Biomedical subjects

Ryuzo Ueda

Publications and source records attributed to Ryuzo Ueda.

At least 37 records · Page 2Linked to original sources

PubMed2005

Differences of hepatocellular carcinoma patients with hepatitis B virus genotypes of Ba, Bj or C in Japan.

Hepatitis B virus (HBV) genotypes B (HBV/B) and C (HBV/C) are prevalent in Asia. Recently HBV/B has been classified into two subtypes, HBV/Ba which is ubiquitously found in Asia, and HBV/Bj which is specific in Japan. In addition, the frequency of positive HBeAg has been reported to be higher in patients with HBV/Ba than those with HBV/Bj. However, little is known about the differences between patients with various genotypes who developed hepatocellular carcinoma (HCC). In 296 serum samples of HCC patients collected from all over Japan, HBV genotypes were determined with the restriction fragment length polymorphism. HBV/A was detected in 1.0%, HBV/Ba in 4.4%, HBV/Bj in 7.4%, and HBV/C in 86.5%. In the Tohoku district and Okinawa, HBV/Ba, HBV/Bj and HBV/C were found in 6.7, 40.0 and 48.9%, compared to 4.0, 1.6 and 93.2% in the other districts in Japan. HBV/Bj patients were more frequently found in the group older than 65 years while HBV/Ba patients were found in all age groups. The frequency of positive HBeAg in HBV/Bj patients was significantly low compared to that in the other patients. More than 60% of the patients with HCC had cirrhosis as the underlying liver diseases. However, in HBV/Ba patients aged 50 years or younger, 80% of them had chronic hepatitis, while 87.5% of those aged older than 50 years had cirrhosis. These data suggest that great differences exist among patients with HCC infected with different genotypes.

Adult↗

PubMed2005

Detection of API2-MALT1 fusion transcripts in cytologic specimens of patients with pulmonary mucosa-associated lymphoid tissue lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma constitutes up to 90% of primary pulmonary lymphomas, but its diagnosis is often difficult. API2-MALT1 fusion is specific to MALT lymphoma and is detected in nearly half of the pulmonary cases. Cytologic examinations have played a pivotal role in the diagnosis of pulmonary tumors; however, cytologic specimens have only infrequently been used for molecular studies. In this study, we performed a multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay to detect the API2-MALT1 fusion transcript in archival cytologic specimens used as RNA sources. We studied 3 pulmonary MALT lymphoma cases that were positive for the fusion gene as detected with RNA extracted from diagnostic histologic specimens. In 1 case, a conventional PCR clonality assay for the immunoglobulin heavy chain gene rearrangement failed to detect the monoclonality. In all 3 cases, the fusion transcript was successfully detected in the cytologic specimens of sputum, bronchoalveolar lavage fluid, bone marrow smears, and pleural effusions. This finding suggests that such specimens can be used as RNA sources in multiplex RT-PCR assays for the API2-MALT1 fusion transcript. The detection of API2-MALT1 fusion as carried out with these specimens would be useful as an ancillary assay for the diagnosis, staging, and follow-up of pulmonary MALT lymphoma.

Aged↗

PubMed2005

Spontaneous hepatic rupture due to metastatic tumor of lung adenocarcinoma.

A 64-year-old man diagnosed as lung adenocarcinoma with hepatic tumor was admitted to our hospital. He carried the hepatitis B virus but was negative for PIVKA-II and alpha-fetoprotein, and hence we diagnosed a case of stage IV lung adenocarcinoma. We planned to administer systemic chemotherapy, but he experienced sudden-onset abdominal discomfort accompanied with decreased blood pressure. We diagnosed hemorrhagic ascites due to spontaneous rupture of the liver tumor. Emergency angiography and therapeutic embolization stabilized his clinical condition. Hemorrhagic ascites due to metastatic liver tumor is rare and the sudden onset of abdominal symptoms is an indicator of rupture.

Adenocarcinoma↗

PubMed2005

Cryptogenic organizing pneumonia after radiotherapy for breast cancer.

We report a case of lasting fever and cough with pulmonary infiltrates progressing 4 months after adjuvant radiotherapy following surgery for breast cancer. Chest radiography and computed tomography demonstrated alveolar opacities outside the irradiated pulmonary area. Laboratory data revealed neutrophilia and increased levels of C-reactive protein. Bronchoalveolar lavage fluid displayed increased lymphocyte counts, and transbronchial lung biopsy revealed histological patterns compatible with cryptogenic organizing pneumonia (COP). Corticosteroid therapy resulted in marked clinical improvement. From the histological and clinical findings, this case was judged to be a case of COP induced after radiotherapy for breast cancer, similar to those reported recently.

Adrenal Cortex Hormones↗

PubMed2005

[A case of thymic carcinoma responding to combination chemotherapy with nedaplatin, etoposide, and ifosfamide].

We described a case of thymic carcinoma that responded remarkably to combined chemotherapy with etoposide (ETP), ifosfamide (IFO) and nedaplatin. A 68-year-old woman was admitted to our hospital because of hoarseness and dysphasia. Chest computed tomographic (CT) scans showed an anterior mediastinal tumor. Using CT-guided needle biopsy, the diagnosis was squamous cell type of thymic carcinoma. We gave her modified VIP therapy with ETP, IFO and nedaplatin. The tumor contraction response was evident after 3 courses of treatment. This case suggested that nedaplatin may be one of the promising agents for thymic carcinoma chemotherapy.

Aged↗

PubMed2005

Global real-time quantification/reverse transcription-polymerase chain reaction for detecting proto-oncogenes associated with 14q32 chromosomal translocation in multiple myeloma.

A global real-time quantitative/reverse transcription-polymerase chain reaction technique for detecting the expression of six 14q32 chromosomal translocation-associated proto-oncogenes in marrow plasma cells was established and applied to myeloma specimens. This technique is an alternative method of detecting 14q32 rearrangements and allows investigation of the relationship between proto-oncogene expression and clinical features.

Chromosomes, Human, Pair 14↗

PubMed2005

Cytotoxic T-lymphocyte antigen 4 gene polymorphisms in sarcoidosis patients.

BACKGROUND AND AIM: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a co-stimulatory molecule that is expressed on activated T-cells, and is an important regulator of T-cell activation in T-cell-dependent immune responses. CTLA-4 signals lead to the downregulation of T-cell proliferation and activation. Sarcoidosis is a systemic granulomatous disorder of unknown etiology, which shows abnormal regulation of T cell activation. Polymorphisms of CTLA-4 have been reported to alter CTLA-4 expression, and are associated with many diseases. In the present study we investigated CTLA-4 polymorphisms of promoter -318(C/T) and exon 1 +49(A/G) in sarcoidosis patients and control subjects to determine whether these genetic variations affect sarcoidosis. METHODS: One hundred and six sarcoidosis patients and 100 healthy control subjects were studied. The polymerase chain reaction technique and direct genomic sequencing were used to determine the genotypes of promoter -318(C/T) and exon 1 +49(A/G) in the CTLA-4 gene. RESULTS: We found no difference in the distribution of either genotype between the healthy control subjects and sarcoidosis patients. Among the sarcoidosis patients, the -318(C/T) CC genotype (p = 0.011) and AG or GG genotype at position +49(A/G) (p = 0.004) were increased with ocular involvement compared with those patients without ocular involvement. Furthermore, the +49(A/G) GG genotype was increased in patients with three or more organs affected compared with patients with fewer organs affected (p = 0.019). CONCLUSIONS: The CTLA-4 polymorphisms are not associated with disease susceptibility of sarcoidosis, but these genetic variations significantly influence phenotypes of sarcoidosis.

Abatacept↗

PubMed2005

Diffuse large B-cell lymphoma with extra Bcl-2 gene signals detected by FISH analysis is associated with a "non-germinal center phenotype".

Amplification and translocation of the Bcl-2 gene has been detected in a certain subset of diffuse large B-cell lymphomas (DLBCL). The correlations among Bcl-2 protein expression, gene translocation or amplification, and the molecular signature determined by cDNA array are poorly understood. This study examined 25 cases with de novo nodal DLBCL. Interphase fluorescence in situ hybridization (FISH) analysis was performed to evaluate the Bcl-2 gene using IGH/BCL2 and CEP18 centromere probes (Vysis). When extra Bcl-2 gene signals were observed in each tumor cell and when these signals were in proportion to the extra CEP18 probe signals, we regarded the findings as indicating the presence of an additional chromosome 18; when extra Bcl-2 signals were observed but additional CEP18 signals were not, we regarded the findings as indicating the presence of gene amplification. A panel of 3 antigens (CD10, Bcl-6, and MUM-1) was applied to categorize each case as either a "germinal center B-cell (GCB) phenotype" or a "non-GCB phenotype." Of the 25 cases examined, 8 cases (32%) were classified as "GCB phenotype" and 17 cases (68%) were classified as "non-GCB phenotype." A FISH analysis revealed that t(14;18) was detected in 2 of the 8 cases (25%) with the "GCB phenotype" but in none of the 17 "non-GCB phenotype" cases. Extra Bcl-2 gene signals were detected in 7 of the 25 (28%) cases examined: n = 5 for an additional chromosome 18, n = 1 for gene amplification, and n = 1 for additional chromosome 18 + gene amplification. Extra Bcl-2 gene signals were exclusively detected in DLBCL with the "non-GCB phenotype"; these cases, with the exception of one, stained strongly positive for Bcl-2. The DLBCLs with Bcl-2 protein overexpression were classified into at least two heterogeneous molecular groups, based on the results of the FISH analysis.

Adult↗

PubMed2004

Efficacy of docetaxel as a second-line chemotherapy for thymic carcinoma.

Thymic carcinoma is a rare and aggressive tumor, and the efficacy of second-line chemotherapy is still unclear. Here, we reported a case of thymic carcinoma that responded well to the administration of docetaxel alone as a second-line chemotherapy. A 64-year-old woman was diagnosed with thymic carcinoma (squamous cell type) with bone metastasis, and she, therefore, received nedaplatin combined with etoposide and ifosfamide. She responded partially, after which she received irradiation for bone metastasis. Two months after chemotherapy, the thymic carcinoma exhibited gradual regrowth and she experienced shoulder pain. We treated this with docetaxel alone (60 mg/m2 every 4 weeks). After three courses of docetaxel, we observed a partial response and her shoulder pain disappeared. This case demonstrated that docetaxel is effective as a second-line chemotherapy for thymic carcinoma.

Antineoplastic Agents, Phytogenic↗

PubMed2004

The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-Cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with dismal prognosis, and no optimal therapy has been developed. We tested the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, KM2760, to develop a novel immunotherapy for this refractory tumor. In the presence of peripheral blood mononuclear cells (PBMCs) from healthy adult donors, KM2760 induced CCR4-specific antibody-dependent cellular cytotoxicity (ADCC) against CCR4-positive ATLL cell lines and primary tumor cells obtained from ATLL patients. We next examined the KM2760-induced ADCC against primary ATLL cells in an autologous setting. Antibody-dependent cellular cytotoxicity mediated by autologous effector cells was generally lower than that mediated by allogeneic control effector cells. However, a robust ADCC activity was induced in some cases, which was comparable with that mediated by allogeneic effector cells. It suggests that the ATLL patients' PBMCs retain substantial ADCC-effector function, although the optimal conditions for maximal effect have not yet been determined. In addition, we also found a high expression of FoxP3 mRNA and protein, a hallmark of regulatory T cells, in ATLL cells, indicating the possibility that ATLL cells originated from regulatory T cells. KM2760 reduced FoxP3 mRNA expression in normal PBMCs along with CCR4 mRNA by lysis of CCR4+ T cells in vitro. Our data suggest not only that the CCR4 molecule could be a suitable target for the novel antibody-based therapy for patients with ATLL but also that KM2760 may induce effective tumor immunity by reducing the number of regulatory T cells.

Antibodies, Monoclonal↗

PubMed2004

Distribution of CXCR3- or CCR4-positive cells in interstitial pneumonia associated with primary Sjogren's syndrome.

Patients with primary Sjogren's syndrome (SS) occasionally develop interstitial pneumonia (SS-IP), the prognosis of which is less grave compared with that of idiopathic pulmonary fibrosis (IPF). We examined distribution of helper T-cell subsets in open lung biopsy specimens from seven patients with SS-IP and, for comparison, ten patients with IPF. The expression of CXCR3 and CCR4, chemokine receptors associated in vitro with Th1 and Th2 cells, respectively, was analyzed in the mononuclear infiltrate using immunohistochemistry. The expression of CD4, CD8, and CD20 in the infiltrate was similarly examined. The positive cells were semiquantified in fibrosing areas and lymphoid clusters of both SS-IP and IPF. In fibrosing areas, CXCR3-positive cells were dominant over CCR4-positive cells in all cases of SS-IP, whereas the two types of cells showed no such difference in cases of IPF. Each of the CXCR3/CD4 and CXCR3/CCR4 ratios was significantly higher in SS-IP than in IPF ( P<0.05 and P<0.05, respectively). The CCR4/CD4 ratio showed a significantly lower value in SS-IP than in IPF ( P<0.05). In lymphoid clusters, prominent in SS-IP and few and small in IPF, CXCR3-positive cells predominated over CCR4-positive cells in both lung lesions. There was no significant difference of CXCR3/CCR4 ratio in lymphoid clusters between SS-IP and IPF ( P=0.33). These findings in SS-IP are in accordance with those reported in previous studies of the salivary glands of SS patients, where most of the infiltrating lymphocytes expressed CXCR3, and the expression of interferon-gamma was upregulated. In contrast, the Th2 cell dominance was reported in IPF in the previous studies. The present findings suggest that the pathogenesis of interstitial pneumonia is different between SS-IP and IPF in regard to the roles of helper T-cell subsets.

Aged↗

PubMed2004

CXC chemokine receptor 3 and CC chemokine receptor 4 expression in T-cell and NK-cell lymphomas with special reference to clinicopathological significance for peripheral T-cell lymphoma, unspecified.

We recently reported expression of the chemokine receptors CXC chemokine receptor 3 (CXCR3) and CC chemokine receptor 4 (CCR4) in adult T-cell leukemia/lymphoma and showed a preferential expression of CCR4 and its association with an unfavorable outcome. In the present study, we extend our adult T-cell leukemia/lymphoma study to other subtypes of T- and NK-cell lymphoma, to clarify whether a characteristic chemokine receptor expression pattern is obtained for each of the subtypes defined by the WHO classification. CXCR3 and CCR4 were rarely expressed in three well-defined subtypes, precursor T-lymphoblastic lymphoma, anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, and extranodal NK/T-cell lymphoma. A CXCR3-dominant expression pattern was observed in angioimmunoblastic T-cell lymphoma, while a CCR4-dominant expression pattern was observed in mycosis fungoides in transformation and in anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. CXCR3 and CCR4 were heterogeneously expressed in peripheral T-cell lymphomas, unspecified (PTCLU). We next focused on PTCLU and analyzed the clinical significance of the chemokine receptors and their association with FoxP3, a hallmark of immunoregulatory T (Treg) cells. Multivariate analysis showed that CCR4 expression was an independent and significant unfavorable prognostic factor (P < 0.001). A significant correlation was found between mRNA expression of CCR4 and FoxP3, suggesting a possible association of CCR4-positive tumors with Treg cells and thereby with an immunocompromised state. Chemokine receptors may be useful not only for further characterization of the T- and NK-cell lymphomas but also in predicting clinical outcomes for patients. We suggest that a specific therapy targeting the CCR4 molecule may be developed as an alternative treatment for patients with CCR4-positive tumors.

Adolescent↗

PubMed2004

Genotype and phylogenetic characterization of hepatitis B virus among multi-ethnic cohort in Hawaii.

AIM: Hepatitis B virus (HBV) genomes in carriers from Hawaii have not been evaluated previously. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Hawaii. METHODS: Genotyping of HBV among 61 multi-ethnic carriers in Hawaii was performed by genetic methods. Three complete genomes and 61 core promoter/precore regions of HBV were sequenced directly. RESULTS: HBV genotype distribution among the 61 carriers was 23.0% for genotype A, 14.7% for genotype B and 62.3% for genotype C. Genotypes A, B and C were obtained from the carriers whose ethnicities were Filipino and Caucasian, Southeast Asian, and various Asian and Micronesian, respectively. All cases of genotype B were composed of recombinant strains with genotype C in the precore plus core region named genotype Ba. HBeAg was detected more frequently in genotype C than in genotype B (68.4% vs 33.3%, P<0.05) and basal core promoter (BCP) mutation (T1762/A1764) was more frequently found in genotype C than in genotype B. Twelve of the 38 genotype C strains possessed C at nucleotide (nt) position 1858 (C-1858). However there was no significant difference in clinical characteristics between C-1858 and T-1858 variants. Based on complete genome sequences, phylogenetic analysis revealed one patient of Micronesian ethnicity as having C-1858 clustered with two isolates from Polynesia with T-1858. In addition, two strains from Asian ethnicities were clustered with known isolates in carriers from Southeast Asia. CONCLUSION: Genotypes A, B and C are predominant types among multi-ethnic HBV carriers in Hawaii, and distribution of HBV genotypes is dependent on the ethnic background of the carriers in Hawaii.

Adult↗

PubMed2004

Two subtypes of genotype B (Ba and Bj) of hepatitis B virus in Japan.

We have previously reported 2 subtypes of hepatitis B virus (HBV) genotype B, one of which has the recombination with genotype C over the precore region plus core gene (Ba) and the other of which does not (Bj). A restriction fragment-length polymorphism method with 2 endonucleases was newly developed for distinguishing between subtypes Ba and Bj and was applied to 313 carriers of HBV genotype B in Japan. Subtype Ba was detected in 38 (12%) and subtype Bj in 275 (88%) of the carriers of HBV genotype B. Hepatitis B e antigen in serum was found more frequently in patients with chronic infection with subtype Ba than in those with chronic infection with subtype Bj (8 [32%] of 25 vs. 25 [9%] of 273; P<.01). The new method for distinguishing between Ba and Bj by restriction fragment-length polymorphism would be useful in examining the distribution of these 2 subtypes in situations in which HBV genotype B is prevalent.

Acute Disease↗

PubMed2004

Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk.

APE1 (apurinic/apyrimidinic endonuclease 1) and XRCC1 (X-ray cross-complementing group 1) are DNA repair proteins that play important roles in the base excision repair (BER) pathway. Polymorphisms in their encoding genes are associated with altered DNA repair capacity and thus may impact on cancer risk. In the present case-control study with 178 Japanese incident lung cancer cases and 449 age- and sex-matched controls, we investigated the gene-environment interaction among APE1 Asp148Glu, XRCC1 Arg399Gln and smoking habit in lung cancer risk. The results were analyzed by using conditional logistic regression models, adjusted for age, sex and smoking status. The adjusted odds ratio for the current smokers with APE1 148Asp/Asp, Asp/Glu and Glu/Glu genotype as compared with the never smokers with the Asp/Asp genotype were 3.01 (95% CI 1.39-6.51, P = 0.005), 2.73 (95% CI 1.29-5.77, P = 0.008) and 7.33 (95% CI 2.93-18.3, P < 0.001), respectively. The gene-environment interaction between current smoking and APE1 148Glu/Glu genotype was statistically significant (OR 3.59, 95% CI 1.28-10.1, P = 0.015). When APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms were evaluated together, the adjusted odds ratios for the current smokers with 0-1, 2 and 3-4 of APE1 148Glu or XRCC1 399Gln alleles as compared with never smokers with the 0 of these alleles were 2.96 (95% CI 1.57-5.58, P = 0.001), 3.86 (95% CI 1.85-8.05, P < 0.001) and 6.01 (95% CI 2.25-16.1, P < 0.001), respectively. The gene-environment interaction between current smoking and three or more APE1 148Glu or XRCC1 399Gln alleles was statistically significant (OR 2.44, 95% CI 1.00-9.22, P = 0.049). The OR for the gene-environment interaction of Glu/Glu genotype of APE1 codon 148 with heavy smoking was 1.04 (95% CI 0.38-2.90, P = 0.936) and that with light smoking was 2.67 (95% CI 1.00-7.68, P = 0.049). These results suggest that APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms might modify the risk of lung cancer attributable to cigarette smoking exposure.

Adult↗

PubMed2004

Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma.

Human IgG1 antibodies with low fucose contents in their asparagine-linked oligosaccharides have been shown recently to exhibit potent antibody-dependent cellular cytotoxicity (ADCC) in vitro. To additionally investigate the efficacy of the human IgG1 with enhanced ADCC, we generated the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) IgG1 antibody KM2760. KM2760 exhibited much higher ADCC using human peripheral blood mononuclear cells (PBMCs) as effector cells compared with the highly fucosylated, but otherwise identical IgG1, KM3060. In addition, KM2760 also exhibited potent ADCC in the presence of lower concentrations of human PBMCs than KM3060. Because CCR4 is a selective marker of T-cell leukemia/lymphoma, the effectiveness of KM2760 for T-cell malignancy was evaluated in several mouse models. First, to compare the antitumor activity of KM2760 and KM3060, we constructed a human PBMC-engrafted mouse model to determine ADCC efficacy with human effector cells. In this model, KM2760 showed significantly higher antitumor efficacy than KM3060, indicating that KM2760 retains its high potency in vivo. Second, KM2760 suppressed tumor growth in both syngeneic and xenograft mouse models in which human PBMCs were not engrafted. Although murine effector cells exhibited marginal ADCC mediated by KM2760 and KM3060, KM2760 unexpectedly showed higher efficacy than KM3060 in a syngeneic mouse model, suggesting that KM2760 functions in murine effector system in vivo via an unknown mechanism that differs from that in human. These results indicate that defucosylated antibodies with enhanced ADCC as well as potent antitumor activity in vivo are promising candidates for the novel antibody-based therapy.

Animals↗

PubMed2004

Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin.

One Japanese pedigree of familial essential thrombocythemia (FET) inherited in an autosomal-dominant manner is presented. A unique point mutation, serine 505 to asparagine 505 (Ser505Asn), was identified in the transmembrane domain of the c-MPL gene in all of the 8 members with thrombocythemia, but in none of the other 8 unaffected members in this FET family. The Ba/F3 cells expressing the mutant Asn505 acquired interleukin 3 (IL-3)-independent survival capacity, whereas those expressing wild-type Ser505 did not. The autonomous phosphorylation of Mek1/2 and Stat5b was observed in the mutant Ba/F3 cells in the absence of IL-3. The former was also found in platelets derived from the affected individual in the absence of thrombopoietin. These results show that the Asn505 is an activating mutation with respect to the intracellular signaling and survival of the cells. This is the first report of FET deriving from a dominant-positive activating mutation of the c-MPL gene.

Cells, Cultured↗

PubMed2004

Predicting relapse after cessation of Lamivudine monotherapy for chronic hepatitis B virus infection.

There have been reports of relapse after cessation of lamivudine monotherapy for hepatitis B virus (HBV) infection. The aim of this study was to examine factors that predict posttreatment relapse. Comparison 22 patients who experienced relapse with 11 who did not after cessation of therapy showed that predictive factors for nonrelapse were hepatitis B e antigen seroconversion and duration of undetectable HBV DNA load (<0.7 log IU/mL), as determined by HBV real-time detection direct testing. However, 7 of 12 patients with seroconversion experienced relapse after cessation of therapy. Multivariate analysis revealed that the duration of an undetectable HBV DNA load was the only independent predictive factor for nonrelapse (odds ratio, 0.50; 95% confidence interval, 0.27-0.9). More-prolonged lamivudine therapy is required after seroconversion, and persistent duration of an HBV DNA level of <0.7 log IU/mL for >6 months can more accurately aid in the decision of when to stop lamivudine therapy.

Adult↗