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Biomedical subjects

W L Chuang

Publications and source records attributed to W L Chuang.

At least 55 records · Page 3Linked to original sources

The status of serum hepatitis B virus DNA in HBSAG-positive hepatocellular carcinoma.

To elucidate the status of serum hepatitis B virus (HBV) DNA in HBsAg-positive hepatocellular carcinoma (HCC), 100 type B chronic liver disease (CLD) patients and 19 HCC patients were studied. The positive rate of serum HBV DNA in HBeAg-positive CLD patients was significantly higher than that in HBeAg-negative CLD patients, and the correlation between the presence of serum HBV DNA and patients' age showed a negative trend. In contrast, the positive rates of serum HBV DNA in HCC patients were not related to the status of HBeAg and age, and the positive rate of serum HBV DNA in HBeAg-negative HCC patients was significantly higher than that in HBeAg-negative CLD patients. Nevertheless, the serum concentrations of HBV DNA in HCC patients were significantly lower than those in CLD patients. These results suggest that replication of HBV in HCC patients might differ from that in CLD patients, and that persistent low-level HBV replication might be related to the presence of HCC.

Adult↗

Treatment of chronic hepatitis C with interferon-alpha: a preliminary report.

Interferon alpha (IFN-alpha) has been indicated to be dramatically effective in some but not all patients with chronic hepatitis C virus (HCV) infection. We investigated prospectively 27 patients of chronic hepatitis C, 12 females and 15 males, treated with IFN-alpha for a better regimen of the therapy and for any effective predictor of response to the treatment. All patients were treated with 3 to 6 million units (MU) of recombinant IFN-alpha 2b (n = 15) or lymphoblastoid IFN-alpha (n = 12) given 3 times weekly for 12 to 36 weeks. Patients with normal alanine aminotransferase (ALT) value during therapy, who sustained this response throughout 6 months follow-up after treatment was completed, were grouped into the complete responders. Patients with normal ALT value during therapy but who relapsed after treatment completed, were grouped as partial responders. Non-responders were defined as patients without normal ALT value during therapy. The rates of complete response, partial response, and non-response were 29.6%, 40.8%, and 29.6%, respectively. The degree of response to IFN-alpha therapy was not related to age, sex, type of IFN-alpha, history of blood transfusion, the state of liver pathology, or pretreatment level of ALT value. The complete responsive rate to IFN-alpha was higher in patients treated with total dose above 215 MU [38.1% (8/21) vs. 0% (0/6), p = 0.06], in patients treated for at least 24 weeks [40% (8/20) vs. 0% (0/7), p < 0.05], and in patients with non-genotype 1b/II HCV infection [40% (8/20) vs. 0% (0/7), p < 0.05]. We concluded that IFN-alpha was effective in the treatment of chronic HCV infection, particularly in those other than HCV genotype 1b/II. A high-dose, and long-duration regimen may be recommended for better response of chronic hepatitis C to IFN-alpha therapy.

Adult↗

The genotypes of hepatitis C virus in patients with chronic hepatitis C virus infection in southern Taiwan.

To investigate the genotype distribution of hepatitis C virus (HCV) in southern Taiwan, the sera from 56 patients with chronic HCV infection were studied. Twenty-nine patients were men and 27 were women. Age ranged from 22 to 65 years (mean, 47.3 +/- 11.4). Eighteen of them had chronic persistent hepatitis, 27 had chronic active hepatitis, and 11 had liver cirrhosis. HCV RNA was detected by reverse transcription-nested polymerase chain reaction using primers derived from the 5'-noncoding region. The genotypes of HCV were determined by amplification of the core region with the type-specific primers as described by Okamoto et al.. All sera were positive for HCV RNA. The prevalence rates of genotypes were as follows: 1b/II, 44.6%(25/56); 2a/III, 41.1%(23/56); 2b/IV, 3.6%(2/56); mixed 1b/I + 2a/III, 5.4%(3/56): mixed 1b/II + 2b/IV, 1.8%(1/56) and type unclassified 3.6%(2/56). The distribution of genotypes was not related to the patients' age, sex, and histological changes. Nevertheless, patients having past history of blood transfusion had a significantly higher rate of HCV type 2a/III infection (72.2% versus 34.2%, p < .05, chi-square test). We concluded that both of the HCV genotypes 1 b/II and 2a/III are predominant types in southern Taiwan and regional HCV genotype distribution may differ even within this island. Selective transmission of specific genotypes may pass along different infectious routes.

Adult↗

The temporal relationship between the severity of hydroureter and the dynamic changes of obstructed ureters in a rat model.

OBJECTIVE: To investigate dynamic changes in the obstructed rat ureter and to evaluate the usefulness of the rat model in the study of obstructive uropathy. MATERIALS AND METHODS: Unilateral ligation of the ureter was performed in 26 rats. After ureteric ligation, four to seven rats were killed and examined after 1, 3, 7, 10, and 14 days. The severity of hydroureter and hydronephrosis was assessed by pyelography and the hydroureter-hydronephrosis index. The middle portion of the ureter was prepared for light and electron microscopic observation. Five rats which received a sham operation were also examined as controls. RESULTS: The severity of hydroureter and hydronephrosis in the ligated ureters progressively increased during the period of obstruction (P < 0.005) and reached a maximum 10-14 days after ligation. Hypertrophy of the smooth muscle layer developed on the third day after ligation and proliferation of submucosal connective tissue occurred on the 10th day after ligation. The changes in smooth muscle and connective tissue layers also progressed consistently during ureteric obstruction (P < 0.001 and < 0.005, respectively). The number and size of granular endoplasmic reticulum and Golgi apparatus in the smooth muscle cells increased after ureteric ligation and then caveolae exocytosis developed. Deposition of collagen fibres between muscle cells became apparent later. CONCLUSION: The rat model of hydrouropathy demonstrated a clear temporal relationship between the severity of hydroureter and the dynamic changes in the obstructed ureter and could be used as a conventional method for the study of obstructive ureter.

Animals↗

Impact of decreased serum transaminase levels on the evaluation of viral hepatitis in hemodialysis patients.

The value of serum transaminases (ST) in evaluating hepatitis B (HBV) and C (HCV) infection was studied in 217 hemodialysis (HD) patients and 804 normal controls. Mean serum aspartate aminotransferase (AST) was 22.3 (22.0-22.7) and 22.6 (21.6-23.6) IU/l or 0.371 (0.366-0.378) and 0.376 (0.36-0.393) mu kat/l in controls and HD patients, respectively (nonsignificant), while mean serum alanine aminotransferase (ALT) was 20.3 (19.9-20.7) and 16.3 (15.3-17.3) IU/l or 0.338 (0.331-0.345) and 0.271 (0.255-0.288) mu kat/l in these two groups (p < 0.001). However, both AST and ALT became significantly depressed in HD patients after adjusting for age, gender, HBV surface antigen (HBsAg) and anti-HCV. The usual practice of regarding AST and ALT as being 'abnormal' in evaluating viral hepatitis when they exceeded the upper reference range (40 and 46 IU/l or 0.666 and 0.766 mu kat/l in our laboratory) was then critically assessed by the receiver operating characteristic (ROC) curve. ROC analysis showed that ST was useless in detecting HBsAg, while the best cutoff point for detecting the presence of anti-HCV was 18 IU/l (0.3 mu kat/l) for AST and 16 IU/l (0.266 mu kat/l) for ALT in HD patients, respectively. These are considerably lower than the conventional criteria for an 'abnormal' ST. We conclude that ST are decreased in HD patients and that the cutoff value of ST for detecting HCV should be set at lower levels to enhance their diagnostic yield.

Alanine Transaminase↗

Prevalence and size of simple hepatic cysts in Taiwan: community- and hospital-based sonographic surveys.

Simple hepatic cysts are now being diagnosed more frequently with the widespread availability of sonographic imaging. Among the general population, the prevalence was reported to be between 0.1 and 2.5%, more so in women, and more often in the right lobe. We conducted this large scale community-based sonographic screening on simple hepatic cysts to explore the age- and sex-specific prevalence in Taiwan. We also conducted another hospital-based study to record the size of simple hepatic cysts. A total of 3,600 subjects in 8 communities were recruited and 156 simple hepatic cysts in 132 study subjects were detected. The overall prevalence is 3.60%. An increasing prevalence with age is demonstrated, ranging from 0.83% from below the age of 40 up to 7.81% of patients over 60 years old. The sizes of 219 simple hepatic cysts of 167 patients out of the hospital-based 5,893 patients were recorded in detail; 53% of cysts were of a diameter of between 1 and 3 cm, and only 7% were larger than 5 cm.

Adult↗

Coinfection study of precore mutant and wild-type hepatitis B-like virus in ducklings.

The precore mutant hepatitis B virus often emerges from a mixed infection with combined wild-type and precore mutant viruses. Nevertheless, the precore mutant does not seem to be an evolutionarily favored strain. To investigate the interaction between wild-type and precore mutant hepadnaviruses in an animal model of perinatal transmission, we used an e antigen-defective mutant duck hepatitis B virus with mutations inside the stem-loop structure of precore messenger RNA for this coinfection study. Thirty 1-day-old ducklings were infected with wild-type duck hepatitis B virus, precore mutant virus or both viruses. The amounts of viremia and the distribution of viruses were analyzed by spot hybridization, polymerase chain reaction, restriction fragment length polymorphism, cloning and sequencing. We found that all the ducklings became chronic carriers of duck hepatitis B virus. The precore mutant replicate was less active than wild-type duck hepatitis B virus, and it could be overgrown by wild-type virus during the course of coinfection. These results demonstrated that wild-type duck hepatitis B virus might become the predominant species in a situation similar to the perinatal cotransmission in human beings. This might at least in part explain why the prototype virus could prevail for years.

Animals↗

Paraumbilical vein tumor thrombosis in hepatocellular carcinoma.

To evaluate the incidence and role of paraumbilical vein tumor thrombosis (PUVT) in hepatocellular carcinoma, we studied 431 patients with hepatocellular carcinoma. Nine patients (2.1%), all male, presented with PUVT. Eight of those patients were positive for hepatitis B surface antigen, with the size of the main tumor being at least 9 cm. All nine patients had a combination of left lobe invasion and left portal vein thrombosis. The dilated paraumbilical vein was not present before the PUVT occurred. The survival time for these nine patients was from 3 to 180 days (median 25 days). The poor prognosis of patients with PUVT resulted from the advanced stage of hepatocellular carcinoma and already poor general physical condition of these patients, but was not a result of the PUVT itself. We present a possible sequence of formation of PUVT.

Adult↗

Hepatitis C virus infection as a risk factor for non-alcoholic liver cirrhosis in Taiwan.

To assess whether hepatitis C virus infection was a risk factor for the development of non-alcoholic liver cirrhosis, antibody to hepatitis C virus (anti-HCV; detected by a second generation HCV enzyme immunoassay), hepatitis B surface antigen (HBsAg; detected by radioimmunoassay) were tested in 150 cirrhotics and 150 sex-matched and age-matched healthy controls. The prevalence of anti-HCV and HBsAg in cirrhotics was higher than in controls (22.0%, 73.3% vs. 2%, 18.7%; P = 0.001). The prevalence of anti-HCV in HBsAg-negative cirrhotics (45.0%) was higher than that in HBsAg-positive patients (13.6%; P = 0.001). Both the anti-HCV and carriage of HBsAg were associated significantly with liver cirrhosis, showing odds ratio of 12.0 for HBsAg carriers and 13.8 for patients with anti-HCV. Compared with those without HBsAg and anti-HCV, there was a significantly positive linear trend for developing cirrhosis with the presence of HBsAg alone (odds ratio = 19.9), anti-HCV alone (odds ratio = 49.0), and those positive for HBsAg and anti-HCV (odds ratio = 81.8) (P = 0.00001). The population-attributable risk for developing liver cirrhosis was estimated as 10.8% for anti-HCV alone, 55.2% for HBsAg alone, and 9.4% for both anti-HCV and HBsAg in southern Taiwan. In conclusion, this study shows that hepatitis B and C virus infection act independently and synergistically in the development of non-alcoholic liver cirrhosis among Chinese in Taiwan.

Age Factors↗

Concentrating missense mutations in core gene of hepatitis B virus. Evidence for adaptive mutation in chronic hepatitis B virus infection.

To elucidate the temporal relationship between liver damage and mutation(s) in hepatitis B virus core gene, serial sera from a progressive liver disease patient and an asymptomatic carrier were studied. By direct sequencing, missense mutations in the core gene were only found in serum from the progressive liver disease patient during the period with frequent exacerbation. Using methods of cloning and sequencing, missense mutations were also found in clones derived from the progressive liver disease patient at a relatively early phase, but strains with a missense mutation from earlier sera did not exist in sera of a later period. Furthermore, there was a tendency of concentrating missense mutations in clones derived from the progressive liver disease patient. These data suggested that missense mutations in the core gene that occurred at an earlier phase might evoke an immune response to eliminate mutated virus and that concentrating missense mutations during a phase of exacerbation might be a result of adaptive mutation.

Adaptation, Physiological↗

Mutations of hepatitis B virus liver disease.

Individuals with chronic hepatitis B virus (HBV) infection are generally divided into asymptomatic healthy carriers and patients with chronic liver disease. Several studies have suggested that the core antigen (HBcAg) could be an immunological target of cytotoxic T lymphocytes (CTL). To investigate the possible pressure site from CTL, the entire core region of HBV DNA was sequenced in 30 subjects (10 asymptomatic healthy carriers and 20 patients with chronic liver disease). No significant changes in the nucleotide sequence and deduced amino acid residue were noted in the 10 healthy carriers. In contrast, a cluster of changes in small segment of 18 amino acids (codon 84 to 101 from the start of the core gene) was found in 15 of the 20 chronic liver disease patients. All these 15 patients had advanced liver diseases (chronic active hepatitis and cirrhosis), whereas only mild liver disease (chronic persistent hepatitis) was found in the 5 patients without mutation. These data suggest that this region with clustering mutations may play an important role in the pathogenesis of B viral liver disease, and the mutations in the region may be related to progressive liver disease.

Amino Acid Sequence↗

The role of hepatitis C virus in chronic hepatitis B virus infection.

To investigate the influence of hepatitis C virus (HCV) infection on patients with chronic hepatitis B virus (HBV), the presence of antibody against C100-3 antigen of HCV (anti-HCV) was examined in 420 patients with chronic HBV infection and 275 healthy subjects. It was found that the prevalence of HCV infection increased in parallel with the severity of liver damage. The positive rates of anti-HCV were as follows: healthy subjects, 2.9% (8/275); asymptomatic carriers, 2.6% (5/193); chronic hepatitis, 5.2% (3/58); liver cirrhosis, 11.4% (8/70); hepatocellular carcinoma (HCC), 12.1% (12/99). To elucidate the interaction of these two viruses in hepatocellular carcinoma, 128 HCC patients and 384 age-matched and sex-matched subjects were further analyzed. Eighty-seven of 128 HCC patients (68.0%) were only positive for HBsAg, 13 patients (10.1%) were only anti-HCV positive, and 12 (9.4%) were positive for both markers. The presence of HBsAg and anti-HCV was associated strongly with HCC. Moreover, the risk of HCC was significantly higher when both HBsAg and anti-HCV were present simultaneously. These results suggested that concurrent HCV infection might accelerate the progression of chronic HBV infection and may contribute to the pathogenesis of HCC in patients with chronic HBV infection.

Carcinoma, Hepatocellular↗

Precore mutations and core clustering mutations in chronic hepatitis B virus infection.

BACKGROUND: Mutant hepatitis B virus is often associated with severe liver damage. The purpose of this study is to elucidate the relationship between mutations in hepatitis B precore/core gene and the severity of liver damage. METHODS: The hepatitis B precore/core gene from 20 patients with chronic hepatitis B virus infection was studied by polymerase chain reaction and direct sequencing. RESULTS: Missense mutations in the core gene were only found in patients with chronic active hepatitis. Three mutation clustering regions of core gene, codons 48-60, 84-101, and 147-155, had higher substitution rates than other regions. All patients with chronic active hepatitis had missense mutation(s) either in codons 84-101 or in codons 48-60. There was a trend of increasing substitutions in the precore/core gene from e antigen-positive asymptomatic carriers to e antibody-positive patients with chronic active hepatitis. CONCLUSIONS: These data suggest that (1) severe liver damage in chronic hepatitis B virus infection is related to the clustering missense mutations in codons 48-60 and 84-101 of core gene and that (2) the emergence of precore stop codon mutation and missense mutations around the carboxy-terminal processing site of precore/core protein (codons 147-155) may be the adaptive mechanisms of hepatitis B virus to decrease production and secretion of viral protein and retain the viral persistence.

Adult↗

Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis.

Infection with hepatitis B virus leads to a wide spectrum of liver injury, including self-limited acute hepatitis, fulminant hepatitis, and chronic hepatitis with progression to cirrhosis or acute exacerbation to liver failure, as well as an asymptomatic chronic carrier state. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes. To investigate the reason why the extreme immunological attack occurred in fulminant hepatitis and severe exacerbation patients, the entire precore and core region of hepatitis B virus DNA was sequenced in 24 subjects (5 fulminant, 10 severe fatal exacerbation, and 9 self-limited acute hepatitis patients). No significant change in the nucleotide sequence and deduced amino acid residue was noted in the nine self-limited acute hepatitis patients. In contrast, clustering changes in a small segment of 16 amino acids (codon 84-99 from the start of the core gene) in all seven adr subtype infected fulminant and severe exacerbation patients was found. A different segment with clustering substitutions (codon 48-60) was also found in seven of eight adw subtype infected fulminant and severe exacerbation patients. Of the 15 patients, 2 lacked precore stop mutation which was previously reported to be associated with fulminant hepatitis. These data suggest that these core regions with mutations may play an important role in the pathogenesis of hepatitis B viral disease, and such mutations are related to severe liver damage.

Adult↗

The role of hepatitis B and C viruses in hepatocellular carcinoma in a hepatitis B endemic area. A case-control study.

To investigate the role of hepatitis B (HBV) and C viruses (HCV) in hepatocellular carcinoma (HCC) in an HBV endemic area and elucidate the interaction of these two viruses, a case-control study of 128 patients with HCC and 384 age-matched and sex-matched control subjects was done. The positive rates of hepatitis B surface antigen (HBsAg, 77.3%, 99 of 128) and anti-HCV (19.5%, 25 of 128) in patients with HCC were significantly higher than in control subjects (P less than 0.001). Both HBsAg and anti-HCV were important risk factors for HCC (relative risks, 13.96 and 27.12, respectively), and the risk for HCC was elevated significantly to 40.05 (95% confidence interval, 12.57 to 127.6) when HBsAg and anti-HCV were considered simultaneously. These results suggested that HBV and HCV were associated highly with HCC in an HBV endemic area and that these two viruses might contribute independent but synergistic effects to the pathogenesis of HCC.

Adult↗

Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization and analysis of prognostic factors.

A total of 100 patients with histologically proven hepatocellular carcinoma (HCC) underwent transcatheter arterial chemoembolization (TACE) and were followed for more than 1 year and 10 months. Portal vein branch thrombosis was diagnosed in 14 patients, and extrahepatic metastasis was noted in 11 subjects. The embolization material used was iodized oil (0.1-0.2 ml/cm tumor area at its maximal diameter), which was prepared by pumping with contrast agent and then mixed with anticancer drugs; Gelfoam particles measuring 1-2 mm in size were subsequently injected. The overall cumulative 0.5- 1-, 2-, and 3-year survival rates were 81%, 57%, 31%, and 21%, respectively. Patients with an intact capsule and those with solitary lesions, especially when the tumor diameter was < 5 cm, achieved a higher survival rate. In contrast, incomplete TACE, extrahepatic metastasis, and portal vein thrombosis were associated with the worst outcome. Patients with positive HBsAG and diffuse or multiple tumors also showed a poor outcome. Early diagnosis and early treatment of HCC are the keys for the achievement of better clinical results.

Adult↗

Radiotherapy in the treatment of hepatocellular carcinoma and its metastases.

A study was conducted to evaluate the effect of external radiation therapy on hepatocellular carcinoma (HCC) and its metastatic lesions. A total of 33 patients with cytopathologically proven HCC were subjected to radiation therapy over a 4-year period, and treatment was discontinued in 8 cases due to jaundice, severe discomfort, or early mortality. Thus, 25 patients with 28 lesions underwent irradiation with a total dose ranging between 3000 and 5600. Of these, seven were irradiated for liver tumors, and the results showed that two lesions decreased in size, the symptoms improved in 1 case, and another patient maintained stable disease for 4 months. Among the 21 metastatic lesions treated, only 2 patients failed respond to the treatment. Nine subjects were irradiated for bone metastases, and the bone pain subsided in all but one case. The survival for bone metastasis was as long as 23 months when the primary tumor was treated effectively. Three of the four cases of irradiated skin nodules disappeared and had not recurred after 5 months, 1 year, and 4 years, respectively. Tumor shrinkage or symptoms of relief were noted for three abdominal lymph nodes, one neck lymph node, one pleural tumor, and one lung tumor. Clinical improvement associated with a stable lesion was observed in two patients with brain metastasis. Follow-up revealed regrowth of the tumor or recurrence of symptoms in most of the patients. However, none of the patients died as a direct result of a metastatic lesion. Although external radiation therapy is palliative in intent, it appears to be useful in the treatment of HCC and its metastatic lesions.

Adult↗