some patients, the damage induced by viral infection is not uniform throughout the entire liver. In addition, interobserver variability in the assessment of histologic abnormalities may occur. Finally, as a snapshot in time, liver biopsy findings cannot be used to predict the rate of progression of chronic hepatitis C.

Other tests for estimating fibrosis in chronic hepatitis C

Liver stiffness can be estimated by using a technique known as vibration-controlled transient elastography or Fibroscan. The test is reportedly capable of diagnosing cirrhosis correctly in about 95% of patients; however it is less accurate in assessing patients with lesser degrees of fibrosis.^[58]Fibroscan was approved for use in the United States in 2013 and, although it is not a replacement for liver biopsy, it can serve as a useful adjunct to help diagnose or exclude advanced fibrosis and cirrhosis.^{[59, 60]}

Liver fibrosis can also be estimated by means of a number of commercial blood tests, including the following:

FIBROSpect II uses measurements of hyaluronic acid, tissue inhibitor of metalloproteinase-1 (TIMP-1) and alpha-2 macroglobulin to estimate liver fibrosis
HepaScore is based on levels of hyaluronic acid, alpha-2 macroglobulin, gamma glutamyl transferase (GGT), and total bilirubin, as well as age and sex
HCV FibroSURE measures alpha-2 macroglobulin, haptoglobin, GGT, bilirubin, ALT, and apolipoprotein A1

In general, these tests are considered accurate in determining the presence or absence of early (stage 1) or advanced (stage 4) fibrosis; however, they are considered to be less accurate in differentiating patients with moderate fibrosis.

At present, most gastroenterologists do not use serologic fibrosis markers as a substitute for liver biopsy. These tests may be useful for identifying patients at low risk for advanced disease (eg, asymptomatic women with HCV RNA positivity, persistently normal liver chemistry values, and no history of alcohol abuse or HIV infection) or for longitudinal follow-up of patients with minimal disease on biopsy who elect not to undergo antiviral therapy. If future generations of these markers achieve greater accuracy, they may obviate the need for liver biopsy.

Hepatitis D and E

A serologic diagnosis of hepatitis delta virus (HDV) infection is made by using immunoglobulin M (IgM) antibody to HDV (anti-HDV) and IgG anti-HDV tests. IgM antibody to hepatitis B core antigen (anti-HBc) should be used to help distinguish between coinfection (positive for IgM anti-HBc) and superinfection (negative for IgM anti-HBc). Detecting HDV RNA in serum is also possible.

A serologic diagnosis of hepatitis E virus (HEV) infection is made by using IgM antibody to HEV (anti-HEV) and IgG anti-HEV. HEV RNA can be detected in the serum and stool of infected patients.

Hepatitis B

Inactive carriers of hepatitis B virus (HBV) have no or minimal histologic abnormalities detected on liver biopsy specimens.

Patients with chronic hepatitis B may have a number of classic histologic abnormalities. Inflammatory infiltrates composed of mononuclear cells may either remain contained within the portal areas or disrupt the limiting plates of portal tracts, expanding into the liver lobule (interface hepatitis). Periportal fibrosis or bridging necrosis (between portal tracts) may be present. The presence of bridging necrosis places the patient at an increased risk for progression to cirrhosis.

Ground-glass cells may be seen (see the image below). This term describes the granular homogeneous eosinophilic staining of cytoplasm caused by the presence of hepatitis B surface antigen (HBsAg). Sanded nuclei reflect the presence of an overload of hepatitis B core antigen (HBcAg). Special immunohistochemical stains may help detect HBsAg and HBcAg.

Viral Hepatitis. Liver biopsy specimen showing ground-glass appearance of hepatocytes in a patient with hepatitis B.

View Media Gallery

Hepatitis C

Pathologists who interpret liver biopsy specimens frequently use a histologic scoring system introduced by Batts and Ludwig in 1995 (see Table 2 below) to grade hepatitis C virus (HCV)-induced disease.^[61]The METAVIR scoring system developed by the French METAVIR Cooperative Study Group uses similar methodology.

Table 2. Histologic Grading for Hepatitis C–Induced Liver Disease (Open Table in a new window)

Grade	Portal Inflammation	Interface Hepatitis	Lobular Necrosis
1 – Minimal	Mild	Scant	None
2 – Mild	Mild	Mild	Scant
3 – Moderate	Moderate	Moderate	Spotty
4 – Severe	Marked	Marked	Confluent

Histologic staging for hepatitis C–induced liver disease is as follows:

Stage 1 – Portal fibrosis
Stage 2 – Periportal fibrosis
Stage 3 – Septal fibrosis
Stage 4 – Cirrhosis

Lymphocytic infiltrates, either contained within the portal tract or expanding out of the portal tract into the liver lobule (interface hepatitis), are commonly observed in patients with chronic hepatitis C. Portal and periportal fibrosis may be present. Other classic histologic features of the disease include bile duct damage, lymphoid follicles or aggregates, and macrovesicular steatosis.

Hepatitis D and E

The pathologic abnormalities associated with HBV-HDV coinfection are the same as those observed in patients infected with HBV alone (see above).

The classic pathologic findings associated with HEV infection include infiltration of portal tracts by lymphocytes and polymorphonuclear leukocytes, ballooned hepatocytes, acidophilic body formation, and intralobular necrosis of hepatocytes. Submassive and massive hepatic necrosis may be observed in severe cases.

Treatment & Management

Wasley A, Grytdal S, Gallagher K, Centers for Disease Control and Prevention (CDC). Surveillance for acute viral hepatitis--United States, 2006. MMWR Surveill Summ. 2008 Mar 21. 57(2):1-24. [QxMD MEDLINE Link]. [Full Text].
Previsani N, Lavanchy D, World Health Organization. Hepatitis B (WHO/CDS/CSR/LYO/2002.2). 2002. [Full Text].
Fattovich G. Natural history of hepatitis B. J Hepatol. 2003. 39 suppl 1:S50-8. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Terrault NA, Bzowej NH, Chang KM, et al, for the American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016 Jan. 63(1):261-83. [QxMD MEDLINE Link]. [Full Text].
[Guideline] World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. 2015 Mar. [QxMD MEDLINE Link]. [Full Text].
Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci. 2006. 3(2):47-52. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Ghany MG, Morgan TR, AASLD-IDSA Hepatitis C Guidance Panel. Hepatitis C guidance 2019 update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America recommendations for testing, managing, and treating hepatitis C virus infection. Hepatology. 2020 Feb. 71(2):686-721. [QxMD MEDLINE Link]. [Full Text].
Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006 Oct. 45(4):529-38. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Viral Hepatitis Surveillance United States, 2014 (revised: 9/26/16). Available at https://www.cdc.gov/hepatitis/statistics/2014surveillance/pdfs/2014hepsurveillancerpt.pdf. Accessed: June 12, 2017.
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008 Dec. 6(12):1315-41; quiz 1286. [QxMD MEDLINE Link]. [Full Text].
Sorrell MF, Belongia EA, Costa J, et al. National Institutes of Health consensus development conference statement: management of hepatitis B. Hepatology. 2009 May. 49(5 suppl):S4-S12. [QxMD MEDLINE Link].
[Guideline] Lok AS, McMahon BJ. AASLD practice guideline update: chronic hepatitis B: update 2009. Hepatology. 2009 Sep. 50(3):661-2. [QxMD MEDLINE Link]. [Full Text].
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States. Clin Gastroenterol Hepatol. 2004 Feb. 2(2):87-106. [QxMD MEDLINE Link].
Tabor E. The role of tumor suppressor genes in the development of hepatocellular carcinoma. In: Okuda K, Tabor E, eds. Liver Cancer. New York, NY: Churchill Livingstone; 1997. 89-95.
Chen CJ, Yang HI, Iloeje UH, for the REVEAL-HBV Study Group. Hepatitis B virus DNA levels and outcomes in chronic hepatitis B. Hepatology. 2009 May. 49(5 suppl):S72-84. [QxMD MEDLINE Link].
Liaw YF, Sung JJ, Chow WC, et al, for the Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7. 351(15):1521-31. [QxMD MEDLINE Link]. [Full Text].
Di Marco V, Marzano A, Lampertico P, et al, for the Italian Association for the Study of the Liver (AISF) Lamivudine Study Group, Italy. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine. Hepatology. 2004 Oct. 40(4):883-91. [QxMD MEDLINE Link]. [Full Text].
World Health Organization. Hepatitis C. Fact sheet no 164. Available at http://www.who.int/mediacentre/factsheets/fs164/en/. Updated: April 2017; Accessed: June 12, 2017.
Centers for Disease Control and Prevention. Viral hepatitis: hepatitis C FAQs for health professionals. Available at https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm. Updated: January 27, 2017; Accessed: June 12, 2017.
[Guideline] World Health Organization. Guidelines for the screening, care and treatment of persons with chronic hepatitis C infection: updated version (April 2016). 2016 Apr. [QxMD MEDLINE Link]. [Full Text].
World Health Organization. Hepatitis E. Fact sheet no 280. Available at http://www.who.int/mediacentre/factsheets/fs280/en/. Updated: July 2016; Accessed: June 13, 2017.
Kumar A, Beniwal M, Kar P, Sharma JB, Murthy NS. Hepatitis E in pregnancy. Int J Gynaecol Obstet. 2004 Jun. 85(3):240-4. [QxMD MEDLINE Link].
Kamar N, Selves J, Mansuy JM, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med. 2008 Feb 21. 358(8):811-7. [QxMD MEDLINE Link]. [Full Text].
Gerolami R, Moal V, Colson P. Chronic hepatitis E with cirrhosis in a kidney-transplant recipient. N Engl J Med. 2008 Feb 21. 358(8):859-60. [QxMD MEDLINE Link]. [Full Text].
Kamar N, Mansuy JM, Cointault O, et al. Hepatitis E virus-related cirrhosis in kidney- and kidney-pancreas-transplant recipients. Am J Transplant. 2008 Aug. 8(8):1744-8. [QxMD MEDLINE Link]. [Full Text].
Centers for Disease Control and Prevention. Viral hepatitis. Available at https://www.cdc.gov/hepatitis/abc/index.htm. Updated: May 26, 2016; Accessed: June 13, 2017.
World Health Organization. Hepatitis A. Fact sheet no 328. Available at http://www.who.int/mediacentre/factsheets/fs328/en/. Updated: July 2016; Accessed: June 12, 2017.
Centers for Disease Control and Prevention. Hepatitis A questions and answers for health professionals. Available at https://www.cdc.gov/hepatitis/hav/havfaq.htm. Updated: July 13, 2016; Accessed: June 13, 2017.
Centers for Disease Control and Prevention. Surveillance for Viral Hepatitis – United States, 2015 (updated: May 11, 2017). Available at https://www.cdc.gov/hepatitis/statistics/2015surveillance/commentary.htm. Accessed: June 12, 2017.
World Health Organization. Hepatitis B. Fact sheet no 204. Available at http://www.who.int/mediacentre/factsheets/fs204/en/. Updated: April 2017; Accessed: June 12, 2017.
Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009 Oct 8. 461(7265):798-801. [QxMD MEDLINE Link]. [Full Text].
Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009 Sep 17. 461(7262):399-401. [QxMD MEDLINE Link].
World Health Organization. Hepatitis D. Fact sheet. Available at https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-d. July 2016; Accessed: June 12, 2017.
Adhami T, Levinthal G. Hepatitis E and hepatitis G/GBV-C. The Cleveland Clinic Disease Management Project. May 29, 2002.
Previsani N, Lavanchy D, World Health Organization. Hepatitis E (WHO/CDS/CSR/EDC/2001.12.). 2001.
Chivero ET, Stapleton JT. Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection. J Gen Virol. 2015 Jul. 96(pt 7):1521-32. [QxMD MEDLINE Link]. [Full Text].
Stanaway JD, Flaxman AD, Naghavi M, et al. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet. 2016 Sep 10. 388(10049):1081-8. [QxMD MEDLINE Link]. [Full Text].
World Health Organization. World hepatitis day: 28 July. Hepatitis A & E. 2014. Available at http://www.who.int/campaigns/hepatitis-day/2014/hepatitis-a-e.pdf?ua=1. Accessed: June 12, 2017.
Thomas E, Yoneda M, Schiff ER. Viral hepatitis: past and future of HBV and HDV. Cold Spring Harb Perspect Med. 2015 Feb 2. 5(2):a021345. [QxMD MEDLINE Link]. [Full Text].
Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011 Aug 13. 378(9791):571-83. [QxMD MEDLINE Link]. [Full Text].
Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004 Mar. 11(2):97-107. [QxMD MEDLINE Link].
National Heart, Lung, and Blood Institute. What are the risks of a blood transfusion?. Available at https://www.nhlbi.nih.gov/health/health-topics/topics/bt/risks. Updated: January 30, 2012; Accessed: June 12, 2017.
Centers for Disease Control and Prevention. Healthcare-associated hepatitis B and C outbreaks reported to the Centers for Disease Control and Prevention (CDC) 2008-2015 (updated: July 14, 2016). Available at https://www.cdc.gov/hepatitis/outbreaks/healthcarehepoutbreaktable.htm. Accessed: June 12, 2017.
Alter MJ. Epidemiology of hepatitis C. Hepatology. 1997 Sep. 26(3 suppl 1):62S-65S. [QxMD MEDLINE Link].
Krawitt EL. Autoimmune hepatitis: classification, heterogeneity, and treatment. Am J Med. 1994 Jan 17. 96(1A):23S-26S. [QxMD MEDLINE Link].
Koneru A, Nelson N, Hariri S, et al. Increased hepatitis C virus (HCV) detection in women of childbearing age and potential risk for vertical transmission - United States and Kentucky, 2011-2014. MMWR Morb Mortal Wkly Rep. 2016 Jul 22. 65(28):705-10. [QxMD MEDLINE Link]. [Full Text].
Dienstag JL. Sexual and perinatal transmission of hepatitis C. Hepatology. 1997 Sep. 26(3 suppl 1):66S-70S. [QxMD MEDLINE Link].
Adhami T, Levinthal G. Hepatitis D. The Cleveland Clinic Disease Management Project. May 29, 2002.
Noureddin M, Gish R. Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery. Curr Gastroenterol Rep. 2014 Jan. 16(1):365. [QxMD MEDLINE Link]. [Full Text].
Kushner T, Serper M, Kaplan DE. Delta hepatitis within the Veterans Affairs medical system in the United States: Prevalence, risk factors, and outcomes. J Hepatol. 2015 Sep. 63(3):586-92. [QxMD MEDLINE Link]. [Full Text].
Sultanik P, Pol S. Hepatitis delta virus: epidemiology, natural course and treatment. J Infect Dis Ther. 2016 Mar 3. 4:271. [Full Text].
Khuroo MS, Kamili S, Khuroo MS. Clinical course and duration of viremia in vertically transmitted hepatitis E virus (HEV) infection in babies born to HEV-infected mothers. J Viral Hepat. 2009 Jul. 16(7):519-23. [QxMD MEDLINE Link].
Mathur P, Arora NK, Panda SK, Kapoor SK, Jailkhani BL, Irshad M. Sero-epidemiology of hepatitis E virus (HEV) in urban and rural children of North India. Indian Pediatr. 2001 May. 38(5):461-75. [QxMD MEDLINE Link].
Previsani N, Lavanchy D, World Health Organization. Hepatitis C (WHO/CDS/CSR/LYO/2003). 2002.
Previsani N, Lavanchy D, World Health Organization. Hepatitis D (WHO/CDS/CSR/NCS/2001.1). 2001.
Smith BD, Morgan RL, Beckett GA, et al, for the Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012 Aug 17. 61(RR-4):1-32. [QxMD MEDLINE Link]. [Full Text].
Waknine Y. FDA approves first rapid HCV test. Medscape Medical News. June 28, 2010. Available at http://www.medscape.com/viewarticle/724236. Accessed: June 30, 2010.
Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008 Apr. 134(4):960-74. [QxMD MEDLINE Link]. [Full Text].
Bonder A, Afdhal N. Utilization of FibroScan in clinical practice. Curr Gastroenterol Rep. 2014 Feb. 16(2):372. [QxMD MEDLINE Link].
Tapper EB, Castera L, Afdhal NH. FibroScan (vibration-controlled transient elastography): where does it stand in the United States practice. Clin Gastroenterol Hepatol. 2015 Jan. 13(1):27-36. [QxMD MEDLINE Link]. [Full Text].
Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995 Dec. 19 (12):1409-17. [QxMD MEDLINE Link].
Schmilovitz-Weiss H, Ben-Ari Z, Sikuler E, et al. Lamivudine treatment for acute severe hepatitis B: a pilot study. Liver Int. 2004 Dec. 24 (6):547-51. [QxMD MEDLINE Link].
Fattovich G, Giustina G, Sanchez-Tapias J, et al. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. European Concerted Action on Viral Hepatitis (EUROHEP). Am J Gastroenterol. 1998 Jun. 93 (6):896-900. [QxMD MEDLINE Link].
Janssen HL, van Zonneveld M, Senturk H, et al, for the HBV 99-01 Study Group, Rotterdam Foundation for Liver Research. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005 Jan 8-14. 365 (9454):123-9. [QxMD MEDLINE Link].
Lau GK, Piratvisuth T, Luo KX, et al, for the Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study Group. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005 Jun 30. 352 (26):2682-95. [QxMD MEDLINE Link].
Marcellin P, Lau GK, Bonino F, et al, for the Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004 Sep 16. 351 (12):1206-17. [QxMD MEDLINE Link].
Dienstag JL. Benefits and risks of nucleoside analog therapy for hepatitis B. Hepatology. 2009 May. 49 (5 suppl):S112-21. [QxMD MEDLINE Link].
Brouwer WP, Xie Q, Sonneveld MJ, et al, for the ARES Study Group. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: a multicenter randomized trial (ARES study). Hepatology. 2015 May. 61(5):1512-22. [QxMD MEDLINE Link]. [Full Text].
Marcellin P, Ahn SH, Ma X, et al, for the Study 149 Investigators. Combination of tenofovir disoproxil fumarate and peginterferon α-2a increases loss of hepatitis B surface antigen in patients with chronic hepatitis B. Gastroenterology. 2016 Jan. 150(1):134-44.e10. [QxMD MEDLINE Link]. [Full Text].
Wursthorn K, Lutgehetmann M, Dandri M, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology. 2006 Sep. 44(3):675-84. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr. 67 (4):1560-99. [QxMD MEDLINE Link]. [Full Text].
Jaeckel E, Cornberg M, Wedemeyer H, et al, for the German Acute Hepatitis C Therapy Group. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med. 2001 Nov 15. 345 (20):1452-7. [QxMD MEDLINE Link].
Nelson DR, Davis GL, Jacobson I, et al. Hepatitis C virus: a critical appraisal of approaches to therapy. Clin Gastroenterol Hepatol. 2009 Apr. 7 (4):397-414; quiz 366. [QxMD MEDLINE Link].
[Guideline] American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Simplified HCV treatment* for treatment-naive adults without cirrhosis. HCV Guidance: recommendations for testing, managing, and treating hepatitis C. Available at https://www.hcvguidelines.org/treatment-naive/simplified-treatment. Updated: August 27, 2020; Accessed: December 9, 2021.
Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8. 383(9916):515-23. [QxMD MEDLINE Link].
Afdhal N, Zeuzem S, Kwo P, et al, for the ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15. 370(20):1889-98. [QxMD MEDLINE Link]. [Full Text].
Nkuize M, Serste T, Buset M, Mulkay JP. Combination ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus infection: a review and clinical perspective. Ther Clin Risk Manag. 2016. 12:861-72. [QxMD MEDLINE Link]. [Full Text].
Feld JJ, Jacobson IM, Hezode C, et al, for the ASTRAL-1 Investigators. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med. 2015 Dec 31. 373(27):2599-607. [QxMD MEDLINE Link]. [Full Text].
Everson GT, Towner WJ, Davis MN, et al. Sofosbuvir with velpatasvir in treatment-naive noncirrhotic patients with genotype 1 to 6 hepatitis C virus infection: a randomized trial. Ann Intern Med. 2015 Dec 1. 163(11):818-26. [QxMD MEDLINE Link].
Agarwal K, Castells L, Mullhaupt B, et al. Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. J Hepatol. 2018 Sep. 69(3):603-7. [QxMD MEDLINE Link]. [Full Text].
Mir F, Kahveci AS, Ibdah JA, Tahan V. Sofosbuvir/velpatasvir regimen promises an effective pan-genotypic hepatitis C virus cure. Drug Des Devel Ther. 2017. 11:497-502. [QxMD MEDLINE Link]. [Full Text].
Zeuzem S, Foster GR, Wang S, et al. Glecaprevir-pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N Engl J Med. 2018 Jan 25. 378(4):354-69. [QxMD MEDLINE Link]. [Full Text].
Forns X, Lee SS, Valdes J, et al. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis. 2017 Oct. 17(10):1062-8. [QxMD MEDLINE Link].
Xu HQ, Wang CG, Xiao P, Gao YH. Efficacy and safety of glecaprevir/pibrentasvir for chronic hepatitis C patients: a systematic review and meta-analysis. J Clin Transl Hepatol. 2020 Sep 28. 8(3):267-76. [QxMD MEDLINE Link]. [Full Text].
Buti M, Gordon SC, Zuckerman E, et al. Grazoprevir, elbasvir, and ribavirin for chronic hepatitis C virus genotype 1 infection after failure of pegylated interferon and ribavirin with an earlier-generation protease inhibitor: final 24-week results from C-SALVAGE. Clin Infect Dis. 2016 Jan 1. 62(1):32-6. [QxMD MEDLINE Link].
Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med. 2015 Jul 7. 163(1):1-13. [QxMD MEDLINE Link].
Feld JJ, Kowdley KV, Coakley E, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014 Apr 24. 370(17):1594-603. [QxMD MEDLINE Link]. [Full Text].
Klibanov OM, Gale SE, Santevecchi B. Ombitasvir/paritaprevir/ritonavir and dasabuvir tablets for hepatitis C virus genotype 1 infection. Ann Pharmacother. 2015 May. 49(5):566-81. [QxMD MEDLINE Link].
Poordad F, Hezode C, Trinh R, et al. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014 May 22. 370(21):1973-82. [QxMD MEDLINE Link]. [Full Text].
Niro GA, Ciancio A, Gaeta GB, et al. Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology. 2006 Sep. 44 (3):713-20. [QxMD MEDLINE Link].
Bourliere M, Gordon SC, Flamm SL, et al, for the POLARIS-1 and POLARIS-4 Investigators. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N Engl J Med. 2017 Jun 1. 376(22):2134-46. [QxMD MEDLINE Link]. [Full Text].
Lawitz E, Sulkowski MS, Ghalib R, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet. 2014 Nov 15. 384(9956):1756-65. [QxMD MEDLINE Link].
Sulkowski MS, Gardiner DF, Rodriguez-Torres M, et al, for the AI444040 Study Group. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16. 370(3):211-21. [QxMD MEDLINE Link]. [Full Text].
Nishiguchi S, Kuroki T, Nakatani S, et al. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet. 1995 Oct 21. 346 (8982):1051-5. [QxMD MEDLINE Link].
Bruno S, Stroffolini T, Colombo M, et al, for the Italian Association of the Study of the Liver Disease (AISF). Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007 Mar. 45 (3):579-87. [QxMD MEDLINE Link].
Poynard T, McHutchison J, Davis GL, et al. Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C. Hepatology. 2000 Nov. 32(5):1131-7. [QxMD MEDLINE Link].
Mallet V, Gilgenkrantz H, Serpaggi J, et al. Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med. 2008 Sep 16. 149 (6):399-403. [QxMD MEDLINE Link].
Da BL, Lourdusamy V, Kushner T, Dieterich D, Saberi B. Efficacy of sofosbuvir/velpatasvir/voxilaprevir in direct-acting antiviral experienced patients with hepatitis C virus. Eur J Gastroenterol Hepatol. 2021 Jun 1. 33(6):859-61. [QxMD MEDLINE Link].
Lau DT, Doo E, Park Y, et al. Lamivudine for chronic delta hepatitis. Hepatology. 1999 Aug. 30 (2):546-9. [QxMD MEDLINE Link].
Yurdaydin C, Bozkaya H, Onder FO, et al. Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon. J Viral Hepat. 2008 Apr. 15 (4):314-21. [QxMD MEDLINE Link].
Fiore AE, Wasley A, Bell BP, for the Advisory Committee on Immunization Practices (ACIP). Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006 May 19. 55(RR-7):1-23. [QxMD MEDLINE Link]. [Full Text].
Vento S, Garofano T, Renzini C, et al. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med. 1998 Jan 29. 338(5):286-90. [QxMD MEDLINE Link]. [Full Text].
Advisory Committee on Immunization Practices. Recommended adult immunization schedule: United States, 2009*. Ann Intern Med. 2009 Jan 6. 150 (1):40-4. [QxMD MEDLINE Link].
Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC). Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007 Oct 19. 56 (41):1080-4. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Hepatitis B FAQs for health professionals. Available at https://www.cdc.gov/hepatitis/HBV/HBVfaq.htm#recctbl. Updated: August 4, 2016; Accessed: June 13, 2017.
Halperin SA, Ward B, Cooper C, et al. Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age. Vaccine. 2012 Mar 28. 30(15):2556-63. [QxMD MEDLINE Link].
Chang MH, Chen TH, Hsu HM, et al, for the Taiwan Childhood HCC Study Group. Prevention of hepatocellular carcinoma by universal vaccination against hepatitis B virus: the effect and problems. Clin Cancer Res. 2005 Nov 1. 11 (21):7953-7. [QxMD MEDLINE Link].
Moorman AC, de Perio MA, Goldschmidt R, et al. Testing and clinical management of health care personnel potentially exposed to hepatitis C virus - CDC guidance, United States, 2020. MMWR Recomm Rep. 2020 Jul 24. 69(6):1-8. [QxMD MEDLINE Link]. [Full Text].
McHutchison JG, Dusheiko G, Shiffman ML, et al, for the TPL102357 Study Group. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007 Nov 29. 357 (22):2227-36. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. HIV and viral hepatitis. Available at https://www.cdc.gov/hiv/pdf/library/factsheets/hiv-viral-hepatitis.pdf. June 2017; Accessed: June 13, 2017.
Brown RS Jr, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology. 2016 Jan. 63 (1):319-33. [QxMD MEDLINE Link].

Media Gallery

Viral Hepatitis. Hepatitis A virus as viewed through electron microscopy.
Viral Hepatitis. Liver biopsy specimen showing ground-glass appearance of hepatocytes in a patient with hepatitis B.
Viral Hepatitis. Liver biopsy with hematoxylin stain showing stage 4 fibrosis (ie, cirrhosis) in a patient with hepatitis B.
Viral Hepatitis. Liver biopsy with trichrome stain showing stage 3 fibrosis in a patient with hepatitis B.
Viral Hepatitis. Hepatic carcinoma, primary. Large multifocal hepatocellular carcinoma in an 80-year-old man without cirrhosis.
Viral Hepatitis. Triple-phase computed tomography scan depicting liver cancer, revealing classic findings of enhancement during the arterial phase and delayed hypointensity during the portal venous phase.

of 6

Table 1. Diagnostic Tests for Hepatitis B

Test	CHB HBeAg Positive	CHB HBeAg Negative	Inactive Carrier
HBsAg	+	+	+
Anti-HBs	-	-	-
HBeAg	+	-	-
Anti-HBe	-	+	+
Anti-HBc	+	+	+
IgM anti-HBc	-	-	-
HBV DNA	>2 × 10⁴ IU/mL* (>10⁵ copies/mL)	>2 × 10³ IU/mL (>10⁴ copies/mL)	< 2 × 10³ IU/mL (< 10⁴ copies/mL)
ALT level	Elevated	Elevated	Normal
ALT = alanine aminotransferase; anti-HBc = antibody to hepatitis B core antigen; anti-HBe = antibody to HBeAg; anti-HBs = antibody to HBsAg; CHB = chronic hepatitis B; HBV = hepatitis B virus; HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; IgM = immunoglobulin M. *Increasingly, experts in the field use IU/mL rather than copies/mL.

Table 2. Histologic Grading for Hepatitis C–Induced Liver Disease

Grade	Portal Inflammation	Interface Hepatitis	Lobular Necrosis
1 – Minimal	Mild	Scant	None
2 – Mild	Mild	Mild	Scant
3 – Moderate	Moderate	Moderate	Spotty
4 – Severe	Marked	Marked	Confluent

Back to List

Author

Naga Swetha Samji, MD Physician, Bellin Clinic, Bellin Health Systems

Naga Swetha Samji, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, Wisconsin Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Adrienne M Buggs, MD, FACEP, FAAEM Medical Policy Advisor, Office of Merchant Mariner Credentialing, United States Coast Guard

Adrienne M Buggs, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Praveen K Roy, MD, MSc Clinical Assistant Professor of Medicine, University of New Mexico School of Medicine

Praveen K Roy, MD, MSc is a member of the following medical societies: Alaska State Medical Association, American Gastroenterological Association

Disclosure: Nothing to disclose.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

Eugene Hardin, FAAEM, FACEP Former Chair and Associate Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science; Former Chair, Department of Emergency Medicine, Martin Luther King Jr/Drew Medical Center

Disclosure: Nothing to disclose.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Joseph K Lim, MD Associate Professor of Medicine, Director, Yale Viral Hepatitis Program, Section of Digestive Diseases, Yale University School of Medicine

Joseph K Lim, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Robert M McNamara, MD, FAAEM Chair and Professor, Department of Emergency Medicine, Temple University School of Medicine

Robert M McNamara, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Association, Pennsylvania Medical Society, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rajeev Vasudeva, MD, FACG Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine

Rajeev Vasudeva, MD, FACG is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Columbia Medical Society, South Carolina Gastroenterology Association, and South Carolina Medical Association

Disclosure: Pricara Honoraria Speaking and teaching; UCB Consulting fee Consulting

David C Wolf, MD, FACP, FACG, AGAF Medical Director of Liver Transplantation, Westchester Medical Center; Professor of Clinical Medicine, Division of Gastroenterology and Hepatobiliary Diseases, Department of Medicine, New York Medical College

David C Wolf, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, and American Gastroenterological Association

Disclosure: Nothing to disclose.

Viral Hepatitis Workup

Approach Considerations

Hepatitis A