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Chuan-Mo Lee

Publications and source records attributed to Chuan-Mo Lee.

52 records · Page 3Linked to original sources

Initiation of RNA replication of cloned Taiwan-3 isolate of hepatitis delta virus genotype II in cultured cells.

Hepatitis delta virus (HDV) genotype II is the predominant genotype in Taiwan and is associated with less progressive disease than genotype I. Although the Taiwan-3 (T3) clone was the first genotype II HDV isolated in Taiwan, its replication in cultured cells has not previously been established. Here, we demonstrate that cloned T3 HDV is capable of replicating in cultured cells. Furthermore, we show that: (1). the replication level of T3 clones is 100-fold lower than that of a genotype I HDV prototype of Italian origin; (2). both forms of the genotype II T3 delta antigen are expressed; and (3). T3 HDV undergoes RNA editing during replication, with 4.8% of the T3 genomes showing evidence of editing. The low level of RNA replication may be related to the milder clinical outcomes of genotype II HDV infections.

Animals↗

Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma.

BACKGROUND: Inactivation of the tumor suppressor gene PTEN/MMAC1/TEP1, located on chromosome 10q23, is a common event in advanced stages of diverse human malignancies. However, the prognostic role of PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized. METHODS: One hundred five resected specimens were collected from patients with HCC. Expression levels of PTEN and p53 in clinical samples were analyzed by immunohistochemistry. RESULTS: Immunohistochemical analysis of 105 HCC tissue specimens revealed that decreased or absence of PTEN immunostaining was found in 43 specimens (40.9%). Reduced PTEN expression levels were correlated with increased tumor grade (P = 0.017), advanced disease stage (P = 0.016), and elevated serum alpha-fetoprotein (alphaFP) levels (P = 0.001). Kaplan-Meier analysis indicated that patients with reduced PTEN levels had shorter overall survival (P = 0.001) and higher recurrence rates (P = 0.0007) compared with patients who had intact PTEN expression. Examining p53 expression unveiled an inverse correlation between p53 overexpression and reduced PTEN expression in patients with HCC (P = 0.004). In addition, patients with p53 overexpression had shorter overall survival compared with patients who were without p53 overexpression (P = 0.0014). Univariate and multivariate analyses revealed that reduced PTEN expression was an independent prognostic factor for survival in patients with HCC. CONCLUSIONS: The current study demonstrated that reduced PTEN expression levels are involved in the pathogenesis of HCC. Moreover, decreased PTEN expression was correlated with tumor progression, high alphaFP levels, p53 overexpression, and poor prognosis in patients with HCC.

Adult↗

Molecular epidemiological and clinical aspects of hepatitis D virus in a unique triple hepatitis viruses (B, C, D) endemic community in Taiwan.

The molecular epidemiological and clinical aspects of hepatitis D virus (HDV) in a unique HBV, HCV, and HDV triple virus endemic community in southern Taiwan were investigated. A total of 2,909 residents aged 45 or older were screened for hepatitis B surface antigen (HBsAg), anti-HCV antibody, and anti-HDV antibody (specifically for HBsAg-positive carriers). Factors that might be associated with HDV infection, viral nucleic acid detection, and genotyping of HBV, HCV, and HDV were investigated. The prevalence of HBsAg and anti-HCV were 12.6% (366/2,909) and 41.6% (1,227/2,909), respectively. For HBsAg carriers, 15.3% (56/366) were positive for anti-HDV assay. Living in a higher endemic district of HCV infection (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.7-6.3), male gender (OR = 1.9; 95% CI = 1.1-3.6) and co-infection with HCV (OR = 1.8; 95% CI = 1.0-3.3) were significantly independent factors associated with HDV infection. The detection rate of HDV RNA among anti-HDV-positive patients was only 12.7% (7/55). The mean HBV titer of triple infection group was significantly lower than in the HBV/HDV co-infection group (2.23 vs 3.05 in log(10), copies/ml, P = 0.046). HCV RNA detection among the triple infection group showed 47.4% (9/19) viremia rate and viral loads of 579,121 IU/ml in median (16,803-1,551,190 IU/ml). The prevalent genotype of HBV was type B (23/25); HCV was 1b (7/9) and HDV was IIa/IIb (4/4). Only the presence of HCV RNA predicted the presence of elevated ALT significantly (OR = 25.0; 95% CI = 3.39-184.6). In conclusion, the geographical aggregation of HDV infection paralleled that of HCV infection in this community. HCV suppressed the replication of HBV among triple vital infection patients. HBV and HDV lapsed into a remission or nonreplicative phase in most cases, and HCV acted as a dominant factor in triple viral-infected individuals. Only the presence of HCV RNA was associated with elevated ALT values, but not HBV or HDV.

Female↗

Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C virus-related cirrhosis.

UNLABELLED: BACKGROUND. We aimed to evaluate the validity of ultrasonography (US) in the diagnosis of cirrhosis in patients with chronic hepatitis B virus (HBV) or C virus (HCV) infection. METHODS: A total of 210 patients, 67 with chronic HBV and 143 with HCV infection, were evaluated for the cirrhotic status of liver by both needle biopsy and US. According to the pathological findings, a fibrosis score 4 on the histology activity index was the gold standard for the diagnosis of cirrhosis. A US scoring system consisting of liver surface, parenchyma, vascular structure, and splenic size was used to describe the severity of hepatic parenchymal damage. RESULTS: Cirrhosis was found in 27 (40%) of the 67 HBV patients and in 51 (36%) of the 143 HCV patients pathologically. The mean fibrosis scores were 0.95, 1.24, 2.35, 2.95, 3.8 and 3.7 in patients with US scores of 4, 5, 6, 7, 8, and 9 or more, respectively. The US scores were significantly correlated with the hepatic fibrosis scores (P < 0.05). Based on the receiver operating characteristic (ROC) curve, a US score of 7 was the best cutoff point for the prediction of HBV-related cirrhosis, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 77.8%, 92.5%, 87.5%, 86.0%, and 86.6%, respectively. In HCV-related cirrhosis, a US score of 6 provided results of 82.4%, 70.7%, 60.9%, 87.8%, and 74.8%, respectively. The specificity, positive predictive value, and accuracy were significantly higher in patients with HBV than in those with HCV infection (P = 0.012, P = 0.032, and P= 0.079, respectively). CONCLUSIONS: Cirrhosis can be predicted well by US, especially in patients with HBV infection.

Adolescent↗

Durability of lamivudine-induced HBeAg seroconversion for chronic hepatitis B patients with acute exacerbation.

BACKGROUND/AIMS: Lamivudine-induced hepatitis B e antigen (HBeAg) seroconversion in patients with chronic hepatitis B was reported to be durable by several studies but controversy still exists. The aim of this study was to evaluate the durability of the responses of lamivudine treatment. METHODS: Among 53 chronic hepatitis B patients who had acute exacerbation and had finished lamivudine therapy after at least 6 months of treatment, 31 patients achieved full HBeAg seroconversion twice at least 1 month apart, and subsequently stopped lamivudine therapy. Post-treatment monitoring was continued for up to 87 weeks. Alanine transaminase (ALT), HBeAg and hepatitis B virus (HBV) DNA were used as indicators for relapse. RESULTS: The cumulative relapse rates at 48 and 72 weeks post-treatment were 45.4% and 56.3%, respectively. During follow up, normal ALT levels precluded relapse while ALT levels over two times the upper limit of normal indicated relapse, which correlated well with HBeAg or HBV DNA reappearance. Patients older than 25 years were more likely to experience post-treatment relapse. CONCLUSIONS: Lamivudine-induced full HBeAg seroconversion was not durable in the Taiwanese population. ALT levels were useful for relapse detection. Age was the only independent predictive factor for relapse.

Acute Disease↗

Lamivudine for the treatment of hepatitis B virus reactivation following chemotherapy for non-Hodgkin's lymphoma.

Chemotherapy for non-Hodgkin's lymphoma (NHL) patients with chronic hepatitis B virus (HBV) infection may be accompanied by severe hepatitis. Of 86 consecutive NHL patients, 11 (12.8%) exhibited a positive serum HBsAg. Six of these patients (54.5%) developed acute exacerbation of chronic HBV infection following chemotherapy and received lamivudine. Five of the six patients demonstrated a clinical improvement, one patient died from fulminant hepatic failure owing to delayed lamivudine therapy and poor compliance. These data suggest that HBsAg screening is necessary before commencing chemotherapy for NHL patients in a hyperendemic area and that lamivudine is effective in treating hepatitis B reactivation during chemotherapy.

Acute Disease↗

Is delayed normalization of alanine aminotransferase a poor prognostic predictor in chronic hepatitis C patients treated with a combined interferon and ribavirin therapy?

BACKGROUND AND AIMS: Decreased alanine aminotransferase (ALT) level is the accepted basic indicator of an interferon (IFN) therapeutic effect in chronic hepatitis C. This study assessed whether delayed normalization of ALT predicts a poor response to a combined therapy of IFN and ribavirin in patients with chronic hepatitis C virus (HCV) infection. METHODS: Patients were treated with IFN-alpha 2b three times weekly and oral ribavirin for 24 weeks. The ALT values were assessed monthly and patterns of changes in ALT activity were analyzed. Serum HCV-RNA was checked at weeks 0, 12, 24, and 48. RESULTS: A total of 103 patients completed therapy and 69 (67%) of them achieved a sustained viral response (SVR). There was no significant difference in the SVR between patients with or without early normalization (week 12) of ALT level (69 vs 56%). Of the sustained responders, nine patients (13%) with delayed ALT normalization had a SVR. Nine of the 12 patients (75%) with abnormal ALT and negative HCV-RNA at week 12 had a SVR compared with none of four patients who had positive HCV-RNA at week 12 (P = 0.0192). CONCLUSIONS: Lack of normalization of the ALT level at week 12 does not preclude successful virological outcome in hepatitis C patients receiving a combined therapy of IFN and ribavirin. Hepatitis C virus RNA at week 12 may be a useful predictor of treatment outcome in patients without early biochemical response.

Alanine Transaminase↗

Comparison of prevalence for paraumbilical vein patency in patients with viral and alcoholic liver cirrhosis.

OBJECTIVES: The patent paraumbilical vein (PUV) is a venous collateral that is often found in patients with cirrhosis and portal hypertension. It can be effectively demonstrated by conventional ultrasonography (US). We conducted this prospective study to elucidate the prevalence and etiology of PUV patency for cirrhotic patients. METHODS: From August, 1997, to July, 1998, one of the authors (S.-N.L.) observed PUV patency for all cirrhotic patients during routine upper abdominal US examination. All cirrhotic patients diagnosed with portal hypertension were further analyzed. Portal hypertension was diagnosed by sonographic evidence of splenomegaly or ascites, or endoscopic varices. Cases presenting with hepatocellular carcinoma and sonographic evidence of prehepatic portal hypertension were excluded. Once a PUV patency with a diameter of > or = 3 mm was suspected based on conventional US, it was confirmed by color Doppler US. Of the 493 cirrhotic patients examined, 252 with portal hypertension and without hepatoma were enrolled in this study. RESULTS: Significant PUV patency was detected in 11.1% of the enrolled patients (28 of 252). With univariate analysis, a significantly higher prevalence was demonstrated for alcoholic patients (p < 0.0001), whereas prevalence was relatively low for those with chronic hepatitis B or C infection (p = 0.0159). A trend toward increased prevalence was noted with Child-Pugh classification (p = 0.001). Furthermore, a higher prevalence was noted in younger cirrhotic patients (p = 0.0037). Alcoholism was still a significant factor despite adjustment of Child-Pugh classification using multiple logistic regression, (OR = 3.88, 95% CI = 1.34-8.55). CONCLUSION: A significantly higher prevalence of PUV patency was demonstrated for patients with alcohol-induced liver cirrhosis in comparison to those with postviral cirrhosis.

Adult↗

Predicting the prevalence of antibody to hepatitis C virus (HCV) in a community by the prevalence of elevated levels of alanine aminotransferase: a method to identify areas endemic for HCV.

To identify areas endemic for hepatitis C virus (HCV), we attempted to predict the prevalence of antibody to HCV (anti-HCV) in a community by the prevalence of elevated levels of alanine aminotransferase (ALT). The results of health examinations of 2,273 women > or = 40 years old in five townships in central Taiwan were analyzed. The overall prevalence of elevated ALT levels was 11.6%. A township (20.3%) and 10 villages were identified as having a high prevalence (17.9-40.0%) of elevated ALT levels. Five communities with variant rates of elevated ALT levels, which ranged from 8.0% to 27.3%, were selected for correlation with the prevalence of anti-HCV among adults (> or = 40 years old). The prevalence of anti-HCV, which ranged from 10.1% to 72.1%, were obtained by community screenings and/or hospital-based studies. The correlation equation used was the prevalence of anti-HCV (%) = 3.33 x (prevalence of elevated ALT levels (%) - 5.7%) (r2 = 0.94, P < 0.01). Using this method, areas endemic for HCV can be identified by determining the community prevalence of elevated ALT levels.

Adult↗

Color Doppler sonography of bile duct tumor thrombi in hepatocellular carcinoma.

OBJECTIVE: To determine with the use of color Doppler sonography whether bile duct tumor thrombi had detectable vasculature in hepatocellular carcinoma. METHODS: Among 491 patients with tissue-proven hepatocellular carcinoma, 9 (1.8%) had bile duct tumor thrombi. All 9 patients had spectral Doppler sonography guided by color Doppler sonography (3.75-MHz convex probe). RESULTS: All 9 patients had dilated bile ducts with isoechoic thrombi. Eight patients had tumors infiltrating into and obstructing adjacent major bile ducts. The other patient had common hepatic duct tumor emboli that were not adjacent to primary tumors. Color signals were detectable within bile duct tumor thrombi in 7 patients. All of them had pulsatile waveforms on spectral analyses. CONCLUSIONS: Bile duct tumor thrombosis with obstructive jaundice was a rare complication of hepatocellular carcinoma. A detectable color signal with pulsatile waveforms was shown in most cases by color Doppler sonography with spectral analyses.

Bile Duct Neoplasms↗

Flash-echo gray-scale imaging in the subtraction mode for assessing perfusion of small hepatocellular carcinoma.

PURPOSE: The aim of this study was to evaluate the effectiveness of using flash-echo imaging (FEI) in the subtraction mode to assess the vascularity of small hepatocellular carcinomas (HCCs) that had been unsatisfactorily assessed with power Doppler sonography. METHODS: Between May 2000 and April 2001, we prospectively assessed nodular small HCCs using FEI in the subtraction mode after power Doppler sonography resulted in unsatisfactory images. After microbubble contrast was injected, we used the FEI technique to assess tumor perfusion in the arterial, portal, and delayed phases. RESULTS: Our study population comprised 14 patients (10 men and 4 women) whose ages ranged from 31 to 79 years (mean, 61 +/- 13.7 years) and whose tumors ranged in size from 0.8 to 3 cm (mean, 1.8 +/- 0.5 cm). Power Doppler sonography was unable to assess tumor vascularity in 6 cases because of interference by heart pulsation, and it failed to detect a color signal in the other 8 cases. All tumors were enhanced with FEI. In the arterial phase, 7 of the 14 tumors (50%) showed hyperperfusion relative to liver parenchyma enhancement, 5 of 14 (36%) showed isoperfusion, and 2 of 14 (14%) showed hypoperfusion. In the portal phase, 3 of the 14 tumors (21%) showed isoperfusion, and the other 11 (79%) showed hypoperfusion. In the delayed phase, all 14 tumors showed hypoperfusion. CONCLUSIONS: Despite heart pulsation and slow vascular flow, FEI in the subtraction mode was sensitive and effective in assessing the perfusion of small HCCs.

Adult↗

Combined cytologic and histologic diagnosis of liver tumors via one-shot aspiration.

BACKGROUND/AIMS: Ultrasound-guided fine needle aspiration is considered to be a safe alternative in diagnosing liver tumors. Combined cytologic and histologic preparation via one-shot fine needle aspiration was evaluated, especially in outpatients. METHODOLOGY: During a 1-year period, 95 patients (including 57 outpatients and 38 inpatients) who had received 97 sessions of fine needle aspiration and had final diagnosis were enrolled. Using a 22-gauge needle, the aspirate from liver tumor was processed for cytology and cell block histology simultaneously in patients without ascites and/or bleeding tendency. RESULTS: From 94 malignant and 3 benign tumors, the accuracy of cytology was 88.7%; while, the difference between outpatients and inpatients was not significant (91.2% vs. 85%). No complication after fine needle aspiration was elicited in both groups. The rates of inadequate specimen preparation for cytology and histology were 0% and 13.4%, the false-negative rates of malignancy were 11.7% for cytology and 16% for histology. The inadequate and false-negative rates of histology were not associated with gender, underlying liver cirrhosis, or tumor size, type, and location. CONCLUSIONS: Ultrasound-guided 22-gauge one-shot fine needle aspiration is safe, convenient and reliable in diagnosing liver tumor, and can be performed in outpatients meticulously.

Adenocarcinoma↗

Correlations between hepatitis B virus genotype and cirrhotic or non-cirrhotic hepatoma.

BACKGROUND/AIMS: Hepatoma arising in cirrhotic and non-cirrhotic livers might have different virological and clinical factors in hepatitis B virus carriers. This study was performed to elucidate the correlation between hepatitis B virus genotypes and clinical characteristics of patients with cirrhotic and non-cirrhotic hepatoma. METHODOLOGY: One hundred and fifty-five hepatitis B virus carriers who received hepatic resection for hepatoma were investigated to determine hepatitis B virus genotypes and clinical features. RESULTS: Of 155 patients, 84 were genotype B infection, and 67 genotype C. Compared to genotype C carriers, genotype B analogs had a significantly lower rate of liver cirrhosis (p=0.005), lower hepatitis B e antigen positive rates (p=0.0008), and lower fibrosis scores (p=0.003). In comparison to cirrhotic hepatoma patients, non-cirrhotic counterparts were younger (p=0.041), had a higher platelet count (p<0.001), lower hepatitis B e antigen positive rates (p=0.023), predominantly genotype B (p=0.005), lower inflammation scores (p<0.001). Using multivariate analysis, non-cirrhotic hepatoma was associated with genotype B infection (OR=2.85, 95% CI=1.44-5.64) and younger age (OR=0.967, 95% CI=0.94-0.99) in hepatitis B virus carriers. CONCLUSIONS: Our study suggested that hepatitis B virus genotype B infection might be an important factor for non-cirrhotic hepatoma.

Adult↗

Telomerase activity and telomerase catalytic subunit in hepatocellular carcinoma.

BACKGROUND/AIMS: Telomerase activation has been found in most malignant tumors. Human telomerase reverse transcriptase is a catalytic subunit of human telomerase and a rate-limiting factor of the enzymatic activity of telomerase. The present study was designed to examine the usefulness of detecting human telomerase catalytic subunit mRNA and telomerase activity as a molecular diagnostic marker for human liver cancers. METHODOLOGY: Thirty-one specimens of hepatocellular carcinoma and corresponding adjacent tissues were analyzed for human telomerase reverse transcriptase expression by reverse transcription polymerase chain reaction and for telomerase activity by polymerase chain reaction-based telomeric repeat amplification protocol. RESULTS: Human telomerase reverse transcriptase mRNA expression was observed in 97% of hepatocellular carcinoma tissues, in contrast none of the non-tumorous liver tissues did. Telomerase activity was detected in 94% of hepatocellular carcinoma and in only 16% of adjacent liver tissues. Human telomerase reverse transcriptase mRNA expression and telomerase activity were observed in all 3 grade I (well-differentiated) hepatocellular carcinoma. Significant correlations between human telomerase reverse transcriptase mRNA expression and hepatocellular carcinoma and also between telomerase activity and HCC were found (both p<0.001). CONCLUSIONS: The results indicate that human telomerase catalytic subunit mRNA expression and telomerase activity might be associated with hepatocellular carcinogenesis and could be as markers for diagnosis of hepatocellular carcinoma.

Adult↗

Prediction of viremia for cases of hepatitis C virus (HCV) infection using a third-generation anti-HCV enzyme immunoassay test.

BACKGROUND/AIMS: Positive results for anti-hepatitis C virus (HCV) testing reveal subjects are infected by HCV, with presence of HCV RNA indicating persistent infection. In this study, we attempted to evaluate the validity of the HCV viremia using a commercially available, third-generation anti-HCV test. METHODOLOGY: Sample rate/cut-off rate (S/CO) ratios for 1,907 anti-HCV-positive tests (S/CO >1, AxSYM HCV 3.0; Abbott, IL, USA), which had been performed during the last three years, were retrospectively analyzed. Cases with S/CO values between 1 and 100 were divided into 20 groups according to S/CO range (in increments of 10) and ALT (normal or elevated). Ten random cases were obtained for each of the 20 groups. If cases in any group numbered < or =10, all were recruited. Totally, 193 cases were enrolled for HCV RNA detection (COBAS Amplicor; Roche Diagnostics, NJ, USA). RESULTS: The S/CO distribution was biphasic, with two S/CO peaks in the ranges 1-10 (10.7%) and 81-90 (24.2%). Regardless of the ALT level, all samples with S/COs < or =10 were negative for HCV RNA. Of the samples with S/CO values >10, the optimal cut-off was 40 with sensitivity and specificity for both of 81%. In conclusion, subjects with S/CO values < or =10 (10.7%) were more likely to be cases of past infection or of non-specific reaction. Most (90%, 108/120) of the subjects with S/COs >40 represent current or persistent infection. To predict viremia in subjects with S/COs between 10 and 40, 6.7% of all anti-HCV-positive subjects was invalid by a cross-sectional observation. CONCLUSIONS: Follow-up or further study is recommended. The third-generation EIA test plays a semiquantitative role for the prediction of viremia in HCV infection.

Hepacivirus↗