الفهرس Only 14 pages are availabe for public view
 |  | from | 128 |  |  |
| | | from | 128 | | |
Abstract
HCV infection is one of the most common causes of chronic liver diseases worldwide. It is estimated that more than 100 million people suffer from chronic hepatitis C, and up to 30% of these will eventually develop cirrhosis and die from the disease or require liver transplantation.
Liver fibrosis is characterized by pathological accumulation of ECM resulting from alterations of synthesis and/ or degradation of matrix proteins. MMPs are capable of degrading collagens; they play an important role in several pathological states including liver fibrosis. These enzymes activities are regulated through the action of TIMPs. The imbalance between MMPs and TIMPs is thought to be an important determinant of ECM deposition and breakdown.
Prognosis and treatment in chronic hepatitis C are partly dependant on the assessment of histological activity and on the degree of hepatic fibrosis. These parameters have so far been provided by liver biopsy, since conventional laboratory tests are unable to precisely evaluate liver lesions. However liver biopsy is an invasive procedure, not free of risks. Besides, the reliability of histological findings may be limited by factors such as the quality of the sample and sampling error.
In view of the high cost and limited efficacy of treatment, it would be important to identify clearly those who are at risk of developing cirrhosis and reliable non invasive parameters for the determination of fibrosis are highly desirable.
The aim of the present work was to study α2-MG, Apo A1, HP and PIIINP as non-invasive index of the presence of cirrhosis in patients with chronic hepatitis C in comparison to the clinical, ultrasonographic and histopathological findings.
The study was conducted on fifty patients classified into three groups; group I consisted of twenty patients with chronic HCV infection with cirrhosis, group II included twenty patients with chronic HCV infection without liver cirrhosis and group III composed of ten healthy subjects as controls.
All patients and controls were subjected to the following:
1. Proper and detailed history taking and thorough clinical examination.
2. Routine laboratory investigations including:
A-Complete blood picture.
B- Liver function tests: serum AST and ALT, serum bilirubin, serum albumin, albumin/globulin (A/G) ratio, prothrombin time and activity, serum alkaline phosphatase and serum GGT.
C-Renal function tests: blood urea and serum creatinine.
3. Viral markers for hepatitis B (HBs Ag) and hepatitis C (anti-HCV) by ELISA and PCR for HCV-RNA.
4. Estimation of serum α2-MG, HP and apo AI levels.
5. Estimation of serum PIIINP level.
6. Calculation of APRI.
7. Calculation of API.
8. Calculation of AST/ALT ratio.
9. Ultrasound examination of the abdomen and dupplex examination of portal circulation.
10. Liver biopsy was done for patients only.
Statistical analysis of data obtained from the present study revealed the following results:
• Serum levels of α2-MG, PIIINP, APRI, API and AST/ALT ratio were significantly higher in group I than in other groups, while serum levels of Apo A1 and HP were significantly lower in group I than in other groups.
• A significant positive correlation was found between serum α2- MG and PIIINP on one hand and, Child-Pugh score on the other hand, while significant negative correlation was observed between serum Apo A1 and HP on one hand and, Child-Pugh score on the other hand.
• In group I patients, significant positive correlation was found between serum PIIINP and serum α2-MG, while significant negative correlations were recorded between serum PIIINP, Apo A1 and HP. Moreover, significant positive correlation was found between APRI and API.
• In group II patients, significant positive correlation was proved between serum PIIINP and serum α2-MG, while significant negative correlation was found between serum Apo A1 and APRI. Moreover, significant positive correlation was exhibited between APRI and API.
• Histopathological examination of liver biopsy specimens revealed the following results in the two patient groups:
- Group I: moderate activity in 60% (grade 6 to 12) and severe activity in 40% (grade 13 to 18), 60% were stage 5 and 40% were stage 6.
- Group II: mild activity (grade 0 to 5) was found in 45% of patients and moderate activity in 55% of patients. All patients revealed stage 0.
• A significant positive correlation was recorded between serum α2-MG, PIIINP, APRI and API scores on one hand and histopathological grading and staging on the other hand. Moreover, significant negative correlation was found between serum Apo A1, HP on one hand and histopathological grading and staging on the other hand.
• α2-MG, showed 90% specificity, 85% sensitivity, 75% positive predictive value and efficacy of 86.6%. As regards Apo A1, it showed 90% specificity, 80% sensitivity, 69% positive predictive value and efficacy of 83%. Regarding HP, it exhibited 70% specificity, 70% sensitivity, 53% positive predictive value and efficacy of 70%. PIIINP recorded 60% specificity, 75% sensitivity, 54.5% positive predictive value and efficacy of 70%. APRI test showed 90% specificity, 80% sensitivity, 69% positive predictive value and efficacy of 83%. API test, it recorded 80% specificity, 60% sensitivity, 50% positive predictive value and efficacy of 66%. Concerning AST/ALT ratio, it showed 60% specificity, 85% sensitivity, 66% positive predictive value and efficacy of 76% in the prediction of cirrhotic changes by histopathological examination.
• Portal vein diameter was significantly higher in group I than in group II, while portal vein mean velocity was significantly lower in group I than in group II.
• Significant positive correlations were found between portal vein diameter on one side and serum α2-MG and PIIINP on the other side. Moreover, significant negative correlation was observed between portal vein diameter and serum Apo A1.
• Significant positive correlation was recorded between portal vein mean velocity and serum Apo A1. Moreover, significant negative correlation was found between portal vein mean velocity and serum α2-MG and PIIINP.
• Significant positive correlation was exhibited between spleen size and serum α2- MG.
• In group I although ten patients proved to be cirrhotic (stage 5/6 and 6/6) by liver biopsy, 30% of those patients showed bright liver, 20% showed normal liver and 50% showed cirrhotic liver by ultrasound. In group II although twenty patients were proved to be non cirrhotic (stage 0/6) by liver biopsy, 15% showed bright liver, 5% showed cirrhotic liver and 80% showed normal liver by ultrasound. Liver echotexure by US showed 50% specificity, 94% sensitivity, 83% positive predictive value and efficacy of 78% in the prediction of cirrhotic changes by histopathological examination.