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1.
Aliment Pharmacol Ther ; 47(9): 1306-1316, 2018 May.
Article in English | MEDLINE | ID: mdl-29520872

ABSTRACT

BACKGROUND: In the large randomised NEPTUNE study, peginterferon alfa-2a 180 µg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) seroconversion rates 24 weeks post-treatment (36%) than a lower dose (90 µg/wk) and/or shorter duration (24 weeks) (range 14%-26%). AIM: To determine seroconversion rates 5 years after completion of treatment in NEPTUNE. METHODS: HBeAg-positive patients who completed 24 weeks' follow-up in NEPTUNE (with peginterferon alfa-2a 90 µg/wk × 24 weeks [group 1]; 180 µg/wk × 24 weeks [2]; 90 µg/wk × 48 weeks [3] or 180 µg/wk × 48 weeks [4]) were followed up. RESULTS: Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements. CONCLUSION: Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 µg × 48 weeks) is more efficacious for HBeAg-positive patients than a lower dose and/or shorter treatment duration.


Subject(s)
Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Sustained Virologic Response , Adult , Antiviral Agents/therapeutic use , DNA, Viral/analysis , Drug Therapy, Combination , Female , Follow-Up Studies , Hepatitis B e Antigens/genetics , Hepatitis B e Antigens/metabolism , Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Humans , Male , Middle Aged , Recombinant Proteins/therapeutic use , Time Factors , Treatment Outcome , Young Adult
3.
Aliment Pharmacol Ther ; 32(11-12): 1323-31, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21050234

ABSTRACT

BACKGROUND: On-treatment predictors of response to peginterferon can guide individualization of therapy in chronic hepatitis B virus infection. AIM: To investigate the use of serum hepatitis B surface antigen quantification to predict sustained response. METHODS: Hepatitis B e antigen-positive chronic hepatitis B patients who received peginterferon for 32-48 weeks with or without lamivudine combination were studied. Sustained response was defined as hepatitis B e antigen seroconversion and chronic hepatitis B virus DNA <10 000 copies/mL until 12 months post-treatment. RESULTS: Twenty-one of 92 (23%) patients achieved sustained response. At month 6, the area under receiver operating characteristics curve for hepatitis B surface antigen to predict sustained response was 0.77 (95% confidence interval 0.65-0.89, P < 0.001). An hepatitis B surface antigen cutoff at 300 IU/mL at month 6 could give the maximum combination of sensitivity (62%) and specificity (89%) to predict sustained response. Nine of 21 (43%) sustained responders vs. 9 of 71 (13%) nonsustained responders had >1 log hepatitis B surface antigen reduction at month 6 (P < 0.001). Combined hepatitis B surface antigen ≤ 300 IU/mL and >1 log reduction at month 6 had sensitivity, specificity, positive and negative predictive values of 43%, 96%, 75% and 85% to predict sustained response, respectively. CONCLUSION: On-treatment serum hepatitis B surface antigen can predict response to peginterferon therapy in chronic hepatitis B.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/drug therapy , Interferons/therapeutic use , Polyethylene Glycols/therapeutic use , Adult , Antiviral Agents/immunology , Drug Therapy, Combination , Female , Hepatitis B e Antigens/immunology , Hepatitis B, Chronic/immunology , Humans , Lamivudine/therapeutic use , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Time Factors , Treatment Outcome , Young Adult
4.
J Viral Hepat ; 16(1): 36-44, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18673426

ABSTRACT

The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.


Subject(s)
Alanine Transaminase/blood , Elasticity Imaging Techniques , Hepatitis B, Chronic/pathology , Liver Cirrhosis/diagnosis , Liver/pathology , Adult , Female , Humans , Male , Middle Aged , ROC Curve , Retrospective Studies , Severity of Illness Index
5.
Gut ; 58(1): 111-7, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18832522

ABSTRACT

BACKGROUND: Metabolic syndrome is associated with non-alcoholic steatohepatitis and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of chronic hepatitis B (CHB) is unclear. AIM: We aimed to study the relationship between metabolic syndrome and the risk of liver cirrhosis in patients with CHB. METHODS: We prospectively recruited patients with CHB from primary care and hospital clinics for liver stiffness measurement (LSM) with transient elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM >or=13.4 kPa. We analysed a subgroup of patients with paired LSM and liver biopsies to validate the accuracy of LSM. RESULTS: 1466 patients had reliable LSM and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients. Histological liver cirrhosis was more common among patients who had metabolic syndrome (38%) versus those who did not (11%, p<0.001). The specificity of probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis was present in 187 (13%) patients. Metabolic syndrome was more prevalent in patients with probable cirrhosis (24%) than those without cirrhosis (11%, p<0.001). After adjustment for anthropometric, biochemical and virological factors, metabolic syndrome remained an independent factor associated with probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7 to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8 to 16.7) in patients with one, two, three, four and five components of metabolic syndrome, respectively. CONCLUSION: Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB.


Subject(s)
Hepatitis B, Chronic/complications , Liver Cirrhosis/etiology , Metabolic Syndrome/complications , Adult , Age Distribution , Biopsy , Body Mass Index , Elasticity Imaging Techniques , Epidemiologic Methods , Female , Hepatitis B, Chronic/epidemiology , Hong Kong/epidemiology , Humans , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/epidemiology , Male , Metabolic Syndrome/epidemiology , Metabolic Syndrome/pathology , Middle Aged , Prospective Studies
6.
Aliment Pharmacol Ther ; 29(4): 387-96, 2009 Feb 15.
Article in English | MEDLINE | ID: mdl-19035982

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in affluent countries. Serum alanine aminotransferase (ALT) level is commonly performed to monitor NAFLD patients, but its clinical relevance is unclear. AIM: To evaluate the metabolic and histological features of NAFLD patients with different ALT levels. METHODS: A total of 173 consecutive patients with biopsy-proven NAFLD were studied. Patients with persistently normal ALT and those with abnormal ALT were compared. RESULTS: Patients with persistently normal ALT had lower steatosis grade than patients with abnormal ALT, but they had similar degree of lobular inflammation, ballooning and fibrosis. Among 19 patients with ALT below 0.5 times the upper limit of normal (ULN) at the time of liver biopsies, 8 (42%) and 3 (16%) had steatohepatitis and significant fibrosis respectively. The within-patient coefficient of variance was similarly high in patients with simple steatosis and steatohepatitis (33.5). Age and glucose, but not ALT, were independent factors associated with significant fibrosis. DISCUSSION: Metabolic factors, but not ALT, are associated with histological severity. Patients with ALT < 0.5 x ULN may still have non-alcoholic steatohepatitis (NASH) and significant fibrosis. Evaluation of NAFLD patients should be based on metabolic risk factors, but not ALT level.


Subject(s)
Alanine Transaminase/metabolism , Blood Glucose/metabolism , Fatty Liver/enzymology , Liver Cirrhosis/enzymology , Analysis of Variance , Anthropometry , Body Mass Index , Fatty Liver/pathology , Female , Humans , Insulin Resistance/physiology , Liver Cirrhosis/pathology , Male , Middle Aged , Prospective Studies , Risk Factors , Severity of Illness Index , Surveys and Questionnaires
7.
J Med Genet ; 45(11): 752-8, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18697825

ABSTRACT

BACKGROUND: Polymorphisms of CLEC4M have been associated with predisposition for infection by the severe acute respiratory syndrome coronavirus (SARS-CoV). DC-SIGNR, a C-type lectin encoded by CLEC4M, is a receptor for the virus. A variable number tandem repeat (VNTR) polymorphism in its neck region was recently associated with susceptibility to SARS infection. However, this association was controversial and was not supported by subsequent studies. Two explanations may account for this discrepancy: (1) there may be an unknown predisposition polymorphism located in the proximity which is linked to the VNTR; or (2) it was a spurious association due to unrecognised population structure in the VNTR. METHODS: We performed a comprehensively genetic association study on this C-type lectin gene cluster (FCER2, CLEC4G, CD209, and CLEC4M) at 19p13.3 by a tagging single nucleotide polymorphisms (SNPs) approach. RESULTS: 23 tagSNPs were genotyped in 181 SARS patients and 172 population controls. No significant association with disease predisposition was detected. Genetic variations in this cluster also did not predict disease prognosis. However, we detected a population stratification of the VNTR alleles in a sample of 1145 Han Chinese collected from different parts of China. CONCLUSION: The results indicated that the genetic predisposition allele was not found in this lectin gene cluster and population stratification might cause the previous positive association.


Subject(s)
Chromosomes, Human, Pair 19/genetics , Genetic Predisposition to Disease , Lectins, C-Type/genetics , Multigene Family , Polymorphism, Single Nucleotide/genetics , Severe Acute Respiratory Syndrome/genetics , Severe acute respiratory syndrome-related coronavirus/pathogenicity , Cell Adhesion Molecules/genetics , China/epidemiology , China/ethnology , Genotype , Humans , Minisatellite Repeats/genetics , Receptors, Cell Surface/genetics , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/ethnology , Young Adult
8.
Aliment Pharmacol Ther ; 25(8): 891-8, 2007 Apr 15.
Article in English | MEDLINE | ID: mdl-17402992

ABSTRACT

AIM: To determine the factors affecting the virological response to adefovir dipivoxil (ADV) among patients with lamivudine resistant chronic hepatitis B. METHODS: Chronic hepatitis B virus (HBV) infected patients, who had virological relapse to lamivudine, were switched to ADV monotherapy. RESULTS: Twenty-six patients were treated by ADV for 23 (12-41) months. At baseline, the median log HBV DNA was 7.70 (4.88-9.01) copies/mL. Six (23%) and 8 (31%) of patients had HBV DNA suppressed to below 1000 copies/mL at month 12 and the last follow-up, respectively. On linear regression, patients who had higher HBV DNA at baseline and month 6 have higher HBV DNA at month 12. On Cox proportional hazard model, the hazard ratio for each log step increase in HBV DNA at baseline and month 6 for HBV DNA <1000 copies/mL at the last visit was 0.39 (P = 0.010) and 0.47 (P = 0.027), respectively. Alanine aminotransferase, HBV genotype, rtL80 M mutation and log HBsAg did not affect the HBV DNA response. CONCLUSIONS: The response of lamivudine-resistant patients to ADV is suboptimal. Treatment with ADV when HBV DNA is low, and rapid viral suppression at month 6 increases the chance of maintained viral suppression.


Subject(s)
Adenine/analogs & derivatives , Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , Lamivudine/therapeutic use , Organophosphonates/therapeutic use , Adenine/therapeutic use , Adult , Aged , Drug Resistance, Viral , Female , Hong Kong , Humans , Male , Middle Aged , Treatment Outcome
9.
Aliment Pharmacol Ther ; 23(12): 1703-11, 2006 Jun 15.
Article in English | MEDLINE | ID: mdl-16817913

ABSTRACT

BACKGROUND: Interleukin-1beta is a pro-inflammatory cytokine that may influence host defence against viral infection. AIM: To investigate the impact of interleukin-1beta gene polymorphism on the response to anti-viral treatment. METHOD: Hepatitis B e antigen-positive chronic hepatitis B patients who have completed a randomized study of peginterferon alpha-2b and lamivudine combination vs. lamivudine monotherapy were included. Sustained responders were patients who had persistent hepatitis B e antigen loss and less than two occasions with hepatitis B virus DNA >100 000 copies/mL at any time up to week 76 post-treatment. Polymorphisms at interleukin-1beta-511, -31 and -3954 and interleukin-1 receptor antagonist (RN) were studied. RESULTS: Eighty-eight patients were studied and 18 (20%) patients developed sustained response. Near complete linkage disequilibrium was observed between interleukin-1beta-511 and -31 loci. After adjustment for the potential confounding effects of treatment allocation, hepatitis B virus genotype, pre-treatment alanine aminotransferase and hepatitis B virus DNA levels, genotype C/T at interleukin-1beta-511 was found to be associated with higher sustained response than genotype C/C (adjusted odds ratio 10.4, 95% CI 1.1, 96.9, P = 0.040). The proportion of sustained responders tend to be higher among patients with allele T at interleukin-1beta-511 (83%) than those without (70%) (P = 0.058). CONCLUSION: High interleukin-1beta production genotype at position -511 has a favourable response to anti-viral treatments.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B, Chronic/genetics , Interferon-alpha/therapeutic use , Interleukin-1/genetics , Lamivudine/therapeutic use , Polyethylene Glycols/therapeutic use , Polymorphism, Genetic/genetics , Adult , Asian People/ethnology , Asian People/genetics , Female , Hepatitis B, Chronic/drug therapy , Humans , Interferon alpha-2 , Male , Recombinant Proteins , Treatment Outcome
10.
Postgrad Med J ; 82(964): 140-4, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16461478

ABSTRACT

BACKGROUND AND AIMS: Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular complications. METHODS AND RESULTS: 121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hospital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (chi(2) = 3.99, p = 0.046) and third week (chi(2) = 6.53, p = 0.01), although it could not explain tachycardia during follow up. CONCLUSIONS: In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.


Subject(s)
Cardiovascular Diseases/virology , Severe Acute Respiratory Syndrome/complications , Blood Pressure , Cardiovascular Diseases/physiopathology , Female , Hospitalization , Humans , Male , Risk Factors , Severe Acute Respiratory Syndrome/physiopathology
11.
Aliment Pharmacol Ther ; 22(6): 519-28, 2005 Sep 15.
Article in English | MEDLINE | ID: mdl-16167968

ABSTRACT

BACKGROUND: Pegylated interferon-alpha has been shown to be more efficacious than conventional interferon in treating chronic hepatitis C. The use of peginterferon in chronic hepatitis B virus infection with positive hepatitis B e antigen has also been tested in a number of trials since 2003. AIM: To systematically summarize and compare the results of these studies. METHODS: Four studies were identified from PubMed, Medline and reference lists. Data from the trials were extracted and analysed. Where appropriate, combined odds ratio of different trials was calculated. Safety data including serious adverse events and emergence of drug-resistant mutants were recorded. RESULTS: Three of the four trials contained predominantly Asian patients. Peginterferon is found to be superior to lamivudine monotherapy and induced sustained biochemical and virological responses in about one-thirds of patients after 12 months of therapy. Coadministration of lamivudine did not result in improvement in viral suppression. Peginterferon appears to reduce the emergence of YMDD mutation in the combination treatment groups. It was well tolerated with serious adverse events reported in <10% of patients in most trials. CONCLUSIONS: Peginterferon-alpha treatment of at least 6 months should be considered as one of the first-line therapeutic options for hepatitis B virus infection.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Humans , Interferon alpha-2 , Randomized Controlled Trials as Topic , Recombinant Proteins
12.
Aliment Pharmacol Ther ; 21(4): 407-13, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15709991

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease is an important cause of chronic hepatitis and cryptogenic cirrhosis. The natural history of non-alcoholic fatty liver disease is not well understood especially in Asian populations. AIM: To investigate the histological progression in Chinese patients with biopsy-proven non-alcoholic fatty liver disease. METHODS: Chinese patients who had liver biopsy at least 3 years ago and confirmed to have non-alcoholic fatty liver disease were invited for a second liver biopsy. Clinical and laboratory parameters related to their liver function and metabolic syndrome were recorded and analysed. Liver biopsies were scored for the degree of steatosis, necroinflammation and fibrosis. Correlation coefficients were calculated to assess the association between changes in histological scores and metabolic parameters. RESULTS: Seventeen patients who had been followed up for a median period of 6.1 (range: 3.8-8.0) years underwent a second liver biopsy. Nine (53%) patients had progressive disease with worsening of fibrosis score. No statistically significant correlation was found between the changes in histological scores and metabolic parameters. Seven patients developed hypertension or diabetes mellitus during the period of follow-up. CONCLUSIONS: Non-alcoholic fatty liver disease is a progressive disease in Chinese patients as in their Caucasian counterparts. Diagnosis of non-alcoholic fatty liver disease may predate development of new components of metabolic syndrome.


Subject(s)
Asian People , Fatty Liver/ethnology , Fatty Liver/pathology , Adult , Biopsy , Disease Progression , Fatty Liver/blood , Female , Follow-Up Studies , Hong Kong , Humans , Male , Metabolic Syndrome/blood , Metabolic Syndrome/ethnology , Middle Aged , Risk Factors , Severity of Illness Index
13.
Gut ; 53(10): 1494-8, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15361502

ABSTRACT

BACKGROUND: Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients. PATIENTS AND METHODS: Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of alpha fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy. RESULTS: In total, 426 patients were followed up for 1664 person years; median 225 (range 12-295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14-236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39-23.89; p<0.001) and 2.84 (95% CI 1.05-7.72; p = 0.040), respectively. Patient age, sex, hepatitis B e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, and basal core promoter mutations did not predict HCC development. Patients infected with HBV genotype C tended to have persistently positive HBeAg or fluctuating HBeAg status and higher ALT levels during the follow up period. CONCLUSION: Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.


Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Liver Neoplasms/virology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Follow-Up Studies , Genotype , Hepatitis B virus/classification , Hepatitis B virus/pathogenicity , Hepatitis B, Chronic/complications , Humans , Liver Cirrhosis/complications , Male , Middle Aged , Prospective Studies , Risk Factors
14.
Aliment Pharmacol Ther ; 20(1): 45-9, 2004 Jul 01.
Article in English | MEDLINE | ID: mdl-15225170

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease is prevalent in affluent countries and is a cause of cirrhosis and possibly hepatocellular carcinoma. AIM: To examine the clinical and histological features of biopsy-proven non-alcoholic fatty liver disease and investigate the predictors of severe histological disease in Chinese patients. METHODS: Electronic records of all patients (n = 247) who underwent liver biopsy between 1996 and 2003 in our hospital were retrieved. Patients who had histological features of non-alcoholic fatty liver disease were identified. The demographic, clinical, laboratory and histological (Brunt's criteria) parameters of these patients were analysed. RESULTS: Forty-two patients had histology-proven non-alcoholic fatty liver disease. The median age was 47 years (range 23-69). All except one patient had features of metabolic syndrome. The median alanine aminotransferase was 93 (range 24-270) IU/L. Thirty-six (85.7%) patients had steatohepatitis and 11 (26.1%) also had fibrosis. Only one patient had stage 3 fibrosis. The presence of diabetes mellitus predicted higher grade steatohepatitis and fibrosis (P = 0.019) whereas alanine aminotransferase level had no correlation with histological severity of steatohepatitis. After a median follow-up of 42 months, no patient developed hepatic decompensation. CONCLUSIONS: Most Chinese patients with non-alcoholic fatty liver disease had features of the metabolic syndrome. Histological activity was generally mild. Diabetes mellitus was the most important predictor of severe histological disease.


Subject(s)
Fatty Liver/ethnology , Adult , Aged , China/ethnology , Fatty Liver/pathology , Female , Hepatitis/ethnology , Hepatitis/pathology , Hong Kong/ethnology , Humans , Male , Middle Aged , Retrospective Studies
15.
J Clin Pathol ; 57(3): 260-5, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14990596

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV). METHODS: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. RESULTS: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. CONCLUSIONS: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.


Subject(s)
Coronavirus/isolation & purification , Lung/pathology , Severe Acute Respiratory Syndrome/pathology , Adult , Aged , Aged, 80 and over , Cell Division , Cell Nucleus/pathology , Cells, Cultured , Female , Humans , Immunohistochemistry/methods , Lung/virology , Male , Microscopy, Electron , Middle Aged , Pulmonary Alveoli/pathology , Severe Acute Respiratory Syndrome/virology
16.
Aliment Pharmacol Ther ; 18(3): 339-45, 2003 Aug 01.
Article in English | MEDLINE | ID: mdl-12895219

ABSTRACT

BACKGROUND: Previous studies suggested that Phyllanthus species have an anti-viral effect on hepatitis B, but methodologies have been inadequate. AIMS: This study aimed to investigate the anti-viral effect of Phyllanthus urinaris. METHODS: Chronic hepatitis B patients with positive hepatitis B e-antigen (HBeAg), hepatitis B virus (HBV) DNA > 500 000 copies/mL and elevated alanine transaminase (ALT) were recruited. Patients were randomized into groups of 12 receiving P. urinaris 1, 2 and 3 g three times daily for 6 months or placebo (six cases). The primary endpoint was HBV DNA reduction, and secondary endpoints were HBeAg seroconversion and ALT normalization. RESULTS: On an intention-to-treat analysis there was no difference in log10[HBV DNA] reduction of the Phyllanthus 1-g (0.18 +/- 1.42), 2-g (0.33 +/- 1.08) and 3-g (0.85 +/- 1.30) groups vs. placebo (0.28 +/- 0.85) (P = 0.90, 0.92 and 0.38, respectively) at the end of treatment. The percentage of patients among the placebo, Phyllanthus 1-g, 2-g and 3-g groups undergoing HBeAg seroconversion (0%, 9.1%, 8.3% and 16.7%, respectively) and ALT normalization (0%, 0%, 8.3% and 33.3%) were not significantly different at the end of treatment. No delayed virological or biochemical response was documented at 24 weeks after the cessation of treatment. No serious adverse event was reported. CONCLUSION: P. urinaris treatment for 6 months has no demonstrable anti-viral effect in chronic hepatitis B.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B, Chronic/drug therapy , Phyllanthus , Phytotherapy/methods , Adult , Double-Blind Method , Humans , Middle Aged , Plant Extracts/therapeutic use , Treatment Outcome
17.
J Viral Hepat ; 9(6): 424-8, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12431204

ABSTRACT

Patients with chronic hepatitis B (CHB) may develop severe disease exacerbations (flare) with jaundice, and some may progress to fulminant hepatic failure. Whether early administration of lamivudine can prevent liver failure and mortality is uncertain. We investigated the role of lamivudine treatment in severe hepatitis B virus (HBV) exacerbations. Consecutive patients presented with severe flare-up of HBV (new onset of jaundice plus alanine aminotransferase greater than five times upper limit of normal) treated with lamivudine and historical controls who did not receive lamivudine were studied. All patients had no hepatic encephalopathy on admission. Univariate analysis and multivariate logistic regression were performed on various clinical and laboratory factors for the prediction of mortality. Twenty-eight patients treated with lamivudine and 18 controls were identified. Overall, nine patients died and two other received liver transplants for fulminant hepatic failure. Six of 28 (21.4%) lamivudine-treated patients vs five of 18 (27.8%) controls died or received a liver transplant (P = 0.62). On multivariate analysis, platelet < or = 143 x 10E9/L (odds ratio 22.4, 95% CI 1.8-281.6) and bilirubin > 172 micromol/L (odds ratio 18.4, 95% CI 1.5-228.5) were independent predictors of liver-related mortality. The mortality of patients who had thrombocytopenia and high bilirubin, thrombocytopenia, high bilirubin, and no risk factor were 69.2%, 11.1%, 12.5% and 0% respectively. Hence lamivudine confers no survival benefit to conventional treatment in severe exacerbations of CHB. Patients with thrombocytopenia and high bilirubin should be considered for liver transplantation.


Subject(s)
Hepatitis B, Chronic , Jaundice , Lamivudine/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Adult , Bilirubin/blood , DNA, Viral/blood , Female , Hepatitis Antibodies/blood , Hepatitis B virus/immunology , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/mortality , Humans , Jaundice/drug therapy , Jaundice/mortality , Male , Middle Aged , Platelet Count , Predictive Value of Tests , Survival Analysis
18.
Hong Kong Med J ; 5(2): 187-190, 1999 Jun.
Article in English | MEDLINE | ID: mdl-11821590

ABSTRACT

To survey the practice patterns of physicians in public hospitals in Hong Kong when treating Helicobacter pylori-associated peptic ulceration, the records of all patients from 22 medical units who had new peptic ulcers that had been diagnosed endoscopically during August 1996 were examined systematically. Patient data were entered on a one-page questionnaire. Five hundred and twelve patients with peptic ulceration were studied; 173 (34%) of whom had presented with gastro-intestinal bleeding. The Helicobacter pylori status had been determined in 449 (88%) patients, 280 (62%) of whom had subsequently tested positive for Helicobacter pylori. The biopsy urease test or histological examination had been performed for more than 95% of patients. Of 260 patients who had tested positive for Helicobacter pylori, 244 (94%) had received eradication therapy to eliminate this organism; a total of 291 patients, however, were receiving eradication therapy. The most commonly used regimen was proton pump inhibitor triple therapy (151 [52%] of 291 patients). Confirmation of the eradication of Helicobacter pylori had been planned for 152 (52%) of the 291 patients, whereas ulcer-healing drugs--mainly H2-receptor antagonists--had been prescribed for 87 (30%) patients after eradication. Curing Helicobacter pylori infection is therefore widely accepted in the management of peptic ulcer disease among physicians working in Hong Kong public hospitals.

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