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các bài tham luận tại hội nghị y khoa quốc tế
1. HỘI NGHỊ GAN MẬT HOA KỲ LẦN THỨ 53 (AASLD Boston 1 - 5/11/2002)
CLINICAL RESEARCH ON THE TREATMENT OF CHRONIC HEPATITIS B WITH THYMOSIN- a1 AND LAMIVUDINE VERSUS INTERFERON-α AND LAMIVUDINE
Dr. Pham Thi Thu Thuy
Head of Hepatology Dep. –Medical Medic Center-HCM City
Thymosin-α1 with lamivudine may be more effective than IFN-α with lamivudine .Compared with IFN-a and Lamivudine , Thymosin a1 and Lamivudine are better tolerated and seem to induce a gradual and more sustained ALT normalization and HBVDNA loss .However such results need to be confirmed with a randomized double blind study with larger number of patients in the future.
Abstract 1843- Hepatology Vol 36 N 4
2. HỘI NGHỊ TIÊU HÓA THẾ GIỚI ( WCOG) Bangkok – Thailand - 24/2 - 1/3/2002
Poster :
Dr.Pham Thi Thu Thuy
MEDIC MEDICAL CENTER
The association of diabetes mellitus with chronic liver disease, particularly cirrhosis, was recognized many years ago. Preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus .To further study the correlation of HCV infection and diabetes, we performed a retrospective analysis of 7234 patients with vial hepatitis and analyzed whether age,sex, hepatitis B virus (HBV) infection, HCV infection, and cirrhosis were independently association with diabetes. Second a case-control study was conducted to determine the seroprevalence of HCV infection in a cohort of 641 diabetic patients . Diabetes was observed in 11.51% of HCV –infected patients compared with 5.18% of HBV –infected patients .The older the age is the higher the prevalence of diabetes mellitus is . In the diabetes cohort , 36.36% were found to be infected with HCV compared with 4% of control patients. HCV serotype 2 was observed in 36.36% of HCV-RNA -positive diabetic patients vesus 10.52% of HCV-infected control . In conclusion ,the data suggest a relatively strong association between HCV infection diabetes, because diabetes have an increased frequency of HCV infection , particularly with serotype 2 .Furthermore , it is possible that HCV infection may serve as an additional risk factor for development of diabetes, beyond that , attributes chronic liver disease alone.
3. HỘI NGHỊ GAN MẬT CHÂU Á –THÁI BÌNH DƯƠNG (APASL) Bali - Indonesia- 18 - 21/8/2005
Poster 327
Prevalence of HCV genotypes in Vietnam
Thu Thuy -Tan Dat- Thanh Tong- BaoToan - Ba Tong- Oanh- Trang
MEDIC Medical Centre, HCM City, Viet Nam
Background:
HCV genotypes are distributed differently depending on geography and etiology of infection. We studied the spectrum of HCV genotypes in chronic liver Vietnamese patients. The incidence of Hepatitis C (HCV) isolates found in clinical practice is of great clinical significance to the treatment of HCV infected patients as different subtypes may respond unequally to therapy. Beside, both viral load and HCV genotype may have relevance in chronically infected
Objectives: To evaluate the prevalence of HCV genotypes in Vietnamese patients.
Comparison of serum virus loads among Patients infected with Hepatitis C Virus (HCV) genotypes 1, 2 and 6
Methods: A total of 202 HCV RNA positive patients with chronic hepatitis were enrolled (Male 59,4%, female 40,6% with mean age of patients 47,89 ± 10,87 years
) from April 2004 to Nov 2004. At the same time, we collected 149 random serums in this group to perform Branched DNA for quantitative HCVRNA.
All samples were amplified RT – PCR (In-house PCR amplification with NP & OP primer from Bayer Corporation) in the 5’ UT region. Biotinylated amplicon, generated by PCR of HCVRNA is hybridized to immobilized probes. The probes, which are bound to a nitrocellulose strip by a poly (T) tail, are specific for the 5’ UT of the different HCV genotypes (The versant HCV Genotype Assay, Bayer).
Statistical analysis: SPSS for Window 7.5 software. The data were expressed as percent, mean±SD. Chi-square test was used to analyze the discontinuous variables.
Results:
Genotypes 1 and 6 were the commonest genotypes, followed by type 2 and the rare genotype 3 in alone patient. Genotype 1 was seen in 58,9% (Type 1: 6,9%; 1a: 6,9%; 1a/1b: 0,5%; 1b: 44,6%) while genotype 6a in 25,2%, genotype 2 in 11,4% (type 2: 2%; type 2a/2c: 9,4%) and genotype 3b was 0,5%, eight samples (4%) were unclassified. Then we performed sequencing based on 5’UT with Trugene system identified genotype 1 (1 case), 1b (2 cases), 6a (5 cases) but not typed by LiPA. 149 patients had viral loads above 3200 copies/ml (Range: 4000 - > 40,000,000 copies/ml, with 5,18x106 ±
6.53x106 copies/ml.
). HCV genotype 1, 2, 6 had quantity HCV RNA above 2x106 copies/ml was 55, 10, 23 cases, and below 2x106 copies/ml was 32, 9, 20 cases, respectively. We observed no significant difference in virus load between patients infected with genotype 1, 2, 6.(P>0,05)
Conclusions:
Our study indicated that HCV genotypes 1 and 6 are common in Viet Nam. With subtype 1b is the most common. A unique genotype 3b was detected in our patients. There isn’t relationship between HCV genotype and viremia levels. The TruGene system, a direct sequencing method, is more efficient in the identification of HCV genotype.
Liver International Hepatology 2005- Abstract book
4. HỘI NGHỊ TIÊU HÓA THẾ GIỚI (WCOG) Montreal – Canada - 12 - 14/9/2005
President poster: PP7
Clinical research on the treatment of chronic hepatitis B with thymosin- a1 and lamivudine versus interferon-α and lamivudine
Pham Thi Thu Thuy - Ho Tan Dat
Medic Medical Center-HCM City
It has recently been shown that thymisin-a 1, a synthetic polypeptide of thymic origin, an immune modifier, is able to promote disease remission and inhibition of hepatitis B virus replication. We evaluated the efficacy and safety of thymosin- a1 and lamivudine treatment compared with interferon -a and lamivudine treatment on the patients with chronic hepatitis B who were difficult to be treated well, failed to lamivudine treatment alone. Eighty three patients (Age: 18-60) with confirmed chronic hepatitis B and positive for HBV DNA with an elevated ALT of at least two times normal who failed to lamivudine treatment alone were entered into this study. Eighty three patients were randomly assigned to receive either thymosin- a1 1.6mg SC twice weekly and lamivudine 100mg p.o daily or 5MU of interferon-a three times weekly and lamivudine 100mg p.o daily for 6 months. At the end of treatment, complete response (defined as ALT normalization and HBVDNA loss) occurred in 11 of 43 (25.58%) in group I and in 22 of 40( 55%) in group II (p<0.01) . After a follow up period of 6 months, a complete response was observed in 18 of 43 (41.86%) in group I and 19 of 40 (47.50%) in group II (p>0.05) . After a follow up period of 12 months, a complete response was observed in 25 of 43 (58.14 %) in group I and 12 of 40 (30%) in group II (p<0.05) . So thymosin- a1 with lamivudine may be more effective than interferon-a and lamivudine by immunomodulatory effect. Compared with interferon-a and lamivudine, thymosin- a1 and lamivudine are better tolerated and seem to induce a gradual and more sustained ALT normalization and HBVDNA loss. Unlike interferon-a , thymosin- a1 was well tolerated by all patients. The side effect of thymosin- a1 group was rare .The better response was in HbeAg-negative and HBVDNA- positive patients. However such results need to be confirmed with a randomized double blind study with larger number of patients in the future.
5. HỘI NGHỊ GAN MẬT THẾ GIỚI Cairo- Ai Cập – 7—11/9/2006
Poster 114
Applying Sequencing To Identify Hepatitis B Virus Genotypes And Mutations
Ho Tan Dat, Pham Thi Thu Thuy,
Nguyen Bao Toan, Nguyen Thanh Tong
MEDIC Medical Center –Ho Chi Minh City-VietNam
Hepatitis B Virus (HBV) can be classified into 8 genotypes A through H based on an intergroup divergence of 8% or more in the complete nucleotide sequence, and the different distribution of various genotypes in different continents, countries. The identification of HBV genotypes are more concerned as it is HBV genotypes relating to clinical manifestation, activity of liver disease as well as treatment responses of Hepatitis B. Additionally, the discovery of resistance to medicines in HBV treatment plays a very important role from which we can have an appropriate and effective choice in Hepatitis B treatment. We have applied the Sequencing by TruGene (Bayer) to identify Hepatitis B Virus Genotypes and Mutations. From August 2004 to November 2005, in MEDIC laboratory, we have implemented sequencing for 69 cases Vietnamese with Chronic Hepatitis B on Lamivudine treatment in which: 55 cases are males (take 79.7%) and 14 cases are females (take 20.3%), medium age: 34.6±10.3. All cases are HBVDNA (+) in which: 50 cases are HbeAg (+) (72.5%) and 19 cases are HbeAg(-) (27.5%). There are only two genotypes of HBV: genotype B and genotype C, in which 45 cases are genotypes B (65.2%) and 24 cases are genotype C (34.8%).
Totally there are 41 cases (59.4%) mutations with following established proportion and types: L180M (5.8%); L180M & M204I (8.7%); L180M & M204V (30.4%); L180M, M204V & V207I (1.4%); M204I (8.7%); M204I&V207I (1.4%); M204V (2.9%).
There are 25 cases mutations in 45 cases of genotypes B (55.6%) and 16 cases in 24 cases of genotypes C (66.7%). All patients are on Lamivudine treatment with average time is 2.4±0.9 years, the corresponding number of patients in treatment period of 1,2,3,4 year are 10, 29, 21, 9. The proportion of developing mutations after 1, 2, 3, 4 years of treatment with Lamivudine is 20%; 55.2%; 76.2%; 77.8%.
We have found that – with above preliminary results – the sequencing plays a very important role in identifying Hepatitis B Virus Genotypes and Mutations. From those results we can approach an optimal treatment course.
Liver International Vol 26-Supp 1
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6. HỘI NGHỊ GAN MẬT CHÂU Á- THÁI BÌNH DƯƠNG (APASL) Kyoto - Japan - 26 - 30/3/2007
Poster 0411: được giải Best Poster
COMPARISON BETWEEN THE TWO PEGINTERFERONS ALFA IN THE TREATMENT OF CHRONIC HEPATITIS C
Dr.Pham Thi Thu Thuy
Dr.Ho Tan Dat
Medic Medical Center-HCM City
In order to have the evaluation of efficacy, safety and to detect the predictors for sustained viral response of two Peginterferons, we have implemented a matched pair study on treatment naïve chronic hepatitis C patients treated with weight –based Peginterferon alfa -2b or fixed dose Peginterferon alfa- 2a plus Ribavirin.
There are 211 naïve chronic hepatitis C patients aged from 18 to 68, divided into two equal groups in clinical manifestations. Group I ( N=116; 67 genotype 1, 15 genotype 2, 34 genotype 6) were treated with Peg-IFN alfa-2b, 1.5mcg/kg qweek plus Ribavirin 15mg/kg/day; Group II ( N=95; 56 genotype 1, 11 genotype 2, 28 genotype 6) were treated with peg-IFN alfa-2a 180mcg/week plus Ribavirin 15mg/kg/ day. The time of treatment was 48 weeks. Sustained viral response was undetectable HCVRNA after 24 weeks of follow-up. The treatment outcome can be predicted by analyzing various data on age, sex, weight, serum ALT, genotype and virus load. The sustained viral response rate of Group I was not different from of GroupII on total patients ( 62.06% vs. 61.05%, p>0.05) . The relapse in two groups were also similar (19.10% vs. 19.44%, p>0.05). The sustained viral response with treatment of Peg-IFN alfa-2b was better than with Peg-IFN alfa- 2a in group of high-weighed patients ( 28.57% vs. 61.9%, p<0.01). Baseline ALT, age, sex, genotype, virus load were not statistically significant predictors of sustained viral response between two Peginterferons .
In conclusion, the sustained viral response rate is similar in naïve chronic hepatitis C patients treated with Peg-IFN alfa-2a or Peg-IFN alfa-2b.Peg-IFN alfa-2b seems to be better in high-weighed patients. Side effect of thrombocytopenia more frequently occurs in treatment with Peg-IFN alfa-2a, however it should be further studied in future.
International Hepatology 2007-Vol1-N1
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7. HỘI NGHỊ GAN MẬT HOA KỲ LẦN THỨ 58 (AASLD) Boston 2 - 6/11/2007
Poster 332
COMPARISON BETWEEN THE TWO PEGINTERFERONS ALFA IN THE TREATMENT OF CHRONIC HEPATITIS C
Dr.Pham Thi Thu Thuy
Dr.Ho Tan Dat
Medic Medical Center-HCM City
Abstract 332, Hepatology Vol 46, N 4
8. HỘI NGHỊ GAN MẬT CHÂU Á –THÁI BÌNH DƯƠNG (APASL) Hongkong 13 - 17/2/2009
Presentation: FP 053
PEGYLATED INTERFERON ALFA-2a PLUS RIBAVIRIN IN CHRONIC HEPATITIS C PATIENTS WITH GENOTYPE 6
DR. Pham Thi Thu Thuy
DR. Ho Tan Dat
Medic Medical Center- HCM City-VN
Aims: The effectiveness of the combined treatment Peginterferon alfa -2a and ribavirin in Hepatitis C were intensively studied, but mainly for genotype 1. Little information was known about the treatment of genotype 6 which occurred at high frequency in several Asian countries, including China, Viet Nam, Hongkong and Thailand etc. The aims of the study therefore are to evaluate the effectiveness, safety and other influential factors at the therapeutic regime of Peginterferon alfa -2a combined with Ribavirin for chronic hepatitis C patients with genotype 6 in Vietnam.
Patients and methods: 75 chronic hepatitis C patients with genotype 6 were classified into two groups. Group I included 42 naïve patients, group II included 33 patients who had previously failed with standard Interferon –alfa. All the patients were treated with Peginterferon alfa-2a 180mcg/w combined with Ribavirin 15mg/kg/day; the period of treatment time was 48 weeks. Sustained viral response was defined as undetectable HCVRNA after 24 weeks of follow-up. Ages, sexes, increase of ALT, AST/ALT ratio and viral load were the factors for evaluating the effectiveness of the treatment and the prognosis.
Results: Sustained virus responses were nearly the same between the two groups (Group I: 69.04%; Group II: 60.60%; p>0.05). Normal transaminase levels at week 72 were 73.80%, 63.63% in group I and group II, respectively. It was found that younger patients , AST/ALT ratio lower than 1 were the factors that could induce a higher sustained viral response in every group. Viral load only affected to sustained viral response in patients were previous treatment failed . Patients who had rapid viral responses, almost all had sustained viral responses.
Conclusion: Patients with chronic hepatitis C genotype 6 who have never been treated or have failed with standard interferon showed good responses when treated by Peginterferon alfa-2a combined with Ribavirin . The sustained viral response was better than that of genotype 1. Patients especially had rapid viral responses; almost all had sustained viral responses. So will the treatment time be shorten for these patients? We will need further studies in future.
International Hepatology- 2009- Vol 3-N 1
Poster E058
ENTECAVIR FOR TREATMENT OF LAMIVUDINE –REFRACTORY PATIENTS CHRONIC HEPATITIS B
Dr.PHAM THI THU THUY
Dr.HO TAN DAT
MEDIC MEDICAL CENTER-HCM CITY
Lamivudine treatment is associated with frequent development of resistant hepatitis B virus. This incidence especially is higher in the longer time of treatment and loss of treatment benefit. Entercavir is a new antiviral agent shown its high efficacy even in cases of mutations with Lamivudine resistance. In this study, we would like to evaluate the efficacy, the safety of Entercavir in treatment of Lamivudine-refractory patients chronic hepatitis B. To analyze factors that influent to the efficacy of treatment.
Sixty chronic hepatitis B patients with evidence of Lamivudine resistance were randomly divided into two groups in proportion of 3:1. Group I (n=45) used Entecavir 1mg/day, group II (n=15) used Lamivudine 100mg/day. Treatment time was 48 weeks. All data were evaluated in the end of the treatment: histology, ALT, HBVDNA. The factors such as: age, sex, ALT, HBVDNA, genotype, HBeAg were analyzed to evaluate their influences to the treatment.
The results have showed HBVDNA<2000 copies/mL in Entecavir group 37.78% vs. 0% Lamivudine group (p<0.01). HBVDNA negative in Entecavir group was 17.77% and incidence of seroconversion of HBeAg was 8.82%. ALT was normal in Entecavir group 77.77% vs. 26.66% in Lamivudine group (p<0.001).Histologic improvement in Entecavir group was 37.77% vs.6.66% in Lamivudine group (p<0.05). Patients with HBeAg negative, genotype B, low virus load were shown better results.
Entecavir was shown to be efficacious in the treatment for chronic hepatitis B patients experienced with Lamivudine resistance. Entercavir is safe, with almost no side effects. Factors such as HBeAg negative, genotype B, low virus load seems to be better in response to the treatment. The recurrence or mutation of Entecavir resistance should be studied further in future.
International Hepatology- 2009- Vol 3-N 1
9. HỘI NGHỊ TIÊU HÓA HOA KY (DDW) Chicago 29/5 - 5/6/2009
Poster M 1795
PEGYLATED INTERFERON ALFA-2a PLUS RIBAVIRIN IN CHRONIC HEPATITIS C PATIENTS WITH GENOTYPE 6
DR. Pham Thi Thu Thuy
DR. Ho Tan Dat
Medic Medical Center- HCM City-VN
10. HỘI NGHỊ TIÊU HÓA THẾ GIỚI (WCOG) London 21 - 28/11/2009
Poster 1978
PEG-INTERFERON ALFA-2a AND RIBAVIRIN IN PATIENTS WITH CHRONIC HEPATITIS C WHO HAVE FAILED PRIOR TREATMENT
Dr.Pham Thi Thu Thuy
Dr.Ho Tan Dat
Medic Medical Center
Summary:
Aims: Chronic hepatitis C patients who were treated with Interferon alfa afterward having a failure of therapy or relapse are not very few. So, a question that if these cases could be retreated with Peginterferon-alfa? The aims of the study are to evaluate the effectiveness, safety and other influenced factors to the therapeutic regime of Peginterferon alfa-2a combined with Ribavirin.
Patients and Methods: 117 chronic hepatitis C patients were classified into two groups. Group I consisted of 63 patients who were previously failed with interferon –alfa, of those including HCV genotype 1 (n=41), genotype 2 (n=7) and genotype 6 (n=15). Group II included 54 patients who had a relapse after stopping treatment, involving HCV genotype 1 (n=40), genotype 2 (n=5) and genotype 6 (n=9). All the patients were retreated with Peginterferon alfa-2a 180mcg/week combined with Ribavirin 15mg/kg/day, period of treatment time were 48 weeks. Sustained viral response was defined as undetectable HCVRNA after 24 weeks of follow-up. Ages, sex, AST/ALT ratio, HCV genotype, viral load, previously treated with interferon alone or combined with Ribavirin were the factors for evaluating the effectiveness of treatment and prognosis.
Results: The results were found that: Sustained viral response was significantly higher in the relapsed group than that in the non-respond group (44.44 % vs. 26.98 %, p<0.05), in particular in patients with genotype 1. The rate of relapse in non-respond group was also higher than that in the relapsed group. We found that younger patients, without HCV genotype 1, AST/ALT ratio lower than 1, previously treated with interferon alone were the factors that could induce a higher sustained viral response in every group. Viral load only affected to sustained viral response in non-respond group. Dose reduction of Peginterferon or Ribavirin do not cause any influences on sustained viral response.
Conclusions: In chronic hepatitis C patients with difficulties of treatment, non-response or relapsed with previous therapy of interferon alfa still being able to gain a sustained viral response when retreated with Peginterferon alfa-2a plus Ribavirin. Relapsed patients or previously treated with interferon alone could have a successful potential of retreatment. Dose reduction of Peginterferon or Ribavirin does not cause any influences on sustained viral response.
An International of journal of Gastroenterology and Hepatology – November 2009- Vol 58- Supp II
11. HỘI NGHỊ GAN MẬT CHÂU Á-THÁI BÌNH DƯƠNG
BẮC KINH –TRUNG QUỐC- 24/3-----28/03/2010
Preaentation : FP 100
AN OPTIMAL DURATION OF TREATMENT FOR CHRONIC HEPATITIS C GENOTYPE 1 PATIENTS
Dr. Pham Thi Thu Thuy
Dr. Ho Tan Dat
Medic Medical Center-HCM City
Summary:
Aims: Combination of peginterferon with ribavirin in treatment for chronic hepatitis C genotype 1 in 48 weeks was shown to have rather high relapse rate. There are different opinions on treatment course, it’s considered that longer treatment course being better outcomes. The aims of the study therefore are to compare the effectiveness between the standard course of treatment (48 weeks) and prolong course (72 weeks). We will consider which factors leading to predict the sustained virologic response.
Patients and methods: 108 hepatitis C patients with genotype 1 were classified into two groups. Group I included 63 patients who received 48 weeks of treatment. Group II included 45 patients received 72 weeks of treatment. All the patients were treated with Peginterferon alfa-2a 180mcg/week combined with Ribavirin 15 mcg/kg/day. Ages, sex, increase of ALT, rate of rapid virological response, viral load were the factors for evaluating the effectiveness of the treatment and the prognosis.
Results: sustained virological response in group II were higher than in Group I (84.44% vs. 55.55%, p<0.01). Patients in group II who became negative for HCVRNA between weeks 12 and 24 had significantly higher SVR rate than that of group I (54.54% vs. 6.66%, p<0.001). Factors associated with an SVR include younger age, an AST/ALT ratio lower than 1, FibroScan from F1 to F3 and lower viral load in group I. In group II, oly age impact on SVR. SVR rates were highest in those patients which achieved an RVR.
Conclusion: Patients with chronic hepatitis C genotype 1 who were treated by peginterferon alfa combined with Ribavirin in 72 weeks extended treatment shown higher sustained viral response than those in 48 weeks. RVR was a very strong predictor of SVR. The patients with late viral negativity for HCVRNA should be treated for 72 weeks. No serious adverse events or withdrawals for safety reasons were seen in both treatment regimens.
Hepatology International 2010 –Vol 40 –N1-FP 100
