Decline in Cancer Diagnoses during the 'Zero COVID' Policy in Hong Kong: Indirect Spillover Impact of the COVID-19 Pandemic.

AIMS: Despite a largely successful 'zero COVID' policy in 2020, the COVID-19 pandemic disrupted routine cancer services in the city of Hong Kong. The aims of this study were to examine the trends in cancer incidence before and during the COVID-19 pandemic and estimate missed cancer diagnoses. MATERIALS AND METHODS: We used population-based data from the Hong Kong Cancer Registry 1983-2020 to examine the trends of age- and sex-standardised cancer incidence before and during the COVID-19 pandemic. We applied: (i) the annual average percentage change (AAPC) calculated using the Joinpoint regression model and (ii) the autoregressive integrated moving average (ARIMA) model to forecast cancer incidence rates in 2020. Missed cancer diagnoses in 2020 were estimated by comparing forecasted incidence rates to reported rates. A subgroup analysis was conducted by sex, age and cancer site. RESULTS: The cancer incidence in Hong Kong declined by 4.4% from 2019 to 2020 (male 8.1%; female 1.1%) compared with the long-term AAPC of 0.5% from 2005 to 2019 (95% confidence interval 0.3, 0.7). The gap between the reported and forecasted incidence for 2020 ranged from 5.1 to 5.7% (male 8.5%, 9.8%; female 2.3%, 3.5%). We estimated 1525-1596 missed cancer diagnoses (ARIMA estimate -98, 3148; AAPC 514, 1729) in 2020. Most missed diagnoses were in males (ARIMA 1361 [327, 2394]; AAPC 1401 [1353, 1460]), with an estimated 479-557 missed cases of colorectal cancer (ARIMA 112, 837; AAPC 518, 597) and 256-352 missed cases of prostate cancer (AAPC 231, 280; ARIMA 110, 594). CONCLUSION: The incidence of new cancer diagnoses declined in 2020 contrary to the long-term increase over the previous decades. Significantly lower diagnoses than expected were observed in males, particularly for colorectal and prostate cancers. Fewer reported cancer cases indicate missed diagnoses and could lead to delayed treatment that could impact future health outcomes.

Cell cycle-dependent expression of potassium channels and cell proliferation in rat mesenchymal stem cells from bone marrow.

OBJECTIVE: Recently, our team has demonstrated that voltage-gated delayed rectifier K(+) current (IK(DR)) and Ca(2+)-activated K(+) current (I(KCa)) are present in rat bone marrow-derived mesenchymal stem cells; however, little is known of their physiological roles. The present study was designed to investigate whether functional expression of IK(DR) and I(KCa) would change with cell cycle progression, and whether they could regulate proliferation in undifferentiated rat mesenchymal stem cells (MSCs). MATERIALS AND METHODS: Membrane potentials and ionic currents were recorded using whole-cell patch clamp technique, cell cycling was analysed by flow cytometry, cell proliferation was assayed with DNA incorporation method and the related genes were down-regulated by RNA interference (RNAi) and examined using RT-PCR. RESULTS: It was found that membrane potential hyperpolarized, and cell size increased during the cell cycle. In addition, IK(DR) decreased, while I(KCa) increased during progress from G(1) to S phase. RT-PCR revealed that the mRNA levels of Kv1.2 and Kv2.1 (likely responsible for IK(DR)) reduced, whereas the mRNA level of KCa3.1 (responsible for intermediate-conductance I(KCa)) increased with the cell cycle progression. Down-regulation of Kv1.2, Kv2.1 or KCa3.1 with the specific RNAi, targeted to corresponding gene inhibited proliferation of rat MSCs. CONCLUSION: These results demonstrate that membrane potential, IK(DR) and I(KCa) channels change with cell cycle progression and corresponding alteration of gene expression. IK(DR) and intermediate-conductance I(KCa) play an important role in maintaining membrane potential and they participate in modulation of proliferation in rat MSCs.

Disease progression in Chinese chronic hepatitis C patients with persistently normal alanine aminotransaminase levels.

BACKGROUND: Although chronic hepatitis C virus-infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression. AIM: To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time. METHODS: Eighty-two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow-up was 8.1 years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. RESULTS: At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03-2.5, P = 0.02). CONCLUSION: Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.

Natural history of patients with recurrent chronic hepatitis C virus and occult hepatitis B co-infection after liver transplantation.

It is uncertain whether occult hepatitis B virus co-infection will hasten progressive liver disease in chronic hepatitis C patients after liver transplantation. This study evaluated fibrosis progression and severe fibrosis in 118 consecutive hepatitis B surface antigen-negative patients with virological and histological evidence of recurrent chronic hepatitis C infection co-infected with occult hepatitis B virus after liver transplantation. HBV DNA was detected from serum at the time of recurrent chronic hepatitis C infection by polymerase chain reaction. Each subject underwent a repeat liver biopsy 5 years post-liver transplantation. Occult hepatitis B virus co-infection was present in 41 of the 118 (34.7%) patients. At 5 years post-liver transplantation, 13 of the 41 occult hepatitis B virus co-infected patients compared with 16 of the 77 patients without occult hepatitis B virus co-infection developed fibrosis progression (31.7% vs. 20.8%, respectively, p = 0.39). Eight of 41 the occult hepatitis B virus co-infected patients compared with 13 of the 77 patients without occult hepatitis B virus co-infection had severe fibrosis (19.5% vs. 16.9%, respectively, p = 0.97). In conclusion, occult hepatitis B virus co-infection in patients with recurrent chronic hepatitis C infection was not associated with accelerated fibrosis progression or severe fibrosis after liver transplantation.

Clusterin plays an important role in hepatocellular carcinoma metastasis.

To identify genes associated with tumor metastasis in hepatocellular carcinoma (HCC), gene expression profiles between a pair of primary HCC (H2-P) and their matched metastatic HCC (H2-M) were compared. Overexpression of clusterin (CLU) was found in H2-M cells. To determine the roles CLU played in HCC metastasis, CLU was transfected into H2-P cells. Overexpression of CLU in H2-P cells increased cell migration by twofold in vitro and formation of metastatic tumor nodules in liver by eightfold in vivo. To evaluate the correlation of CLU expression with HCC metastasis, the expression levels of CLU in HCCs were investigated using a tissue microarray (TMA) containing 104 pairs of primary HCCs and their matched metastases. The frequency of CLU overexpression increased significantly in metastatic HCCs (59.1%) compared with that in primary tumors (32.6%, P<0.001). To gain additional insight into the function of CLU, the expression profile of H2P-CLU was compared with vector-transfected H2-P cells by cDNA microarray. A total of 35 upregulated and 14 downregulated genes were detected in H2P-CLU. One of the upregulated genes known as YKL-40, which is implicated in matrix-remodeling and metastasis, was further studied using TMA. A significant correlation (P<0.001) between the expression levels of YKL-40 and CLU was observed, implying that the CLU-YKL-40 pathway may play an important role in HCC metastasis.

Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy.

BACKGROUND: The hepatic outcome of hepatitis B surface antigen (HBsAg) positive patients undergoing chemotherapy after withdrawal of pre-emptive lamivudine is unknown. AIMS: To examine the occurrence of hepatitis B virus (HBV) reactivation after withdrawal of pre-emptive lamivudine. METHODS: Pre-emptive lamivudine was started one week before initiation of chemotherapy in 46 consecutive HBsAg positive patients and continued for the entire duration of chemotherapy. Pre-emptive lamivudine was stopped at a median 3.1 (range 3.0-3.4) months after completion of chemotherapy. Patients were longitudinally followed up after withdrawal of pre-emptive lamivudine. RESULTS: Median time of follow up after withdrawal of lamivudine was 25.7 (range 5.7-75.7) months. Eleven of the 46 patients (23.9%) developed HBV reactivation after withdrawal of pre-emptive lamivudine. Eight of the 16 patients with high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) compared with three of the 30 patients with low pre-chemotherapy HBV DNA (<10(4) copies/ml) developed HBV reactivation (50.0% v 10.0%, respectively; p<0.001). Hepatitis B e antigen positive patients were also more likely to develop HBV reactivation (5/11 (45.5%) v 6/35 (17.1%), respectively; p = 0.041). A high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) was the most important risk factor for HBV reactivation after withdrawal of pre-emptive lamivudine on Cox proportional hazards analysis (relative risk 16.13, (95% confidence interval 2.99-87.01; p = 0.001). CONCLUSIONS: HBV reactivation is more likely to occur in patients with high pre-chemotherapy HBV DNA after withdrawal of pre-emptive lamivudine. A more prolonged course of antiviral therapy may be necessary in these patients after completion of chemotherapy in order to reduce post-chemotherapy HBV reactivation.

Liver graft-versus-host disease after donor lymphocyte infusion for relapses of hematologic malignancies post allogeneic hematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is the commonest complication after donor lymphocyte infusion (DLI). In 19 patients undergoing DLI for relapses of hematologic malignancies post hematopoietic stem cell transplantation (HSCT), 11 developed GVHD, of whom nine had isolated liver involvement, and two had liver and skin involvement. The clinical diagnosis of liver GVHD was hepatitic in six patients (55%) and classical in five patients (45%). Patients with GVHD post-DLI showed a different clinical pattern when compared to a cohort of 106 cases of GVHD post-HSCT, in having significantly more isolated liver involvement (9/11 vs 17/106, P<0.001), and less skin (2/11 vs 80/106, P<0.001) and gut (0/11 vs 28/106, P<0.001) involvement. However, liver GVHD post-DLI and post-HSCT had comparable patient characteristics, underlying diseases, clinical subtypes (classical and hepatitic) and response to treatment.

Emergency living related liver transplantation for fulminant reactivation of hepatitis B virus after unrelated marrow transplantation.

We report a unique case of emergency living related donor orthotopic liver transplantation (OLT) for late fulminant reactivation of hepatitis B virus (HBV) after matched unrelated bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Cessation of lamivudine after BMT for HBV positive patients may carry risks of late fatal HBV reactivation. Similar to fulminant HBV reactivation in the general population, OLT under resumption of lamivudine can be life saving. In our case, concomitantly molecular relapse of CML at the time of liver failure was also cleared by OLT, possibly via a 'liver-graft vs. leukemia' effect. Liver rejection (graft vs. graft disease) was mild due to inherent immunocompromise of the marrow graft. Hence BMT recipients in stable remission should not be denied the opportunity for life-saving solid organ transplantation. A choice of marrow and liver donors with innate HBV immunity may be needed to give the additional advantage of long-term HBV clearance.

Ten-year experience with liver transplantation at Queen Mary Hospital: retrospective study.

OBJECTIVE: To report the experience with liver transplantation at the Queen Mary Hospital from 1991 to 2000. DESIGN: Retrospective study. SETTING: Liver transplant centre of a University teaching hospital, Hong Kong. PATIENTS: One hundred and forty-eight patients (127 adults and 21 children) who underwent a total of 155 liver transplants using 75 cadaver grafts (full-size, 67; reduced-size, 5; split, 3) and 80 living donor grafts (left lateral segment, 15; left lobe, 6; right lobe, 59) from October 1991 to December 2000 were reviewed. MAIN OUTCOME MEASURES: Graft and patient survival rate. RESULTS: The most common disease indications for liver transplantation were chronic hepatitis B-related liver disease (n=74) in adults and biliary atresia (n=14) in children. Eighteen patients had hepatocellular carcinoma. Forty-eight (31%) liver transplants (three ABO-incompatible) were performed in high-urgency situations for patients requiring intensive care. The proportion of living donor liver transplants was 47.7% in adults and 73.9% in children. The overall 1-year and 5-year patient survival rates were 82% and 77%, respectively. The survival of high-risk recipients, such as those with fulminant hepatic failure (80%), chronic hepatitis B (81%), or hepatocellular carcinoma (94%), was not inferior to that of other patients. CONCLUSION: Over the last decade, the promotion of (cadaver) organ donation through public education coupled with innovative techniques in living donor liver transplantation have enabled a liver transplantation programme to be established in Hong Kong with gratifying results.

Aggressive hepatocellular carcinoma complicating pregnancy after autologous bone marrow transplantation for non-Hodgkin's lymphoma.

In the Asia-Pacific region, autologous and allogeneic bone marrow transplantation (BMT) in patients infected with the hepatitis B virus (HBV) may be complicated by fatal hepatic failure due to viral reactivation. Survivors may suffer from accelerated hepatitis and cirrhosis. We report the first case of hepatocellular carcinoma (HCC) after autologous BMT for mediastinal B cell lymphoma. The tumor developed rampantly during a planned pregnancy 5 years after BMT. Less than 40 cases of HCC complicating pregnancy have been reported, and outcome is invariably poor. Immunosuppression and HBV reactivation after autologous BMT, as well as immune tolerance and hormonal changes associated with pregnancy may contribute to the rapid tumor growth. Biochemical and radiological surveillance for HCC should be strengthened in HBV carriers after BMT, especially in patients with the histology of chronic liver disease, or biochemical/ virological evidence of increased HBV activity.

Arginine reverses ethanol-induced inflammatory and fibrotic changes in liver despite continued ethanol administration.

We investigated the potential of arginine to reverse pathological changes in alcohol-induced liver injury. Four groups (six rats/group) of male Wistar rats were fed a fish oil-ethanol diet for 6 (group 2) or 8 (group 1) weeks. Rats in group 3 were fed fish oil-ethanol for 6 weeks, after which they were administered arginine with fish oil-ethanol for an additional 2 weeks. Rats in group 4 were fed fish oil-dextrose for 8 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, cytochrome P4502E1 activity, nuclear factor-kappaB, and levels of messenger RNA for tumor necrosis factor-alpha, cyclooxygenase-2, and inducible nitric oxide synthase. Concentrations of endotoxin were measured in plasma. The most severe inflammation and fibrosis was detected in groups 1 and 2, as were the highest levels of endotoxin, lipid peroxidation, cytochrome P450 2E1 activity, activation of nuclear factor-kappaB, and mRNA levels for tumor necrosis factor-alpha, cyclooxygenase-2, and inducible nitric oxide synthase. Plasma nitric oxide was also increased as was nitrotyrosine in liver. After arginine was administered, there was marked improvement in the pathological changes accompanied by decreased levels of endotoxin, lipid peroxidation, activation of nuclear factor-kappaB, tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitric oxide, and nitrotyrosine staining. The therapeutic effects of arginine are probably secondary to increased levels of nitric oxide but other effects of arginine cannot be excluded.

Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy--pathogenesis and management.

In an endemic area for chronic hepatitis B infection, reactivation of this virus is a serious cause of morbidity and mortality in patients undergoing cytotoxic or immunosuppressive therapy. Careful prospective serological testing has shown that hepatitis B virus reactivation is a two-staged process. The initial stage occurs during intense cytotoxic or immunosuppressive therapy and is characterised by enhanced viral replication, as reflected by increases in the serum levels of hepatitis B virus DNA, hepatitis B e antigen, hepatitis B virus DNA polymerase and infection of naïve hepatocytes with hepatitis B virus. The second stage is related to restoration of immune function following withdrawal of cytotoxic or immunosuppressive therapy, which causes rapid immune-mediated destruction of infected hepatocytes. Clinically, this can lead to hepatitis, hepatic failure and even death. The occurrence and severity of hepatitis B virus reactivation after various cytotoxic or immunosuppressive therapy is unpredictable and treatment has been disappointing, largely due to the late administration of therapy. Recently, pre-emptive treatment of chronic hepatitis B patients undergoing cytotoxic or immunosuppressive therapy, with potent nucleoside analogues has shown some promising results. Further controlled studies are needed to define the incidence and risk factors of hepatitis B reactivation so that pre-emptive treatment with nucleoside analogues could be administered to those patients at high risk of disease.

Macrophage migration inhibitory factor expression in male and female ethanol-fed rats.

Macrophage migration inhibitory factory (MIF) regulates macrophage accumulation at sites of injury and can promote the inflammatory response. We studied MIF expression in the intragastric feeding rat model for alcoholic liver injury. Male and age-matched female rats were fed ethanol or dextrose with fish oil. Two groups of male rats were fed medium-chain triglycerides with ethanol or dextrose. Analysis of liver histopathology, lipid peroxidation, endotoxin, mRNA, and immunohistochemistry for MIF, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were carried out. Male and female rats fed fish oil and ethanol showed necroinflammatory liver injury and had the highest expression of MIF, TNF-alpha, and IFN-gamma in the liver. Decreased levels of MIF protein were seen in rats with higher endotoxin levels, suggesting that preformed MIF is released into the circulation. MIF is an important mediator of the inflammatory response in alcoholic liver disease and a potential therapeutic target.

Evaluation of a new referral system for the management of dyspepsia in Hong Kong: role of open-access upper endoscopy.

BACKGROUND: In the management of dyspepsia, upper endoscopy is an important component. In our locality, patients requiring upper endoscopy are conventionally referred to specialist clinics by family physicians. We have introduced the first open-access upper endoscopy service in Hong Kong, which has allowed family physicians to arrange endoscopy without prior specialist consultation. A study on the outcome of open-access upper endoscopy in contrast with the conventional referral system was conducted. METHODS: For patients presenting with dyspepsia, family physicians in our region were given the option to arrange upper endoscopy directly with our Medical Endoscopy Unit in addition to the conventional referral to specialist clinics. The results were compared with those from the specialist clinic. A detailed prospective follow up was performed from June to September 1997 to evaluate the outcome and impact of open-access upper endoscopy. RESULTS: From November 1996 to September 1999, 978 referrals for open-access upper endoscopy were received. The service significantly reduced the waiting time for the procedure by 16 weeks. Open-access upper endoscopy had similar detection rates for peptic ulcers and cancers compared with referrals from specialist clinics. Seventy-five percent of patients did not require further consultation with their family physicians within 2 months after endoscopy. It is a safe and effective procedure in establishing a definitive diagnosis. All family physicians were satisfied with the open-access upper endoscopy service. CONCLUSIONS: This is the first Asian report on this service. Open-access upper endoscopy reduced waiting time from the patient perspective, decreased subsequent consultations with family physicians and reduced referral to specialist clinics as well as increased patient and doctor satisfaction. Both referral systems for endoscopy were similar in terms of the diagnostic yield.

(13)C-urea breath test without a test meal is highly accurate for the detection of Helicobacter pylori infection in Chinese.

BACKGROUND: Conventional (13)C-urea breath testing ((13)C-UBT) includes a test meal to delay gastric emptying, which, theoretically, improves the accuracy of the test. Citric acid has been proposed as the best test meal. However, recent studies have suggested that a test meal may not be necessary. AIM: To investigate a new (13)C-UBT protocol without a test meal in a Chinese population. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. (13)C-UBT was performed on two separate days with or without a test meal (2.4 Gm citric acid) and compared with the 'gold standard' (CLO test and histology). RESULTS: Two hundred and two patients were tested. Using receiver operating characteristics (ROC) analysis, the optimal delta-value and optimal measurement interval for UBT were 5% and 30 min, respectively, both with or without a test meal. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (13)C-UBT with citric acid (96.5%, 97.7%, 98.2%, 95.6%, 97.0%) were similar to (13)C-UBT without a test meal (94.7%, 97.7%, 98.2%, 93.5%, 96.0%). CONCLUSION: This simplified (13)C-UBT protocol without a test meal produced highly accurate and reliable results in the Chinese population.

Use of immunomodulatory therapy (other than interferon) for the treatment of chronic hepatitis B virus infection.

Chronic hepatitis B virus (HBV) infection is a major health threat in Asia. In order to design a better therapeutic regimen, the underlying mechanism of HBV viral persistence must be understood. Immunological studies have found that impaired HBV virus-specific T cell reactivity is the major cause of chronic infection, whereas strong and multispecific T cell responses to HBV are associated with long-term control, but not elimination of the virus. Furthermore, in the serological clearance of hepatitis B surface antigen (HBsAg) in allogeneic haematopoietic cell transplantation, HBsAg seroconversion is associated with activation of the donor's hepatitis B core antigen-specific CD4+ T lymphocytes. This suggests that the donor's hepatitis B core antigen-specific CD4+ T cells provide 'intermolecular T cell help' for the HBsAg seroconversion. These findings are relevant to the future development of therapeutic vaccines or DNA vaccine as immunotherapy for chronic hepatitis B. Apart from interferon-alpha, thymosin alpha1 (Talpha1) has been investigated for treatment of chronic hepatitis B. Meta-analysis of 4 randomized controlled studies investigating the safety and efficacy of Talpha1 monotherapy for the treatment of chronic hepatitis B showed that 6 months treatment with Talpha1 (1.6 mg twice weekly) almost doubles the sustained response rate (36%) compared with controls (19%; P=0.04). However, more specific immunological approaches are being developed; notably, hepatitis B core antigen-based therapeutic vaccine was found to induce T cell proliferative responses in chronically infected hepatitis B patients to the T helper epitope included in the construct. However, the cytokine profile observed suggested the induction of a T helper 0/T helper 2 CD4+ T cell response rather than T helper 1 response. Thus, its combination with interferon-gamma or interleukin-12, which might reverse the CD4+T cell response, should be considered. In the future, it is likely that different types of combination therapy may have to be tailor-made for chronic HBV infection with different virological and immunological profiles and different degrees of liver damage.

A case-controlled study on the use of HBsAg-positive donors for allogeneic hematopoietic cell transplantation.

To compare the clinical and serological outcomes of patients receiving donors' marrow positive or negative for hepatitis B surface antigen (HBsAg), we studied 18 patients of allogeneic hematopoietic cell transplantation receiving HBsAg-positive marrow (group 1) and 18 receiving HBsAg-negative marrow (group 2). The recipients of the 2 groups were matched for hepatitis B virus (HBV) serology, sex, age, underlying hematological diseases, conditioning regimen, and prophylaxis against graft-versus-host diseases. Eight (44.4%) recipients in group 1 and 2 (11.1%) in group 2 suffered from HBV-related hepatitis posttransplant (P =.03). Furthermore, HBV-related hepatic failure was seen in 6 group 1 patients, but in none of the group 2 patients (P =.007). Five of the 9 (55.5%) HBsAg-negative recipients in group 1 became positive after receiving HBsAg-positive marrow. Serum HBV DNA was positive in all 5 donors of these patients, but in none of the donors of recipients who remained HBsAg negative (P =.008). Group 1 patients developing HBV-related hepatitis posttransplant were more likely to have a donor carrying a precore A(1896 )and/or core promoter T(1762)/A(1764) HBV variant (62. 5% versus 0%, P =.007). This study has demonstrated that a high incidence of HBV-related hepatitis was associated with the use of HBsAg-positive marrow for transplant, and a high viral load in the donor appeared to predispose recipients to the development of HBV-related hepatitis posttransplant. Further clinical trials will be necessary to determine the optimal management approach to this problem, including the use of the antiviral agents in the donors and the recipients. (Blood. 2000;96:452-458)

Reactivity of 13 in vitro expressed hepatitis B surface antigen variants in 7 commercial diagnostic assays.

The primary marker of current hepatitis B infection is the surface antigen (HBsAg), however HBsAg negativity does not exclude hepatitis B viremia. HBsAg variants can be responsible for such diagnostic failures. Here 13 different HBsAg variants were cloned, variant protein produced in a mammalian expression system, and tested using 7 commercial HBsAg diagnostic assays. Of 12 variants analyzed, 6 samples displayed similar reactivity to the positive control (containing standard HBsAg sequence) in most of the assays, but 6 samples, containing various mutations throughout the entire major hydrophilic region (MHR), showed reduced reactivity. It was found that the loss of cysteine at amino acid (aa) 124 in 1 sample affected the secretion as well as the reactivity of HBsAg in the expression system. Thus, not all assays are equally able to detect HBsAg variants, implying that, to attain an acceptable level of sensitivity, the antibody repertoire of the current assays should be extended.

An evaluation of whole blood testing for Helicobacter pylori infection in the Chinese population.

BACKGROUND: Near patient tests for Helicobacter pylori were developed to assist in the management of dyspepsia patients in general practice. Most studies were performed in western populations. AIM: To evaluate the rapid whole blood test (Flexpack HP) for H. pylori in the Chinese population. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During upper endoscopy, biopsies were taken from the antrum and corpus for rapid urease test (CLO test) and histological examination. After endoscopy, the whole blood test (FlexPack HP) was performed according to the manufacturer's instruction. Patients then received a 13C-urea breath test. Results of the whole blood test were compared with the gold standard (CLO test, histology and 13C-urea breath test). RESULTS: A total of 294 consecutive patients gave a valid Flexpack HP result for interpretation. The mean age of patients was 47.7 (range 15-85) years. Analysis showed a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 58%, 92%, 91%, 63% and 73% respectively. CONCLUSION: The FlexPack HP whole blood test showed good specificity but lacked sensitivity. It is not sensitive enough to be used in a general practice setting for the test-and-treat approach in the Chinese population.