Five-year experience with the development of a liver transplant program in Hong Kong.
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Biomedical subjects
Publications and source records attributed to C L Lai.
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BACKGROUND: Chronic hepatitis C virus (HCV) infection is prevalent among patients on renal replacement therapy. Viral genomic differences can contribute to diversities in clinical manifestation. The distribution of HCV genotypes depends on the geographical region and risk factors unique to the patient population. We determined the HCV genotypes in patients on renal replacement therapy in order to define the genotypic profile and examine the relationship between genotype, mode of renal replacement therapy, and the prevalence as well as severity of liver disease. METHODS: HCV genotypes were determined by restriction fragment length polymorphism and sequencing of the 5'-untranslated region in 21 renal allograft recipients, 29 patients on dialysis, and 26 non-renal failure controls. RESULTS: The most prevalent genotype among patients with renal failure was 1b (78%), followed by 1a (10%) and 6a (8%). 2 renal allograft recipients with 6a infection probably acquired HCV from the same donor. The relative prevalence of HCV genotypes was similar to that of controls. While renal allograft recipients demonstrated more severe liver disease than dialysis patients, the prevalence and severity of chronic hepatitis were similar between patients with 1b and non-1b infection. CONCLUSIONS: Resemblance of genotype distribution in Hong Kong to that of southern China and east Asia suggests common epidemiological evolution of HCV infection in these regions. Our results imply that in addition to viral characteristics, host factors such as the immunosuppressed state play an important role in the pathogenesis of liver disease in these patients.
OBJECTIVE: To determine the incidence rate (IR) and subtypes of dementia in southern Taiwan. METHODS: From a cohort of 2,915 community inhabitants aged 65 years and over, 2,507 and 2,175 subjects participated in the first- and second-year follow-up surveys, respectively. A two-phase study used the Mini-Mental State Examination in phase I and the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) neuropsychological battery and the neurobehavioral examination in phase II. We applied International Classification of Diseases (ICD)-10NA criteria for dementia, National Institute of Neurological and Communication Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) guidelines for Alzheimer's disease (AD), and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria for vascular dementia (VaD). RESULTS: The annual IR for total dementia was 1.28%, which increased with age from 0.77% for 65- to 74-year-olds to 6.19% for persons aged 85 years or older. AD (25 cases, 41.7%, IR=0.54%) was the most common cause of dementia, followed by VaD (19 cases, 31.7%, IR=0.41%) and mixed dementia (9 cases, 15.0%). After adjusting for sex, increasing age was significantly associated with total dementia and AD (p < 0.01). Illiteracy was associated with a marginally increased risk for total dementia (aRR=1.59, p < 0.1) as was being female for AD (aRR = 1.92, p < 0.1). The 2-year mortality rate was high among the demented (48% in total dementia, 38% in AD, and 60% in VaD). CONCLUSIONS: The age-specific incidence of dementia in Taiwan is approaching that of developed countries and the low prevalence of dementia (especially VaD) may be mainly due to the high mortality. Age was the major risk factor for total dementia and AD. Being female was probably a risk factor for AD, as was illiteracy for total dementia.
Stroke patients were assessed by brain CT scan, accompanied by demographic and clinical factors to predict the development of dementia following an ischemic episode. Vascular dementia was defined by NINDS-AIREN criteria. From 50 demented and 50 non-demented stroke patients, we analyzed the location of lesion, counted the numbers of lacunae, and semiquantitatively assessed the size of infarction, severity of overall white matter lesions (WML), and degree of brain atrophy. Compared to the non-demented patients, the demented patients: 1) encountered more stroke episodes (p < 0.001); 2) had more lacunae at bilateral basal ganglion (p < 0.001) or thalamus (p < 0.01); and 3) tended to have lesions in left cortex (p < 0.001), particularly a large infarct at the parietal (p < 0.001) or temporal lobe (p < 0.001). Periventricular changes (p < 0.001), subcortical WML (p < 0.001), overall WML (p < 0.001), and brain atrophy (p < 0.05) were also more severe in the demented group. However, no difference existed in demographic factors between the two groups. We concluded that several factors were important in developing dementia following an ischemic stroke, and the order by logistic regression would be: the severity of overall WML, left parietal infarct, and numbers of thalamic lacunae.
Somato-Sensory Evoked Potential (SSEP) and Peripheral Nerve Conduction (PNC) studies were performed in twenty patients with primary hypothyroidism to elucidate the changes of central and peripheral nervous systems in hypothyroid state and the effects of thyroxine replacement. Before thyroxine replacement therapy, eleven patients had significantly delayed SSEP (prolonged latencies of N9, N13, or N20), and only three patients had prolonged central conduction time (between N13 and N20). PNC abnormalities with decreased conduction velocity and diminished amplitudes were found in fourteen patients. After thyroxine treatment, both SSEP and PNC studies demonstrated significant improvement and paralleled the clinical neurological amelioration. The central and peripheral conduction velocities returned to normal limits, while the abnormality in amplitude still persisted. There were also discrepancies between SSEP and PNC studies in both the abnormality pattern and the recovery potential. Our observations may suggest: firstly, both the SSEP and PNC studies may be useful, alternative tools in monitoring the neurological disorders in hypothyroidism; and secondly, the pathogenesis of central and peripheral nervous dysfunction in hypothyroidism may be via different mechanisms.
This study was designed prospectively to evaluate the development of anti-p53 antibodies (Abs) in lung cancer patients in relation to their clinical outcome. Sera, derived from 125 lung cancer patients, consisting of 14 small cell lung cancers (SCLC) and 111 non-SCLCs (NSCLC), were surveyed. The p53-null human NSCLC cell line, NCI-H1299, transfected with a human mutant p53 gene was prepared as the source of p53 antigen for immunoblotting analyses to detect the presence of serum anti-p53 Abs. The control group included sera from 10 healthy adults and 14 patients with benign pulmonary diseases. Clinical data including staging and survival were recorded for statistical analyses. The anti-p53 Abs were found in 8% (10 of 125) of the lung cancer patients studied (8.1% of NSCLC versus 7.1% of SCLC patients), whereas none of the control sera had detectable anti-p53 Abs. The presence of anti-p53 Abs was closely associated with malignant pleural effusions (P = 0.001). The p53 Ab-positive patients had a worse prognosis than the p53 Ab-negative patients (P < 0.02; median survival, 20 versus 41 weeks). In both univariate and multivariate analyses, the tumor extension and probably the presence of anti-p53 Abs were significant predictors for cancer death. The development of anti-p53 Abs (n = 9) was also a predictor for poor survival in patients with malignant effusions (n = 51). In conclusion, the presence of serum anti-p53 Abs is closely associated with malignant pleural effusions in lung cancer patients. It may serve as a negative prognostic factor for survival independent of malignant pleural effusions and tumor staging.
Employing a Nicolet CA 100 machine, 20 patients of primary hypothyroidism were selected for electrophysiological studies, including somato-sensory evoked potential (SSEP), brainstem auditory evoked potential (BAEP), and visual evoked potential (VEP), to assess the central nerve conduction before and after administration of the thyroid hormone. Before thyroxine replacement therapy, the latencies of N9, N13, and N20 in SSEP showed significant delay, while the central conduction time (CCT) merely had a tendency of prolongation. In BAEP, the peak and interpeak latencies delayed significantly. Additionally, the latency and amplitude of VEP also had significant difference between patients and controls. After thyroxine replacement, the SSEP, BAEP, and VEP studies revealed significant improvement, in correlation with clinical amelioration. In conclusion, the central nerve conduction would be affected in primary hypothyroidism and the improvement was usually the case, reflecting the clinical recovery after appropriate treatment. The electrophysiological study provides an objective method for monitoring the function of central nervous system in hypothyroidism before and after thyroxine treatment.
In order to detect the dysfunction of central and peripheral nervous systems among rats with varied duration of hypothyroidism and to elucidate the pattern of recovery after thyroxine replacement, a series of BAEP and PNCS (Peripheral Nerve Conduction Study) were conducted and compared with age-matched controls. BAEP and PNCS were performed in three groups of hypothyroid animals 1, 3 and 5 months after thyroidectomy, respectively. Following initial electrophysiological assessment, thyroxine replacement was administered to each group of hypothyroid rats, and BAEP and PNCS were performed at two month intervals, up to two successive normal studies, or six months after the initiation of therapy, whichever came first. For BAEP, prolonged I-V interpeak latency was the most consistent abnormal finding in all groups of hypothyroid rats, and longer hypothyroid states correlated well with more severe central conduction disorder. Nevertheless, these abnormalities usually returned to normal after thyroxine replacement if the duration of hypothyroidism was less than 5 months. Regarding PNCS, all groups of thyroidectomized rats showed normal conduction before and after thyroxine therapy. The present study indicates that, in rats: (1) the peripheral nervous system seems to be more resistant to hypothyroidism than the central nervous system, or (2) the pathogenesis of central and peripheral nerve dysfunction in hypothyroid rats may occur through different mechanisms.
Lamivudine is a novel 2',3'-dideoxy cytosine analogue that has potent inhibitory effects on hepatitis B virus replication in vitro and in vivo. We performed a single-blind, placebo-controlled study to assess its effectiveness and safety in Chinese hepatitis B surface antigen (HBsAg) carriers. Forty-two Chinese HBsAg carriers were randomized to receive placebo (6 patients) or lamivudine orally in dosages of 25 mg, 100 mg, or 300 mg daily (12 patients for each dosage). The drug was given for 4 weeks. The patients were closely monitored clinically, biochemically, and serologically up to 4 weeks after drug treatment. All 36 patients receiving lamivudine had a decrease in hepatitis B virus (HBV) DNA values of >90% (P < .001 compared with placebo). Although 25 mg of lamivudine was slightly less effective than 100 mg (P = .011) and 300 mg (P = .005), it still induced 94% suppression of HBV DNA after the fourth week of therapy. HBV DNA values returned to pretreatment levels within 4 weeks of cessation of therapy. There was no change in the hepatitis B e antigen status or in aminotransferase levels. No serious adverse events were observed. In conclusion, a 4-week course of lamivudine was safe and effective in suppression of HBV DNA in Chinese HBsAg carriers. The suppression was >90% but reversible. Studies with long-term lamivudine administration should be performed to determine if prolonged suppression of HBV DNA can be achieved.
Adoptive immunity transfer has been reported to be effective in clearing chronic hepatitis B virus (HBV) infection. Two hundred twenty-six patients who received allogeneic bone marrow transplantation (BMT) between May 1990 and September 1995 were screened for hepatitis B markers. Twenty-one patients were hepatitis B surface antigen (HBsAg) positive before BMT. The median follow-up period was 20 months (range, 2-59 months). Two of these patients had sustained clearance of HBV infection after transplantation. Both patients were hepatitis B e antigen (HBeAg)-negative, hepatitis B e antibody (anti-HBe)-positive, and serum HBV DNA-negative (by dot-blot hybridization) before BMT. Both had a flare in the serum alanine transaminase (ALT) level around the time of HBsAg clearance. Sustained clearance of HBsAg was observed in 2 of the 5 patients who received hepatitis B surface antibody (anti-HBs)-positive marrow but in none of the 16 patients who received anti-HBs-negative marrow (P < .05). One additional patient who received anti-HBs-positive marrow had transient HBsAg seroconversion. Among the 18 patients who remained persistently HBsAg-positive after BMT, 3 had HBeAg seroconversion and 3 had reversion to HBeAg positivity. In this study, we found a significant association between clearance of HBV infection and anti-HBs-positive bone marrow donors. Adoptive immunity transfer is effective in clearing HBV from patients with chronic HBV infection.
The relationship between serum hepatitis Be antigen (HBeAg) and serum hepatitis B virus (HBV) DNA determined by two commercially available assays was examined in 345 Chinese patients with chronic HBV infection. HBV DNA was detected by these commercial assays in 85% of the HBeAg-positive patients. Discrepancies between test results were found to occur when serum HBV DNA levels were low (< 5 pg ml-1 for the Abbott Genostics and < 100 MEq ml-1 for Chiron Quantiplex assays). An equation for the conversion between results generated by these two assays was derived, which was found to be very similar to the equation recently described by Kapke et al.
BACKGROUND & AIMS: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for ethanol metabolism in humans. The human stomach has been documented to be involved in the metabolism of first-passed alcohol. The aim of this study was to determine ethanol-metabolizing activities in the stomach with regard to sex, age, enzyme pattern, and polymorphism. METHODS: A total of 209 surgical gastric mucosal specimens were investigated. The expression patterns of ADH and ALDH were identified by isoelectric focusing, and the activities were assayed spectrophotometrically. RESULTS: At 33 or 500 mmol/L ethanol, pH 7.5, the activities in the ADH3 1-1 phenotypic and mu-ADH-expressing mucosal specimens were significantly greater than that in the ADH3 1-2 phenotypic and mu-ADH absent mucosal specimens, respectively. The activities of the ALDH2-inactive phenotypes were significantly lower than that of the ALDH2-active phenotypes at 200 micromol/L acetaldehyde. The gastric ADH and ALDH activities were not significantly different between men and women with respect to age and genetic polymorphism. CONCLUSIONS: The stomach may contribute only a small portion of the alcohol metabolism observed in humans, and the liver may be the major site for first-pass metabolism. Differential expression patterns of ADH and ALDH in the alimentary tract suggest that different vulnerabilities to ethanol-induced mucosal injury may exist.
BACKGROUND: This study examined the efficacy and tolerability of interferon alpha-2b (IFN) in the treatment of chronic hepatitis C virus (HCV) infection in patients on maintenance haemodialysis. METHODS: A 24-month prospective cohort study was performed in 11 HCV RNA-positive haemodialysis patients, who were treated with IFN at 3 MU thrice weekly for 6 months. Serial biochemical and virological monitors included serum alanine aminotransferase levels, and HCV RNA by both qualitative PCR assay and quantitative bDNA assay. HCV genotypes were determined by PCR and nucleotide sequencing. Ten patients had baseline liver biopsy. RESULTS: HCV genotypes 1b and 2b were identified in 10 and one patients respectively. Six (55%) patients had biochemical and/or histological features of chronic active hepatitis before treatment. All 11 patients became HCV RNA-negative by PCR, with normalization of deranged aminotransferase levels, within 2-8 weeks of IFN therapy. HCV RNA reappeared in eight (73%) patients 2-8 weeks after the cessation of IFN, while biochemical relapse occurred in six (55%) patients. Sustained eradication of HCV was achieved in three (27%) patients. Sustained responders were characterized by pretreatment HCV RNA level < 3.5 x 10(5) Eq/ml as determined by the bDNA assay, and less severe histological abnormalities ('Total score' 1.7 +/- 1.2 compared to 5.4 +/- 2.2 in relapsers, P < 0.05). HCV RNA levels were similar before and after IFN treatment in non-responders and relapsers. Persistent malaise and poor appetite were noted in eight (73%) patients during IFN therapy. Other side-effects of IFN included the exacerbation of anaemia, induction of resistance to erythropoietin, weight loss, and reduced serum albumin level. CONCLUSIONS: Eradication of chronic HCV infection with IFN can be achieved in 27% of haemodialysis patients. Predictors of sustained response include low baseline HCV RNA level and mild liver pathology. Virological relapse can occur despite normal liver biochemistry. Exacerbation of anaemia, erythropoietin resistance, and malnutrition constitute the side-effects of IFN that deserve special attention in uraemic subjects.
OBJECTIVE: The authors report their experience with living donor liver transplantation (LDLT) using extended right lobe grafts for adult patients under high-urgency situations. SUMMARY BACKGROUND DATA: The efficacy of LDLT in the treatment of children has been established. The major limitation of adult-to-adult LDLT is the adequacy of the graft size. A left lobe graft from a relatively small volunteer donor will not meet the metabolic demand of a larger recipient. METHODS: From May 1996 to November 1996, seven LDLTs, using extended right lobe grafts, were performed under high-urgency situations. All recipients were in intensive care units before transplantation with five having acute renal failure, three on mechanical ventilation, and all with hepatic encephalopathy. The median body weight for the donors and recipients was 58 kg (range, 41-84 kg) and 65 kg (range, 53-90 kg), respectively. The body weights of four donors were less than those of the corresponding recipients, and the lowest donor-to-recipient body weight ratio was 0.62:1. The extended right lobe graft was chosen because the left lobe volume was <40% of the ideal liver mass of the recipient. RESULTS: Median blood loss for the donors was 900 mL (range, 700-1600 mL) and hospital stay was 19 days (range, 8-22 days). Homologous blood transfusion was not required. Two donors had complications (one incisional hernia and one bile duct stricture) requiring reoperation after discharge. All were well with normal liver function 5 to 10 months after surgery. The graft weight ranged from 490 g to 1140 g. All grafts showed immediate function with normalization of prothrombin time and recovery of conscious state of the recipients. There was no vascular complication, but six recipients required reoperation. One recipient died of systemic candidiasis 16 days after transplantation and 6 (86%) were alive with the original graft at a median follow-up of 6.5 months (range, 5-10 months). CONCLUSIONS: When performed by a team with experience in hepatectomy and transplantation, LDLT, using an extended right lobe graft, can achieve superior results. The technique extends the success of LDLT from pediatric recipients to adult recipients and opens a new donor pool for adults to receive a timely graft of adequate function.
PROBLEM: To develop simple and rapid assay procedures for determining human sperm acrosome reaction under various experimental conditions. METHODS: Specific monoclonal antibodies against human sperm acrosome were generated and utilized as probes for acrosome reaction assays by direct labelling of antibodies with fluorescein-isothiocyanate (FITC). RESULTS: Among the generated monoclonal antibodies, HS-63 was shown to react with antigens in the acrosome content of permeabilized acrosome-intact human sperm, but not with those of the live ones. HSA-10 was found to recognize antigens on the surface of sperm inner acrosome and to react with acrosome-reacted human sperm in suspension. Following a swim-up procedure, highly motile sperm were recovered and incubated in BWW medium at 37 degrees C for 18 h. The percentages of acrosome-reacted sperm were determined at various incubation times by using FITC-labeled HS-63 or HSA-10 as the indicators in 10 min direct immunofluorescent assay. With the FITC-labeled HS-63 probe, the percentage of positively stained human sperm fixed in methanol decreased significantly after 18 h of incubation from > 90 to 70-80%. In contrast, positively stained live human sperm by HSA-10 increased significantly from < 1% to 15-30%. A high correlation was obtained between the use of monoclonal antibodies and PSA (Pissum sativum agglutinin) for direct assessment of human sperm acrosome reaction. CONCLUSION: In view of the simplicity in assay procedures and evaluations, these FITC-labeled monoclonal antibodies are reliable probes for direct assessment of acrosomal status of human sperm.
BACKGROUND: Treatment of Helicobacter pylori infection prevents duodenal ulcer relapse. It has not been established if treatment of the infection heals duodenal ulcer. AIM: To test the hypothesis that treatment of the infection was associated with healing of duodenal ulcer. METHODS: A randomised, double blind placebo controlled trial was performed to study the efficacy of an antibiotic only regimen consisting of 300 mg metronidazole, 500 mg amoxycillin, and 250 mg clarithromycin, each given four times daily for two weeks, in the healing of duodenal ulcer as assessed by endoscopy. Symptoms were controlled with acetaminophen and antacids. RESULTS: Of 100 consecutive patients with endoscopically established duodenal ulcer, 97 with positive rapid urease test on antral biopsy specimens were admitted into the study and 81 completed the trial. Of these, 40 were randomised to receive antibiotics and 41 to receive placebo. Treatment with antibiotics resulted in 92.5% (95% confidence interval (95% CI) 84.3-100) healing at four weeks and 100% at eight and 12 weeks; the corresponding healing rates for placebo treatment were respectively, 36.6%, 61%, and 63.4% (95% CIs 21.8-51.3, 46.0-75.9, and 48.7-78.2 respectively). The differences between the two treatment groups were significant at p < 0.001 at each time point and by life table analysis. Clearance of H pylori as assessed by urease test on antral biopsy specimens at four weeks and eradication of the organism as determined by 13C-urea breath test at eight weeks were achieved in 85% and 62.5% of patients respectively. Duodenal ulcer healed at four weeks in 87.2% and 86.2% (95% CIs 76.7-97.7 and 73.7-98.8) of patients in whom H pylori clearance or eradication, was achieved, versus 42.9% and 51.9% (95% CIs 27.9-57.8 and 38.3-65.5; p < 0.001 and < 0.003 respectively) in whom these processes failed. Stepwise discriminant analysis on 32 clinical, personal, and endoscopic characteristics as well as H pylori clearance and eradication identified H pylori clearance as the most discriminative variable for the healing of duodenal ulcer at four weeks, followed by ulcer depth and eradication of the organism. CONCLUSIONS: Treatment with an antibiotic only regimen was effective for the healing of duodenal ulcer, and clearance as well as eradication of H pylori contributed significantly to the healing. The results constituted the strongest evidence to date that H pylori infection was aetiologically related to duodenal ulceration, and support the concept of treating duodenal ulcer associated with H pylori as an infection and relieving its symptoms with acid reducing agents such as antacids.
Pleural effusion is often a manifestation of the superior vena cava (SVC) syndrome. However, pleural effusion has never been reported to be a cause of the SVC syndrome. We report the case of a 68 yr old male patient who presented with SVC syndrome and respiratory failure, both attributable to an encapsulated pleural effusion over the right upper mediastinum. Simple drainage was performed as a diagnostic and therapeutic procedure. The pleural effusion was confirmed to be a tuberculous empyema. Chest computed tomography (CT) scan is the most appropriate initial diagnostic procedure for superior vena cava syndrome.