Biomedical subjects

Yoshiyuki Suzuki

Publications and source records attributed to Yoshiyuki Suzuki.

At least 19 recordsLinked to original sources

PubMed2007

Long-term outcome after interferon therapy in elderly patients with chronic hepatitis C.

OBJECTIVE: The purpose of this study was to elucidate the long-term outcome after interferon (IFN) therapy in chronic hepatitis C elderly patients. METHODS: We studied the incidence of hepatocellular carcinoma (HCC) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients >60 years. The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years. Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy. Sustained virological response (SVR) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy. Non-response (NR) was applied to patients who did not show SVR. Hepatic fibrosis was defined as the fibrosis score (score 0-4) according to Knodell et al. RESULTS: 140 patients (28%) had an SVR and 360 patients (72%) had an NR. 71 of 500 patients developed HCC during follow-up. The cumulative incidence of HCC was 9.6% at the 5th year, 17.4% at the 10th year, and 31.3% at the 15th year. HCC developed with significance when: (1) HCV was not cleared after IFN therapy (p < 0.0001), (2) sex was male (p < 0.0001), and (3) staging of liver fibrosis was >2 (p = 0.008). 53 of the patients died. The cumulative survival probability was 95.7% at the 5th year, 86.4% at the 10th year, and 78% at the 15th year. Patients achieved a long survival with significance when: (1) staging of liver fibrosis was 1 (p < 0.0001), (2) HCV was cleared after IFN therapy (p = 0.034), and (3) sex was female (p = 0.015). CONCLUSION: Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are > or =60 years.

Aged↗

PubMed2006

Genome Information Broker for Viruses (GIB-V): database for comparative analysis of virus genomes.

Genome Information Broker for Viruses (GIB-V) is a comprehensive virus genome/segment database. We extracted 18 418 complete virus genomes/segments from the International Nucleotide Sequence Database Collaboration (INSDC, http://www.insdc.org/) by DNA Data Bank of Japan (DDBJ), EMBL and GenBank and stored them in our system. The list of registered viruses is arranged hierarchically according to taxonomy. Keyword searches can be performed for genome/segment data or biological features of any virus stored in GIB-V. GIB-V is equipped with a BLAST search function, and search results are displayed graphically or in list form. Moreover, the BLAST results can be used online with the ClustalW feature of the DDBJ. All available virus genome/segment data can be collected by the GIB-V download function. GIB-V can be accessed at no charge at http://gib-v.genes.nig.ac.jp/.

Databases, Nucleic Acid↗

PubMed2006

Correlation between survivin expression and locoregional control in cervical squamous cell carcinomas treated with radiation therapy.

OBJECTIVE: Survivin is a member of the inhibitors of apoptosis and has been implicated in both the regulation of cell division and the suppression of apoptosis. Over-expression of cytoplasmic survivin correlates with an unfavorable prognosis in many malignant tumors. However, the prognostic value of nuclear survivin expression is still equivocal. Here, we investigated the prognostic value of survivin expression in cervical cancer treated with radiation therapy. METHODS: Tissue sections were obtained from 72 patients with cervical squamous cell carcinoma treated with radiation therapy alone. Survivin expression levels were determined by immunohistochemical staining and evaluated for cell positivity. The correlation between survivin expression and clinical outcome endpoints including cause-specific survival and local control were evaluated. RESULTS: A total of 14% (10/72) of tissue specimens had greater than 5% nucleus positivity, while 47% (34/72) had greater than 50% cytoplasmic positivity. Local control rate of the cytoplasmic survivin-negative tumors was 94%, significantly higher than the 76% of the positive tumors (p=0.046). Local control rate of the nuclear survivin-positive and cytoplasmic survivin-negative patients was 95%, significantly higher than the 74% of the other patients (p=0.02). In contrast, no significant correlation was noted between survivin expression and disease-free survival. CONCLUSIONS: The cytoplasmic survivin expression alone and the combination of nuclear and cytoplasmic expression were suggested to be predictors for local control in patients with cervical squamous cell carcinoma treated with radiation therapy alone.

Adult↗

PubMed2006

Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels.

BACKGROUND/AIMS: We showed previously that amino acid (aa) substitutions in the HCV core region (HCV-CR) are predictors of non-virological response (NVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy. Here, we determined the predictive factors of sustained virological response (SVR) and early virologic response (EVR) to this treatment. METHODS: We evaluated the response to 48-week PEG-IFN-RBV therapy in 114 Japanese adults infected with HCV genotype 1b and determined the predictors of EVR and SVR. RESULTS: EVR was achieved by 70% and SVR by 45% of patients. 64% of patients who achieved EVR also showed SVR, while none of non-EVR achieved SVR. Multivariate analysis identified low-density lipoprotein cholesterol (LDL-C) (>or=86 mg/dl), aa substitutions in HCV-CR (double-wild-type; arginine at aa 70/leucine at aa 91), gamma-glutamyl transpeptidase (GGT) (<109 IU/l), RBV dose (>or=11.0mg/kg), and leukocyte count (>or=4500/mm3) as significant determinants of EVR, and aa substitutions in HCV-CR (double-wild-type), LDL-C (>or=86 mg/dl), male gender, ICG R15 (<10%), GGT (<109 IU/l), and RBV dose (>or=11.0 mg/kg) as determinants of SVR. Prediction of response to therapy based on combination of these factors had high sensitivity, specificity, positive, and negative predictive values. CONCLUSIONS: Our study identified aa substitutions in the core region and serum LDL-C as predictors of response to PEG-IFN-RBV therapy in Japanese patients infected with HCV genotype 1b.

Adult↗

PubMed2006

Motor and reflex testing in GM1-gangliosidosis model mice.

A large number of genetic disease model mice have been produced by genetic engineering. However, phenotypic analysis is not sufficient, particularly for brain dysfunction in neurogenetic diseases. We tried to develop a new assessment system mainly for motor and reflex functions in G(M1)-gangliosidosis model mice. Two genetically engineered model mouse strains were used for this study: the beta-galactosidase-deficient knockout mouse representing infantile G(M1)-gangliosidosis (severe form), and transgenic mouse representing juvenile G(M1)-gangliosidosis (mild form). We modified human child neurology techniques, and selected eleven tests for motor assessment and reflex testing. The test results were scored in four grades: 0 (normal), 1 (slightly abnormal), 2 (moderately abnormal), and 3 (severely abnormal). Both disease model mouse strains showed high scores even at the apparently pre-symptomatic stage of the disease, particularly with abnormal tail and hind limb postures. Individual and total test scores were well correlated with the progression of the disease. This method is simple, quick, and reproducible. The testing is sensitive enough to detect early neurological abnormalities, and will be useful for monitoring the natural clinical course and effect of therapeutic experiments in various neurogenetic disease model mice, such as chemical chaperone therapy for G(M1)-gangliosidosis model mice.

Age Factors↗

PubMed2006

Long-term follow-up of HBeAg-positive young adult Japanese patients treated with corticosteroid withdrawal therapy for chronic hepatitis B.

OBJECTIVES: To evaluate the long-term effects of corticosteroid withdrawal therapy (CSWT) in young adult Japanese patients with chronic hepatitis B (CH-B) virus infection. METHODS: The subjects were 106 patients with CH-B who received CSWT, were less than 35 years of age and had been followed for more 10 years after CSWT. RESULTS: Retreatment was not required in 41 patients (38.7%; retreatment(-) group) while 65 (61.3%) received treatment after the initial CSWT (retreatment(+) group). Larger proportions of patients of the retreatment(-) group were females, had liver histology stage F2/F3, high ICG R15, and genotypes A/B/D/E, compared with the retreatment(+) group. At the last follow-up examination, the HBeAg seronegative rate was 90.2% in the retreatment(-) group and 98.5% in retreatment(+) group. In the retreatment(-) group, the rate of liver cirrhosis (LC; 7.3%, 3 patients) was lower, but the rate of hepatocellular carcinoma (HCC; 12.2%, 5 patients) was higher than in the retreatment(+) group (20%, 13 patients, and 4.6%, 3 patients, respectively). At the 10-year period, the overall HBsAg loss, LC and HCC rates were 2.8, 13.2 and 1.9%, respectively. CONCLUSIONS: Our results suggest that CSWT is good short-term therapy and has possible long-term effects in young adult Japanese patients with CH-B.

Adolescent↗

PubMed2006

Differential evolutionary rates of duplicated genes in protein interaction network.

In the network of protein-protein interactions (PPIs), a loss and gain of the partnering proteins can cause drastic changes of network formation during evolution. With the aim of examining the evolutionary effects of the loss and gain of the partnering proteins on PPIs, we examined a relationship between evolutionary rates and losses and/or gains of PPIs for duplicated gene pairs encoding proteins involved in the PPI network. For duplicated pairs, which provided us with a unique opportunity of making fair comparisons of the genes with the same initial condition, we found that the evolutionary rate of the protein with more PPI partners is much slower than that of the other with fewer PPI partners. Moreover, when the ratio of evolutionary rates (faster rate/slower rate) was computed for each of the duplicated pairs, the ratio for the duplicated pair sharing any PPI partners was significantly lower than that for the pair sharing no PPI partners. These results indicate that the duplicated gene pairs differentiate through the losses and/or gains of the PPI partners, resulting in a change in their evolutionary rates. In particular, we point out that the PPI losses for the duplicated gene products that are involved in the functional classes of 'transcription' and 'protein fate' have an impact on their evolutionary rates more than the PPI losses for others.

Biological Evolution↗

PubMed2006

Natural selection on the influenza virus genome.

Influenza viruses are the etiological agents of influenza. Although vaccines and drugs are available for the prophylaxis and treatment of influenza virus infections, the generation of escape mutants has been reported. To develop vaccines and drugs that are less susceptible to the generation of escape mutants, it is important to understand the evolutionary mechanisms of the viruses. Here natural selection operating on all the proteins encoded by the H3N2 human influenza A virus genome was inferred by comparing the numbers of synonymous (d(S) [D(S)]) and nonsynonymous (d(N) [D(N)]) substitutions per site. Natural selection was also inferred for the groups of functional amino acid sites involved in B-cell epitopes (BCEs), T-cell epitopes (TCEs), drug resistance, and growth in eggs. The entire region of PB1-F2 was positively selected, and positive selection also appeared to operate on BCEs, TCEs, and growth in eggs. The frequency of escape mutant generation appeared to be positively correlated with the d(N)/d(S) (D(N)/D(S)) values for the targets of vaccines and drugs, suggesting that the amino acid sites under strong functional constraint are suitable targets. In particular, TCEs may represent candidate targets because the d(N)/d(S) (D(N)/D(S)) values were small and negative selection was inferred for many of them.

Antigens, Viral↗

PubMed2006

Fibroblast screening for chaperone therapy in beta-galactosidosis.

We performed screening of beta-galactosidase-deficient fibroblasts for possible chemical chaperone therapy using N-octyl-4-epi-beta-valienamine (NOEV) in patients with GM1-gangliosidosis and Morquio B disease (beta-galactosidosis). Fibroblasts were cultured with NOEV for 4 days and beta-galactosidase activity was measured. Mutation analysis was performed simultaneously. Two separate criteria were set for evaluation of the chaperone effect: a relative increase of enzyme activity (more than 3-fold), and an increase up to more than 10% normal enzyme activity. Among the 50 fibroblast strains tested, more than 3-fold increase was achieved in 17 cell strains (34%), and more than 10% normal activity in 10 (20%). Both criteria were satisfied in 6 (12%), and either of them in 21 (42%). Juvenile GM1-gangliosidosis was most responsive, and then infantile GM1-gangliosidosis. This enhancement was mutation-specific. We estimate that the NOEV chaperone therapy will be effective in 20-40% of the patients, mainly in juvenile and infantile GM1-gangliosidosis patients. A molecular design may produce mutation-specific chaperone compounds for the other disease phenotypes. This cellular screening will be useful for identification of human patients with beta-galactosidase deficiency for chaperone therapy to be started in the near future.

Arginine↗

PubMed2006

Carbon beam therapy overcomes the radiation resistance of uterine cervical cancer originating from hypoxia.

PURPOSE: High linear energy transfer (LET) particles are believed to decrease tumor radiation resistance originating from hypoxia. However, no proof of this effect has been provided by clinical trials and related clinical research. Hence, we investigated the radiation biological aspects of high LET carbon beam therapy on cervical cancer. EXPERIMENTAL DESIGN: This study involved 49 patients with stage IIIb bulky and stage IVa cervical cancer treated with high LET carbon beams between October 1995 and June 2000. Oxygen partial pressure (pO(2)) was measured by using a needle-type polarographic oxygen electrode. RESULTS: The 4-year disease-free survival rates of patients with pO(2) </= 20 mm Hg (hypoxic tumor) and pO(2) > 20 mm Hg (oxygenated tumor) before treatment were 37% and 21%, respectively. The local control rates of hypoxic and oxygenated tumors before treatment were 58% and 54%, respectively. The disease-free survival rates of hypoxic and oxygenated tumors assessed by oxygen status at the 5th day of irradiation were 33% and 32%, respectively. The local control rates of hypoxic and oxygenated tumors at the 5th day were 60% and 58%, respectively. There was no significant prognostic difference between hypoxic and oxygenated tumors. CONCLUSION: The similar disease-free survival and local control rates between hypoxic and oxygenated tumors before and during treatment indicated that the role of the tumor oxygenation status was not so important in local control in carbon beam therapy. These results indicated that high LET carbon beam irradiation might reduce the radiation-resistant nature stemming from tumor hypoxia.

Carbon↗

PubMed2006

Prediction model of hepatocarcinogenesis for patients with hepatitis C virus-related cirrhosis. Validation with internal and external cohorts.

BACKGROUND/AIMS: To estimate hepatocarcinogenesis rates in patients with hepatitis C virus (HCV)-related cirrhosis, an accurate prediction table was created. METHODS: A total of 183 patients between 1974 and 1990 were assessed for carcinogenesis rate and risk factors. Predicted carcinogenesis rates were validated using a cohort from the same hospital between 1991 and 2003 (n=302) and an external cohort from Tokyo National Hospital between 1975 and 2002 (n=205). RESULTS: The carcinogenesis rates in the primary cohort were 28.9% at the 5th year and 54.0% at the 10th year. A proportional hazard model identified alpha-fetoprotein (>or=20 ng/ml, hazard ratio 2.30, 95% confidence interval 1.55-3.42), age (>or=55 years, 2.02, 95% CI 1.32-3.08), gender (male, 1.58, 95% CI 1.05-2.38), and platelet count (<100,000 counts/mm3, 1.54, 95% CI 1.04-2.28) as independently associated with carcinogenesis. When carcinogenesis rates were simulated in 16 conditions according to four binary variables, the 5th- and 10th-year rates varied from 9 to 64%, and 21-93%, respectively. Actual carcinogenesis rates in the internal and external validation cohorts were similar to those of the simulated curves. CONCLUSIONS: Simulated carcinogenesis rates were applicable to patients with HCV-related cirrhosis. Since, hepatocarcinogenesis rates markedly varied among patients depending on background features, we should consider stratifying them for cancer screening and cancer prevention programs.

Adult↗

PubMed2006

Ancient positive selection on CD155 as a possible cause for susceptibility to poliovirus infection in simians.

Poliovirus is the etiological agent of poliomyelitis. From the observations that only simians are susceptible to poliovirus infection and that 37 amino acid sites (the poliovirus-binding associated [PBA] sites) in the domain D1 of CD155 are involved in the binding to poliovirus, it is considered that the susceptibility to poliovirus infection evolved through amino acid substitutions that occurred at the PBA sites on the ancestral branch of simians. Here it is shown that positive selection has operated on these substitutions by analyzing the nucleotide sequences encoding almost the entire region of D1 in humans, non-human hominoids (chimpanzees and gorillas), Old World monkeys (African green monkeys), New World monkeys (brown capuchins, squirrel monkeys, and marmosets), prosimians (ring-tailed lemurs), and non-primate mammals (rabbits). Positive selection is unlikely to have operated on the susceptibility to poliovirus infection, but possibly on the binding to another molecule. Elimination of susceptibility to poliovirus infection in simians may be difficult, because it also requires elimination of advantageous effects that have been exerted by CD155.

Amino Acid Sequence↗

PubMed2006

Differential effects of x-irradiation on immature and mature hippocampal neurons in vitro.

X-irradiation to neuronal progenitor cells causes brain dysfunctions, such as a mental retardation, in adulthood. However, little has been known about the degree of radiosensitivity of neurons in the developmental stages at which they are most vulnerable. In this study we compared the effect of irradiation on mature neurons with that on immature neurons. Primary dissociated neuronal cultures were prepared from fetal rat hippocampi of embryonic day 18. X-irradiations were performed on the cultured cells at 7 or 21 days in vitro (DIV), and the cells were fixed at 12 or 24 h after irradiation. Then the cells were stained with 4',6-diamidino-2-phenylindole (DAPI) or terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The apoptotic changes were measured quantitatively by nuclear pyknosis and DNA fragmentation-both characteristic morphological changes of apoptosis. Light microscopy with differential interference contrast showed that 30 Gy of irradiation increased cellular shrinkage in 7-DIV neurons but not in 21-DIV neurons. Quantitative analysis using DAPI imaging showed that 30 Gy of irradiation significantly enhanced pyknotic changes in 7-DIV neurons after 24 h. In contrast, this irradiation did not enhance any pyknotic changes in 21-DIV neurons after 24 h. Further TUNEL staining also showed that the irradiation did not enhance any DNA fragmentation in nuclei of 21-DIV neurons after 24h. Hence, we showed that the radiosensitivity of 21-DIV postmitotic neurons was significantly lower than that of 7-DIV neurons, indicating that the susceptibility of such neurons depends on their developmental stage.

Animals↗

PubMed2006

Dysplastic nodules frequently develop into hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosis.

BACKGROUND: Advances in imaging technology have enhanced the detection of small nodular lesions during the course of chronic liver disease. METHODS: Between 1995 and 2002, the authors examined 154 consecutive patients with small hepatic nodules without hepatocellular carcinoma (HCC) over a median duration of 2.8 years. The median size of these nodules was 14 mm (range, 7-40 mm). The initial histopathologic diagnosis included high-grade dysplastic nodule (HGDN) (n=13), low-grade dysplastic nodule (LGDN) (n=42), and regenerative nodule (RN) (n=99). RESULTS: A total of 29 (18.8%) nodules developed into HCC during the observation period. Cumulative HCC development rates at the first, third, and fifth year were 46.2%, 61.5%, and 80.8% for HGDN; 2.6%, 30.2%, and 36.6% for LGDN; and 3.3%, 9.7%, and 12.4% for RN, respectively. The rate of HCC development was significantly higher in the HGDN group than for other types (P<0.001). Multivariate analysis disclosed that histopathologic diagnosis (P<0.001) and findings on computed tomographic arterial portography (CT-AP) (P=0.004) were significantly associated with future HCC development. The hazard ratios of HGDN and LGDN were 16.8 (95% confidence interval [CI], 6.19-45.6) and 2.96 (95% CI, 1.20-7.31), respectively. A decrease in portal blood flow also showed a significantly high hazard ratio of 3.04 (95% CI, 1.42-6.50). Approximate annual development rate to HCC was 20% in patients with HGDN and 10% in LGDN. CONCLUSION: HGDN should be considered a precancerous lesion when it appears during follow-up of chronic viral hepatitis or cirrhosis. Reduced portal blood flow in the nodule on computed tomography-AP is also an important predictor for development of hepatocellular carcinoma.

Adult↗

PubMed2006

Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C.

In a single hospital in Tokyo, the 87 patients infected persistently with hepatitis B virus (HBV) genotype A, the 413 with B, and the 3,389 with C were compared for virological outcome. Hepatitis B surface antigen (HBsAg) was cleared from the serum in 12% (3/26), 2% (2/112), and 3% (23/826) of patients with genotypes A, B, and C, respectively, at 5 years of follow-up (P = 0.0395). Hepatitis B e antigen (HBeAg) was cleared from serum more frequently in patients with genotype B than those with A or C (78% [32/41] vs. 58% [11/19] or 45% [251/562], P = 0.00001) at 5 years. Of the 45 individuals infected with genotype A and followed for 3 years or longer, HBeAg was more frequent (16% [3/19] vs. 73% [19/26], P = 0.0002) and levels of HBV DNA higher (median <2.6 [range: <2.6-5.6] vs. >7.6 [<2.6->7.6] log copies/ml, P = 0.001) in the 26 patients with biopsy-proven chronic hepatitis than the 19 asymptomatic carriers. Among the 26 hepatitis patients infected with HBV genotype A, decreases in HBV DNA were less frequent (20% [1/5] vs. 93% [13/14] or 86% [6/7], P = 0.0095) and increases in serum levels of hyaluronic acid > or =10 ng/ml commoner (80% [4/5] vs. 14% [2/14] or 14% [1/7], P = 0.017) in the patients who kept HBeAg than in those who seroconverted or who remained HBeAg-negative. In conclusion, patients persistently infected with HBV genotype A fare better than those with genotype B or C. However, high levels of HBV DNA continue in those in whom HBeAg persists along with fibrosis in the liver.

Adolescent↗

PubMed2006

Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype 1b and high viral load.

Patients with high viral load (> or =1.0 x 10(5) IU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve high sustained virological response rates to interferon (IFN)/ribavirin combination therapy. Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core region could affect virological non-response especially in patients who could not achieve HCV-RNA negativity during treatment. The present study evaluated 167 consecutive Japanese adults with high HCV genotype 1b viral load who received combination therapy for > or =24 weeks. A case-control study matched for age, sex, genotype, and viral load was conducted to investigate the predictive factors for virological non-response, especially absolute virological non-response (patients who could not achieve >2 log decline of HCV RNA from baseline during the initial 24 weeks of therapy). Virological non-response was identified in 26.3% of patients, and 45.5% of these were absolute virological non-responders. Multivariate analysis identified ribavirin dose <11.0 mg/kg, moderate-to-severe hepatocyte steatosis, and substitutions of aa 70 and/or 91 in the core region as significant independent factors associated with virological non-response. The majority of absolute virological non-responders had such substitutions in the core region (95.0%), as well as substitution of glutamine at aa 70 and/or methionine at aa 91 (90.0%). In the present work, such substitutions significantly affected the viral kinetics in virological non-responders. The results suggest that viral, host, and treatment-related factors determine the response to IFN/ribavirin combination therapy in patients with high HCV genotype 1b viral load, and that amino acid substitution patterns in the core region is potentially useful pretreatment predictor of virological non-response.

Adult↗

PubMed2006

Clinical and virological features of non-breakthrough and severe exacerbation due to lamivudine-resistant hepatitis B virus mutants.

Patients who develop YMDD mutant during lamivudine therapy for hepatitis B virus (HBV) infection exhibit various clinical courses. Some patients show normal ALT levels, whereas others develop severe hepatitis exacerbations (SHEs) due to YMDD mutants. We studied 136 patients with YMDD mutant among 362 Japanese adult patients on lamivudine therapy. Clinical and virological features of patients without elevated HBV DNA after emergence of YMDD mutant (non-elevated group) were investigated. Moreover, virological analysis was also performed in patients with SHE due to YMDD mutants. Patients in the non-elevated group were characterized by HBeAg-negative pretreatment, HBeAg loss during therapy, a longer duration from commencement of therapy until emergence of YMDD mutant, and no mixed-type YMDD mutants. Patients with SHE had more substitutions in the reverse transcriptase (rt) region within the polymerase gene at the time of exacerbation than those without SHE, although no specific substitutions were noted. Sequence analysis of full-length HBV genome showed more substitutions in X, rt, and surface proteins in patients with SHE than in those without elevated HBV DNA level. In conclusion, negativity for HBeAg at commencement of therapy or before emergence of YMDD mutant was an important factor among non-elevated group. More substitutions in the rt region and the other proteins may be related to the emergence of severe hepatitis caused by lamivudine-resistant virus.

Adult↗

PubMed2006

Natural history of compensated cirrhosis in the Child-Pugh class A compared between 490 patients with hepatitis C and 167 with B virus infections.

Natural histories of compensated cirrhosis in the Child-Pugh class A were compared between the 490 patients infected with hepatitis C virus (HCV) and 167 patients with hepatitis B virus (HBV) who were followed for more than 1 year up to 20 years without antiviral treatment. Patients with HCV were older (median age: 59 vs. 45 years), less predominantly male (59.0% vs. 76.0%), transfused more frequently (49.2% vs. 9.0%), and had higher aminotransferase as well as lower albumin levels and fewer platelets (P < 0.001 for all). Death was commoner (55.1% vs. 35.9%, P < 0.001) and hepatocellular carcinoma developed more often (53.9% vs. 28.7%, P < 0.001) in patients with HCV than HBV. In multivariate analysis, low albumin levels (hazard ratio: 1.65), alpha-fetoprotein (1.55), alcohol consumption (1.49), age >55 years (1.47), and retention of indocyanine green (1.39) were independent risk factors for the survival in patients with HCV, while male gender (4.43), age >45 years (2.24), retention of indocyanine green (2.14), hepatitis B e antigen (2.11), and low platelet counts (1.91) were in those with HBV. Chances for survival was significantly different (P < 0.001) among patients with HCV having low (number of factors: 0-1), medium (2-3), and high risks (4-5), as well as in those with HBV having low (0-1), medium (2-4), and high risks (5-6). In conclusion, survival and development of hepatocellular carcinoma, and factors for survival, are considerably different between patients with compensated cirrhosis infected with HCV and HBV, which would need to be taken into consideration in their management and planning treatment strategies.

Adult↗