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Reduction of liver stiffness by antiviral therapy
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Reduction of liver stiffness by antiviral therapy

Backgroud and Aim: Liver stiffness (LS) measured by FibroScan has been reported to correlate with fibrosis stage in various liver diseases. In chronic hepatitis C, IFN treatment has been reported to reduce LS. In the present study, the correlation between LS and fibrosis stage and the reduction of LS by antiviral therapy were examined in the patients with chronic hepatitis B.

Methods: LS were measured in 270 HBV infected patients by FibroScan. In 43 patients, liver biopsies were done. In 35 patients treated with nucleotide or nucleoside analogs and 52 patients without antiviral therapy, the changes of LS were assessed.

Results: LS was 5.1 ± 1.7 kPa in F0-1 (n=3), 8.6 ± 3.2 kPa in F2 (n=15), 10.6 ± 4.6 kPa in F3 (n=13) and 18.3 ± 5.9 kPa in F4 (n=12).

LS was significantly higher in F4 than in F0-1, F2 and F3 (p<0.005). LS was significantly correlated with fibrosis stage (r=0.666, p or = 2, 10.7 kPa for F > or =3 and 16.0 kPa for F4. In the patients with antiviral therapy, LS was 13.9 ± 7.8 kPa at the 1st measurement and significantly reduced to be 7.9 ± 5.1 kPa at the latest measurement (p<0.0001). 2-point or greater reduction of deduced stage by antiviral therapy was observed in 10 of 18 patients in whom LS at the 1st measurement was 10.7 kPa or higher and fibrosis stages were deduced as F3-4. The longer periods between the two measurements were associated with a 2-point or greater decrease of deduced fibrosis stage in tendency (p=0.0914). In the patients without antiviral therapy, LS was 6.7 ± 3.7 kPa at the 1st measurement and increased to be 7.9 ± 4.4 kPa at the latest measurement (p=0.0682). A 1-point or greater increase of deduced stage was observed in 11 of 50 patients without antiviral therapy in whom LS at the 1st measurement was less than 16.0 kPa and fibrosis stages were deduced as F0-3. The higher AST levels (p=0.0592), the higher hyaluronic acid levels (p=0.0893) and the lower albumin levels (p=0.0092) were associated with a 1-point or greater increase of deduced fibrosis stage.

Conclusions: LS was significantly correlated with fibrosis stage in the patients with chronic hepatitis B, and was suggested to be useful to assess liver fibrosis stage noninvasively. Significant reduction of LS was observed in the patients treated with antiviral therapy and can be attributed to the regression of fibrosis. Increase of LS of the patients without antiviral therapy was observed and can indicate the progression of fibrosis.
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cirrhosis regression after 1 year of antivral therapy

Background and Aims: Recent studies suggest that fibrosis/cirrhosis may regress following successful treatment for chronic hepatitis B (CHB) with nucleoside analogs (NA). In this study, transient elastography was used to estimate fibrosis regression among CHB patients in treatment with NA.

Methods: Patients with CHB, followed at twelve hepatitis centers in Scandinavia, were offered participation in the study. Inclusion criteria were a liver biopsy showing severe fibrosis (F3 in the Metavir classification)/cirrhosis or decompensated cirrhosis, followed by a treatment with NA for at least one year.

Patients were examined with transient elastography for assessment of fibrosis/cirrhosis. Conversion from liver stiffness measurement (LSM) to the Metavir classification was performed with cut-off values 7.2 kPa for F2, 8.1 kPa for F3 and 11.0 kPa for F4 as suggested by Marcellin et al. (Liver Int. 2009 Feb:29:242-7).

Results: Seventy-one patients were included and of these a valid LSM (10 valid measurements, success rate >60%, IQR < 25%) could be obtained in 62 (87.3%) patients. Median age was 50 years (IQR 40; 48), 46 (74%) of the patients were males, and median BMI was 25.2 (23.2; 27.7) kg/m2. Median follow-up time since start of NA treatment was 50 (29; 79) months. Prior to treatment, 26 patients (42%) were HBeAg positive. At the time of examination, 10 (39%) of these patients had seroconverted to HBeAg negative. 58 (94%) patients had undetectable HBV-DNA after treatment with NA. LSM results are shown in Table.

Among 49 patients with cirrhosis prior to NA treatment, 47% had a LSM less than 11 kPa after treatment with nucleoside analogs indicating regression of cirrhosis. For patients with severe fibrosis before treatment, 77% had an LSM indicating regression.

Conclusion: Liver stiffness measurements with transient elastography suggest that 53% of patients with CHB and severe fibrosis or cirrhosis will experience regression of fibrosis after treatment with nucleoside analogs. Although conversion from LSM to Metavir fibrosis stage is considered a methodological limitation of the study, our findings indicate a favourable effect of NA treatment by regression of liver fibrosis.

Table: LSM after treatment for CHB with NA for at least one year in patients with cirrhosis or severe fibrosis prior to treatment.
Before Treatment After Treatment No of Patients
11 kPa
Cirrhosis 17 (35%) 0 (0%) 6 (12%) 26 (53%) 49
Severe Fibrosis 7 (54%) 3 (23%) 3 (23%) 0 (0%) 13
Total 24 (39% 3 (5%) 9 (15%) 26 (42%) 62
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