Viral Hepatitis

Umar Zein
Faculty of Medicine
Universitas Islam Sumatera Utara
2021
Acute VH Definition:
Diffuse liver inflammation lasting
less than 6 months
 Causes:
Hepatitis A Hepatitis B Hepatitis Hepatitis C Hepatitis E
HAV HBV D HCV HEV
Infective serum HDV Post transfusion Epidemic/
hepatitis hepatitis hepatitis Entral

virus 27 nm RNA 42 nm DNA 35 nm 30 – 60 nm 32 nm RNA

Hepa virus Incomplete RNA flavi firus
RNA+HBsAg
transmission Feco-oral Paraentral and post transfusion Feco-oral
Sexual low risk 1-5 %
Intrauterine low risk <5%
Incubation p. 2 – 6 weeks 2 – 6 months 2 – 6 months 2 – 6 months 2 – 6 weeks

Chronicity no Yes Yes Yes No

&liver cancer
Immunization Non specific Specific Ig IgM Non specific
-passive Ig Ig

-active HAV vaccine HBV vaccine HBV vaccine

 Pathogenesis

Initial viremia, with inflammation of GIT mucosa.

Intrahepatic localization lead to

A- diffuse centrilobular necrosis, with cellular infiltration around portal tracts
B- intrahepatic cholestasis due to cellualar edema

Other organ: splenomegaly – lymphoadenopathy

Hypoplasia of BM
 Clinical picture
1. Preicteric stage or prodromal stage: 3 – 9 days

Sudden onset of influenza like picture: fever - headache –

malaise – muscular pain
Anorexia is marked with nausea – vomiting – distension
Pain in Rt hypochondrium & epigastrium
Dark urine – pale stool
Transient itching
Examination: fever with relative bradycardia + enlarged
tender liver
 Clinical picture
2. Icteric stage: 2-4 w

Jaundice with fever & improvement of general

condition
Anorexia nausea & vomiting diminish or disappear
Urine is dark brown & frothy
Stool are clay in color – bulky – offensive – greasy

Examination:
Soft tender enlarged liver Spleen is enlarged in 20 %
10% geralized lymphoadenopathy with Triangle of neck
Clinical Picture

3. Convalescence stage:

Signs & symptoms gradually

disappear
Jaundice may persist for some
times due to affinity of bile pigment
to elastic tissue
Complete recovery of liver may take
up to 6 months
 Investigation:

LFT:
1. serum bilirubin : total, direct and indirect

2. ALT – AST : from 500 – 2000 IU/L ALT > AST

3. Alkaline phosphatase – 5’nucleotidase – GGT:

Blood :
Leucopenia with relative lymphocytosis, ESR
 Urine :
Early bilirubin appearance
Bile salt : granular casts – frothy
urine - +ve hay sulfur test

Stool:
Pale – clay with staetorrhea
Diminished stercobilinogen

Serology
others Chronic stage Acute stage
Fecal Anti HAV IgG Anti HAV IgM Hepatitis A
HAV
Anti HDV IgG Anti HDV IgM Hepatitis D
Anti HEV IgG Anti HEV IgM Hepatitis E
 Hepatitis B marker:
significance Corresponding Significance antigen
Ab
Appear after 3 m Anti HBs Appear after 6 week HBsAg
Reflecting recovery & Acute infection, remain (surface)
immunity for 3 ms
Chronic infection if >6
ms
Appear after 2 m Anti HBc Detected on Liver HBcAg
Reflecting severe Biopsy only (not serum) (core)
acute & chronic form
Appear after 2.5 m Anti HBe Reflect ongoing viral HBeAg
Non replicating virus replication (chronicity) (envolop)
Most sensitive indication for viral replication & chronicity (and particle) HBV DNA
It is detected by PCR
 Hepatitis C markers:
significance time technique Marker

Exposure to infection After 3 – 6 ms of 2nd & 3rd generation ELISA or RIBA HCV Ab
not immunity infection test

Indicate active virus After 1 – 2 weeks PCR – quantitative PCR is more HCV
accurate & assess interferon ttt RNA
 • Serological gap:
It is a window last several weeks between
disappearing of HBs Ag & appearance of Anti
Hbs. Anti HBc Ab may represent serological
evidence of recent HBV infection

Blood free from Hbs Ag & Anti Hbs (but

containing anti – HBC) is the major cause of
transfusion HBV infection
 Course & Complication:
Complete recovary:
Occur in most cases of virus A – E
Less common in virus B – D & in small case of virus C

Relapse:
Characteristic of virus C – less common in B – D
Present by reappearance of CL.p. or
biochemical
Abnormalities ( bilirubin & enzymes )
 Extrahepatic manifestation of hepatitis
comments Associated Clinical condition
virus
60 % have HBV HBV Polyarteitis nodosea

Mainly mesengioproliferative –result in CRF HCV & HBV Glomeronephritis

Blistering lesion on back of hands HCV Porphyria cutnea tarda
Type 2 (mixed – essential) HCV Cryoglobulinemia
Virus isolated from salivary tissue HCV Sjogren syndrom
60 % have HCV HCV Lichen planus
Studies involve small number of patients Others associated with HCV
Impotance need evaluation Erythema nodusm – erythema multiforme
Polymyosistis – hachimoto’s thyroiditis
Diabetes mellitus – bahcet’s syndrome
Down syndrome – Aplastic anemia
Rest:
Treatment:
Bed rest till LFT normal

Diet:
Protein: gives freely except with Liver failure
CHO: gives freely
Fats: better avoided
Alcohol & hepatotoxic: contraindicated
 Goals and endpoints of therapy
Goals
Improve survival and quality of life by preventing disease progression and HCC
Prevent mother-to-child transmission, hepatitis B reactivation, and prevent and treat
HBV-associated extrahepatic manifestations

Recommendations Grade of evidence Grade of recommendation

Main endpoint
• Induction of long-term suppression of HBV DNA I 1

Valuable endpoint
• Induction of HBeAg loss (± anti-HBe seroconversion) in HBeAg-positive patients with II-1 1
chronic hepatitis B*
Additional endpoint
• ALT normalization (biochemical response) † II-1 1

Optimal endpoint
• HBsAg loss (± anti-HBs seroconversion) ‡ II-1 1

*Often represents a partial immune control of the chronic HBV infection;

†
Achieved in most patients with long-term suppression of HBV replication;
‡
Indicates profound suppression of HBV replication and viral protein expression
EASL CPG HBV. J Hepatol 2017;67:370–98
 Indications for treatment
Primarily based on the combination of 3 criteria
– HBV DNA, serum ALT and severity of liver disease

Recommendations Grade of evidence Grade of recommendation

Should be treated
• Patients with HBeAg-positive or -negative chronic hepatitis B* I 1
• Patients with cirrhosis, any detectable HBV DNA, regardless of ALT level I 1
• Patients with HBV DNA >20,000 IU/mL and ALT >2x ULN, regardless of severity of
histological lesions II-2 1

May be treated
• Patients with HBeAg-positive chronic HBV infection † III 2
>30 years old, regardless of severity of liver histological lesions
Can be treated
• Patients with HBeAg-positive or -negative chronic HBV infection and family history of III 2
HCC or cirrhosis and extrahepatic manifestations ‡

*Defined by HBV DNA >2,000 IU/ml, ALT >ULN and/or at least moderate liver necroinflammation or fibrosis;
†
Defined by persistently normal ALT and high HBV DNA levels;
‡
Even if typical treatment indications are not fulfilled
EASL CPG HBV. J Hepatol 2017;67:370–98
 Monitoring of patients currently
not treated
Patients with no current indication of antiviral therapy should be monitored
– Periodical assessments of serum ALT, HBV DNA and non-invasive markers for liver fibrosis

Recommendations Grade of evidence Grade of recommendation

Follow-up at least every 3–6 months

• HBeAg-positive chronic HBV infection, <30 years old II-2 1

Follow-up at least every 6–12 months

• HBeAg-negative chronic HBV infection and serum HBV DNA <2,000 IU/ml II-2 1

Follow-up every 3 months for the first year and every 6 months thereafter
• HBeAg-negative chronic HBV infection, serum HBV DNA ≥2,000 IU/ml III 1

EASL CPG HBV. J Hepatol 2017;67:370–98

 Algorithm for the management
of chronic HBV infection
Suspected chronic HBV infection

HBsAg positive HBsAg negative, anti-HBc positive

Chronic HBV infection* Chronic hepatitis B No specialist follow-up

(no signs of chronic hepatitis)
Monitor
(includes HBsAg, HBeAg, HBV
DNA, ALT, fibrosis assessment)
± cirrhosis* but inform patient and general
practitioner about the potential
risk of HBV reactivation
Start antiviral treatment

NO
Consider
Risk of HCC, risk of HBV
reactivation, extrahepatic In case of immunosuppression,
manifestations, risk of YES start oral antiviral prophylaxis
HBV transmission or monitor

*See new nomenclature slide.

EASL CPG HBV. J Hepatol 2017;67:370–98
 HCV DAAs approved in Europe in 2018 and
recommended in this document
Product Presentation Posology
Pangenotypic drugs or drug combinations
Sofosbuvir Tablets containing: 400 mg SOF 1 tablet QD
Sofosbuvir/velpatasvir Tablets containing: 400 mg SOF, 100 mg 1 tablet QD
VEL
Sofosbuvir/velpatasvir/ Tablets containing: 400 mg SOF, 100 mg 1 tablet QD
voxilaprevir VEL, 100 mg VOX
Glecaprevir/pibrentasvir Tablets containing: 100 mg GLE, 40 mg 3 tablets QD
PIB
Genotype-specific drugs or drug combinations
Sofosbuvir/ledipasvir Tablets containing: 400 mg SOF, 90 mg 1 tablet QD
LDV
Ombitasvir/ Tablets containing: 75 mg PTV, 12.5 mg 2 tablets QD
paritaprevir/ritonavir OBV, 50 mg RTV
Dasabuvir Tablets containing: 250 mg DSV 1 tablet BID (am &
pm)
Grazoprevir/elbasvir Tablets containing 100 mg GZR, 50 mg 1 tablet QD
EBR

EASL CPG HCV. J Hepatol 2018;69:461–511.

 Treatment Hepatitis C:
Direct acting antiviral (DAA) tablets.

Highly effective at clearing the infection in more than 90% of people.

The tablets are taken for 8 to 12 weeks.
The length of treatment will depend on which type of hepatitis C you have.
Some types of hepatitis C can be treated using more than 1 type of DAA.
NHS-approved hepatitis C medicines:

• Simeprevir, Sofosbuvir
• a combination of ledipasvir and sofosbuvir
• a combination of ombitasvir, paritaprevir and ritonavir,
taken with or without dasabuvir
• a combination of sofosbuvir and velpatasvir
• a combination of sofosbuvir, velpatasvir and voxilaprevir
• a combination of glecaprevir and pibrentasvir ribavarin