Publications by authors named "Nancy Wai Yee Leung"

8 Publications

  • Page 1 of 1

Redefining fatty liver disease: an international patient perspective.

Lancet Gastroenterol Hepatol 2021 01 5;6(1):73-79. Epub 2020 Oct 5.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia. Electronic address:

Despite its increased recognition as a major health threat, fatty liver disease associated with metabolic dysfunction remains largely underdiagnosed and undertreated. An international consensus panel has called for the disease to be renamed from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD) and has suggested how the disease should be diagnosed. This Viewpoint explores the call from the perspective of patient advocacy groups. Patients are well aware of the negative consequences of the NAFLD acronym. This advocacy group enthusiastically endorses the call to reframe the disease, which we believe will ultimately have a positive effect on patient care and quality of life and, through this effect, will reduce the burden on health-care systems. For patients, policy makers, health planners, donors, and non-hepatologists, the new acronym MAFLD is clear, squarely placing the disease as a manifestation of metabolic dysfunction and improving understanding at a public health and patient level. The authors from representative patient groups are supportive of this change, particularly as the new acronym is meaningful to all citizens as well as governments and policy makers, and, above all, is devoid of any stigma.
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January 2021

A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone.

Ann Intern Med 2005 Feb;142(4):240-50

Chinese University of Hong Kong and Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China.

Background: Conventional interferon and lamivudine monotherapy are unsatisfactory in treating hepatitis B virus (HBV) infection.

Objective: To evaluate the efficacy and safety of pegylated interferon-alpha2b and lamivudine combination therapy for chronic hepatitis B.

Design: Randomized, controlled, open-label trial.

Setting: Outpatient clinic in a referral center.

Participants: 100 treatment-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and moderately elevated alanine aminotransferase levels.

Measurement: The primary end point was sustained virologic response (HBeAg seroconversion and HBV DNA level < 500,000 copies/mL) at 24 weeks after cessation of treatment.

Intervention: A staggered regimen of combination therapy with pegylated interferon-alpha2b (1.5 microg/kg of body weight per week; maximum, 100 microg) given for 32 weeks plus lamivudine (100 mg daily) given for 52 weeks versus lamivudine (100 mg daily) monotherapy given for 52 weeks. Of the 100 participants, 96% completed treatment and 80% completed post-treatment follow-up.

Results: The rate of sustained virologic response was 36% for the combination treatment group and 14% for the lamivudine monotherapy group (absolute difference, 22 percentage points [95% CI, 6 to 38 percentage points]). End-of-treatment outcomes showed that, compared with monotherapy, patients receiving combination therapy more often had virologic response (60% vs. 28% [absolute difference, 32 percentage points (CI, 14 to 50 percentage points)]); had more substantial reductions of HBV DNA (3.91 log10 copies/mL vs. 2.83 log10 copies/mL); and less often had lamivudine-resistant mutants (21% vs. 40%). The percentages of patients with normalization of alanine aminotransferase levels and histologic improvement did not differ. Adverse effects, such as transient influenza-like symptoms, alopecia, and local erythematous reactions, were more common with combination therapy.

Limitations: This study lacked a double-blind design and was conducted at 1 institution. Because of the staggered pegylated interferon-lamivudine regimen, patients assigned to combination therapy received treatment for 8 weeks longer than those assigned to monotherapy.

Conclusions: In patients with HBeAg-positive chronic hepatitis B, staggered combination treatment with pegylated interferon-alpha2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy.
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February 2005

Quantitative assessment of fibrosis in liver biopsies from patients with chronic hepatitis B.

Liver Int 2004 Dec;24(6):611-8

Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.

Background/aim: Accurate histological assessment of liver fibrosis is essential in the management of chronic hepatitis B (CHB). Although semi-quantitative scoring systems describe well the pathological patterns of hepatic structure, they produce fibrosis evaluation that is not very precise. Image analysis or morphometry has the theoretical advantage of providing truly quantitative data.

Patients And Methods: The present study aimed at validating a new image analysis system, Bioquant Nova Prime, in estimating collagen content in liver biopsy samples from patients with CHB. The biopsies were stained with picrosirius red and the areas of collagen were measured. The results were correlated with laboratory parameters and Ishak modified histological scores. Discriminative reliability of morphometry was determined using receiver operating characteristics (ROC) analysis.

Results: There was excellent interobserver agreement (r=0.84-0.94, P<0.01) in the morphometric analysis. Significant correlations between the quantitative morphometric data and the semi-quantitative score (Spearman's r=0.68-0.78, P<0.001) were also demonstrated. Excellent discriminative power of morphometry in differentiating mild from advanced fibrosis and cirrhosis from absence of cirrhosis was shown by the ROC analysis.

Conclusions: Our results validated the use of Bioquant Nova Prime in estimating collagen content in liver biopsies. We showed that morphometry is a sensitive method of liver fibrosis quantification in CHB and complements semi-quantitative histological scoring system. This tool, with its reliable intraassay variability, could be of special value in assessing histological response to treatment after anti-viral or anti-fibrotic therapy.
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December 2004

Fulminant hepatic failure in a patient with inactive HBsAg carrier state, acute hepatitis E and thyrotoxicosis.

Hepatol Res 2003 Nov;27(3):248-251

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong

A 38-year-old man presented with jaundice and significant weight loss. Investigations found positive hepatitis B surface antigen (HBsAg). His hepatitis B e antigen (HBeAg) was negative and HBV DNA was not detectable in the blood. Further tests revealed that he also had acute hepatitis E infection and uncontrolled thyrotoxicosis. The hypercatabolic state of coexisting thyrotoxicosis and acute hepatitis caused marked weight loss and clinical deterioration with fulminant hepatic failure. Institution of successful anti-thyroid treatment and supplemental nutrition effectively reversed the disease progression and the patient recovered fully.
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November 2003

Genotype B hepatitis B virus is associated with severe icteric flare-up of chronic hepatitis B virus infection in Hong Kong.

Am J Gastroenterol 2002 Oct;97(10):2629-33

Objective: We aimed to investigate the association of viral genotype and the development of icteric flare-up (IF) in chronic hepatitis B virus (HBV) infection.

Methods: Twenty-one consecutive patients suffering from IF of chronic HBV infection, defined as elevation of ALT over five times the upper limit of normal, together with either bilirubin > 50 IU/L or elevated bilirubin plus PT > 3 s prolonged, were studied. Patients from three stages of HBV-related chronic liver disease were studied as controls: 1) asymptomatic carriers (31 patients), defined as persistent normal ALT for at least 2 yr; 2) active early cirrhosis (49 patients), defined as Child's A liver cirrhosis plus HBV DNA > 106 Eq/ml; and 3) decompensated cirrhosis (31 patients), defined as Child's B or C liver cirrhosis with complications. Restriction fragment length polymorphism was used for genotyping.

Results: Only genotype B and C HBV were identified in our studied cohort. Ninety-one percent of patients suffering from IF were infected by genotype B HBV (p < 0.001 vs asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients). On the contrary, genotype C HBV was the predominant strain at different stages of chronic liver disease; no statistical difference was found on the relative prevalence of genotype B/C HBV among asymptomatic carriers, early cirrhosis patients, and decompensated cirrhosis patients.

Conclusions: Genotype B HBV is associated with IF among chronic HBV-infected patients in Hong Kong, whereas genotype C HBV is more prevalent at all stages of chronic liver disease. Our findings suggested that the two different HBV genotypes might have different pathogenic mechanisms of liver damage.
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October 2002

Occult HBV infection in cryptogenic liver cirrhosis in an area with high prevalence of HBV infection.

Am J Gastroenterol 2002 May;97(5):1211-5

Department of Medicine & Therapeutics and Microbiology, the Chinese University of Hong Kong, Shatin.

Objectives: Hepatitis B surface antigen (HBsAg) is often used as the serological marker to screen for hepatitis B virus (HBV) infection in the investigation of liver cirrhosis. In Hong Kong, where HBV infection is endemic, some patients may have persistent viral infection after the loss of HBsAg. We aimed to investigate 1) the prevalence of occult HBV infection in cryptogenic liver cirrhosis in Hong Kong and 2) the role of HBV "a" determinant mutations among these patients.

Methods: Twenty-eight patients with cryptogenic liver cirrhosis (group I), 49 subjects with no liver disease (group II), and 26 patients with HBV-related cirrhosis (group III) were studied. HBV DNA was determined by the cross-linking assay (sensitivity = 0.5 mEq/ml) and polymerase chain reaction (PCR). Occult HBV infection was defined as HBV DNA detectable by PCR among patients with negative HBsAg.

Results: Eighty-nine percent and 92% of patients in groups I and II, respectively, had positive anti-HBs and/or anti-hepatitis B core. Nine (32%), no (0%), and 14 (54%) patients in groups I, II, and III, respectively, had detectable HBV DNA by PCR (group I vs group II, p < 0.001; group I vs group III, p = 0.36). Four patients in group I had HBV DNA detectable by the cross-linking assay (median = 5.98 mEq/ml, range = 3.1-8.01). "a" determinant mutations were detected in two patients in group I (K122N and G145R, C125A) and one patient in group II (1126N).

Conclusions: Occult HBV infection is common among patients with cryptogenic liver cirrhosis, and it cannot be explained by mutations in the HBV "a" determinant.
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May 2002

Survival and prognostic indicators in patients with hepatitis B virus-related cirrhosis after onset of hepatic decompensation.

J Clin Gastroenterol 2002 May-Jun;34(5):569-72

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong ROC.

Goals: To determine the 2-year survival and prognostic indicators of hepatitis B virus-related cirrhosis after the onset of hepatic decompensation.

Background: Chronic hepatitis B (CHB) patients with cirrhosis and resultant hepatic decompensation have reduced survival. However, the natural history of these patients has not been well characterized in previous studies. Better understanding of survival and prognostic indicators is essential in management of these patients, especially in determining who should be candidates for orthotopic liver transplantation.

Study: This is a retrospective longitudinal study of 96 patients with CHB-related cirrhosis after the onset of hepatic decompensation. The overall survival was ascertained, and clinical and laboratory variables were analyzed. Significant prognostic indicators for survival at 2 years were determined using univariate and multivariate analyses with Cox regression model.

Results: The overall survival was 80% at 2 years after onset of decompensation. With univariate and multivariate analyses, hepatic encephalopathy and hypoalbuminemia less than 2.8 g/dL were significant prognostic indicators of poor survival probability. The hazard ratios were 5.22 (95% confidence interval, 1.67-16.3) and 8.57 (95% confidence interval, 1.94-37.8), respectively. Patients with hypoalbuminemia less than 2.8 g/dL had a 2-year survival of only 62%.

Conclusions: Our study showed that of CHB patients who developed the first episode of hepatic decompensation, those with hepatic encephalopathy or significant hypoalbuminemia or both have worse prognoses. They should be considered potential candidates for liver transplantation.
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June 2002

Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection.

Am J Gastroenterol 2002 Feb;97(2):406-12

Department of Medicine, The Chinese University of Hong Kong.

Objectives: We aimed to study the relationship between the hepatitis B virus (HBV) genotypes, core promoter/precore stop codon mutations, and histological liver damage among hepatitis B e antigen (HBeAg)-negative patients.

Methods: Liver biopsy specimens of 55 HBeAg-negative chronic HBV-infected patients were studied. A histological activity index was scored for degree of necroinflammation (HAI-NI) and fibrosis (HAI-F) as described by Knodell et al. HBV DNA was determined by a cross-linking assay and polymerase chain reaction (PCR) at the core promoter/precore region and the S region. PCR-positive samples were directly sequenced for core promoter and precore mutations and examined by restriction fragment length polymorphism for genotyping.

Results: Forty-one males and 14 females at a median age of 43 were studied. HBV DNA was detectable in 32 (58%) and 37 (67%) patients by the cross-linking assay and PCR, respectively, at the time of liver biopsy. The median (range) HAI-NI and HAI-F scores were 5 (1-10) and 2 (0-4), respectively. HBV DNA detectable by either the cross-linking assay or PCR was associated with a higher HAI-NI score. Eleven and 31 patients had genotypes B and C HBV, respectively. Genotype C HBV was associated with higher HAI-NI than genotype B HBV. Core promoter mutations and precore stop codon mutation were detected in 74% and 40% patients, respectively, but they were not associated with higher HAI-NI or HAI-F scores.

Conclusions: Detectable HBV DNA and genotype C HBV, but not core promoter or precore stop codon mutations, are associated with more severe liver damage in HBeAg-negative patients.
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February 2002