Hepatitis E Virus

Slide 1 · Hepatitis E Virus

Transmission · Pathogenesis · Clinical pathology

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning goals

Describe the routes and epidemiology of hepatitis E virus (HEV).

Relate viral properties and host immunity to liver injury.

Interpret the temporal sequence of HEV RNA, IgM, and IgG.

Recognize severe pregnancy-associated disease and persistence during immunosuppression.

Slide 3 · Where hepatitis E fits among hepatotropic viruses

Hepatotropic hepatitis viruses

Hepatitis A, B, C, D, and E cause viral hepatitis.

Different viruses produce overlapping hepatitis patterns.

Hepatitis E emphasis

Commonly an acute enterically transmitted infection.

Chronicity depends strongly on immune status.

Slide 4 · Hepatitis E: The core disease concept

Enteric infection with a strong acute-hepatitis phenotype

Frequently water-borne and transmitted by the fecal–oral route.

Most infections resolve; Clinical risk differs in pregnancy and immunosuppression.

Clinical chemistry and serology reflect the host response to infection.

Slide 5 · Fecal–oral transmission is the principal route

Infected host

Sheds HEV in stool

Environmental contamination

Food or water carries virus

New host

Virus ingested

Hepatitis

Acute infection develops

The portal of exposure is enteric, although organ-related exposures also occur.

Slide 6 · Water-borne transmission explains epidemics

Contaminated water

Shared exposure

Multiple individuals

Common-source transmission

Regional outbreak

Epidemic hepatitis

Water quality and sanitation are critical to this epidemiologic pattern.

Slide 7 · HEV is also a zoonosis

HEV

Pigs

Monkeys

Cats

Dogs

Animal reservoirs described in the Robbins text; Reservoir status does not imply equal public-health importance.

Slide 8 · Zoonotic exposures broaden the epidemiology

Exposure setting

Contact with pigs or pig farming.

Consumption of organ meat.

Epidemiologic implication

Infection occurs outside classic water-borne epidemic settings.

HEV may be encountered in high-income countries.

Slide 9 · Why pig farming matters clinically

Occupational context may provide the exposure clue

The textbook associates cases in high-income countries with pig farming.

Relevant exposure history can direct consideration of HEV.

Absence of travel does not exclude hepatitis E.

Slide 10 · Food-associated exposure in high-income settings

Consumption of organ meat is a documented association

Dietary exposure complements the water-borne epidemiologic pattern.

Food exposure is relevant to a targeted clinical history.

The supplied text does not quantify the risk of any individual food item.

Slide 11 · Geographic distribution of epidemics

Reported epidemic settings

Teaching implication

Asia / Indian subcontinent

Endemic or outbreak-associated exposure

Sub-Saharan Africa

Epidemic hepatitis may be HEV-related

Middle East and China

Include HEV in acute hepatitis evaluation

Mexico

Reported epidemic location

Slide 12 · Sporadic hepatitis E: The India example

More than 30% of sporadic acute hepatitis cases in India

This is the figure reported 11th edition.

In the stated setting, HEV exceeds hepatitis A in frequency.

Do not generalize this proportion to every population or year.

Slide 13 · Travel history can redirect the differential

Acute hepatitis

Symptoms / abnormal enzymes

Travel to an affected region

Potential enteric exposure

Consider hepatitis E

Use molecular/serologic studies

Travel is one clue, not a requirement for HEV infection.

Slide 14 · Two epidemiologic patterns of HEV

Water-borne epidemics

Fecal–oral transmission.

Clusters in endemic regions.

Potential for common-source exposure.

Zoonotic/sporadic infection

Associated with animals or organ-meat exposure.

Reported in high-income nations.

May occur without travel.

Slide 15 · Epidemiologic assessment: Focused questions

Was the patient exposed to potentially contaminated water?

Was there travel or residence in an epidemic region?

Is there occupational contact with pigs?

Was organ meat consumed?

Is the patient pregnant or immunosuppressed?

Slide 16 · HEV virology: Source-described classification

Family

Hepeviridae

Genus terminology used by Robbins

Orthohepevirus

Taxonomic nomenclature reproduced from the supplied edition.

Slide 17 · HEV is described as a nonenveloped RNA virus

Positive-stranded RNA virus without a conventional envelope

The HEV particle as unenveloped.

This is a textbook virion-level description.

The source does not elaborate on alternative particle forms.

Slide 18 · Positive-strand RNA is the HEV genetic material

Positive-stranded RNA

Viral coding capacity

Multiple open reading frames

Replication-associated proteins

Viral protease and RNA polymerase

Original conceptual schematic; Not a scaled physical genome map.

Slide 19 · Genome size reported

Approximately 7.3 kilobases (kb) of RNA

The viral genetic material is a single positive-sense RNA genome.

Genome length and coding organization are viral properties, not diagnostic thresholds.

Do not infer sequence-level detail from this schematic.

Slide 20 · The HEV genome contains four open reading frames

ORF 1

ORF 2

ORF 3

ORF 4

Four coding regions → multiple viral proteins

Four open reading frames are reported; Lengths and order are not depicted to scale.

Slide 21 · Encoded proteins support replication

Viral RNA

Genetic instructions

Open reading frames

Protein coding

Viral protease

Protein-processing function

RNA polymerase

RNA synthesis function

These are examples of proteins named in the primary text, not a complete proteome.

Slide 22 · The virus itself is not directly cytopathic

HEV infection

Hepatocytes contain viral infection.

HEV as noncytopathic.

Hepatic injury

Primarily associated with the host response to infected cells.

Pathology can therefore reflect immune-mediated injury.

Slide 23 · The host response links infection to hepatitis

HEV-infected hepatocyte

Viral infection

Host immune response

Recognition of infected cells

Hepatocyte damage

Necrosis / apoptosis

Clinical hepatitis

Enzyme elevation / symptoms

General morphological endpoints are drawn from the adjacent viral-hepatitis section.

Slide 24 · Virologic infection and tissue injury differ

Virologic evidence

HEV RNA in serum or stool.

Virion shedding in stool.

Tissue response

Host-driven hepatocyte injury.

Serum aminotransferase elevation.

Slide 25 · Acute infection begins before symptoms

Exposure

Enteric acquisition

Incubation

Average 4–5 weeks

Preclinical phase

RNA detectable

Symptomatic onset

IgM and enzymes rise

Slide 26 · Virions are shed in stool during acute illness

Hepatic infection

Active illness

Virions in stool

Enteric shedding

Fecal contamination

Transmission opportunity

Stool contains both diagnostically relevant viral material and a transmission hazard.

Slide 27 · The incubation period averages 4–5 weeks

Exposure precedes the typical clinical presentation by several weeks

The textbook gives an average incubation interval, not a fixed patient-level value.

Incubation should be considered when taking a travel or exposure history.

Clinical illness does not begin at the moment of infection.

Slide 28 · HEV RNA can be detected before clinical illness

Serum

PCR may detect HEV RNA before symptoms.

Stool

PCR may detect HEV RNA before symptoms.

Virions may also be detected.

Slide 29 · PCR provides direct virologic evidence

Specimen

Serum or stool

Molecular assay

PCR for HEV RNA

Detected RNA

Evidence of viral genetic material

Interpret timing, clinical context, and assay availability together.

Slide 30 · Clinical onset aligns with three changes

Symptoms begin

Aminotransferases rise

IgM anti-HEV appears

These changes are described as virtually simultaneous at clinical onset.

These events as virtually simultaneous.

Slide 31 · Aminotransferases reflect hepatocellular injury

Biochemistry

Serum aminotransferase elevation accompanies illness onset.

Mechanistic explanation

Host-mediated hepatocyte injury drives a biochemical hepatitis phenotype.

Slide 32 · IgM anti-HEV is an acute-phase serologic marker

IgM anti-HEV appears with clinical onset

The temporal association is central to acute infection recognition.

Serologic data are interpreted with exposure, chemistry, and PCR.

An antibody result alone does not describe liver-injury severity.

Slide 33 · IgG anti-HEV persists after recovery

Acute infection

IgM anti-HEV appears

Recovery

IgM gives way to IgG

Later phase

IgG persists

Persistent IgG differs conceptually from persistent viremia.

Slide 34 · Integrated timeline of HEV markers

Exposure

No immediate symptoms

Presymptomatic

RNA in serum / stool

Onset of hepatitis

IgM + enzyme rise

Recovery

Persistent IgG

Slide 35 · Usual acute hepatitis resolves in 2–4 weeks

Self-limited disease is the usual clinical course

The onset follows the average 4–5-week incubation period.

Most patients then recover over approximately 2–4 weeks.

This describes typical, not universal, outcomes.

Slide 36 · Immune status determines whether HEV persists

Immunocompetent host

Persistent viremia is not observed in the Robbins description.

Chronic liver disease from HEV is not observed.

Immunosuppressed host

Chronic HEV infection can occur.

Examples include AIDS and transplant recipients.

Slide 37 · Acute disease and chronic infection are distinct

Acute HEV infection

Often self-limited

Host immune status

Key modifier

Resolution or persistence

Different clinical trajectories

The source does not describe a persistent immunocompetent carrier state.

Slide 38 · Pregnancy is a major severity modifier

Acute HEV can be particularly severe during pregnancy

High pregnancy-associated mortality.

The adjacent syndrome section identifies HEV as a cause of liver failure in pregnancy.

A pregnant patient with acute hepatitis requires careful etiologic assessment.

Slide 39 · Pregnancy-associated mortality: Source figure

Mortality may approach 20% in pregnant females

This is the value stated section.

It should not be treated as a universal contemporary case-fatality rate.

It identifies pregnancy as a high-risk clinical setting.

Slide 40 · HEV can contribute to acute liver failure

Severe viral hepatitis

Extensive hepatocyte injury

Massive necrosis

Loss of functioning parenchyma

Acute liver failure

Potentially fatal syndrome

The adjacent Robbins section specifically highlights HEV-associated liver failure in pregnancy.

Slide 41 · The pathology of severe acute hepatitis

Milder hepatocellular injury

Inflammatory infiltrates.

Hepatocyte apoptosis or focal necrosis.

Severe injury

Confluent and bridging necrosis.

Massive necrosis can produce liver failure.

Slide 42 · Immunosuppression permits chronic HEV

Chronic HEV infection can occur when host defense is impaired

The source highlights recipients of transplanted organs.

It also includes patients with AIDS.

Persistence changes the expected acute, self-limited course.

Slide 43 · Immunocompromised hosts: Two examples

Chronic HEV risk

Transplant recipient

Patient with AIDS

Illustrative categories named; The source does not quantify subgroup risks.

Slide 44 · Persistent viremia is different from IgG persistence

Persistent viral RNA

Suggests ongoing viral genetic material detection.

Relevant when HEV is suspected to be chronic.

Persistent IgG antibody

Expected after recovery.

Does not, by itself, show ongoing viral replication.

Slide 45 · Chronic hepatitis: Context

Continuing or relapsing disease beyond 6 months and/or fibrosis

This is the general clinicopathologic definition of chronic hepatitis.

It is not provided as an HEV-specific PCR cutoff in this text.

Chronic HEV is described particularly in immunosuppressed patients.

Slide 46 · Viral-hepatitis morphology is not HEV-specific

Morphologic patterns overlap among hepatotropic viruses

Acute hepatitis shows lobular injury and inflammation.

Autoimmune hepatitis and drug reactions can show similar changes.

Virologic testing is required for attribution to HEV.

Slide 47 · Acute hepatitis: Gross appearance varies

Less severe disease

Liver may be normal-sized or enlarged.

Inflammation can contribute to enlargement.

Acute liver failure

Liver can be shrunken.

Extensive parenchymal loss underlies the change.

Slide 48 · Acute hepatitis: Inflammation is portal and lobular

Portal tract

Lobular cells

Simplified architectural schematic of generic acute viral hepatitis—not histopathologic evidence.

Slide 49 · Lymphocytes predominate in viral hepatitis

Portal and lobular infiltrates are mainly lymphocytic

Plasma cells and eosinophils may be variably admixed.

Inflammation accompanies hepatocyte injury.

Cellular composition alone does not identify the hepatitis virus.

Slide 50 · Hepatocyte injury: Necrosis and apoptosis

Injured hepatocyte

Apoptotic cell

Necrotic cell

Original conceptual cells; Not an H&E photomicrograph.

Slide 51 · Macrophages remove hepatocyte debris

Cell death

Apoptosis / necrosis

Cellular debris

Damaged-cell remnants

Macrophage clearance

Pigmented aggregates may remain

This morphologic response is shared among causes of acute hepatitis.

Slide 52 · Confluent necrosis indicates more extensive injury

Individual hepatocytes

Focal damage

Groups of hepatocytes

Confluent necrosis

Extensive hepatic regions

Severe acute hepatitis

Extent matters more than a purported HEV-specific histologic sign.

Slide 53 · Bridging necrosis connects vascular structures

BRIDGING NECROSIS

Portal tract

Central vein

Anatomical schematic of generic severe hepatitis; Not drawn to histologic scale.

Slide 54 · Massive hepatocellular necrosis can cause failure

Panlobular / panacinar necrosis

Widespread cell loss

Reduced functional hepatocyte mass

Impaired liver function

Acute liver failure

Potential need for transplantation

Acute viral hepatitis to acute liver failure through massive necrosis.

Slide 55 · Chronic hepatitis changes the tissue architecture

Active inflammation

Portal lymphocytes or lymphoplasmacytic cells.

Interface activity at the limiting plate.

Fibrotic remodeling

Portal / periportal fibrosis.

Possible bridging fibrosis and cirrhosis.

Slide 56 · Acute versus chronic morphology

Characteristic

Acute viral hepatitis

Chronic viral hepatitis

Principal pattern

Lobular inflammation / injury

Portal inflammation / fibrosis

Hepatocyte damage

Apoptosis or necrosis

Interface activity may occur

Advanced change

Confluent or massive necrosis

Bridging fibrosis / cirrhosis

Slide 57 · The histology cannot type HEV infection

Hepatitis on biopsy

Morphologic pattern

Etiologic overlap

Virus / autoimmunity / drugs

Serology and molecular testing

Identify etiology

Do not call HEV on nonspecific tissue morphology alone.

Slide 58 · Hepatitis A versus E: Shared and distinct features

Feature

Hepatitis A

Hepatitis E

Transmission

Fecal–oral

Fecal–oral

Course in competent host

Typically self-limited

Typically self-limited

Chronic hepatitis

Not observed

In immunosuppressed hosts

High-risk theme

Acute liver failure possible

Severe disease in pregnancy

Slide 59 · Viral-hepatitis diagnosis requires specific markers

Virus

Selected source-listed approach

HAV

IgM anti-HAV

HBV

HBsAg / anti-HBc; HBV DNA PCR

HCV

Anti-HCV; HCV RNA PCR

HDV

IgM/IgG anti-HDV; HDV RNA PCR

HEV

IgM/IgG anti-HEV; HEV RNA PCR

Slide 60 · A source-grounded HEV testing framework

Clinical suspicion

Acute hepatitis + exposure/risk

Specific evidence

HEV RNA and anti-HEV antibodies

Clinical classification

Acute illness vs possible persistence

Risk assessment

Pregnancy / immunosuppression

This is an educational interpretation framework, not a validated clinical guideline.

Slide 61 · Antibody and RNA tests answer different questions

Molecular testing

HEV RNA shows detectable viral genetic material.

Can be positive before symptoms.

Serologic testing

IgM accompanies the acute clinical phase.

IgG persists during recovery.

Slide 62 · Case: Acute hepatitis after travel

A young adult develops acute hepatitis several weeks after returning from a region where HEV epidemics occur. An exposure to unsafe water is possible.

What makes HEV a defensible diagnosis to investigate?

Fecal–oral, water-borne exposure fits the epidemiology.

The interval fits the average 4–5-week incubation.

Order appropriate HEV serology and/or HEV RNA testing.

Slide 63 · Case: Acute hepatitis in pregnancy

A pregnant patient presents with newly symptomatic acute hepatitis. An enterically transmitted hepatitis virus is under consideration.

What changes the urgency of recognizing HEV?

Unusually severe HEV disease in pregnancy.

HEV can lead to acute liver failure in this population.

Etiologic assessment and clinical monitoring must account for that risk.

Slide 64 · Case: Ongoing hepatitis after transplantation

An organ-transplant recipient has persistently abnormal liver tests after an episode of suspected viral hepatitis.

Which HEV-related deviation from the usual course matters?

Chronic infection can occur with immunosuppression.

Persistent HEV RNA is different from persistent IgG.

Virologic testing is needed to establish current infection.

Slide 65 · Clinical synthesis: Four decisive distinctions

Question

HEV-specific answer

How acquired?

Enteric / water-borne, with zoonotic associations

Why hepatocyte injury?

Predominantly host immune response

How recognize the phase?

RNA, acute IgM, recovery-phase IgG

Who develops severe/persistent disease?

Pregnancy (severity); immunosuppression (persistence)

Slide 66 · Key learning points

HEV commonly causes an acute fecal–oral hepatitis.

HEV is an RNA virus, with injury attributed mainly to host response.

RNA detection can precede symptoms; IgM rises with illness; IgG persists in recovery.

Severe pregnancy-associated disease and chronic infection with immunosuppression are major exceptions.

Morphology is not etiologically specific: Use appropriate molecular and serologic tests.

Slide 67 · Reference and source boundaries

Primary textbook

Robbins, Cotran & Kumar: Pathologic Basis of Disease, 11th edition (2026). Chapter 18: Liver and Gallbladder.

Sections used

Hepatitis E Virus (p. 760).

Clinicopathologic Syndromes of Viral Hepatitis and Table 18.3 (pp. 760–761).

Morphology of Viral Hepatitis (pp. 761–762).

Hepatitis A Virus and Viral Hepatitis parent context (pp. 755–756).