History

Fact Explanation
Asymptomatic [1,5] Some patients may remain asymptomatic. Usually symptoms appear within 6 weeks to 6 months after the exposure. [8]
Fever [5,10] Cell death and release of pyrogens due to the inflammation results in fever. Fever is usually mild and may be absent.
Fatigue and malaise [5,8] Due to systemic viral infection.
Anorexia [5,8] This is very significant and appear in the prodromal period. Often people dislike the smell of food.
Right upper quad-rant discomfort [5] Inflammation and congestion of the liver causes stretching of the liver capsule.
Flu-like symptoms Coryza, photophobia, headache, and myalgia may be the presenting complaint.
Yellow discoloration of eyes and skin [8] Jaundice appares wthin 10 days of the symptom onset.
Serum sickness like illness [1,2] This is a relatively rare presentation. Fever, skin rash and polyarthritis precede the appearance of jaundice. [11,12]
Polyarteritis nodosa [1,2] Patients present with high fever, arthralgia, gastrointestinal disturbances and skin manifestations. [11,12]
Arthralgia [8] This is a relatively rare presentation.
Symptoms of fulminant hepatitis [3] Rarely acute HBV infection may cause fulminant hepatitis and acute liver failure. Features of coagulopathy (Spontaneous gum bleeding,cannula site bleeding), encephalopathy and cerebral edema develops. Once patients develop hepatic encephalopathy they have altered sleep wake cycle, somnolence, confusion and in extreme they develop coma. [1]
Dark urine and pale stools Acute hepatitis B sometimes result in cholestasis, resulting dark urine and pale stools. [8]
Features of Gianotti-Crosti syndrome This occurs in acute anicteric hepatitis. Infectious exanthema and lymphadenopathy occurs. [9,11]
Features of Guillain-Barre syndrome Causes tingling, muscle weakness, and ascending paralysis. [13]
Aplastic anemia [1,2] This is an extremely uncommon presentation.
History of accidental needle prick injury [1,8] Hepatitis B is spread by contact with infected blood.
History of unprotected sexual exposure [1,8] The body fluids (semen, vaginal fluids) also contain hepatitis B virus. This is a main mode of transmission in countries with low prevalence of hepatitis B. [1]
History of parenteral drug use [1] When the needles are shared among infected and non-infected persons there is risk of infection. This mode of transmission is common in countries with low prevalance of the disease. [1]
Infants born to Hepatitis B Virus (HBV) infected mothers. [1,8] Hepatitis B virus is vertically transmitted to the fetus across the placenta and also during the process the labor.
History of blood transfusion [1,6,8] Although there are donor selection criteria and donor blood is screened before transfusion there is risk of hepatitis B infection after blood transfusion. [6]
History of hemodialysis [1] Hepatitis can transmit via poorly sterilized equipment.
History of hepatitis B vaccination There is a small risk of development of hepatitis B infection after hepatitis B vaccination. [7]
References
  1. HESHAM M. ELGOUHARI, TAREK I. ABU-RAJAB TAMIMI, WILLIAM D. CAREY. Hepatitis B virus infection: Understanding its epidemiology, course, and diagnosis [online] Journal of Medicine December 2008 vol. 75 12 881-889. [viewed 4 April 2014] Available from: doi: 10.3949/ccjm.75a.07019
  2. CACOUB P, SAADOUN D, BOURLIÈRE M, et al.. Hepatitis B virus genotypes and extrahepatic manifestations. J Hepatol [online] 2005;43:764–770.
  3. WRIGHT TL, LAU JY. Clinical aspects of hepatitis B virus infection. Lancet. 1993;342:1340–1344. [viewed 4 April 2014] Available from: doi: 10.1016/0140-6736(93)92250-W.
  4. ANTONIU E, LUCA V. Features of clinical evolution of severe acute viral hepatitis. Series of 72 cases. Rev Med Chir Soc Med Nat Iasi. [online] 2010;114:95–100. [viewed 4 April 2014] Available from:http://www.ncbi.nlm.nih.gov/pubmed/20509283
  5. RYDER S D, BECKINGHAM I J, Acute hepatitis. BMJ [online] 2001; 322 [viewed 4 April 2014] Available from: doi: http://dx.doi.org/10.1136/bmj.322.7279.151
  6. SOLDAN K, RAMSAY M, COLLINS M. Acute hepatitis B infection associated with blood transfusion in England and Wales, 1991-7: review of database. BMJ. [online] Jan 9, 1999; 318(7176): 95. [viewed 4 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC27683/
  7. PAULG. M., JANEN. ZUCKERMAN, ARIEJ. Z. , SHEILA M. B., PAMELA J. at el. Acute hepatitis B infection after vaccination. The Lancet, [online] 28 January 1995: 345 (8944), 261 – 263. [viewed 4 April 2014] Available from: doi:10.1016/S0140-6736(95)90259-7
  8. Hepatitis B FAQs for the Public. [online] [viewed 4 April 2014] Available from: http://www.cdc.gov/hepatitis/b/bfaq.htm
  9. TAÏEB A, PATRICE PLANTIN, DU PASQUIER P, GUILLET G, MALEVILLE J. Gianotti-Crosti syndrome: a study of 26 cases. British Journal of Dermatology. [online] July 1986 115 (1): 49–59. [viewed 4 April 2014] Available from: DOI: 10.1111/j.1365-2133.1986.tb06219.x
  10. CHISARI FV, FERRARI C. Viral Hepatitis. ed: Nathanson N et al., Viral Pathogenesis, Philadelphia, Lippincott - Raven, 1997:745-778.
  11. HOLLINGER FB, LIANG TJ. Hepatitis B Virus. ed: Knipe DM et al. Fields Virology, 4th ed. Philadelphia, Lippincott Williams & Wilkins, 2001:2971-3036.
  12. ROBINSON WS. Hepatitis B virus and hepatitis D virus. ed: Mandell GL, Bennett JE, Dolin R,. Principles and Practice of Infectious Diseases, 4th ed. New York, Churchill Livingstone, 1995:1406-1439.

Examination

Fact Explanation
Icterus [1] Jaundice develops due to reduced hepatic metabolism of bilirubin. Patients with anicteric or subclinical hepatitis may not have icterus. This is commoner in children. [1] Patients develop jaundice after about 10 days of prodromal period and may last for months.
Mildly tender hepatomegaly [1] Stretching of the liver capsule due to inflammation.
Splenomegaly Splenomegaly occurs secondary to hepatic congestion. [2]
Palmar erythema Relatively rare finding. Occurs due to reduced hepatic metabolism of nitric oxide, a vasodilator.
References
  1. HESHAM M. ELGOUHARI, TAREK I. ABU-RAJAB TAMIMI, WILLIAM D. CAREY. Hepatitis B virus infection: Understanding its epidemiology, course, and diagnosis [online] Journal of Medicine December 2008 vol. 75 12 881-889. [viewed 4 April 2014] Available from: doi: 10.3949/ccjm.75a.07019
  2. PODDAR U, THAPA BR, PRASAD A, SINGH K. Changing spectrum of sporadic acute viral hepatitis in Indian children. J Trop Pediatr. [online] 2002 Aug;48(4):210-3. [viewed 4 April 2014] Available from:http://www.ncbi.nlm.nih.gov/pubmed/12200981
  3. N. NISHINO, T. NISHIKAWA, M. UEDE, I. YATAKA, K. KUSUI. A clinical significance of vascular spider and palmar erythema in liver diseases. Gastroenterologia Japonica. [online] 1967: 2 (2), 142. [viewed 4 April 2014] Available from: DOI: 10.1007/BF02801516

Differential Diagnoses

Fact Explanation
Alcoholic Hepatitis Jaundice, fever, tachycardia and tender hepatomegaly occurs. History of harmful use of alcohol favors the diagnosis. [1] About 40 -60% of the patients have jaundice. [1]
Autoimmune Hepatitis Common in females and other features of autoimmune diseases may present. Diagnosis is often favored by exclusion of other possible etiologies and by demonstrating the presence of auto-antibodies. [2,3] The definitive diagnosis is made according to the diagnostic criteria of the International Autoimmune Hepatitis Group. [10]
Cholangitis Obstruction of the bile duct occurs due to inflammation and infection of the bile duct. Presence of the Charcot’s triad (high fever,right upper quadrant or epigastric abdominal pain, and jaundice) is diagnostic of acute cholangitis. [11,12] Rapid diagnosis and treatment is necessary. [4]
Drug-Induced Liver Injury Acetaminophen overdose [5], valproate overdose are common causes. [6]
Hemochromatosis Results due to chronic iron overload. [7]
Hepatitis A Transmitted feco-orally. Patients develop jaundice and fever with many extra-hepatic manifestations. [8]
Hepatitis C,D and E Serology will help to establish the definitive diagnosis.
Wilson Disease Presence of neurological manifestations (Chorea, parkinsonism), Kayser-Fleischer rings, low serum caeruloplasmin, and increased 24 hour urinary copper excretion will help in diagnosis. [9]
References
  1. GURJOT BASRA, SARPREET BASRA, AND SREERAM PARUPUDI. Symptoms and signs of acute alcoholic hepatitis. World J Hepatol. [online] May 27, 2011; 3(5): 118–120. [viewed 4 April 2014] Available from: doi: 10.4254/wjh.v3.i5.118
  2. CZAJA AJ, FREESE DK. Diagnosis and treatment of autoimmune hepatitis. Hepatology. [online] 2002;36:479–497. [viewed 4 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12143059
  3. ALBERT J. C. Autoimmune Hepatitis – Approach to Diagnosis. MedGenMed. [online] 2006; 8(2): 55. [viewed 4 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1785222/#!po=8.82353
  4. PATRICK M. Management of Acute Cholangitis. Gastroenterol Hepatol [online]Feb 2011; 7(2): 121–123. [viewed 4 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061017/
  5. POLSON J, LEE WM. AASLD position paper: the management of acute liver failure. Hepatology [online] 2005;41:1179-1197. [viewed 4 April 2014] Available from:DOI: 10.1002/hep.20703
  6. VICTOR J. N, JOHN R. S., Drug-Related Hepatotoxicity. N Engl J Med [online] 2006; 354:731-739. [viewed 4 April 2014] Available from:DOI: 10.1056/NEJMra052270
  7. ANTONELLO P. Hereditary Hemochromatosis: Pathogenesis, Diagnosis, and Treatment. Gastroenterology. [online]August 2010 139(2): 393-408. [viewed 4 April 2014] Available from:doi:10.1053/j.gastro.2010.06.013
  8. NAGA C. NORMAN G. ACUTE HEPATITIS A: WHAT'S NEW WITH IT? American Journal of Gastroenterology [online] (1998) 93, 2305–2306; [viewed 4 April 2014] Available from:doi:10.1111/j.1572-0241.1998.02305.x
  9. GOWA P J, SMALLWOODA R A, ANGUSA P W, SMITHB A L, WALLC A J, SEWELLA R B. Diagnosis of Wilson's disease: an experience over three decades. Gut [online] 2000;46:415-419 [viewed 4 April 2014] Available from: doi:10.1136/gut.46.3.415
  10. ALVAREZ F, BERG PA, BIANCHI FB, BIANCHI L, BURROUGHS AK, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. [online] 1999 Nov;31(5):929-38. [viewed 5 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10580593
  11. KEITA WADA, TADAHIRO TAKADA, MYUNG-HWAN KIM. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. [online] Jan 2007; 14(1): 52–58. [viewed 5 April 2014] Available from: doi: 10.1007/s00534-006-1156-7
  12. JEAN LOUIS F., FLORENT B. Charcot's triad. Int J Emerg Med. [online] 2011; 4: 18. [viewed 5 April 2014] Available from: doi: 10.1186/1865-1380-4-18

Investigations - for Diagnosis

Fact Explanation
Liver transaminases Both ALT and AST are markedly elevated. [1] Hepatocyte necrosis releases the enzymes to the circulation.
Serum bilirubin Bilirubin levels are raised. [1] Usually the bilirubin rise is preceded by the rise of ALT.
Prothrombin time (PT) and International Normalised Ratio (INR) PT is prolonged due to reduced synthesis of coagulation factors by the liver. [2]
Hepatitis B Surface Antigen During the window period the HBSAg may not be detected. However this rises very early in the course of illness and aids early diagnosis. [1,3]
Hepatitis B DNA [1] This is an early marker of HBV infection. DNA may be very low during the window period due to the rapid clearance of the viral load. [1,3]
Hepatitis B e Antigen [1] A marker of disease activity and infectivity. Higher the HBeAg levels higher the infectivity. [3]
Anti-Hepatitis B core Antibody IgM type of antibodies indicate an acute infection. [1,3] IgM antibodies are detected even during the window period of the illness. [1]
References
  1. HESHAM M. ELGOUHARI, TAREK I. ABU-RAJAB TAMIMI, WILLIAM D. CAREY. Hepatitis B virus infection: Understanding its epidemiology, course, and diagnosis [online] Journal of Medicine December 2008 vol. 75 12 881-889. [viewed 4 April 2014] Available from: doi: 10.3949/ccjm.75a.07019
  2. DAVID E J. All patients with acute hepatitis must be observed until the acute liver injury resolves. West J Med. [online] Jan 2000; 172(1): 32–33. [viewed 4 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1070719/
  3. Hepatitis B FAQs for the Public. [online] [viewed 4 April 2014] Available from: http://www.cdc.gov/hepatitis/b/bfaq.htm

Investigations - Followup

Fact Explanation
Hepatitis B Surface antigen (HBSAg) [2] Hepatitis B tend to follow a chronic course if acquired during the neonatal period or during childhood rather than acquired during adulthood. [1] If HBSAg persists in serum for more than 6 months, chronic hepatitis B is diagnosed. [1]
Hepatitis B Virus (HBV)-DNA Clearance indicates successful treatment. [2,3] Persistent HBV-DNA indicates the risk of chronic hepatitis B. Around 15% to 40% of patients with chronic hepatitis B develop cirrhosis and subsequently hepatocellular carcinoma. [4]
Anti-HBs Antibodies Development of anti- HBs antibodies indicates immunity and recovery from the infection. [3]
Hepatitis B e Antibody Indicates that the viral load and the infectivity is less. [3]
Ultra-sound scan of the abdomen If the patient develops chronic hepatitis ultrasound scan of the abdomen detects the development of cirrhosis. [5] It is about 60% sensitive in detection of cirrhosis and done 6 months to 12months intervals.
Serum alpha-feto protein. (AFP) AFP is a tumor marker. It is combined with the ultrasound assessment for the surveillance of hepatocellular carcinoma. [5]
References
  1. HESHAM M. ELGOUHARI, TAREK I. ABU-RAJAB TAMIMI, WILLIAM D. CAREY. Hepatitis B virus infection: Understanding its epidemiology, course, and diagnosis [online] Journal of Medicine December 2008 vol. 75 12 881-889. [viewed 4 April 2014] Available from: doi: 10.3949/ccjm.75a.07019
  2. GIUSEPPE VITTORIO LUIGI DE SOCIO, ALESSIO SGRELLI, FRANCO BALDELLI. Severe Acute Hepatitis B Treated With Entecavir. Mediterr J Hematol Infect Dis. [online] 2011; 3(1): e2011010. [viewed 4 April 2014] Available from: doi: 10.4084/MJHID.2011.010
  3. Hepatitis B FAQs for the Public. [online] [viewed 4 April 2014] Available from: http://www.cdc.gov/hepatitis/b/bfaq.htm
  4. MEL KRAJDEN, GAIL MCNABB, MARTIN P. The laboratory diagnosis of hepatitis B virus. Can J Infect Dis Med Microbiol. [online] 2005 Mar-Apr; 16(2): 65–72. [viewed 4 April 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095015/
  5. SINGAL A., VOLK M.L., WALJEE A., SALGIA R., HIGGINS P., ROGERS M.A., et al. (2009) Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther [online] 2009: 30 (1): 37–47. [viewed 4 April 2014] Available from: doi: 10.1111/j.1365-2036.2009.04014.x

Investigations - Screening/Staging

Fact Explanation
Hepatic transaminases In severe acute hepatitis B infection ALT rises more than 10times of the upper limit of the normal value.[2]
Serum bilirubin [1] Serum bilirubin of more than 85 μm indicates acute severe hepatitis B infection. [2]
Prothrombin time and INR [1] If prothrombin time increases more than 50% it indicates severe infection. [2]
Hepatitis B Surface antigen (HBSAg) This is used in screening of high risk population. [3]
References
  1. GIUSEPPE VITTORIO LUIGI DE SOCIO, ALESSIO SGRELLI, FRANCO BALDELLI. Severe Acute Hepatitis B Treated With Entecavir. Mediterr J Hematol Infect Dis. [online] 2011; 3(1): e2011010. [viewed 4 April 2014] Available from: doi: 10.4084/MJHID.2011.010
  2. J. WIEGAND, H. WEDEMEYER, A. FRANKE, S. ROBLER, S. ZEUZEM, at el. Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial. Journal of Viral Hepatitis. [online] 2013: 21(4). [viewed 4 April 2014] Available from: DOI: 10.1111/jvh.12210
  3. Hepatitis B. World health organization. [online] [viewed 4 April 2014] Available from: http://www.who.int/mediacentre/factsheets/fs204/en/

Management - General Measures

Fact Explanation
Rest [2,3] Physical rest will quicken the recovery.
Adequate nutrition [2,3] Since the oral intake was poor due to severe anorexia nutritional status of the patient should be optimized.
Adequate fluids [2,3] Patient has lost significant amount of body fluids due to vomiting and poor oral intake.
Vaccination [1] High risk individuals can be vaccinated for the primary prevention of the infection. [2]
References
  1. STANLEY PLOTKIN, ELKE LEURIDAN, PIERRE VAN DAMME. Hepatitis B and the Need for a Booster Dose. Clin Infect Dis. [online] (2011) 53 (1): 68-75. [viewed 4 April 2014] Available from: doi: 10.1093/cid/cir270
  2. Hepatitis B FAQs for the Public. [online] [viewed 4 April 2014] Available from: http://www.cdc.gov/hepatitis/b/bfaq.htm
  3. Hepatitis B. World health organization. [online] [viewed 4 April 2014] Available from: http://www.who.int/mediacentre/factsheets/fs204/en/

Management - Specific Treatments

Fact Explanation
Conservative managment In majority of patients no treatment is necessary and patients recover spontaneously. [4] Antiviral therapy is proven to reduce the appearance of anti-HBs Antibodies and may dilute the immune response. [5]
Vaccination Hepatitis B vaccine if taken within 24 hours provides post-exposure prophylaxis. [11]
Hepatitis B immune globulin This is also effective in post-exposure prophylaxis if taken within 24 hours of exposure. Protective effect lasts for about three months. This is also used in in neonates born to hepatitis B infected mothers. [11]
Emergency liver transplantation This is the best possible treatment option in fulminant hepatitis and acute liver failure. [1,8]
Entecavir [1,3,10] Entecavir is the commonly used first line therapy. It is a guanosine analogue and inhibits viral polymerase enzyme. [12]
Lamivudine [7] Acts and clears the viral load very rapidly. Recently lamivudine resistance is detected. [1] Lamivudine is proven to prevent the development of acute fulminant hepatic failure if started early in the illness. [9]
Adefovir [4] Nephrotoxicity is a possible side effect. However this is used as a second line treatment. [12]
Tenofovir [4] Tenofovir has risk of nephrotoxicity however it is one of the first line treatment options.
Telbivudine [2] This is also an antiviral drug. The antiviral drugs are continued for 3 months after the appearance of Anti-HBS antibodies [6]. However some guidelines recommend that continuation of antiviral therapy until the clearance of HBs antigen is adequate. ( no need to continue for three months) [4]
Pegylated interferon alfa This is one of the first line treatment options. It has antiviral, antiproliferative, and immunomodulatory effects.
References
  1. DE SOCIO GV, MERCURI A, DI CANDILO F, BALDELLI F. Entecavir to treat severe acute hepatitis B. Scand J Infect Dis. [online] 2009;41:703–704. [viewed 4 April 2014] Available from: doi: 10.1080/00365540903062705.
  2. GIUSEPPE VITTORIO LUIGI DE SOCIO, ALESSIO SGRELLI, FRANCO BALDELLI. Severe Acute Hepatitis B Treated With Entecavir. Mediterr J Hematol Infect Dis. [online] 2011; 3(1): e2011010. [viewed 4 April 2014] Available from: doi: 10.4084/MJHID.2011.010
  3. JOCHUM C, GIESELER RK, GAWLISTA I, FIEDLER A, MANKA P, SANER FH, ROGGENDORF M, GERKEN G, CANBAY A. Hepatitis B-associated acute liver failure: immediate treatment with entecavir inhibits hepatitis B virus replication and potentially its sequelae. Digestion. [online] 2009;80:235–40. [viewed 4 April 2014] Available from: doi: 10.1159/000236009
  4. LOK ASF, MCMAHON BJ. Chronic Hepatitis B: Update 2009. AASLD practice guideline update. Hepatology. [online] 2009;50:661–662. [viewed 4 April 2014] Available from: doi: 10.1002/hep.23190.
  5. YU JW, SUN LJ, ZHAO YH, KANG P, LI SC. The study of efficacy of lamivudine in patients with severe acute hepatitis B. Dig Dis Sci. [online] 2010;55:775–783. [viewed 4 April 2014] Available from: doi: 10.1007/s10620-009-1060-5.
  6. EASL Clinical Practice Guidelines: management of chronic hepatitis B. European Association For The Study Of The Liver. J Hepatol. [online] 2009;50:227–42. [viewed 4 April 2014] Available from: doi: 10.1016/j.jhep.2008.10.001.
  7. ANDREA LISOTTI, FRANCESCO AZZAROLI, FEDERICA BUONFIGLIOLI, MARCO MONTAGNANI, FLAVIO ALESSANDRELLI, GIUSEPPE MAZZELLA. Lamivudine treatment for severe acute HBV hepatitis. Int J Med Sci [online] 2008; 5(6):309-312. [viewed 4 April 2014] Available from: doi:10.7150/ijms.5.309.
  8. HOOFNAGLE JH, DOO E, LIANG TJ, FLEISCHER R LOK AS. Management of hepatitis B: summary of a clinical research workshop. Hepatology. [online] 2007;45:1056-75. [viewed 4 April 2014]
  9. WIEGAND J, WEDEMEYER H, FRANKE A, ROBLER S, ZEUZEM S, at el. Treatment of severe, nonfulminant acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial. Journal of Viral Hepatitis. [online] 2013: 21(4). [viewed 4 April 2014] Available from: DOI: 10.1111/jvh.12210
  10. GIUSEPPE VITTORIO LUIGI DE SOCIO, ALESSIO SGRELLI, ANDREA TOSTI, FRANCO BALDELLI. Severe acute hepatitis b treated with entecavir. Mediterr J Hematol Infect Dis [online] 2011: 3(1). [viewed 4 April 2014] Available from: http://www.mjhid.org/article/view/7536
  11. Hepatitis B FAQs for the Public. [online] [viewed 4 April 2014] Available from: http://www.cdc.gov/hepatitis/b/bfaq.htm
  12. KUO A, GISH R. Chronic hepatitis B infection. Clin Liver Dis. [online] May 2012;16(2):347-69. [viewed 4 April 2014]