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home - Liver - Hepatitis B - Hepatitis B Natural History Written by Dr Sebastian Zeki

Understands the serological interpretation categorisation and
investigation of patients with chronic hepatitis B and/or C with
particular emphasis on the need for treatment and surveillance

Recognises the particular populations at risk
Aware of national and international agreed guidelines on viral
hepatitis management and use of interferon and antiviral drugs

Aware of hepatitis B reactivation in the context of immunosuppression
Uses appropriate diagnostic modalities including serology
genotyping viral load measurements liver biopsy and related

Monitors anti-viral and immunomodulatory therapies with appropriate

Communicates effectively with patients and relatives in the context of
viral liver disease and underlying social and psychological risk factors

Marshals multi-disciplinary support networks and in particular
recognise the crucial role of nurse practitioners in disease



Identifies patients with acute hepatitis B and can a rtain the
severity of their illness

Defines the different phases of chronic hepatitis B infection with a
clear understanding of serological results

Appreciates risks of transmission to close contacts
Has awareness of indications for therapy in both HBeAg positive and
negative hepatitis and the potential influence of genotype on choice of

Identifies patients where prophylaxis is required to prevent
reactivation and vertical transmission

Can determine an appropriate surveillance programme for those
patients with varices and/or hepatocellular carcinoma

Identifies patients who are appropriate candidates for liver transplant

Demonstrates ability to take a relevant history perform examination
and organise appropriate investigations

Able to advise risks of viral transmission
Interprets results of blood tests for hepatitis B antigen and antibody
Appreciates when liver biopsy is appropriate
Be able to select the most appropriate treatment and how to monitor
patient response

Able to select appropriate imaging techniques for evaluation of
abnormal results
Appreciates the cultural differences in the ethnic populations infected
and the influence this may have on screening

Provides advice and education to families and shows appreciation of
the potential difficulties that may arise

Understands the importance of cooperation with virologists and staff
in other clinical laboratories

Hepatitis B Natural History

Extrahepatic manifestations —Thought to be mediated by circulating immune complexesOccur in 10 to 20 % of patients with chronic HBV infection.The two major extrahepatic complications of chronic HBV are polyarteritis nodosa and glomerular disease. Causes of reactivation following seroconversion: HBV genotype C.Male sex.Serum ALT levels >5 X the upper limit of normal during the HBeAg-positive phase.Age at HBeAg seroconversion >40. Resolution Immune response Immunological tolerance Phase Conversion of e antigen positive to e antibody positive Immune control- Inactive carrier state Cirrhosis HBeAg+HBV DNA +ALT normalMinimal change on liver biopsy Anti HBe +HBV DNA +ALT raised Anti-HBe +HBV DNA -HBeAg -ALT Fulminant hepatitis 0.1 to 0.5 % of patients due to massive immune-mediated lysis of infected hepatocytes:Risk factors for fulminancy unclear:Acetaminophen during their illnessAlcohol and methamphetamine abuseGenotype D. Rate of progression from acute to chronic determined by age at infection.Perinatal: 90 % 1-5 years old: 35 % Adult: <5% Outcome Complete eradication of HBV rarely occurs after recovery from acute HBV infection.Traces of HBV can be found after many years which may maintain the T cell response for decades. Replicative phase: Immune clearance-During HBeAg seroconversion patients often get ALT rises due to immune-mediated lysis of infected hepatocytes.-ALT rises are often preceded by an increase in serum HBV DNA and a shift of HBcAg (hepatitis B core antigen) from nuclear to cytoplasmic sites within hepatocytes.-Exacerbations may be associated with an elevation in the IgM anti-HBc titer, which may lead to misdiagnosis of acute HBV infection, and an increase in the [serum alpha-fetoprotein].Patients with severe exacerbations should be referred to specialized centers for liver transplantation or treatment with new antiviral agents such as lamivudine, adefovir, entecavir, telbivudine, or tenofovir.Interferon is not indicated in this setting since it can cause further exacerbation of the disease. Resolution of chronic HBV infection The clearance rate of HBSAg = 1%/yr in West / 0.5%/yr in Asia.Many who clear HbSAg still have HBV DNA on PCR.Recrudescence of liver disease may occur when these patients are immunosuppressed. Immune system unable to seroconvert HBeAg and clear HBV DNA- get recurrent exacerbations+ intermittent disappearance of serum HBV DNA +/-transient loss of HBeAg.Such repeated episodes of hepatitis may increase the risk of developing cirrhosis and hepatocellular carcinoma (HCC). Abortive Immune Clearance Replicative Phase (= Immune clearance phase) Risk factors for progression :Immune-tolerant to immune clearance progression.-Delayed HBeAg seroconver-sion.-Reactivation of HBV replication after HBeAg seroconversion. Natural History Hepatitis B Infection Ineffective cytotoxic T cell lysis of infected hepatocytes. 10-30 years with HBeAg clearance rate of 15% after 20 years Late/low replicative phase; remission of liver disease. Early replicative phase with active liver disease HBeAg-HBV DNA +Anti-HBe+ALT normalMinimal change on liver biopsy The replicative phase selects out precore mutations Most HbeAAg-ve patients are due to precore mutations HCC Hepatic decompensation: 30% death at 1 year once decompensated 15% in 5yrs 21% in 5 years 12 % in 5 years HBSAg seroconversion Immune escape (=reactivation) >10(5) copies/mL HBV DNA differentiates HBeAg -ve chronic hepatitis from inactive carrier state (ie, HBeAg -ve,normal ALT) Acute Hep B Infection Risk factors for progression:Host factors ie: Age>40y;M;Immunocompromised.Viral factors ie high HBV DNA levels, Genotype C; Delayed HBeAg seroconversion; precore and core promoter mutations.Environmental factors ie Alcohol; Diabetes; Obesity; Hep C or D coinfection. HBV DNA Serum ALT HBeAg Anti-HBe Immune tolerance phase Immune clearance phase Nonreplicative phase Reactivation 10^7-10^8 >10^5 <10^3 Written by Dr Sebastian Zeki

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