PRIMARY HEPATOCELLULAR CARCINOMA RESEARCH IN ZIMBABWE AND C - PowerPoint Presentation

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PRIMARY HEPATOCELLULAR CARCINOMA RESEARCH IN ZIMBABWE AND CO-INFECTIONS WITH VIRAL DISEASESHilda T Marima- MatariraProfessor of Chemical PathologyUniversity of ZimbabweSlide2

ObjectivesTo evaluate the clinical utility of biochemical tests, ie. Alpha-Fetoprotein

(AFP) , Alkaline Phosphatase

(ALP), Gamma-glutamylase transferase (GGT

) isoenzymes of ALP and GGT in the diagnosis of

PHC

To

determine the

seroprevalence

of HBV and HCV

in

PHC and HBV in HIV

To

establish some aetiological factors associated

with

PHC Slide3

MethodsLFT: RA1000 Technicon, ALP and GGT isoenzymes: PAGE in Bio-Rad Dual Slab Gel and LKB laser densitometerAFP:RIA I125

kitHBsAg: Bioelisa

Biokit; Anti HCV: MUREX kit ABBOTT and substrate TMBFibro Test: Alpha-2-macroglobulin, haptoglobin, Apo A-1, Total Bilirubin and GGT on Beckman Coulter AU680 Chemistry AnalyserCalculated on

www.biopredictive.comFIB-4 index calculation: (age in years X AST IU/L X Platelets X 109)/L)/(ALT IU/L).Slide4

Methods7 Cross-Sectional Studies, 1998-2015Sites: Parirenyatwa & Harare Hospitals, Opportunistic Infection Clinics

National Blood Transfusion Services, Zimbabwe571 Patients 18-55 years, healthy controls:

331Slide5

MethodsThe liver function tests and alpha-fetoprotein were determined as in method section in 160 patients with a clinical diagnosis of PHC. Data was interpreted using Biochemical Reference Values in Zimbabwe (Marima-Matarira 1989) except for Alpha-fetoprotein.Slide6

MethodsThe haematological and biochemical investigations were carried out on 160 patients with a clinical diagnosis of PHC. The methods are as described in the method section. Data from patients was interpreted using the reference values of healthy donors in Zimbabwe (Marima-Matarira 1989)Slide7

Table 1: Abnormal Liver Function Results and Alpha-Fetoprotein in PHCTestCut-Off Point

PercentageAspartate Aminotransferase

Alkaline phosphataseGamma-glutamyl TransferaseTotal Bilirubin

Conjugated BilirubinAlanine AminotransferaseAlpha-fetoproteinAlbumin

Cholesterol (random)

10. Total Protein

> 50 IU/l

> 120

IU/l

> 40 IU/l

>

40

umol

/l

>

14

umol

/l

> 50 IU/l

> 400

ng/ML

<

30

g/l

> 8.5 mmol/l

< 2.4 mmol/L

> 84 g/l

< 54 g/l

83%

81%

75%

50%

48%

48%

47%

10%

9%

7%

6%

6%Slide8

Males : Female Ratio 4:1Mean ages of 3 studies in years56, 46,

43.8declining

Patients who took alcohol : abstainers6:1

Patients who admitted to heavyalcohol use52%Mean survival period

5.3 months

Mean symptoms before hospital

Presentation

5.2

PATIENTS DATA AND SOCIAL HISTORYSlide9

Table 2: HAEMATOLOGICAL,BIOCHEMICAL INVESTIGATIONS IN PHC [ n=85]

TEST

CUT-OFF POINTPERCENTAGE1. Haemoglobin< 12.5 g/l

47%2. RBS< 4.2 x 10 12/1

47%

3. WBC

> 10.5 x 10

9

/

1

26%

4. Urea

> 6.0 mmol/l

23%

5. Creatinine

> 190 µmol/l

23%

6. Sodium

< 126 mmol/l

18%

7. Chloride

< 99 mmol/l

7%

8. Potassium

> 5.6 mmol

1%

9. Albumin

< 30g/l

10% Slide10

TABLE 4: THE HISTOLOGICAL ANALYSIS OF LIVER TISSUE OF PATIENTS WITH A CLINICAL DIAGNOSIS OF PHC

PATHOLOGY

PERCENTAGE OF TOTALPHC 47PHC

and Cirrhosis 12PHC and Haemochromatosis 2PHC,

Cirrhosis and Haemochromatosis

2

Secondary Hepatocellular Carcinoma

2

Cirrhosis only

12

Cirrhosis and Haemochromatosis

1

Haemachromatosis

only

7

Others

11

Normal

4

Total

100Slide11

Table 4 continued:-Others included: malaria,schistomiosis, adenocarcinoma, apudoma, drug induced cholestasis, fibrotic gall bladder, lymphoid tissue tumour cells, cholestasis, bile thrombi and chronic cholecystitis.

In the PHC patients with cirrhosis, 70% had micronodular while 30% had macronodularSlide12

Table 6: ALKALINE PHOSPHATASE AND GGT ISOENZYMES IN HEALTHY CONTROLS, PHC PATIENTSPatientsAnodal (%)

Cathodal (%)Healthy Controls

(100)(3.9)PHC (100)83.3 p

< 0.05GGT Isoenzyme 1Abnormal96 p < 0.05

Sera from healthy controls, patients with PHC was run on PAGE electrophoresis.

A highly specific substrate for ALP, p-touluidinium-5-bromo-4 chloro-3-indoyl phosphate was used to stain the isoenzyme at

room temperature (17˚C).

For GGT

trichloroacetic

acid and glycerol gave lilac bands at 17˚C.Slide13

SEROPOSITIVITY FOR HBV AND HCV IN PHC AND HEALTH BLOOD DONORS

Test PHC (%) (n=60) Controls

(%) (n=30) Anti HCV positive 20 0HBsAg positive 48.3 13.3

 Dual Anti-HCV and 8.3 0 HBs Ag positive 

Anti-

HCV and or 60 13.3

HBsAg positiveSlide14

THE DISTRIBUTION OF STAGES OF LIVER FIBROSIS IN HIV POSITIVE on HAART AND HIV NEGATIVE PARTICIPANTS Slide15

THE PREVALENCE OF CLINICALLY SIGNIFICANT FIBROSIS IN HIV POSITIVE on HAART AND HIV NEGATIVE PATIENTS

HIV negative

(n=32)HIV positive

(n = 79)Total(n = 111)AST/ALT ratioN (%)84.4%

79.7%

(Over estimates)

81.1%

APRI test

N (%)

6.3%

13.9%

(Under estimates)

11.7%

FIB-4 index

N (%)

9.4%

22.8%

18.9%

The prevalence of clinically significant

fibrosis in HIV positive patients as determined by the AST/ALT ratio

APRI test and FIB-4 index were 79.7%, 13.9% and

22.8% respectively.Slide16

HBV CO-INFECTION IN HIV POSITIVE PATIENTSSlide17

ReferencesCentral African Journal of Medicine,

(1985)31 No 11:211-214.

Central African Journal of Medicine,(1985) 31 No 5:98-100.Central African Journal of Medicine,

(1988) 34. No. 7: 169-170. Annals of Clinical Biochemistry,(1991)

28:512-513.

Afro-Arab Liver Journal, 1: (1994)69-75

.

Afro-Arab Liver Journal 1

: (1994)

137-142

.

Afro-Arab Liver Journal 1:

(1994) 137-142

.

Infectious

Agents and Cancer 4:15: 1- 6/www.infectagentscancer.com/content/4/15

. (2009)

Journal of Biomedical sciences and Public Health(2015)1:3 and 9Slide18

AcknowledgementsOM Gudza, B Chimusoro, L Mutengwa, H

Mapira, N Chin’ombe, B Nherera, A Makura, K Mhandire, E Chavhunduka

University of Zimbabwe, Chem PathNBSZHarare HospitalParirenyatwa ZACB, AFCC, IFCCParticipants

PublishersSponsorsSlide19
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