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Ching Lung Lai

Publications and source records attributed to Ching Lung Lai.

13 recordsLinked to original sources

Mannose-binding lectin in chronic hepatitis B virus infection.

Mannose binding lectin (MBL) is a pattern-recognition molecule of the innate immune system. The roles of MBL and its gene (mbl2) polymorphisms, -221X/Y and codon 54A/B, in hepatitis B virus (HBV) infection were investigated in this study. We recruited 320 nonprogressed hepatitis B surface antigen (HBsAg) carriers; 199 progressed HBsAg carriers with hepatocellular carcinoma or cirrhosis; 87 spontaneously recovered individuals who were HBsAg negative and anti-HBs and anti HBc positive; and 484 controls who were naïve to HBV. There was no significant difference between nonprogressed carriers, spontaneously recovered individuals, and controls in terms of serum MBL levels and mbl2 polymorphisms distributions. However, the low MBL genotypes had a dose-dependent correlation with the cirrhosis and hepatocellular carcinoma in progressed carriers with odds ratios of 1.36 and 3.21 for the low and extremely low MBL genotypes, respectively (P = .01). The low-expression promoter haplotype XA (OR = 1.97) and the mutant haplotype YB (OR = 1.90) were also associated with the cirrhosis and hepatocellular carcinoma (P = .002). As expected, the lower serum MBL levels in progressed carriers as compared with nonprogressed carriers were due to an overrepresentation of low and extremely low MBL genotypes. Moreover, MBL could bind HBsAg in a dose- and calcium-dependent and mannan-inhibitable manner in vitro, suggesting that binding occurs via the carbohydrate recognition domains. This binding also enhanced C4 deposition. In conclusion, these results suggest that low MBL genotypes associate with the occurrence of cirrhosis and hepatocellular carcinoma in progressed HBsAg carriers, and MBL can bind HBsAg.

Adult↗

PIN1 overexpression and beta-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma.

The peptidyl-proplyl-isomerase, PIN1, upregulates beta-catenin by inhibiting its interaction with APC. beta-catenin accumulation occurs in about 70% of hepatocellular carcinoma (HCC), of which only 20% are due to beta-catenin mutations. The role of PIN1 in beta-catenin upregulation in HCC was investigated. PIN1 was shown to be overexpressed in more than 50% of HCC. All cases with PIN1 overexpression also showed beta-catenin accumulation, with 68% of cases showing concomitant beta-catenin and cyclin D1 accumulation. PIN1 was shown to contribute to beta-catenin and cyclin D1 overexpression directly by in vitro cell-line transfection experiments. Finally, we showed that PIN1 overexpression and beta-catenin gene mutations appeared to be mutually exclusive events, leading to beta-catenin accumulation in HCC. These results showed that PIN1 overexpression leading to beta-catenin accumulation might be a critical event in hepatocarcinogenesis, and that PIN1 is a potential target for therapeutic intervention in HCC.

Carcinoma, Hepatocellular↗

Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation: a protocol with early elimination of steroids and reduction of tacrolimus dosage.

A prospective evaluation was performed to study the potential benefits of the use of interleukin-2 receptor antibody (IL-2Rab) in the induction therapy with early elimination of steroid and reduction of tacrolimus dosage in liver transplant recipients among whom 94% had chronic hepatitis B infection. Thirty-one liver transplant recipients who underwent right-lobe live donor (n = 19) or cadaveric (n = 12) liver transplantation received IL-2Rab, basiliximab 20 mg intravenously within 6 hours of graft reperfusion and on postoperative day 4 (IL-2ab group). Two doses of steroid injection were given intraoperatively and on postoperative day 1. Postoperative immunosuppression was maintained with oral tacrolimus and mycophenolate mofetil without the use of steroids. The operative outcomes were compared with those of 49 patients who received standard immunosuppressive regimen consisting of tacrolimus and corticosteroid (steroid group). The overall postoperative morbidity and hospital stay were comparable between the 2 groups. There were significantly lower incidences of postoperative new-onset diabetes (0% vs 28%, P =.011), acute cellular rejection (6% vs 27%, P =.038), and cytomegalovirus (CMV) antigenemia (0% vs 18%, P =.011) in the IL-2Rab group compared with the steroid group. The blood cholesterol level at 6 months after transplantation was significantly lower in the IL-2Rab group (median, 4.0 vs 4.4 mmol/L, P =.007). On follow-up, none of the patients in the IL-2Rab group had hepatitis B viral breakthrough or hepatocellular carcinoma (HCC) recurrence, whereas 1 and 3 patients in the steroid group developed these complications, respectively. In conclusion, treatment of liver transplant recipients with IL-2Rab with early withdrawal of steroids and reduction of tacrolimus dosage is associated with lower incidences of postoperative new-onset diabetes, acute cellular rejection, and CMV antigenemia, as well as a lower serum cholesterol level. Further studies and long-term follow-up are required to document their potential benefits on hepatitis B and HCC recurrences.

Adrenal Cortex Hormones↗

Lessons learned from one hundred right lobe living donor liver transplants.

OBJECTIVE: To evaluate the first 100 adult right lobe living donor liver transplants (LDLT) in a single center to determine whether the results have improved with technical modifications and better experience. SUMMARY BACKGROUND DATA: Right lobe LDLT has been increasingly performed for adults with end-stage liver disease. Numerous modifications in technique have been introduced, and a learning curve is likely in view of its complexity. METHODS: One hundred consecutive adult right lobe LDLTs performed between May 1996 and May 2002 were retrospectively studied by comparing the first 50 (group 1) with the last 50 cases (group 2). The median follow-up was 37 (27 to 79) months for group 1 and 15 (7 to 27) months for group 2. RESULTS: The characteristics of donors and liver grafts were similar. In group 2, fewer recipients were intensive care unit (ICU)-bound or had hepatorenal syndrome before transplantation, and there was a lower disease severity as shown by a lower Child-Pugh score and Model for End-Stage Liver Disease (MELD) score. Significant improvements were found in the operation time, blood loss, ICU stay, and postoperative complication rate of the donors and in the operation time, transfusion requirements, number of reoperations, ICU stay, and hospital stay of the recipients in group 2. The hospital mortality rate of recipients was reduced from 16% to 0% (P = 0.006). Graft survival rates at 12 months and 24 months were improved from 80% and 74%, respectively, in group 1 to 100% and 96%, respectively, in group 2 (P = 0.002). After adjusting for differences in recipient risk factors (ICU-bound, hepatorenal syndrome, Child-Pugh score, and MELD score) in a multivariate Cox model, recipients in group 2 had significantly lower risk of graft loss (relative risk compared with group 1, 0.13; 95% CI, 0.03 to 0.66; P = 0.014). CONCLUSIONS: There is a learning curve in adult right lobe LDLT. The results have significantly improved with technical refinement and better experience.

Adult↗

Therapeutic advances in chronic hepatitis B.

In conclusion, most patients with CHB have their disease controlled by lamivudine therapy, and those with elevated ALT respond well. The incidence of YMDD-variant increases with duration of treatment, although patients with YMDD still gain clinical benefit from continued lamivudine therapy and seroconversion can still be achieved. Lamivudine has shown efficacy in HBeAg-negative patients and those with decompensated cirrhosis. In long-term use, lamivudine has been found to be well tolerated. Even in patients with YMDD-variant HBV, no increase in hepatic serious adverse events was seen. In patients with decompensated CHB the combination of lamivudine and adefovir dipivoxil showed significant efficacy. After only 24 weeks, clinical improvements in liver function were seen.

Clinical Trials as Topic↗

Practical difficulties in the management of hepatitis B in the Asia-Pacific region.

The Asia-Pacific Expert Committee on Hepatitis B Management recently reviewed the impact of hepatitis B in the region and assessed the differences and similarities observed in the practical management of the disease in individual Asia-Pacific countries. Hepatitis B is a major health concern in the Asia-Pacific region, and of all chronically infected carriers worldwide, approximately 75% are found in Asia. The disease poses a considerable burden on healthcare systems, and is likely to remain a cause of substantial morbidity and mortality for several decades. Disease prevention activities, including screening and vaccination programs, have been implemented successfully in some Asia-Pacific countries and similar measures are being established in other parts of the region. The management of hepatitis B in the Asia-Pacific varies throughout the region, with each country confronting different issues related to treatment options, disease monitoring and duration of therapy. The influence of cost, availability of diagnostic equipment, and patient awareness and compliance are of additional concern. Although guidelines such as those developed by the Asian Pacific Association for the Study of the Liver have been created to address problems encountered in the management of hepatitis B, many physicians in the region still find it difficult to make satisfactory management decisions because of the treatment choices available. This article examines the different approaches to hepatitis B management in a number of Asia-Pacific countries, and highlights the difficulties that can arise when adhering to treatment guidelines and disease prevention solutions that have proved to be successful in the region.

Asia↗

Viral hepatitis B.

More than 400 million people worldwide are chronically infected by the hepatitis B virus. The virus is responsible for more than 300000 cases of liver cancer every year and for similar numbers of gastrointestinal haemorrhage and ascites. Major breakthroughs have been achieved in diagnosis and treatment of this virus. Hepatitis B vaccine reduces incidence of liver cancer. As with hepatitis C, advances have been made in molecular virology, especially for naturally occurring and treatment-induced mutant viruses. The clinical significance of low viral load and genotypes are also under investigation. Currently available monotherapies-interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus, but greatly reduce its replication, necroinflammatory histological activity, and progression of fibrosis. Lamivudine, and presumably other nucleoside analogues, can reverse cirrhosis of the liver.

Adenine↗

Viral hepatitis C.

More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for more than 100000 cases of liver cancer per year, with similar numbers of digestive haemorrhage and ascites episodes. Major breakthroughs have been made in diagnosis and treatment, and advances in molecular biology mean that the replicative state of the virus can now be assessed. Genotype and serum viral load are useful predictors of response to treatment. The combination of pegylated interferon and ribavirin can eradicate the virus in more than 50% of patients. These antiviral treatments reduce liver fibrosis progression and can reverse cirrhosis. Unfortunately, even in developed countries, death due to hepatitis C is increasing because of inadequate detection and treatment.

Adult↗

Significance of hepatitis B genotype in acute exacerbation, HBeAg seroconversion, cirrhosis-related complications, and hepatocellular carcinoma.

The pathologic role of hepatitis B virus (HBV) genotype in Chinese patients with HBV infection is largely unknown. We examined the relationship between HBV genotypes, and hepatitis B e antigen (HBeAg) seroconversion, acute exacerbation, cirrhosis-related complications, and precore/core promoter mutations. Three hundred forty-three HBV patients (288 were asymptomatic, 55 presented with cirrhosis-related complications) were recruited. HBV genotypes and precore/core promoter mutations were determined by line probe assays. Genotypes B and C were the 2 most common genotypes, contributing 28% and 60%, respectively. The median age of HBeAg seroconversion for patients with genotype B was 9 years earlier than patients with genotype C (P =.011). There were no differences in the liver biochemistry, HBV DNA level, and cumulative risk of acute exacerbation (defined as increased alanine aminotransferase level > or =1.5 x upper limit of normal) between patients with genotypes B and C. There was a trend for patients with genotype B to have a higher cumulative rate of HBeAg seroconversion compared with patients with genotype C at the initial follow-up of 6 years (P =.053), but this difference became insignificant during subsequent follow-up. The prevalence of both genotypes was the same in patients with and without cirrhosis-related complications and/or hepatocellular carcinoma. Genotype B was associated with precore mutations (P <.0001), whereas genotype C was associated with core promoter mutations (P <.0001). In conclusion, although patients with genotype B had earlier HBeAg seroconversion, there was no significant reduction in the risk of development of complications. Genotypes B and C are associated with high prevalence of precore and core promoter mutations, respectively.

Adolescent↗

Transarterial chemoembolization for inoperable, early stage hepatocellular carcinoma in patients with Child-Pugh grade A and B: results of a comparative study in 96 Chinese patients.

OBJECTIVE: The efficacy of transarterial chemoembolization (TACE) in prolongation of survival is controversial. We conducted a comparative study to determine whether TACE treatment had any survival benefit for patients with unresectable hepatocellular carcinoma (HCC) and with relatively preserved liver function. METHODS: In all, 96 patients with unresectable HCC of Okuda stage I or II and Child-Pugh grade A or B were recruited. A total of 80 patients (group 1) who received TACE were compared to 16 patients (group 2) who were treated conservatively. RESULTS: The median survival time of group 1 patients was significantly longer than that of group 2 patients (31.2 vs 14.1 months respectively, p = 0.0126). The cumulative survival rates at 6 months, 1 yr, 2 yr, 3 yr, and 4 yr of group 1 compared to group 2 were as follows: 93.8% versus 62.5% (p = 0.002); 86.3% versus 62.5% (p = 0.023); 78.8% versus 50% (p = 0.017); 57.5% versus 50% (p = ns); and 51.3% versus 43.8% (p = ns), respectively. Tumor response was observed in 28% of patients receiving TACE. Patients with higher pretreatment albumin levels, lower pretreatment alpha-fetoprotein levels, and Okuda stage I disease were associated with a favorable response to TACE. CONCLUSION: TACE treatment improved survival in patients with unresectable HCC in the early stages and with relatively preserved liver function.

Adult↗

Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use.

BACKGROUND: The role of gastric acid suppression in preventing the recurrence of ulcer complications after the eradication of Helicobacter pylori infection in patients taking long-term low-dose aspirin is uncertain. METHODS: We enrolled 123 patients who had ulcer complications after using low-dose aspirin continuously for more than one month and who had H. pylori infection. After the ulcers had healed and the H. pylori infection was eradicated, the patients were randomly assigned to treatment with 30 mg of lansoprazole daily or placebo, in addition to 100 mg of aspirin daily, for 12 months. The primary end point was the recurrence of ulcer complications. RESULTS: During a median follow-up of 12 months, 9 of the 61 patients in the placebo group (14.8 percent), as compared with 1 of the 62 patients in the lansoprazole group (1.6 percent), had a recurrence of ulcer complications (adjusted hazard ratio, 9.6; 95 percent confidence interval, 1.2 to 76.1). Of these 10 patients, 4 had evidence of a recurrence of H. pylori infection and 2 had taken nonsteroidal antiinflammatory drugs before the onset of complications. Patients in the lansoprazole group were significantly less likely to have a recurrence of ulcer complications than patients in the placebo group (P=0.008). There was no significant difference in mortality between the two groups. CONCLUSIONS: In patients who had ulcer complications related to the long-term use of low-dose aspirin, treatment with lansoprazole in addition to the eradication of H. pylori infection significantly reduced the rate of recurrence of ulcer complications.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Pyogenic liver abscess: retrospective analysis of 80 cases over a 10-year period.

BACKGROUND: A total of 80 patients with pyogenic liver abscess managed at a single institution over a 10-year period were studied. METHODS: The clinical features, laboratory, imaging, and microbiologic findings, management strategy, and final outcome were studied. RESULTS: Fever and chills, leucocytosis and elevated alkaline phosphatase were the most common clinical and laboratory findings. Forty-one percent of patients were diabetic and 61% had biliary pathology. Systemic antibiotics and image-guided aspiration had a success rate of 94%. By multiple logistic regression analysis, malignancy on presentation (P = 0.011) was an independent risk factor associated with mortality. A past history of endoscopic sphincterotomy was an independent factor associated with resolution of liver abscess within 6 weeks (P = 0.03). CONCLUSION: Pyrexia, leucocytosis, elevated alkaline phosphatase, presence of diabetes, and underlying biliary pathology are common clinical and laboratory findings in patients with pyogenic liver abscess. Malignancy was associated with a poor outcome. Previous endoscopic sphincterotomy was a good prognostic factor for early resolution.

Adult↗