Non-alcoholic fatty liver disease: an expanding problem with low levels of awareness in Hong Kong.

BACKGROUND AND AIM: With the Westernization of the lifestyle and the rising prevalence of obesity and diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is an emerging health problem in the Asia-Pacific region. The purpose of this study was to determine the awareness of NAFLD among the general population in Hong Kong. METHODS: A random telephone survey was conducted from September 2007 to January 2008 using a structured multiple-choice questionnaire. Subjects were Hong Kong residents aged 18 or above who spoke Cantonese. RESULTS: In the first phase of the telephone survey, 521 subjects were interviewed and the results showed that as high as 83% of respondents had never come across the term 'NAFLD'. Upon completion of the second phase telephone survey, a total of 508 respondents who had heard of NAFLD were successfully interviewed. Of the 508 respondents, nearly half of them (42%) expressed no idea about the prevalence of NAFLD in Hong Kong. About half of respondents (47%) knew nothing about the clinical presentation of NAFLD. The majority of them (78%) had a misconception that blood tests could provide a definite diagnosis of NAFLD. Smoking, hepatitis B carriage and a past history of hepatitis A infection were cited as risk factors of NAFLD by 52%, 57% and 42% of respondents, respectively. Of the 508 respondents who had heard of NAFLD, most of them perceived that their knowledge of NAFLD was either inadequate (46%) or highly inadequate (35%). CONCLUSION: This survey revealed an inadequate knowledge of NAFLD among the general population in Hong Kong.

Risk factors associated with life-threatening rickettsial infections.

We retrospectively analyzed 92 cases of severe rickettsial infections in patients (median age = 49 years, 57% male, 37.0% with scrub typhus) in Hong Kong. Immunofluorescence assay was used for diagnostic confirmation. Identification of > or = 1 diagnostic sign (exposure history, rash, or eschar) was possible in 94.6% of the cases. Multivariate analysis suggested that pulmonary infiltrates (odds ratio [OR] = 25.2, 95% confidence interval [CI] = 3.9-160.9, P = 0.001) and leukocytosis (OR = 1.3, 95% CI = 1.0-1.5 per unit increase, P = 0.033) were independent predictors of admission to an intensive care unit (14.1%). Delayed administration of doxycycline was independently associated with major organ dysfunction (23.9%; oxygen desaturation, renal failure, severe jaundice, encephalopathy, cardiac failure) (OR = 1.2, 95% CI = 1.0-1.5 per day delay, P = 0.046; adjusted for age and rickettsia biogroup) and prolonged hospitalization > 10 days (25%) (OR = 1.4, 95% CI = 1.1-1.9 per day delay, P = 0.014). Treatment with fluoroquinolone/clarithromycin did not correlate with clinical outcomes (P > 0.05). Early empirical doxycycline therapy should be considered if clinico-epidemiologic signs of rickettsial infections are present.

Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B.

BACKGROUND/AIMS: We aimed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB). METHODS: One hundred and fifteen HBeAg-positive patients received lamivudine 100 mg daily plus placebo (monotherapy) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily (combination therapy) for 104 weeks in a randomized double-blind study. RESULTS: Time-weighted average change in serum HBV DNA from baseline up to week 16 was -4.20 log(10)copies/mL for both groups (p=0.936). At week 104, median serum HBV DNA change from baseline (log(10)copies/mL) for monotherapy and combination therapy was -3.41 versus -5.22, respectively. HBV DNA breakthrough was detected in 44% of monotherapy and 19% of combination therapy patients. The M204V/I mutation was detected in 43% (15/35) and 15% (6/41) of each group, respectively. ALT normalization at week 100 and 104 was 34% (19/56) in the monotherapy group and 45% (23/51) in the combination therapy group (p=0.018). By week 104, HBeAg seroconversion occurred in 20% of monotherapy and 13% of combination therapy patients. Both regimens were well tolerated. CONCLUSIONS: Lower rates of resistance to lamivudine, lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years. However, serological outcomes were similar.

Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: identification of 17 novel mutations and its genetic heterogeneity.

Wilson disease (WD), an autosomal recessive disorder of copper transport, is the most common inherited liver disorder in Hong Kong Chinese. This was the first local study to elucidate the molecular basis and establish an effective DNA-based diagnostic protocol. The ATP7B genes of 65 patients were amplified by polymerase chain reaction (PCR) and sequenced. Haplotype analysis was performed using D13S301, D13S314, and D13S316. The p.L770L/p.R778L status in 660 subjects was determined to estimate WD prevalence. Allele age of p.R778L was determined by the smallest homozygosity region between D13S301 and D13S270. We identified 42 different mutations with 17 being novel. p.R778L (17.3%) was the most prevalent. Exons 2, 8, 12, 13, and 16 harbored 70% mutations. Thirty-two haplotypes were associated with WD chromosomes. The estimated prevalence rate was 1 in 5,400. Three out of 660 normal subjects had p.L770L/p.R778L. In the remaining 657 individuals, neither p.L770L nor p.R778L was found. We characterized a Hong Kong Chinese-specific ATP7B mutation spectrum with great genetic diversity. Exons 2, 8, 12, 13, and 16 should be screened first. The perfect linkage disequilibrium suggested that p.R778L and its private polymorphism p.L770L originated from a single ancestor. This East-Asian-specific mutation p.R778L/p.L770L is aged at least 5,500 years.

Sustained disease remission after spontaneous HBeAg seroconversion is associated with reduction in fibrosis progression in chronic hepatitis B Chinese patients.

UNLABELLED: Recently, controversies have arisen about whether hepatitis B e antigen (HBeAg) seroconversion can result in regression of fibrosis, thus improving the clinical outcome of Chinese patients with chronic hepatitis B. In this study, we determined if spontaneous HBeAg seroconversion is associated with regression of fibrosis in Chinese chronic hepatitis B patients. We evaluated the histology of liver samples from 128 HBeAg-positive treatment-naive Chinese patients who had undergone 2 liver biopsies over the years. Regression of fibrosis was defined as a decrease in fibrosis stage of at least 1 point. Sustained disease remission was defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA < 10(4) copies/ml at follow-up liver biopsy. The mean duration (+/- standard error of the mean) between the initial and follow-up liver biopsies was 43.9 +/- 3.4 months. Regression of fibrosis was higher in patients with sustained disease remission (5 of 13 [38.5%] versus 22 of 115 [19.1%], P < 0.00005), patients who were younger (20-29 years old) at initial liver biopsy (17 of 54 [31.5%] versus 10 of 74 [13.5%], P = 0.0004), and patients with genotype B (17 of 43 [39.5%] versus 10 of 85 [11.8%], P = 0.004). On multivariate analysis, sustained disease remission (relative risk [RR] 3.00, 95% confidence interval [95% CI] 1.29-7.01, P = 0.01) and being 20-29 years old at initial liver biopsy (RR 2.94, 95% CI 1.01-8.62, P = 0.04) were independently associated with regression of fibrosis. The rate of fibrosis progression was lower in patients with sustained disease remission than in those who remained HBeAg positive (median 0 fibrosis units/year, range -2.00 to -0.70 fibrosis units/year, versus median 0.51 fibrosis units/year, range 0 to +2.03 fibrosis units/year, P = 0.02). CONCLUSION: Spontaneous sustained remission of disease is associated not only with little progression of fibrosis but also with regression of fibrosis.

Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong.

BACKGROUND: Severe acute respiratory syndrome (SARS) has become a global public health emergency. OBJECTIVE: To evaluate the characteristics and outcomes of patients with SARS in Hong Kong and to identify predictors of mortality. DESIGN: Retrospective cohort study. SETTING: Quarantine hospital for patients with SARS in Hong Kong. PATIENTS: 267 consecutive patients hospitalized from 26 February to 31 March 2003 for probable or confirmed SARS. MEASUREMENTS: Clinical, laboratory, and radiographic measures; 3-month mortality rate. RESULTS: According to our case definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS. Common presenting symptoms were fever (99% of patients), chills (74%), malaise (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%), thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate dehydrogenase (47%) and C-reactive protein (75%). During hospitalization, incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%) increased. Sixty-nine patients (26%) required intensive care because of respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%). Factors contributing to mortality were respiratory failure, acute renal failure, and nosocomial sepsis. On multivariate Cox regression, age older than 60 years (relative risk, 5.10 [CI, 2.30 to 11.31]; P < 0.001) and lactate dehydrogenase level greater than 3.8 micro kat/L at presentation (relative risk, 2.20 [CI, 1.03 to 4.71]; P = 0.04) were independent predictors of mortality. CONCLUSION: Because of the longer follow-up period in our cohort, the mortality rate in these patients is higher than rates reported in previous studies. Advanced age and high lactate dehydrogenase level at presentation predict mortality. *For members of the Princess Margaret Hospital SARS Study Group, see the Appendix.

Coronavirus-positive nasopharyngeal aspirate as predictor for severe acute respiratory syndrome mortality.

Severe acute respiratory syndrome (SARS) has caused a major epidemic worldwide. A novel coronavirus is deemed to be the causative agent. Early diagnosis can be made with reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal aspirate samples. We compared symptoms of 156 SARS-positive and 62 SARS-negative patients in Hong Kong; SARS was confirmed by RT-PCR. The RT-PCR-positive patients had significantly more shortness of breath, a lower lymphocyte count, and a lower lactate dehydrogenase level; they were also more likely to have bilateral and multifocal chest radiograph involvement, to be admitted to intensive care, to need mechanical ventilation, and to have higher mortality rates. By multivariate analysis, positive RT-PCR on nasopharyngeal aspirate samples was an independent predictor of death within 30 days.

Transjugular liver biopsy with an automated trucut-type needle: comparative study with percutaneous liver biopsy.

OBJECTIVE: Transjugular liver biopsy using the suction method usually produces small specimens with excessive fragmentation, hence the diagnosis adequacy of specimens and the clinical impact of performing the biopsy have been questioned. An alternative biopsy needle, the Quick-Core needle system, which uses an automated trucut-type mechanism, has been shown to produce non-fragmented tissue specimens. The aim of the present study was to evaluate the safety, adequacy and clinical impact of the transjugular liver biopsy by comparing it with the standard percutaneous liver biopsy. DESIGN: We recruited all patients who underwent liver biopsies by percutaneous or transjugular routes in the Department of Medicine, Princess Margaret Hospital, Hong Kong between January 1998 and December 1999. METHOD: We recorded demographics and clinical features of patients, indications and complications, and the clinical impact of the liver biopsy procedure. All liver biopsy specimens were reviewed by the histopathologist, who was blinded to the approach of taking the biopsy. All variables between patients undergoing transjugular and percutaneous liver biopsies were compared. RESULTS: During the study period, 50 percutaneous and 18 transjugular liver biopsies were performed. All transjugular liver biopsies were performed successfully with adequate tissue for diagnosis. Although specimens obtained by the transjugular technique tended to be shorter (10 mm v. 18 mm by the percutaneous approach, P < 0.001), the presence of fragmentation was similar to that in biopsies obtained by the percutaneous approach. Respectively, 100% and 98% of specimens obtained by the transjugular and percutaneous approaches were considered to be adequate for histological assessment. The clinical impact of transjugular and percutaneous liver procedures was comparable (89% v. 76%, P = 0.25). CONCLUSION: Specimens obtained by a transjugular automated trucut needle are sufficient for histological assessment, and carry clinical impact in patient management.