Viral hepatitis (hepatitis)

1. Hepatitis

HEPATITIS
Head of the Department of
Pathological Anatomy of the
Chita State Medical Academy
Olga Gruzdeva

2.

• HEPATITIS IS DIFFUSE INFLAMMATION OF HEPATIC TISSUES OF
VARIOUS ETIOLOGY. IT MANIFESTS WITH PARENCHYMAL
DYSTROPHY AND NECROSIS, AS WELL AS INFLAMMATORY
STROMAL AND PARENCHYMAL INFILTRATION. HEPATITIS CAN BE
PRIMARY (INDEPENDENT NOSOLOGICAL ENTITY) OR SECONDARY
(DEVELOPING IN OTHER DISEASES).
• ACCORDING TO ITS ETIOLOGY, PRIMARY HEPATITIS CAN BE
VIRAL, ALCOHOLIC, DRUG-INDUCED, AND AUTOIMMUNE.
ACCORDING TO THE COURSE, HEPATITIS CAN BE ACUTE (UP TO 6
MONTHS) OR CHRONIC (OVER 6 MONTHS).

3.

• THE PATHOLOGY OF ACUTE AND CHRONIC HEPATITIS IS DIFFERENT. ACUTE
HEPATITIS MAY BE EXUDATIVE AND PRODUCTIVE. IN EXUDATIVE HEPATITIS,
THE EXUDATE MAY BE SEROUS OR PURULENT. IN PURULENT CHOLANGITIS,
THE INFILTRATE HAS A PURULENT CHARACTER AND MAY BE LOCATED
DIFFUSELY IN PORTAL TRACTS OR FORM ABSCESSES. ACUTE PRODUCTIVE
HEPATITIS IS CHARACTERIZED BY DYSTROPHY AND NECROSIS OF
HEPATOCYTES IN DIFFERENT ACINUS REGIONS, RESPONSE OF
RETICULOENDOTHELIAL LIVER CELLS. GRANULOMAS WITH DIFFERENT
CELLULAR COMPOSITION DEPEN¬DING ON THE ETIOLOGY MAY DEVELOP IN
TUBERCULOSIS AND SARCOIDOSIS. THE LIVER APPEARANCE IN ACUTE
HEPATITIS DEPENDS ON THE CHARACTER OF INFLAMMATION.

4.

• CHRONIC HEPATITIS IS USUALLY CAUSED BY DIFFERENT TYPES OF
HEPATOTROPIC VIRUSES. THEY HAVE AN OVERT OR ASYMPTOMATIC
COURSE LASTING OVER 6 MONTHS AND ARE MORPHOLOGICALLY
CHARACTERIZED BY DIFFUSE DYSTROPHY AND INFLAMMATION WITH
HISTIOLYMPHOCYTIC INFILTRATION OF PORTAL FIELDS, FIBROSIS OF
INTERLOBULAR AND INTRALOBULAR STROMA, HYPERPLASIA OF KUPFER
CELLS WITH INTACT LOBULAR LIVER STRUCTURE. THE LIVER IN CHRONIC
HEPATITIS IS USUALLY ENLARGED AND DENSE. ITS CAPSULE IS THICKENED
AND WHITISH. THE SECTION OF THE LIVER TISSUE HAS A MOTTLED
APPEARANCE.

5. Classification of chronic hepatitis

CLASSIFICATION OF CHRONIC HEPATITIS
• ACCOUNTS FOR THREE HEPATITIS EVALUATION CATEGORIES:
ETIOLOGY, ACTIVITY GRADE, AND DISEASE STAGE. ACCORDING
TO ETIOLOGY, CHRONIC HEPATITIS CAN BE VIRAL,
AUTOIMMUNE, DRUG-INDUCED, AND CRYPTOGENIC (I.E., OF
UNKNOWN ETIOLOGY).

6.

• THE ETIOLOGICAL CRITERION FOR EVALUATION AND
SYSTEMATIZATION OF CHRONIC HEPATITIS IS SUPPLEMENTED
WITH TWO CLINICAL-MORPHOLOGICAL CRITERIA: GRADE OF
ACTIVITY AND STAGE OF THE DISEASE. ALL CHRONIC
HEPATITIDES ARE CONSIDERED ACTIVE. THE ACTIVITY GRADE IS
SCORED USING A HISTOLOGICAL ACTIVITY INDEX (HAI, OR
KNODELL INDEX). THE STAGE OF CHRONIC HEPATITIS OR
FIBROSIS IS DETERMINED BY SEMIQUANTITATIVE EVALUATION OF
HEPATIC FIBROSIS SEVERITY. LIVER CIRRHOSIS IS CONSIDERED AN
IRREVERSIBLE STAGE OF CHRONIC HEPATITIS.

7.

• VIRAL HEPATITIS IS ONE OF THE MOST COMPLEX MEDICAL AND SOCIAL
PROBLEMS, AS THEY ARE WIDELY PREVALENT AND HAVE POOR OUTCOMES.
CHRONIC HEPATITIS IS ALSO OFTEN FORMED AFTER A PRIOR ACUTE
INFECTION (ESPECIALLY COMMON IN HEPATITIS C); LIVER CIRRHOSIS MAY
DEVELOP; AN ETIOLOGICAL LINK HAS BEEN CONFIRMED BETWEEN
HEPATOCELLULAR CARCINOMA AND HEPATITIS B/C VIRUSES.
• FIVE HEPATOTROPIC VIRUSES HAVE BEEN DISCOVERED, NAMED AFTER
ENGLISH ALPHABET LETTERS FROM A TO E. NEW ONES ARE ADDED
ANNUALLY TO THIS LIST. THUS, VIRUSES F, G, TTV CAUSING PARENTERAL
HEPATITIS HAVE BEEN IDENTIFIED RECENTLY.

8. Periods of hepatitis

PERIODS OF HEPATITIS
• ALL VIRAL HEPATITIDES WITH A MANIFEST COURSE PROGRESS OVER 4 PERIODS:
INCUBATION PERIOD (2-26 WEEKS); PRODROMAL (PRE-ICTERIC) PERIOD
CHARACTERIZED BY NON-SPECIFIC SYMPTOMS; ICTERIC PERIOD (OR OVERT CLINICAL SIGNS);
AND CONVALESCENCE PERIOD.
• THERE ARE SEVERAL CLINICAL AND MORPHOLOGICAL FORMS OF ACUTE VIRAL HEPATITIS:
CYCLIC ICTERIC HEPATITIS IS A CLASSIC MANIFESTATION OF VIRAL HEPATITIS A
(VHA);
NON-ICTERIC HEPATITIS IN 80% CASES OF VIRAL HEPATITIS C AND 70% CASES OF
VIRAL HEPATITIS B;
SUBCLINICAL (INAPPARENT) DISEASE;
FULMINANT HEPATITIS WITH MASSIVE PROGRESSIVE HEPATOCYTE NECROSIS;
CHOLESTATIC HEPATITIS WITH THE INVOLVEMENT OF SMALL BILE DUCTS.

9. Viral hepatitis A

VIRAL HEPATITIS A
• VIRAL HEPATITIS A (BOTKIN’S DISEASE) IS AN ACUTE ENTEROVIRUS CYCLIC
INFECTION WITH THE PREDOMINANT FECAL-ORAL MECHANISM OF
TRANSMISSION.
• ETIOLOGY. HEPATITIS A VIRUS (HAV) BELONGS TO THE PICORNAVIRIDAE
FAMILY.
• EPIDEMIOLOGY. THE SOURCE OF INFECTION IS USUALLY AMONG PATIENTS
WITH ASYMPTOMATIC DISEASE, NON-ICTERIC AND LATENT INFECTION
COURSE. THE LEADING TRANSMISSION MECHANISM IS FECAL-ORAL, WHICH
IS IMPLEMENTED VIA CONTACT COMMUNITY ROUTES. THE SUSCEPTIBILITY
TO HAV IS UNIVERSAL. AROUND 80% PATIENTS ARE CHILDREN UNDER 15.
THE VIRUS IS UBIQUITOUS. HEPATITIS A HAS A SEASONAL INCIDENCE
INCREASE IN THE SUMMER AND AUTUMN.

10. Pathogenesis.

PATHOGENESIS.
• AFTER CONTAMINATION, HAV ENTERS THE BLOOD FROM THE INTESTINE
AND ENDS IN THE LIVER, WHERE IT PENETRATES HEPATOCYTES AFTER
FIXING ON THEIR RECEPTORS. VIRUS REPLICATION OCCURS IN
HEPATOCYTES. DURING THE PRIMARY REPLICATION STAGE, NO CLEAR
HEPATOCYTE INJURY IS OBSERVED. NEW VIRUS GENERATIONS ARE
EXCRETED INTO BILE TUBULES, ENTER THE BOWEL, AND ARE EXCRETED WITH
FECES. SOME VIRUSES PASS INTO THE BLOOD, LEADING TO THE
DEVELOPMENT OF PRODROMAL SYMPTOMS. HEPATOCYTE LESIONS
EMERGING LATER IN THE DISEASE ARE POSSIBLY RELATED TO TRIGGERED
IMMUNOPATHOLOGICAL MECHANISMS. ACTIVATION OF ALL IMMUNE
SYSTEM LINKS LEADS TO QUICK ACCUMULATION OF ANTIVIRAL
ANTIBODIES, WHICH PROMOTE THE TERMINATION OF VIRAL REPLICATION
AND VIRUS CLEARANCE FROM THE BODY WITH COMPLETE RECOVERY.

11.

CLINICAL PRESENTATIONS.
• HAV IS CHARACTERIZED BY POLYMORPHIC CLINICAL SIGNS. THE DISEASE
USUALLY HAS A MILD CYCLIC COURSE, ACCOMPANIED BY MILD JAUNDICE,
DARK URINE, LIGHT STOOLS, AND NON-SPECIFIC SYMPTOMS (TOXIC, FLULIKE, DYSPEPTIC, ASTHENIC SYNDROMES). LIVER TESTS SHOW
ABNORMALITY. THE MAJORITY OF INFECTED PEOPLE HAVE NON-ICTERIC
AND OFTEN SUBCLINICAL DISEASE. FULMINANT HEPATITIS OCCURS IN 0,1%
CASES. THE DIAGNOSIS IS CONFIRMED BY THE DETECTION OF SPECIFIC
MARKERS IN THE BLOOD SERUM: ANTIVIRAL IGM ANTIBODIES (ANTI HAVIGM) AND HAV RNA. AFTER THE DISEASE PATIENTS HAVE LIFE-LONG
IMMUNITY RELATED TO ANTI-HAV IGG-ANTIBODIES. SOMETIMES, THE
DI¬SEASE COURSE MAY BE ALTERED IN CASES OF CO-INFECTIONS AND
SUPERINFECTIONS WITH OTHER HEPATOTROPIC VIRUSES.

12. Pathology

PATHOLOGY
• AT THE HAV DISEASE HEIGHT, MORPHOLOGICAL EXAMINATION REVEALS
HYDROPIC
DYSTROPHY
OF
HEPATOCYTES,
INFLAMMATORY
LYMPHOMACROPHAGAL INFILTRATES PREDOMINANTLY IN THE PERIPORTAL ZONE
OF LIVER LOBULES AND PORTAL TRACTS, NECROBIOSIS AND HEPATOCYTE
NECROSIS, FORMATION OF APOPTOTIC BODIES. SCLEROSIS OF PORTAL TRACTS
AND FOCAL INTRALOBULAR SCLEROSIS DEVELOP IN LOCATIONS OF DEAD
HEPATOCYTES IN THE OUTCOME.
• COMPLICATIONS ARE OBSERVED IN
EXACERBATIONS, BILE DUCT LESIONS.
THE FORM
OF
DISEASE
RELAPSES,
• THE OUTCOME IS USUALLY FAVORABLE. 90% OF PATIENTS RECOVER COMPLETELY,
OTHERS DE¬MONSTRATE RESIDUAL DISORDERS IN THE FORM OF HEPATIC
SCLEROSIS, ASTHENIC (POST-HEPATITIS) SYNDROME, BILE SYSTEM LESIONS
(DYSKINESIA AND CHOLECYSTITIS) WHILE LIVER TESTS ARE WITHIN NORMAL.

13. Viral hepatitis B (VHB)

VIRAL HEPATITIS B (VHB)
• MAY MANIFEST AS A MONOINFECTION OR A MIXED INFECTION (IN CASES OF
SIMULTANEOUS OR CONSEQUENTIAL INFECTION WITH SEVERAL HEPATOTROPIC
VIRUSES).
• CLINICAL PRESENTATIONS. BOTH CLINICALLY SIGNIFICANT AND ASYMPTOMATIC
DISEASE FORMS ARE OBSERVED. THE DISEASE IS USUALLY MILD, CHARACTERIZED
BY JAUNDICE, ACHING PAIN IN THE RIGHT UPPER QUADRANT, SIGNS OF
CHOLESTASIS IN THE FIRST WEEK. TWO OR FOUR WEEKS LATER, SYMPTOMS
REGRESS, AND PATIENTS RECOVER.
• ETIOLOGY. VHB IS CAUSED BY THE HEPATITIS B VIRUS (HBV) FROM THE
HEPADNAVIRIDAE FAMILY. THIS VIRUS CONTAINS CIRCULAR DOUBLE-STRANDED
DNA, A DNA POLYMERASE ENZYME, AND SEVERAL VIRAL ANTIGENS: HBCAG
(CORE ANTIGEN), HBEAG (REPLICATION OR INFECTIVITY ANTIGEN), HBXAG (THE
LEAST STUDIED ONE).

14. Epidemiology.

EPIDEMIOLOGY.
• ONE THIRD OF THE EARTH POPULATION IS INFECTED WITH HEPATITIS B
VIRUS; APPROXIMATELY 4 MILLION CASES OF ACUTE HEPATITIS B OCCUR
ANNUALLY, WHILE 1 MILLION PEOPLE DIE FROM COMPLICATIONS OF
CHRONIC HEPATITIS B. THE DISEASE COMMONLY AFFECTS ADULTS
(INCIDENCE PEAKS AT 20-49 YEARS OF AGE). MAIN SOURCES OF INFECTION
IN VHB INCLUDE PEOPLE WITH ASYMPTOMATIC AND OVERT ACUTE AND
CHRONIC DISEASE INCLUDING THOSE WITH LIVER CIRRHOSIS. THE VIRUS IN
THEM IS PRESENT IN BLOOD, SALIVA, URINE, SPERM, VAGINAL SECRETIONS,
MENSTRUAL BLOOD, ETC. HOWEVER, PATIENTS WITH CHRONIC VHB COURSE
HAVE THE LARGEST EPIDEMIOLOGICAL SIGNIFICANCE.

15. Transmission paths

TRANSMISSION PATHS
• THE MAIN MECHANISM OF INFECTION TRANSMISSION IS PARENTERAL.
TRANSMISSION ROUTES MAY BE NATURAL, DUE TO WHICH HBV PERSISTS IN
NATURE, AND ARTIFICIAL. NATURAL TRANSMISSION ROUTES FOR VIRAL
HEPATITIS B INCLUDE SEXUAL CONTACTS, ESPECIALLY HOMO- AND
BISEXUAL ONES; VERTICAL ROUTE FROM THE MOTHER TO THE FETUS;
COMMUNITY ROUTE: PARENTERAL INFECTIONS VIA SHAVING DEVICES,
TOOTHBRUSHES, WASHCLOTHS, ETC. THE ARTIFICIAL ROUTE OF
TRANSMISSION IS PARENTERAL. IT IS IMPLEMENTED WHEN THE VIRUS
PENETRATES THE INJURED SKIN, MUCOUS MEMBRANES DURING
THERAPEUTIC, DIAGNOSTIC, AND OTHER MANIPULATIONS (INJECTION,
SURGERY, BLOOD TRANSFUSION, ENDOSCOPIC PROCEDURE, ETC.).

16. Pathogenesis.

PATHOGENESIS.
• WHEN HBV ENTERS THE BODY, PRIMARY VIRAL CIRCULATION IN BLOOD
(VIREMIA) DEVELOPS. THE VIRUS ACCUMULATES IN HEPATOCYTES AND
KUPFER CELLS, MONONUCLEAR PHAGOCYTES OF THE BONE MARROW,
BLOOD, LYMPH NODES, AND THE SPLEEN. PRIMARY IMMUNE RESPONSE
DEVELOPS AFTER ITS INTRODUCTION INTO THE BODY. IF THIS RESPONSE IS
ADEQUATE, THE VIRUS IS ELIMINATED, AND THE PATIENT DEVELOPS NONICTERIC VHB (70%). SECONDARY GENERALIZATION DEVELOPS IN CASES OF
INADEQUATE IMMUNE RESPONSE.

17. Pathology

PATHOLOGY
• THE LIVER BECOMES LARGE AND RED. MICROSCOPY SHOWS HEPATOCYTE
NECROSIS, WHICH CAN BE SPOTTY, PERIPORTAL, CENTRILOBULAR,
BRIDGING, SUBMASSIVE, AND MASSIVE. HEPATOCYTES ARE IN THE STATE
OF HYDROPIC AND BALLOONING DEGENERATION. SOME HEPATOCYTES
ARE IN APOPTOSIS WITH THE FORMATION OF COUNCILMAN BODIES (FIG.
13.4). PROFUSE INFILTRATION (PREDOMINANTLY LYMPHOCYTIC AND
MACROPHAGAL) IS OBSERVED IN PORTAL TRACTS AND ACINI, WITH
ADMIXTURE OF A SMALL NUMBER OF LEUKOCYTES (FIG. 13.5).
HYPERPLASIA AND FOCAL PROLIFERATION OF KUPFER CELLS ARE
OBSERVED IN COMBINATION WITH REGENERATING HEPATOCYTES.
CHOLESTASIS IS POSSIBLE.

18.

Viral hepatitis B. Balloon dystrophy and
apoptosis of hepatocytes, apoptotic
Councilman’s body in the center. Hematoxylin
and eosin staining
Viral hepatitis B. Spotty necrosis in patients
with lympho-macrophage infiltration of
hepatic parenchyma. Hematoxylin and eosin
staining

19.

• IN SOME CASES, SUBMASSIVE AND MASSIVE HEPATOCYTE NECROSIS
DEVELOPS IN VHB. THIS DISEASE IS CALLED FULMINANT OR RAPIDLY
PROGRESSIVE. CLINICALLY, IT IS CHARACTERIZED BY THE DEVELOPMENT OF
ACUTE HEPATOCYTE FAILURE AND IS OFTEN FATAL. SURVIVING PATIENTS
DEVELOP POSTNECROTIC LIVER CIRRHOSIS.
• CHOLESTATIC VHB VARIANTS ARE ACCOMPANIED BY LESIONS OF
INTRAHEPATIC BILE DUCTS WITH THE FORMATION OF BILE THROMBI IN
THEM, ACCUMULATION OF BILIRUBIN IN HEPATOCYTES. THE PRESENCE OF
THE VIRUS IN THE CELL MAY BE DETECTED USING IMMUNOHISTOCHEMICAL,
HISTOCHEMICAL, AND MORPHOLOGICAL MARKERS.

20.

CLINICAL PRESENTATIONS
• THE FOLLOWING VHB FORMS ARE DESCRIBED BASED ON THE COURSE
PERIODICITY: CYCLIC DISEASE, WHICH CAN BE ASYMPTOMATIC, NONICTERIC, ICTERIC, OR WITH A CHOLESTATIC SYNDROME; PERSISTING
DISEASE, CHARACTERIZED BY HBV CARRIAGE AND CHRONIC VHB COURSE
IN THE INTEGRATIVE PHASE; PROGRESSIVE DISEASE, WHICH INCLUDES
FULMINANT, SUBACUTE, AND CHRONIC VHB IN THE REPLICATIVE PHASE
INCLUDING THOSE WITH LIVER CIRRHOSIS; DISEASES COMBINED WITH
OTHER HEPATOTROPIC VIRUSES.

21.

• COMPLICATIONS INCLUDE EXACERBATIONS, RELAPSES, HEMORRHAGIC AND
EDEMATOUS-ASCITIC SYNDROMES, ACUTE HEPATOCYTE FAILURE WITH THE
DEVELOPMENT OF HEPATIC ENCEPHALOPATHY (PRECOMA, COMA),
ASSOCIATED INFECTIONS (PNEUMONIA, INTESTINAL INFLAMMATION,
SEPSIS, ETC.).
• VARIANTS OF HBV-INFECTION COURSE AND OUTCOMES OF VIRAL
HEPATITIS B. COMPLETE RECOVERY IS POSSIBLE, AS WELL AS RECOVERY
WITH RESIDUAL EVENTS (POST-HEPATITIS SYNDROME, BILIARY DYSKINESIA,
HEPATIC FIBROSIS). THE DISEASE BECOMES CHRONIC IN 5-10% PATIENTS,
ESPECIALLY MALES. THERE IS A RISK OF LIVER CIRRHOSIS AS WELL.

22.

• THE LEADING ROLE IN THE PATHOGENESIS OF CHB BELONGS TO
VIRAL INTEGRATION INTO THE CELL GENOME, ITS ACTIVE
REPLICATION DURING EXACERBATION, AND THE CHARACTER OF
IMMUNE RESPONSE IN THE BODY. PATIENTS WITH CHB ARE
CONSIDERED MAIN SOURCES OF INFECTION ALONG WITH
“HEALTHY” HBSAG CARRIERS.

23.

CLINICAL PRESENTATIONS.
• THE DISEASE MAY MANIFEST WITH EXACERBATIONS, WHEN CLINICAL AND
LABORATORY PARAMETERS BECOME MORE PRONOUNCED, AND REMISSIONS, DURING
WHICH CLINICAL SYMPTOMS ARE ABSENT OR MILD.
• PATHOLOGY. CHRONIC HEPATITIS OF LOW AND MODERATE ACTIVITY CORRESPONDS
TO THE OLDER DEFINITION “CHRONIC PERSISTING HEPATITIS”. MICROSCOPICALLY,
SUCH CHB IS CHARACTERIZED BY A COMBINATION OF THE FOLLOWING SIGNS:
SIGNIFICANT POLYMORPHISM OF HEPATOCYTES, MILD OR MODERATE HYDROPIC AND
BALLOONING DEGENERATION OF HEPATOCYTES, SMALL AMOUNT OF APOPTOTIC
(COUNCILMAN) BODIES, SPOTTY AND/OR PERIPORTAL NECROSIS OF HEPATOCYTES,
MILD OR MODERATE LYMPHO-MACROPHAGAL INFILTRATION BOTH IN THE
PARENCHYMA AND PORTAL TRACTS, HYPERTROPHY AND PROLIFERATION OF KUPFER
CELLS, SCLEROSIS (FIBROSIS) OF PORTAL TRACTS OF VARIABLE DEGREES.

24.

• CHRONIC HEPATITIS OF HIGH ACTIVITY (OBSOLETE TERM “CHRONIC ACTIVE
HEPATITIS”). MICROSCOPICALLY, IT IS CHARACTERIZED BY PROFOUND HYDROPIC
AND BALLOONING DEGENERATION OF HEPATOCYTES, MULTIPLE APOPTOTIC
BODIES, SPOTTY, CONFLUENT, BRIDGING, AND PERIPORTAL NECROSIS OF
HEPATOCYTES, PROFOUND HYPERTROPHY AND PROLIFERATION OF KUPFER CELLS,
SCLEROSIS OF PORTAL TRACTS OF VARIABLE DEGREES.
• ALL TYPES OF CHB COURSE MAY BE ACCOMPANIED BY DETECTION OF DIRECT HBV
INFECTION MARKER GROUND-GLASS HEPATOCYTES AND “SANDY” NUCLEI OF
HEPATOCYTES.
• COMPLICATIONS. HEPATIC ENCEPHALOPATHY, BLEEDING FROM ESOPHAGEAL
VARICES, GASTROINTESTINAL BLOOD VESSELS AND HEMORRHOIDS, INTESTINAL
INFLAMMATION, ASCITES-PERITONITIS, SEPSIS, ETC.

25. Viral hepatitis С (VHC)

VIRAL HEPATITIS С (VHC)
• VIRAL HEPATITIS С (VHC) IS CAUSED BY A SMALL SINGLE-STRANDED RNAVIRUS OF THE FLAVIVIRIDAE FAMILY. THE GENOME OF THE HEPATITIS C
VIRUS (HCV) CODES THE FORMATION OF STRUCTURAL AND NONSTRUCTURAL VIRAL PROTEINS. THE FORMER INCLUDE THE NUCLEOCAPSID
PROTEIN C AND ENVELOPE GLYCOPROTEINS (E1, E2/NS1). NONSTRUCTURAL PROTEINS (NS2-NS5) INCLUDE ENZYMATICALLY ACTIVE
PROTEINS. ANTIBODIES (ANTI-HCV) ARE FORMED IN RESPONSE TO ALL
THESE PROTEINS IN THE PATIENT’S BODY. MODERN CLASSIFICATIONS
DEFINE OVER 11 HCV GENOTYPES AND OVER 100 ITS SUBTYPES.

26. Epidemiology.

EPIDEMIOLOGY.
• HCV SOURCES ARE PATIENTS WITH ACUTE AND CHRONIC INFECTION. THE
MECHANISM AND ROUTES OF TRANSMISSION ARE RATHER COMPARABLE
WITH THOSE OF HBV. THE PARENTERAL TRANSMISSION ROUTE HAS THE
GREATEST EPIDEMIOLOGICAL SIGNIFICANCE. MOST OFTEN, PEOPLE
BECOME INFECTED DURING TRANSFUSION OF BLOOD AND ITS PRODUCTS.
THE INFECTION FREQUENTLY OCCURS IN PATIENTS WITH HEMOPHILIA.
ILLICIT PARENTERAL DRUG USERS ARE ONE OF THE MOST
EPIDEMIOLOGICALLY SIGNIFICANT RISK GROUPS FOR THE HCV INFECTION.
THE CAUSATIVE AGENT TRANSMISSION IN DOMESTIC CONDITIONS, DURING
HETERO- AND HOMOSEXUAL CONTACTS, FROM THE INFECTED MOTHER TO
THE NEONATE IS POSSIBLE, BUT OCCURS VERY RARELY.

27. Clinical signs.

CLINICAL SIGNS.
• CLINICAL SIGNS. THE MEAN INCUBATION PERIOD LASTS 6-8
WEEKS. THE COURSE OF HCV HAS ACUTE AND CHRONIC STAGES.
THE ACUTE HCV STAGE IS USUALLY ASYMPTOMATIC AND MAY
END IN RECOVERY. HOWEVER, THE MAJORITY OF PATIENTS (7580%) DEVELOP THE CHRONIC HCV STAGE, IN WHICH THE LATENT
PHASE USUALLY PRECEDES THE REACTIVATION PHASE. THE
LATENT PHASE LASTS 10-20 YEARS. DURING THIS PERIOD, THERE
ARE NO SIGNS OF CHRONIC HEPATITIS.

28.

• THE REACTIVATION PHASE IS CAUSED BY INCREASED REPLICATIVE HCV
ACTIVITY AND CLINICALLY CORRESPONDS TO THE MANIFEST COURSE OF
THE ACUTE DISEASE STAGE. PATIENTS DEMONSTRATE SIGNS OF ASTHENIC
SYNDROME,
OFTEN
ACCOMPANIED
BY
SUBFEBRILE
FEVER,
HEPATOSPLENOMEGALY, UNDULATING 2-5-FOLD INCREASES IN THE
ACTIVITY OF SERUM AMINOTRANSFERASES, WITH EXTRAHEPATIC
MANIFESTATIONS IN SEVERAL CASES. HCV PLAYS A ROLE IN THE
FORMATION OF LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA.

29. Pathogenesis.

PATHOGENESIS.
• THE VIRUS ENTERS THE BODY JUST LIKE HBV, BUT MAY POSSIBLY PASS
THROUGH EVEN INTACT SKIN. AFTER ENTERING THE HUMAN BODY,
HEPATOTROPIC HCV REPLICATES PREDOMINANTLY IN HEPATOCYTES. THE
VIRUS CAN HAVE A DIRECT CYTOPATHIC ACTION AGAINST THEM. HCV
PROTEINS MAY INDUCE APOPTOSIS OF HEPATOCYTES. HEPATOCYTE
LESIONS MAY ALSO BE RELATED TO SPECIFIC OR NON-SPECIFIC IMMUNE
RESPONSE OF THE BODY.
• SOME VIRUSES MAY REPLICATE IN THE CELLS OF THE MONONUCLEAR
PHAGOCYTE SYSTEM (PARTICULARLY IN MONONUCLEAR CELLS OF THE
PERIPHERAL BLOOD).

30.

• CHRONIC HEPATITIS C (CHC) HAS A WIDE RANGE OF CLINICAL AND
MORPHOLOGICAL SIGNS: FROM MINIMALLY ACTIVE DISEASE TO SEVERE
PROGRESSIVE ONE WITH THE DEVELOPMENT OF LIVER CIRRHOSIS AND
HEPATOCELLULAR CARCINOMA. IN 50% OF PATIENTS CHC IS FORMED
AFTER ACUTE HEPATITIS C. THERE IS A CLEAR PATTERN: ACUTE HEPATITIS CHRONIC HEPATITIS - LIVER CIRRHOSIS - HEPATIC CARCINOMA. 30%
PATIENTS HAVE NO HISTORY OF AN ACUTE INFECTION EPISODE. CHC HAS A
LONG COURSE OF MINIMALLY SIGNIFICANT CLINICAL AND BIOCHEMICAL
ACTIVITY SIGNS, WHICH EXPLAINS THE LATE DIAGNOSIS.

31.

CLINICAL PRESENTATIONS.
• THE FIRST CLINICAL AND LABORATORY SIGNS OF CHRONIC HEPATITIS ARE
DETECTED 10-15 YEARS AFTER THE INFECTION; LIVER CIRRHOSIS - 20-21
YEARS AFTER IT; AND HEPATOCELLULAR CARCINOMA - 23-29 YEARS AFTER
IT. 50-55% PATIENTS SHOW HEPATOMEGALY, ASTHENIC SYNDROME,
PERIODIC INCREASES IN AST ACTIVITY (1,5-2 FOLD); 40-45% PATIENTS
DEVELOP EXTRAHEPATIC MANIFESTATIONS.

32. Pathology.

PATHOLOGY.
• MICROSCOPICALLY, HCV IS CHARACTERIZED BY A COMBINATION OF THE
FOLLOWING SIGNS: MODERATE HETEROGENICITY (POLYMORPHISM) OF
HEPATOCYTES, FATTY DYSTROPHY OF HEPATOCYTES ALONG WITH THEIR
HYDROPIC AND BALLOONING DEGENERATION, APOPTOTIC BODIES,
RATHER MILD HEPATOCYTE NECROSIS; LYMPHOID AGGREGATES CAN BE
DETECTED IN PORTAL TRACTS AND THE PARENCHYMA, SOMETIMES WITH
CLEAR GERMINAL CENTERS; HYPERTROPHY AND PROLIFERATION OF
KUPFER CELLS; INCREASED NUMBER OF LYMPHOCYTES IN SINUSOIDS;
SOMETIMES, LYMPHOCYTES ARE CLUSTERED IN CHAINS; LESIONS OF BILE
DUCTS WITH THEIR DESTRUCTION AND SUBSEQUENT PROLIFERATION; RARE
EPITHELIOID CELLULAR GRANULOMAS.

33.

Viral hepatitis C. Apoptotic body (in the center),
lymphomacrophagal infiltrate in the portal tract, and
periportal necrosis. Hematoxylin and eosin staining
Viral hepatitis C. Fatty dystrophy of
hepatocytes, and lymphocytic chains in
sinusoid lumina. Hematoxylin and eosin
staining

34.

• MORPHOLOGICAL HEPATIC CHANGES IN VHC OFTEN ARE OFTEN
INCONSISTENT WITH CLINICAL AND BIOCHEMICAL ONES, SO
EVEN LIVER CIRRHOSIS MAY BE ASYMPTOMATIC. DUE TO THIS,
LIVER BIOPSY IS PERFORMED IN ALL PATIENTS TO DEFINE THE
HISTOLOGICAL ACTIVITY AND FIBROSIS STAGE.

35. Liver cirrhosis

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