Pathological and clinical analysis of 204 cases of chronic hepatitis B virus carriers

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Chang Weihong 1   , 2; Wang Suiguo(1) Changsha Institute of infectious diseases, Changsha hospital,, Hunan 2, China; Department of

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Chang Weihong 1   , 2; Wang Suiguo

(1) Changsha Institute of infectious diseases, Changsha hospital,, Hunan 2, China; Department of liver disease, the 180 Hospital of PLA, Beijing 410011, China; 2

 

[Abstract] Objective: To investigate the relationship between the clinical and pathological changes of chronic hepatitis B virus carriers (ASC) and to provide evidence for the treatment of ASC patients with normal liver function ( ). Methods   was performed in 204 patients with ASC who were admitted to the hospital for liver biopsy and pathological examination. The results were compared with the laboratory, ultrasound and clinical data. Results: 204 cases of chronic hepatitis B virus carriers liver pathological detection of G2 and S2 were accounted for 30.4% and 28.4%; the age >40 years old. The pathologic change of liver G2, S2 of the cases accounted for 59.6% (31/52) and (37/75) 49.3%, and there was significant difference between less than 40 years old group (P < 0.05), 3 ALT and AST in the normal range, but 30u/L cases by G1 - G4 and S1---S4 is increased gradually, the ultrasonic detection of spleen, the spleen thickness more than 4.0cm with liver tissue inflammation (G1---G4) and deepen fibrosis (S1---S4) increased (P < 0.05 groups), the HBeAg negative ASC in patients with G3, S3, G4 and S4 each accounted for 40%, 60%, 70% and 75% was significantly higher than that of eAg positive. Conclusion   most chronic HBV carriers have mild liver inflammation, with no or mild fibrosis and inflammation and fibrosis with age and the variation of HBeAg with different degree of progress, at least 25% of the ASC to antiviral therapy.

Key words: chronic hepatitis B;   liver pathology; hepatitis B virus carriers

 

At present, domestic and international guidelines for the treatment of chronic hepatitis B antiviral indications are for alanine aminotransferase (ALT) increased 2 times and the patients with high viral load, and remained normal in ALT of chronic hepatitis B virus carriers (ASC) with no uniform understanding, to explore the characteristics of ASC patients with liver pathology and clinic. The detection of hepatitis B virus, serology, liver function test and ultrasound examination of the May 2000 to May 2007 clinic 204 cases of ASC patients with liver tissue in relation to liver inflammation and fibrosis in patients with ASC and clinical.

1 materials and methods

1.1    research object; from May 2000 to May 2007 in our hospital 204 cases of ASC patients, male 118 cases, female 86 cases, age 16 ~ 61 years old (31.6 + 11.8) years old, meet the following criteria: (1) HBVDNA in the 105-107 /ml copy for 6 months or more, HBsAg (+), eAg (+) / (-). (2) and those with HCV or other alcoholic liver disease and. (3) no clinical symptoms were found in liver cirrhosis and liver cancer. (4) all patients were followed up for more than 2 months (months -1 years) for ALT and AST.

1.2  method   automatic biochemical analyzer was used to detect ALT and AST in the blood collection 4H the normal value of ALT was less than 40u/L and AST was less than 37u/L. Determination of serum HBVDNA by fluorescence quantitative PCR. Hepatitis B surface antigen (HBsAg), e antigen (eAg) and e antibody (eAb) were examined by ELISA.

1.3  liver   all patients platelet routine examination before liver biopsy, bleeding time, clotting time and prothrombin activity, liver biopsy underwent B type ultrasonic inspection and positioning, measurement of spleen thickness (when spleen thickness over 4.0cm for splenomegaly). Qualified under ultrasound guidance, second liver biopsy needle of disposable 18G needle production of Budd Company in the United States, liver puncture specimens length not less than 1.5cm.

1.4    liver biopsy; liver tissues were fixed with 10% formalin, paraffin embedded, sliced, stained with hematoxylin eosin staining and reticular fibers, histopathological characteristics evaluation of specimens. According to the pathological diagnosis of chronic hepatitis B (G0-G4) evaluation of inflammation grade and fibrosis stage (S0-S4).

1.5     statistics; measurement data with x + s, statistical analysis using F test, count data by using the 2 test, P < 0.05, the difference was statistically significant.

 

2 Results

2.1  liver biopsy results in 204 patients with ASC. Table 1 shows: G0, G1, and S0, S1 were up to 69.6% and 71.6%, respectively, G2 and S2 cases accounted for more than 30.4% and 28.4%.

Table 1    pathological grading and staging of ASC in 204 cases of   cases (%)

Pathological grade

Fibrosis stage

Total

S0

S1

S2

S3

S4

G0

Forty-six

Two

48 (23.52)

G1

Twenty-seven

Forty-seven

Eighteen

Two

94 (46.07)

G2

Five

Eighteen

Sixteen

Two

One

42 (20.58)

G3

One

Five

Four

Five

15 (7.35)

LG4

One

Two

Two

5 (2.45)

Total

78 (38.24)

68 (33.33)

40 (19.61)

10 (4.90)

8 (3.92)

Two hundred and four

2.2  age, ALT, AST and B ultrasonography in 204 patients with different stages of inflammation and fibrosis staging in ASC. Table 2 shows that older than 40 years of age, G2, S2 and above accounted for only 20.4% (31/152) and 16.3% (31/129). And >40 years old, G2, S2 patients accounted for 59.6% (31/52) and (37/75) (P) 30u/L ratio of S0-S4 increased gradually (each of the two groups was P40

4 (8.33)

17 (18.09)

21 (50)

6 (40)

4 (80)

8 (10.26)

30 (44.12)

25 (62.50)

8 (80)

4 (50)

ALT (u/L)

 

 

 

 

 

 

 

 

 

 

Less than or equal to 30

46 (95.83)

53 (56.38)

20 (47.62)

1 (6.67)

72 (92.31)

36 (52.94)

8 (20)

1 (10)

>30

2 (14.17)

41 (43.62)

22 (52.38)

14 (93.33)

5 (100)

6 (7.69)

32 (47.06)

32 (80)

9 (90)

8 (100)

AST (u/L)

 

 

 

 

 

 

 

 

 

 

Less than or equal to 30

46 (95.83)

61 (64.89)

15 (35.71)

2 (13.33)

74 (94.87)

42 (61.76)

11 (27.50)

4 (40)

2 (25)

>30

2 (4.17)

33 (35.11)

27 (64.29)

13 (86.67)

5 (100)

4 (5.12)

26 (38.24)

29 (72.50)

6 (60)

6 (75)

Spleen (CM)

 

 

 

 

 

 

 

 

 

 

Less than or equal to 4

47 (97.92)

66 (70.21)

18 (42.86)

4 (26.67)

1 (20)

68 (87.18)

31 (45.59)

16 (40)

4 (40)

>4.0

1 (2.08)

28 (29.79)

24 (57.14)

11 (73.33)

4 (80)

10 (12.82)

37 (54.41)

24 (60)

6 (60)

8 (100)

2.3  comparison of different grades of inflammation, fibrosis staging in patients with HBV markers detection results, table 3 shows that the negative rate of HBeAg gradually increased from G0-G4, S0-S4, G0, G1 and S0, S1, HBeAg negative, 17.02 accounted for only 4.17% and 8.97%, 13.24%, and G3, G4 and S3, S4, HBeAg negative rate was 40% 60%, 70%, and 75% (the comparison between two groups of P is one of the serious harm to human health problems, about 320 million of the world China chronic HBV infection accounted for 1/3 (3). And most patients with hepatitis B virus infection without any symptoms, liver function is normal, it is often thought that this part of the patient is in the immune tolerance period, do not need antiviral therapy, just outpatient follow-up. Resulting in some patients delayed treatment period. The author in the clinic also often encounter some liver function or ALT mild elevated HBV virus carriers, for the first time due to ascites, portal hypertension gastrointestinal bleeding or liver cancer hospital.

This study also suggested that ALT and AST normal chronic carriers of hepatitis B virus in liver tissue inflammation and fibrosis in different degree, G2 and S2 were accounted for 30.9% and 28.4% of these cases should not be excluded according to the ALT level of antiviral therapy, according to a variety of factors other than ALT, especially the liver pathological changes to consider whether antiviral.

This study shows that the age >40 ASC in patients with liver histological examination of G2 and S2 respectively accounted for 59.6% and 49.3%, and even some have been developed to the G4, S4, ASC in patients with occult development, its clinical manifestations, serum AST, ALT, evolution can not accurately represent the disease of this kind of patients, especially >40 years old patients undergoing liver histological examination, such as antiviral indication, active antiviral therapy, in order to delay the occurrence of liver cirrhosis, liver cancer.

HBV C G1896A or A1762T and G1764A core promoter mutation is the main mechanism of HBeAg negative chronic hepatitis B, but also one of the reasons for the degree of liver damage and liver cirrhosis caused by serious progress or primary liver cancer (4). Many scholars believe that the HBV front C gene mutation occurred, due to the termination codon before C promoter encoding termination, the virus can not express HBeAg, but the HBeAg non structural protein, which is not affected by mRNA virus replication, transcription still continue, the HBV replication and damage to the liver is still in. For (5). This study also found in HBeAg negative group than in HBeAg positive group, the liver histological fibrosis degree detection significantly increased, S3 and S4 accounted for 70% and 75%, confirmed that the stage of liver fibrosis and HBeAg have a certain correlation.

The results of this study also suggest that ASC in some patients with fibrosis, and with the development of the disease progress, ultrasonic quantitative examination of spleen thickness more than 4.0cm in the case of S3, S4 and fibrosis than S1, S0 were significantly increased, the difference was statistically significant.

      these results suggest that ASC patients according to the high values of age, ALT, AST in the normal range, the change of HBeAg, the size of the spleen, ultrasound as a clinical predictor of changes in condition, a strong indicator of the severity of liver disease. Because of non-invasive liver fibrosis detection index and the teaching model is still not perfect, so the pathological examination of liver in patients with ASC should be used as the main basis to judge whether hepatitis activity and antiviral treatment, the best treatment time in order to avoid premature initiation of antiretroviral treatment cost money and resistance risk or delay patient.

 

Reference

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(2)                                   Society of infectious and parasitic diseases, Liver Disease Society of Chinese Medical Association, letter J infectious disease prevention scheme for viral hepatitis in interest 2000, 13 (4) 141~150

(3)                                   Liang Xiaofeng, Chen Guosheng, Wang Xiaojun, etc., seroepidemiological study of hepatitis B in 3 years Chinese, the epidemiology magazine, 2005,26:655--658

(4)                                   Rezende RE.Fonseca BA. Ranalho LN, etal. The precore mulation is associated with severity of liver damage in Braziliam patients with chronic hepatitis B.J Chin Virol. 2005 53~59, 32;

(5)                                   He Weihua, Hu Jinhua, Wang Lin. Analysis of e antigen negative chronic hepatitis B clinical pathological correlation. The liver, 2008, 13 (1): 11 ~ 13

 

                                          published in Chinese Medical Journal 2008, 12 (in Chinese),   (in Chinese),   (in Chinese),

 

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