[SLIDE 34] Acute Hepatitis B Virus Infection with Recovery: Typical Serologic CourseSerologic markers of HBV infection vary depending on whether the infection is acute or chronic.The first serologic marker to appear following acute infection is HBsAg, which can be detected as early as 1 or 2 weeks and as late as 11 or 12 weeks (mode, 30‑60 days) after exposure to HBV. In persons who recover, HBsAg is no longer detectable in serum after an average period of about 3 months. HBeAg is generally detectable in patients with acute infection; the presence of HBeAg in serum correlates with higher titers of HBV and greater infectivity. A diagnosis of acute HBV infection can be made on the basis of the detection of IgM class antibody to hepatitis B core antigen (IgM anti‑HBc) in serum; IgM anti‑HBc is generally detectable at the time of clinical onset and declines to subdetectable levels within 6 months. IgG anti‑HBc persists indefinitely as a marker of past infection. Anti‑HBs becomes detectable during convalescence after the disappearance of HBsAg in patients who do not progress to chronic infection. The presence of anti‑HBs following acute infection generally indicates recovery and immunity from reinfection.
[SLIDE 35] Progression to Chronic Hepatitis B Virus Infection: Typical Serologic CourseIn patients with chronic HBV infection, both HBsAg and IgG anti‑HBc remain persistently detectable, generally for life. HBeAg is variably present in these patients. The presence of HBsAg for 6 months or more is generally indicative of chronic infection. In addition, a negative test for IgM anti‑HBc together with a positive test for HBsAg in a single serum specimen usually indicates that an individual has chronic HBV infection.
AST & ALT: 1000-2000iU/L, bilirubin may be >30 mg/dl. ALP is just modestly elevated (2-10times)
Recombinant HBsAg produced in the yeast
HEPATITIS B Dr. Situ Oladele South Atlantic Petroleum Medical Centre, Nasarawa State University, Keffi, Nasarawa State, Nigeria
INTRODUCTION• Viral hepatitis refers to a group of inflammatory diseases of the liver caused by viruses that have affinity for the liver.• Clinically relevant ones are typed A, B, C, D and E. Hepatitis B and C are the most clinically important ones.• DNA hepadnavirus (retrovirus). 3.2 kilobase pairs virus discovered in 1965 however it was first seen in 1970.• HBV is 50 -100 times more infectious than HIV
EPIDEMIOLOGY• HBV affects about 2 billion (about 1/3 world population) worldwide (past or present infections) and of those affected, 600,000 die annually.• About 300-350 million are lifelong carriers worldwide• Low prevalence areas (0.1-2%): New Zealand, Australia, USA, Canada and Western Europe.• Intermediate prevalent areas (3-5%) Japan, Middle East, Latin and South America, central Asia• high prevalence areas (10-20%) China, Indonesia, Pacific Islands, south East Asia, sub-Saharan Africa
EPIDEMIOLOGY: NIGERIA• 70% of population showing evidence of past infection.• 7.3-24% (average 13.7%) of the population has serological evidence of current infection.• Going by the 2006 national census, 19 million Nigerians are currently infected and about 5 million of these are expected to die as a consequence of the disease.
MODES OF INFECTION:• Perinatal (high prevalence area),• early childhood household contact,• unsafe injections (intermediate and high prevalence areas),• blood transfusion,• sex (low, intermediate and high prevalence areas).Sex is the overall most common mode.
Concentration of HBVin Various Body FluidsHIGH MODERATE LOW/UNDETECTABLEBlood semen UrineSerum Vaginal secretions FaecesWound exudates saliva Sweat Tears breast milk
NATURAL HISTORY AND RISK OFCHRONICITY• The virus can survive at least 7 days (up to 15yrs at 20oC) outside human body• The incubation period is 90 days (30-180 days). Virus becomes detectable 30-60 days post infection• Up to 90-95% of adults recover fully within 6 months of infection.• Infected Infants: have a 70-90% risk of chronicity• Childhood infections (1-4years) have a 30-50% risk of chronicity.
NATURAL HISTORY AND RISK OFCHRONICITY• Estimated 10-30% of patients are expected to progresses to cirrhosis without treatment. 25% of adult who were chronically infected from childhood die from HBV cancer or cirrhosis.• Adults and adolescent have a 1-3% risk of chronicity.• Elderly individuals have about 25% risk of chronicity and only about 0.1-0.5% of adults have fulminant hepatic failure
• Relative Risk of Chronic hepatitis B for Hepatocellular carcinoma (HCC) is 100 and 10 year risk of HCC may be as high as 15%• Hepatocellular carcinoma usually 25- 30years after initial HBV
OUTCOME BY AGE OF INFECTION 100 100 80 80 60 Chronic Infection 60 40 40 20 20 Symptomatic Infection 0 0
SYMPTOMS• Hyperacute: hepatic encephalopathy• Acute(nonspecific symptoms): anorexia, nausea, vomiting, low grade fever, myalgia, fatigability, aversion for food and cigar, dark coloured urine.• Sub-acute: gynaecomastia, hair changes, testicular atrophy.• Chronic: peripheral stigmata of chronic liver disease• Reactivation of chronic hepatitis: mixed symptomsJAUNDICE• Starts 10days post onset of constitutional nonspecific symptoms. Lasts 1-3months
DIAGNOSIS AND LIVER DISEASESTAGINGPhase one:• Liver function tests (ALT, AST, ALP, PT, Total protein and Albumin) and viral markers of possible hepatotoxic viruses (HDV, HEV, HAV, HIV)• Full blood count and platelets & Urinalysis• Hepatic ultrasound and other liver imaging techniquesPhase two:• Molecular biology: HBV DNA• Liver biopsy and staging:
HBsAg Anti Anti Interpretation of Results HBs HBe+ve -ve -ve Characteristic of early acute HBV infection+ve +ve/-ve +ve Implies either acute or chronic HBV infection which may be differentiated with respect to IgM anti HBc-ve +ve +ve Characteristic of previous HBV infection and current immunity to the virus-ve -ve +ve No clear interpretation Could be due past HBV infection Low level of HBV infection False +ve /non specific reaction-ve -ve -ve Suggests liver toxicity due to other agents other than HBV-ve +ve -ve Typical of vaccinated individual
OTHER TESTS• Thyroid function test• Body mass index• Fasting blood sugar and insulin assay for resistance• Neropsychiatric evaluation• Alcohol and drug abuse evaluation
WHO TO SCREEN?• All Nigerians HBsAg and HBcAg are used for sreening:• every new visit to the clinic,• pre-school, pre-employment, pre-insurance,• pre-blood donation,• pre-marriage and pregnancy,• sexual history, STI,• illegal drug users,• healthcare workers, morgue works,• chronic alcoholics,
WHO TO SCREEN?• Children or spouses of HBsAg positive individuals• All HIV positive patients• Cirrhosis patients or nodular liver or big liver• Jaundiced patients especially after blood transfusion• Patients with bleeding problems especially if it started after blood transfusion.• Chronic Renal Failure patients especially after haemodialysis.
TREATMENTS• Generally, there is no specific treatment for HBV infection. Comfort, nutritional balance, avoidance of hepatotoxic drugs, etc., are essential.• HBV drugs are expensive and not readily available• Chronically infected people respond less and patient with significant cirrhosis respond less with increased chance for serious side effects.
INTERFERONS IFN (PEGYLATED)• IFN is given as S/C injection, 180mcg weekly for 4months (up to 12months in patients with high viral loads and patients with negative HBeAG). 30-40% on treated patients sustained suppression of HBV. Some will also lose their HBsAg.• There yet no known resistance to the drug• Marketed as PEGASYS®• Avoid in advanced stage (decompensated disease)
LAMIVUDINE – Use when PEGASYS is not available or affordable – Taken as Tab 100mg daily and is well tolerated orally – Can be used in decompensated patients DISADVANTAGE – High rate of drug resistance (15-30% in 1yr, 50% in 3yrs, 70% in 5yrs). – Infinite duration of treatment (cannot stop until at least 1yr after HBeAg seroconversion occurs)
DIETARY LIMITATIONS• Patients with acute or chronic HBV infection without cirrhosis have NO dietary restrictions.• For individuals with decompensated cirrhosis (portal hypertension, encephalopathy), a low sodium/salt diet (1.5gm/d), high protein diet (i.e. white meat like pork, turkey, fish), and, in cases of hyponatremia, fluid restriction (1.5L/d) are indicated.
WHY TREAT THE HBV PATIENT?• To limit active liver disease and prevent liver disease progression to cirrhosis, liver failure or cancer• To prevent transmission of HBV infection• To improve quality of life• To limit active viral replication and achieve sustained virological response
GENERAL INDICATIONS FORTREATMENT/MANAGEMENTChronic HBeAg Chronic HBeAgpositive patients negative patientsHBV DNA >20,000 I.U/ml (105 HBV DNA >2000 I.U/ml (104copies/ml and when ALT is ↑ for copies/ml and when ALT is3-6months ↑(>20 U/L in females; 30 U/L in males ) for 3-6monthsAll patients with histologic All patients with histologicevidence of active liver evidence of active liverdisease/inflammation disease/inflammation
PREVENSION AND VACCINE:• HBV vaccine has been available since 1982 and is about 95% effective. In 1992 31 countries have HBV vaccination schedule. In 2011, the number has increased to 179 countries.• protects for 5-10 yrs. Use HB Ig for sudden needle pricks. Rate of HBV transmission after an occupationally related needle stick injury is 30% in unvaccinated health worker (unlike 0.3 % in HIV, 3% in HCV infection)
PREVENSION AND VACCINE:• Take at birth, 6weeks and 10 weeks of life• Uninfected and unvaccinated adults will take 3 subcutanous injections at intervals unmissed or would start again.• A booster dose in 10yrs
PATIENT MORNITORING ANDEVALUATION• FBC: every 4-8 weeks• ALT (LFT): every 4-8weeks• HBV DNA: at 12, 24 and 48 weeks• HBeAg and anti-HBeAg: every 6months till seroconversion• Liver histology: NOT CURRENTLY RECOMMENDED FOR ROUTINE MONITORING
TREATMENT RESPONSE• Primary response: ↓ viral load more than 10 folds after 12 weeks of treatment.• Primary non-response: ↓ viral load less than 10 folds after 12 weeks of treatment.• Complete response: undetectable viral load after 24 weeks of treatment• Partial response: detectable but ↓ viral load <10,000copies/ml after 24 weeks of treatment• Inadequate response: detectable but ↓ viral load >10,000copies/ml after 24 weeks of treatment• Sustained virological response (Virological breakthrough): undetectable virus for >6months• Treatment failure
CONTRAINDCATION TOTREATMENT• Pregnancy*• continued alcohol abuse• sever cardiac disease• uncontrolled psychiatric illness• uncontrolled seizure disorder• untreated thyroid disorder
SPECIAL CATEGORIES• Pregnancy and newborns: Those born to mothers with active HBV infection must be vaccinated with HBIG within 12hrs of birth and the vaccinated with HBV vaccine• HIV/HBV co-infection: both diseases must be treated together. Tenofovir + emtricitabine (Truvada®)/Lamivudine with a NNRTI or PI is preferred.• Diabetes: current guideline recommends that all patients with diabetes (type 1 or 2) from 19-59 yrs should be vaccinated with HBV vaccine.
OTHER SIDE EFFECTS OF HBVINFECTION• Pleural effusion, hepatopulmonary and portopulmonary syndrome may occure in patients with cirrhosis• Myocarditis and pericarditis and arrhythmias may occur primarily in patients with fulminant hepatitis• DIC may occur in patients with fulminant hepatitis.• Athralgias and arthritis (serum sickness) with subcutaneous nodules may occur, but are very rare• Encephalitis, aseptic meningitis, Guillain-Barre syndrome and mononeuritis complex may occur in patients with acute hepatitis B
OTHER SIDE EFFECTS OF HBVINFECTION• Aplastic anaemia is uncommon and agranulocytosis is very rare• Pancreatitis• Chronic renal failure• Polyarteritis nodosa• Fleeting rash and hives (common in women)• Popular acrodermatitis may be seen in acute infection in children (Gianotti-Crosti syndrome)