ACUTE AND CHRONIC HEPATITIS

A
 Causes
 Viral hepatitis, hepatotropic viruses{A,B,C,D,E}
 Other viruses; EBV, CMV, herpes, yellow fever in
immunocompromised
 Non viral; leptospira, klebsiella, toxoplasma
 Drugs- direct toxic e.g. acetaminophen, amoxicillin, /idiosyncratic
e.g. chlorpromazine
 Toxins- mushroom, carbon tetrachloride, alfa toxins
 Alcohol
 Hypo perfusion/shock pts, severe hypotension, severe LV failure
 Hereditary- Wilson’s dx
 Pregnancy associated dx.
 Factor interfering with venous return to heart-
hepatic occlusion/ veno occlusive dx, constrictive
pericarditis
 malignancies
 Incubation period
 Prodormal symptoms
 Jaundice phase
 Recovery phase
 HAV- picornaviridae,1973
 HBV-hepadnaviridae,1970
 HCV,flaviviridae,1988
 HDV
 HEV
 HFV-not a separate virus, a mutant of HBV
 HGV,flaviviridae
 Related to enteroviruses
 Difficult to grow in cell culture
 4 genotypes exist
 Contaminated water/food
 close personal contact
 Preicteric/prodromal phase:fatigue, jnt and
abdominal pain,anorexia, vomiting,
Hepatomegaly
 Icteric phase: icterus/jaundice, high bilirubin
 Feco oral transmission
 Intestinal epithelium multiplication
 Hematogenous spread to liver
 Reach liver in 1 week
 Shed into intestine with bile
 Then appearance in faeces
 Incubation period 2-6/52
 After replication and discharge hepatic injury
begins
 Activated T-cell releace Y-INF that promote the
representation of HLA on liver cells
 CTL may kill the target cell infected with HAV
 Demonstration of virus in faeces\
 Detection of ab by ELISA
 LFTs: ALT,bilirubib , protein,ALP marginally
elvtd
 PCR—faeces
 Imaging:abd u/s, CT scan
 Member of the hepadnaviridae
 Circular,partially double stranded DNA virus
 Replication involves a RT
 Impossible to propagate in cell culture
 Reverse transcriptase
 RNA intermediate
 Integration
 Parenteral
 Vertical(HBeAg+ve)
 sexual
 350m carriers globally
 120m carriers in China
 50% of children born to mothers with chronic
HBV in US are Asian American
 Prevalence of hepatitis B in Kenya is between 2-5
%
 IVD abusers
 Babies of mothers with chronic HBV
 People with multiple sexual partners
 Healthcare personnel
 Pts requiring blood and blood products
 Virus enters hepatocytes hematogenously
 Immune response to viral Ags expressed on
hepatocyte cell surface is responsible for clinical
presentation
 5% become chronic carriers
 Hep B surface ab may confer lifelong immunity
 Low transmissibility if there is hep Be ab
 Incubation period: av. 60-90/7,range 45-180/7
 Insidious onset
 1/3 of adults asymptomatic
 Jaundice 30- 50%
 Premature death from chronic liver failure-15-
25%
 Anorexia
 fatigability
 Pegylated Interferon alfa,response rate 30-40%
 3TC, well tolerated, resistance
 Adefovir, less likely to develop resistance than 3tc
 Entecavir, most powerful antiviral,compare with
adefovir
 TDF
 Successful tx—disappearance of HBsAg,HBV DNA
 Vaccination: recombinant vaccines
 Hep B Ig(HBIG): exposed within 48hrs of
incident/neonates whose mothers are hepatitis B
sAg +ve and Hep Be Ag +ve
 Other measures: blood /blood product screening
 Spectra of disease similar to those of chronic Hep
B,albeit at a lower frequency
 Sex
 Hemodialysis
 Transfusion/transplant-infected donor
 Accidental injuries with needles/sharps
 Birth to HCV infected mother
 IV drug abuse
 HCV Ab-gen used for dx of HCV,unuseful in
acute phase
 HCV RNA-various techniques-PCR and
branched DNA
 HCV Ag-used in same capacity as HCV RNA
 Pegylated interferon alfa 2a: a) 180ug sc weekly .b)
peg interferon 2b 1.5 ug/kg sc once weekly
 Peg interfon contraindicated for use in pts with
hepatic decompensation eg in ascites
 Ribavirin dose 1000mg(<75kg), 1200mg(>75kg)
 Monotx not recommended
 Sofosbuvir-oral,,,FDA approval in 2013
 Ledispasvir/sofosbuvir comb,FDA approval in 2014
 Drug and toxin induced hepatitis
 Good history
 Specific assay
 TBC- eosinophilia
 Liver biopsy occasionary
 Hepatic inflammation and necrosis >6/12
 Milder forms are non progressive or only slow
progressive
 Severe do progress to chronic
 Viral; HBV, HBV/HDV, HCV
 Drugs e.g. methyl dopa, isoniazid, ketoconazole,
nitrofurantoin
 Auto immune- SLE
 Alcohol
 Metabolic hereditary causes- Wilson’s,
hemochromatosis, alpha anti trypsin deficiency
 Idiopathic- cryptogenic
 Based on etiology
 Histological activity index which primarily a
grade ( necro inflammation) & Degree of
progression- fibrosis( stage )
 Liver biochemistry
 HBV CH;/ 1st HBsAg if positive, do HBeAg, anti
HBeAg, HBV DNA and rarely genotype
 HCV CH- anti HCV, HCV RNA, genotype to
plan management
 HDV CH;back ground of positive HBsAg, anti
HDV RNA, anti-HDV, IgG anti HBc
 Auto immune hepatitis-
 anti nuclear antibodies- ANA, SMA,
 anti SLA,
 LKM ant,
 hyper globulinemia.
 Wilson's - serum ceruloplasmin and Cu/ 24hrs urine for
Cu
 Hemochromatosis- % in transferin saturation, feritin high,
HFE genes
 Imaging- ultra sound, CT scan
 Liver biopsy
 HB CH- interferons{ pegylated }, nucleoside
/nucleotide analogues
 HCV CH- interferons {pegylated}and ribavirine
 AIH- steroid, azithioprine
 Alcohol- stop/ vitamins B
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