Viral hepatitis


Acute:

  • hep A

  • Hep E

  • Sometimes B/D


Chronic:

  • hep B

  • Hep C


Clinical features of acute hepatitis:

  • mild flu like symptoms with fever

  • Fatigue

  • Urine darkens

  • Stool lightens

  • Abdo pain in RUQ

  • Jaundice

  • Loss of appetite

  • Itching

  • Nausea


Mnemonic for transmission:

  • A and E bowels and vowels (faeco-oral)

  • BCD blood, sex and drugs


Hepatitis A


Type:

  • virus is non-enveloped single stranded RNA


Transmission:

  • faeco-oral route


Incubation period:

  • 28 days (ranges from 15 to 40 days


Family:

  • hepatovirus genus of picornaviridae family


How transmission is reduced:

  • hand washing

  • Good hand hygiene


Common groups of people:

  • travellers to endemic areas

  • Those engaging in higher-risk sexual activities


Difference in symptomatology between adults and children:

  • 70-95% of adults show symptoms when infected - mild self limiting illness manifesting with flu like symptoms, abdominal discomfort, nausea

  • Children under age of 5 frequently asymptomatic


Risk factors/risk groups:

  • travel (to endemic areas)

  • Sexual (high risk activities e.g. analingus, chem sex, multiple partners, digital rectal contact

  • Haematological disorders - VIII, IX concentrates have been implicated in transmission

  • Occupational risks - more common in lab or sewage workers

  • IVDU - intravenous drug use


Clinical phases:

  1. Incubation - relatively long period, may last from2-6 weeks

  2. Prodromal - early part of disease, characterised by fever, joint pain and rash, flu like symptoms may be present

  3. Icteric - jaundice, anorexia, abdominal pain, change in bowel habit

  4. Convalescent - recovery phase and body returns to normal and symptoms subside


Symptoms:

  • abdominal discomfort

  • Nausea

  • Anorexia

  • Diarrhoea

  • Flu like illness

  • Itching

  • Dark urine, pale stools

  • Rash


Signs:

  • Jaundice

  • RUQ tenderness

  • Hepatomagaly (85%)

  • Splenomegaly (15%)

  • Lymphadenopathy (5%)


Markers:

  • hep A IgM = HAV-IgM (Recent/current infection)

  • Hep A IgA = HAV-IgG (immunity)


LFT:

  • transaminases

  • Bilirubin

  • Prothrombin time


Serology:

  • Positive and positive - likely acute hepatitis A infection

  • Positive and negative - may indicate acute or false positive IgM

  • Negative and positive - indicates previous infection or vaccine based immunity

  • Negative and negative - no evidence of infection, may be very early or incubation phase


Management:

  • advise good oral hydration and rest, alcohol avoided

  • Nausea - metoclopramide for max 5 days or cyclizine if no significant liver impairment

  • Itchiness - chlorphenamine in absence of liver impairment

  • Reduce transmission by staying at home, good hygiene, avoid unnecessary contact and raw sex for 7 days after jaundice/symtoms appear/began

  • Consult specialist if trying to treat liver impairment


Notifiable disease:

  • contact proper officer or local authority in appropriate time

  • At risk contacts reviewed and offered vaccine if dont already have


Further care:

  • referral - need for GUM clinic or drug rehabilitation services

  • Follow up - review on weekly basis for clinical review and repeat LFTs (refer to specialists if worsening or persistently abnormal LFTs)


Who to offer hep A vaccine to:

  • those at risk of infection and complications of infection

  • Travellers

  • Chronic liver disease

  • Sexual reasons

  • Occupational risks

  • IVDU


Ways and when hep A vaccine offered:

  • monovalent or in combination with hep B or typhoid

  • First dose 2-3 weeks prior to travel

  • Extra doses recommended if long term protection needed


Complications of hep A:

  • Relapsing hepatitis (in 5-15%)

  • Sudden onset liver failure

  • Prolonged cholestasis

  • Acute pancreatitis

  • Interstitial nephritis


Hepatitis B


Acute hep B:

  • occurs at any age

  • In adults and older children usually a self limiting illness

  • In young children more likely to develop into chronic infection

  • Majority of patients have subclinical illness

  • Incubation period of 1-4 months


Chronic hep B:

  • Caused by failure to clear hep B after acute infection

  • Defined as persistence of hep B surface antigen

  • HBsAg for more than 6 months

  • Chronic hep B can lead to cirrhosis and hepato-cellular carcinoma


Virus:

  • Enveloped DNA virus

  • 8 distinct genotypes

  • Nucleocapsid and outer envelope

  • Hepadnaviridae family

  • Most predominant genotype is A in UK

  • 4 major genes writhing genome - S (encodes HBsAg), C (encodes HBcAg) and helps form (HBeAg), P (encodes DNA polymerase/reverse transcriptase), X (encodes HBx)


4 major genes:

  • surface one needed for construction of outer HBV envelope

  • Core one composed within nucleocapsid that contains viral DNA

  • E antigen acts as immune decoy to promote viral persistence, presence is marker of viral replication and infectivity

  • DNA polymerase involved in synthesis of DNA molecules, has reverse transcriptase which means it can form DNA from RNA

  • X protein is a transcriptional regulator that promotes cell cycle progression


Process of replication:

  • once infected HBV enters hepatocytes

  • Viral particle removes outer envelope and forms covalently closed circular DNA - DNA forms template for transcription of HBV proteins

  • CccDNA enters nucleus of cell where transcription takes place

  • Core proteins, polymerase proteins and pregenomic RNA packaged into core particles

  • Pregenomic RNA reverse transcribed into HBV DNA whilst surface proteins attached to create outer envelope

  • Full viral particle may then be secreted to infect other hepatocytes


Modes of transmission:

  • Perinatally

  • Parenterally - infected needles

  • Percutaneously

  • Sexual contact


Risk of progression:

  • inverse relationship with age

  • Perinatal transmission - 90% risk of chronic infection

  • Early childhood transmission - 25-50% risk of chronic infection

  • Adult transmission - < 5% risk of chronic infection


Main determinants if acute progresses to chronic:

  • age

  • Immune status of patients


5 phases:

  • phase 1 - HBeAG positive chronic infection, previously immune tolerant

  • Phase 2 - positive chronic hepatitis, previously immune clearance

  • Phase 3 - negative chronic infection, previously inactive carrier

  • Phase 4 - negative chronic hepatitis, previously reactivation phase

  • Phase 5 - HBsAg negative phase, previously occult hep B infection


Marker that indicates spontaneous clearance:

  • loss of HBsAg indicates clearance

  • Accompanied by development of surface antibodies, core antibodies and undetectable HBV DNA levels


Markers in phase 5:

  • HBsAg: negative (spontaneous clearance)

  • HBsAb: negative/positive

  • HBcAb: positive

  • HBV DNA levels: absent/very low

  • LFTs: normal

  • Liver disease: absent inflammation


Clinical features of acute:

  • Majority - subclinical hepatitis

  • Less than 5% of adults will develop CI

  • Spectrum: subclinical, anicteric, icteric, fulminant


Clinical features of chronic:

  • majority - asymptomatic

  • May display features of fatigue and RUQ pain

  • May develop exacerbations that can be asymptomatic or mimic acute

  • May present with complications of chronic hep B

  • Spectrum: asymptomatic carrier state, chronic hepatitis, cirrhosis, decompensated cirrhosis