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Exacerbation of an
 unrecognized autoimmune
    hepatitis and sustained
virologic response in the case
of antiviral therapy for chronic
           hepatitis C
                       MD PhD Oleksandra Popovych
                                MD PhD Larysa Moroz
                                   MD Felix Chabanov
                              MD PhD Svetlana Kulias
                  Vinnytsia National Medical University
                                               Ukraine
Patient history
   Sex: male
   Age: 26 years (DOB: 19/JAN/1983)
   First detection of anti-HCV: 24/NOV/2008
(accidentally during examination due to
intense hair loss)
 Epidemiological risks: 23 operations have
  performed since 1986 to 1989 (1 for
  congenital hypospadias and 22 for
  postoperative fistula)
 Approximate duration of epidemiological
  anamnesis – 20 years
Life history
 Vision: mild myopia (current)
 Skin: allergic dermatitis (past),

        intense hair loss (past)
 Urogenital system: urolithiasis (current)
 Respiratory system: Pneumonia (past)
 Blood: thrombocytopenia (65-80 THOU/mkl)

(since 1989, current)
Physical examination
 Height:  160 cm
 Weight: 60 kg
 Ps: 68 beats per minute
 Arterial pressure: 120/80 mmHg
 The lower edge of the spleen is palpated
 Other organs without significant deviations
  from the norm
Preliminary findings
           anti-HCV, Epidemiological risks
                     20 years ago
         Intense hair loss, allergic dermatitis
                 Thrombocytopenia
                Enlargement of spleen




Acute problem?                      Chronic problem?
 Probably not                         Probably yes



                                  Autoimmune process?
                                     Hypersplenism?
                                     Other reasons?
Laboratory evaluation (primary data)
                     CBC
   RBC 4,72 TI/L
   MCV 79,54 FL
   HB 135,2 G/L
   Ht 37,5%
   WBC 4,1Gi/L               PLT
   Neutrophils 2,42/mkl   67 THOU/mkl
   Lymphocytes 1,27/mkl
   Monocytes 0,33/mkl
   Eosinophils 0,08/mkl
                0,08
Laboratory evaluation (primary data)

            Coagulation tests
 APTT 59 sec
 INR 1,37           MILD INCREASE
 PT 21,6 sec


              Urine analysis
   Without clinically significant changes
Laboratory evaluation (primary data)

   Urea nitrogen 3.5 mmol/l          Protein total 73 G/L
   Creatinine 61umol/l               Albumin 46 G/L
   Glucose 5.1 mmol/l                Calcium 2.36 mmol/l
   Sodium 139 mmol/l                 Chloride 104 mmol/l
   Potassium 3.7 mmol/l              Magnesium 0.74 mmol/l
   Alkaline Posphatase 117 u/l       Uric Acid 368 umol/l
   Bilirubin total 24 umol/l         Phosphorus inorganic
   Bilirubin indirect 18 umol/l       0.98mmol/l
   Bilirubin direct 6 umol/l         Insulin 42 PMOL/L
   Serum iron 18.5 umol/l            ATTPO 6 ME/ml
   Ferritin 153.9 ng/ml              TSH 0,983 mkME/ml
Laboratory evaluation (continued )

           ASAT 142 U/L
           ALAT 143 U/L
 three times the upper limit of normal,
              ALAT≈ASAT

(1 episode was presented with tenfold increase of
         ALAT and ASAT three years ago )
Laboratory evaluation (continued )

 Anti-HCV  - positive
 HCV RNA, PCR, QUANT - 70 000 IU/ML
 HCV genotype (LIPA) – 1b
 Anti HIV ½ - negative
 HBsAg – negative, Anti HBcor -
  negative
 ANA – negative
Ultrasound
 Increased echogenicity of liver with irregular
  appearing areas
 SPLENOMEGALY
 V.PORTAE – 14mm       upper limit of normal
 V.LIENALIS – 10mm

    Esophagogastroduodenoscopy
 Esophageal varices, stage II   !!!
                      ECG
     Without clinically significant changes
Diagnosis
Liver cirrhosis of HCV etiology
(anti-HCV-positive, low viral load, 1b genotype),
Child-Pugh class A with moderate inflammatory
activity. Esophageal varices II, moderate
thrombocytopenia.



              The patient needs treatment

(The patient refused liver biopsy, FibroScan - !!!!!!!!!!)
TREATMENT
               Thrombopoietin PegInterferon   Ribavirin
               receptor       α-2b
               agonist
Dose           dependently on 80mkg           400mg
               platelets’ level
Frequency      q.d.           once a week     b.i.d

Route of       po             sc              po
administration

Duration       dependently on 48 weeks        48 weeks
of treatment   platelets’ level
Week 9 (stop antiviral therapy)
 ALAT   250 U/L ASAT 289 U/L
 HCV RNA, PCR, QUANT - negative
 Anti HAV-, Anti Bcor-, Anti HEV- CMV-,
  Epstein-Barr VCA- IgM, ANA, ActionAb,
  SMA, AMA IgG – negative
 LKM-1 ANTIBODY IGG 46.1 UNITS
  (positive >=25). Manifestation of autoimmune
  hepatitis II type
 Ultrasound (New changes): mild thickening
  of caudate lobe, V.Portae – 15mm, V.Lienalis
  – 11mm, Ascites – 300-350ml
U/L
            B
                ef
                   or
  St                  e
     ar               tre
        t




                                     0
                                         100
                                               200
                                                     300
                                                           400
                                                                 500
                                                                       600
         of               at
                            m                                                                    700
             an               en
                tiv              t
                    ira
                        lt
                           he
                             ra
                               py
                              W
                                                                                                       treatment



                                 1
(s                            W
  to                             2
     p                        W
       an                        4
   (s     ti v
     ta ir                    W
        rt al                    6
          Pr t h
              e d er          W
                 ni ap 8
                    so y)
                        lo W
                           n) 9
                              W
                                12
                             W
                               14
                             W
                               15
                             W
                               16
                             W
                               17
                             W
                                                                         ALAT 612 U/L ASAT 585 U/L




                               21
                             W
                               29
                             W
                               41
                                                                                                       Dynamics of ALAT and ASAT for the




                                                     ALAT
                                                     ASAT
Preliminary results of the treatment
   Ascites was resolved in a 2 weeks after
    Prednisolone therapy
   All the biochemical data were normalized after 2
    month of Prednisolone therapy
   Prednisolone therapy lasted 1 year
   Normal biochemical data and negative HCV
    RNA have been retained till now
   Total duration of virologic remission is 1 year 3
    months
   LKM-1 ANTIBODY IGG - negative
Key issues
                              ???




Overlap syndrome is                          Avowed duration
  a contraindication
                         ANA examination
                            is enough        of antiviral therapy
 for antiviral therapy
   of HCV-infection         to start of          is 48 weeks
          ?              antiviral therapy
                                                     ?
                                ?
THANK YOU !

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Hcv

  • 1. Exacerbation of an unrecognized autoimmune hepatitis and sustained virologic response in the case of antiviral therapy for chronic hepatitis C MD PhD Oleksandra Popovych MD PhD Larysa Moroz MD Felix Chabanov MD PhD Svetlana Kulias Vinnytsia National Medical University Ukraine
  • 2. Patient history  Sex: male  Age: 26 years (DOB: 19/JAN/1983)  First detection of anti-HCV: 24/NOV/2008 (accidentally during examination due to intense hair loss)  Epidemiological risks: 23 operations have performed since 1986 to 1989 (1 for congenital hypospadias and 22 for postoperative fistula)  Approximate duration of epidemiological anamnesis – 20 years
  • 3. Life history  Vision: mild myopia (current)  Skin: allergic dermatitis (past), intense hair loss (past)  Urogenital system: urolithiasis (current)  Respiratory system: Pneumonia (past)  Blood: thrombocytopenia (65-80 THOU/mkl) (since 1989, current)
  • 4. Physical examination  Height: 160 cm  Weight: 60 kg  Ps: 68 beats per minute  Arterial pressure: 120/80 mmHg  The lower edge of the spleen is palpated  Other organs without significant deviations from the norm
  • 5. Preliminary findings anti-HCV, Epidemiological risks 20 years ago Intense hair loss, allergic dermatitis Thrombocytopenia Enlargement of spleen Acute problem? Chronic problem? Probably not Probably yes Autoimmune process? Hypersplenism? Other reasons?
  • 6. Laboratory evaluation (primary data) CBC  RBC 4,72 TI/L  MCV 79,54 FL  HB 135,2 G/L  Ht 37,5%  WBC 4,1Gi/L PLT  Neutrophils 2,42/mkl 67 THOU/mkl  Lymphocytes 1,27/mkl  Monocytes 0,33/mkl  Eosinophils 0,08/mkl 0,08
  • 7. Laboratory evaluation (primary data) Coagulation tests  APTT 59 sec  INR 1,37 MILD INCREASE  PT 21,6 sec Urine analysis Without clinically significant changes
  • 8. Laboratory evaluation (primary data)  Urea nitrogen 3.5 mmol/l  Protein total 73 G/L  Creatinine 61umol/l  Albumin 46 G/L  Glucose 5.1 mmol/l  Calcium 2.36 mmol/l  Sodium 139 mmol/l  Chloride 104 mmol/l  Potassium 3.7 mmol/l  Magnesium 0.74 mmol/l  Alkaline Posphatase 117 u/l  Uric Acid 368 umol/l  Bilirubin total 24 umol/l  Phosphorus inorganic  Bilirubin indirect 18 umol/l 0.98mmol/l  Bilirubin direct 6 umol/l  Insulin 42 PMOL/L  Serum iron 18.5 umol/l  ATTPO 6 ME/ml  Ferritin 153.9 ng/ml  TSH 0,983 mkME/ml
  • 9. Laboratory evaluation (continued ) ASAT 142 U/L ALAT 143 U/L three times the upper limit of normal, ALAT≈ASAT (1 episode was presented with tenfold increase of ALAT and ASAT three years ago )
  • 10. Laboratory evaluation (continued )  Anti-HCV - positive  HCV RNA, PCR, QUANT - 70 000 IU/ML  HCV genotype (LIPA) – 1b  Anti HIV ½ - negative  HBsAg – negative, Anti HBcor - negative  ANA – negative
  • 11. Ultrasound  Increased echogenicity of liver with irregular appearing areas  SPLENOMEGALY  V.PORTAE – 14mm upper limit of normal  V.LIENALIS – 10mm Esophagogastroduodenoscopy  Esophageal varices, stage II !!! ECG Without clinically significant changes
  • 12. Diagnosis Liver cirrhosis of HCV etiology (anti-HCV-positive, low viral load, 1b genotype), Child-Pugh class A with moderate inflammatory activity. Esophageal varices II, moderate thrombocytopenia. The patient needs treatment (The patient refused liver biopsy, FibroScan - !!!!!!!!!!)
  • 13. TREATMENT Thrombopoietin PegInterferon Ribavirin receptor α-2b agonist Dose dependently on 80mkg 400mg platelets’ level Frequency q.d. once a week b.i.d Route of po sc po administration Duration dependently on 48 weeks 48 weeks of treatment platelets’ level
  • 14. Week 9 (stop antiviral therapy)  ALAT 250 U/L ASAT 289 U/L  HCV RNA, PCR, QUANT - negative  Anti HAV-, Anti Bcor-, Anti HEV- CMV-, Epstein-Barr VCA- IgM, ANA, ActionAb, SMA, AMA IgG – negative  LKM-1 ANTIBODY IGG 46.1 UNITS (positive >=25). Manifestation of autoimmune hepatitis II type  Ultrasound (New changes): mild thickening of caudate lobe, V.Portae – 15mm, V.Lienalis – 11mm, Ascites – 300-350ml
  • 15. U/L B ef or St e ar tre t 0 100 200 300 400 500 600 of at m 700 an en tiv t ira lt he ra py W treatment 1 (s W to 2 p W an 4 (s ti v ta ir W rt al 6 Pr t h e d er W ni ap 8 so y) lo W n) 9 W 12 W 14 W 15 W 16 W 17 W ALAT 612 U/L ASAT 585 U/L 21 W 29 W 41 Dynamics of ALAT and ASAT for the ALAT ASAT
  • 16. Preliminary results of the treatment  Ascites was resolved in a 2 weeks after Prednisolone therapy  All the biochemical data were normalized after 2 month of Prednisolone therapy  Prednisolone therapy lasted 1 year  Normal biochemical data and negative HCV RNA have been retained till now  Total duration of virologic remission is 1 year 3 months  LKM-1 ANTIBODY IGG - negative
  • 17. Key issues ??? Overlap syndrome is Avowed duration a contraindication ANA examination is enough of antiviral therapy for antiviral therapy of HCV-infection to start of is 48 weeks ? antiviral therapy ? ?