| Part1 Investigation of the efficacy and resistance in therapy of chronichepatitis B patients with nucleos(t)ide analogueObjective: The aim of this study was to evaluate the effectiveness and resistance in patients with chronic hepatitis B who treated with nucleos(t)ide analogue, and then provided evidence for Clinicians to determined treatment strategies.Methods: 383 chronic hepatitis B patients treated with nucleos(t)ide analogues were enrolled between 2006 and 2014 in our hospital. 121 cases treated with lamivudine, 89 cases with adefovir dipivoxil, 55 cases with telbivudine and 121 cases with entecavir. ALT, HBs Ag, HBs Ab, HBe Ag, HBe Ab HBc Ab and HBV DNA in serum were detected at baseline, 24 weeks, 48 weeks, 96 weeks and 144 weeks. We also detected HBV genotype resistance gene. Statistical analysis was performed using SPSS 13.0 statistical software, Chi-square test or Fisher’s exact test were used to compare rates. Among these four drugs, compared HBV DNA negative rate in the treatment of 24 weeks, Undetectable rate, HBV rebound at 48 weeks, 96 weeks and 144 weeks,and analysised the relationship between baseline ALT, serum HBV DNA levels, 24 weeks serum HBV DNA levels and HBe Ag status and occurrence of resistance, and definited related factors that causing NAs resistance.Results: NAs treatment response situations: The virological and serological response of lamivudine, adefovir, telbivudine and entecavir groups were different according to duration of the treatment and therapeutic agents. Twenty four weeks of treatment, HBV DNA undetectable rates were 74%, 67.4%, 74%, 94.2%, respectively. Patients treated with entecavir were significantly higher than the other three groups(Χ2=23.144, P<0.001) and the other three groups were no significant difference. During the 48 W, there was no significant difference between the four groups at the HBe Ag undetectable rate and at 96 W, 144 W. HBe Ag undetectable rate was statistically difference, Χ2=40.973, 26.132, P<0.001. Between lamivudine and telbivudine group, HBe Ag undetectable rate was no significant difference, but higher than the entecavir group at 96 W, 144W(Χ2=10.488, P=0.001; Χ2=11.481, P=0.001 and Χ2=10.488, P=0.001, Χ2=19.394, P=0.000, respectively). Between adefovir and telbivudine group, Χ2=10.051, P=0.002.NAs treatment viral rebound situation: Viral rebound rate between four drugs was statistically significant at 48 W,96W,144 W. We found no viral rebound at initial treatment with entecavir group and Only three cases in adefovir group. There was no significant difference between lamivudine(6.5%)and telbivudine(5.8%)in viral rebound rate at first year. The rate of viral rebound in lamivudine(28.5%, 42.3%) was higher than telbivudine(11.5%, 15.4%) at 96 W and144W(Χ2=8.844, P=0.003 and Χ2=18.306, P=0.000). High baseline viral load, baseline ALT levels< 5ULN, HBe Ag-positive were associated with a higher rebound rates(Χ2 was 27.142, 25.311, 15.885, respectively, all with P<0.001). Baseline ALT levels< 5ULN in telbivudine was also associated with a higher rebound rate Χ2=49.982, P=0.000.Resistance locus: Resistance genes were detected in 97 patients, lamivudine-resistant up to 74 cases(76.3%), mainly for L180 M or(and) M204I/V sites. Entecavir resistance locus occurred on the basis of lamivudine, therefore, lamivudine resistance lead to entecavir resistance, easily.Conclusion:1 High baseline viral load, baseline ALT levels< 5ULN, HBe Ag-positive, lower virologic response rate at week 24 were associated with a higher rebound rate.2 Lamivudine has the highest resistance rates, entecavir resistance locus occurred on the basis of lamivudine, lamivudine resistance lead to entecavir resistance,easily. Part 2 Investigation of etiology and clinical characteristics of 573 patients suffered from Primary liver cancerObjective: To investigate the etiology, risk factors and clinical characteristics of primary hepatic carcinoma(PLC) in Hebei province to better strategies for disease prevention, diagnosis and treatment.Methods: 573 cases of PLC, which diagnosed by serology and hepatic imaging, were enrolled from January 2005 to January 2014 in the department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China, 467 cases of male, and 104 cases of female. A retrospective study was carried out for analysis of the incidence of age, sex, etiology, family history, personal history and clinical features. Laboratory tests: Virological markers; HBs Ag, HBs Ab, HBe Ag, HBe Ab HBc Ab, anti-HCV; Liver biochemical, ALB, AST, GGT, ALKP, TBIL; Virus, HBV DNA, HCV RNA; Tumor markers,AFP. Liver Imaging: Liver ultrasound, Liver and portal system unenhanced and enhanced CT scan, Liver MRI. Statistical analysis was performed using SPSS13.0 statistical software,Χ2 test was used to compare rates. Difference among groups were compared using ANOVA. Count data(non-normal distribution) were compared using the Wilcoxon test.Results: 573 cases of PLC, 491 cases(86.9%) were advanced liver cirrhosis. The cases(rates) of HBV infection, HBV infection with alcoholic liver disease(ALD),HCV infection and alcoholic liver disease were 317(59.7%), 154(29.0%), 38(7.2%) and 22(4.1%). Respectively, 100(17.4%) and 53(9.2%) had a family history of HBV infected and PLC. Other risk factors including 30.4% had alcohol history, 15.4% had smoking history, 14% had diabetes mellitus history. The mean age of the patients was 58.7±10.8 years(range 17 to 91 years), of which 79.4% incidence were 40-69 years old, especially the patients during 50 to 69 years presented the highest ratio, 61.6%. The ratio of male to female was 4.5:1 and the average age of onset was 57.4±10.3 and 64.5±11years, P<0.001. Among HBV infection, HBV infection with ALD, HCV infection and ALD, the average age was 58.6 ± 10.6, 54.3 ± 8.4, 67.0 ± 7.8 and 58.4 ± 11.4 years, respectively, P<0.001. HBV infection with alcoholic liver disease occurred the earliest, significantly lower than the other groups. Among the PLC patients which infected with HBV, 240(72.1%) HBV DNA was positive, in which HBV DNA> 104 IU / ml accounted for 53.2%, HBs Ag, anti-HBe, and anti-HBc positive mode was 57.4%. The level of ALT, AST, AKP, GGT in HBV infection group were 45.0(7~420)U/L, 65.0(12~740)U/L, 112.0(23~791)U/L, 97.0(9~668) U/L, significantly lower than the HBV infection with ALD group 62.5(9~453)U/L, 90.5(15~812)U/L, 146.0(5.9~842)U/L, 115.0(15~289)U/L, P<0.001; lower than ALD group, excepted the levels of ALT 37.0(10~223)U/L, 85.0(16~160)U/L, 125.0(51 ~381)U/L, 157.5(18~554)U/L; P<0.001; higher than the HCV group, excepted the levels of AST 40.0(13~317)U/L, 67.0(20~240) U/L, 106.0(40~277) U/ L,68.5(21~350)U/L, P<0.001; The level of ALT,AST,AKP, GGT in HBV infection with ALD group were significantly higher than HCV infection group and ALD group(excepted GGT), P<0.001. The level of α-fetoprotein(AFP) was elevated in 394(79.1%) of the PLC patients, in which 197(39.6%) were beyond 400 μg/L.Conclusion:1 HBV infection was the main risk factor of PLC.2 Liver cirrhosis was the main pathology for PLC incidence.3 On the basis of HBV infected, alcohol promoted PLC development. Besides, family history of hepatic carcinoma, alcohol ingestion and smoking were also be involved in hepatic carcinogenesis.4 Although AFP was the marker of PLC diagnosed, the specificity and sensitivity of AFP in diagnosis of PLC ought to be investigated. |
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