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.

The associations among executive planning, self-determination, and quality of life in adolescents with intellectual disability.

BACKGROUND: Skills such as planning and problem solving that are required in self-determination can be cognitively demanding. It has not yet been examined whether executive functions and intelligence are associated with levels of self-determination in individuals with intellectual disability (ID), and how that is related to quality of life (QoL). This study examined the associations among executive functions, intelligence, self-determination, and QoL in adolescents with ID. METHODS: Seventy-nine adolescents aged between 17 and 20 years with mild ID participated in the study. Executive functions were assessed by experimental tasks. Non-verbal IQ and survey data regarding QoL and self-determination capacity were collected from the participants. RESULTS: In a regression model with QoL as the dependent variable, only executive planning and self-determination capacity (but not working memory, inhibition and IQ) were significant predictors of QoL. Two mediation models were tested based on the hypotheses, literature and current findings. Model 1 revealed that executive planning had a negative direct effect on QoL when the mediator, self-determination capacity, was held constant. Model 2 indicated that the significant association between self-determination and QoL was not mediated by executive planning. CONCLUSIONS: The findings highlighted the crucial significance of self-determination, in comparison with executive functions and intelligence, for improving the QoL in adolescents with ID. Importantly, higher executive planning skill was even associated with lower QoL if self-determination was not concurrently strengthened. These findings carry implications for the design of education and intervention programmes aimed at improving QoL of adolescents with ID.

Correction to: Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update.

The article Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update, written by [Shiv Sarin], was originally published electronically on the publisher's internet portal (currently SpringerLink) on June 06, 2019 without open access.

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.

Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922). RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001). CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update.

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

Central nervous system inflammatory demyelinating disorders among Hong Kong Chinese.

Classical multiple sclerosis (CMS) and neuromyelitis optica spectrum disorders (NMOSD) are distinct central nervous system inflammatory demyelinating disorders (CNS IDD). Early diagnosis of CNS IDD is important as appropriate immunotherapies to optimize prognosis. We studied the diagnoses of CNS IDD among Hong Kong Chinese in a hospital-based setting. Consecutive Chinese patients who presented to our hospital with clinically isolated syndrome and subsequently diagnosed to have CNS IDD from 1980 to 2010 were reviewed. Patients with known diagnosis of CNS IDD referred for further care were excluded. Serial sera were assayed for aquaporin-4 autoantibodies (AQP4 Ab), at least 3 assays within 2-5years. A total of 210 patients diagnosed to have CNS IDD with disease duration of at least 2years were studied. Among 198 patients with serial sera available, 40 (20.2%, 20 had NMO and 20 other NMOSD) were AQP4 Ab-positive. Four patients who were AQP4 Ab-negative on the initial assay converted to AQP4 Ab-positive on repeated assays. The diagnoses of 210 patients were CMS in 88 (41.9%), NMOSD 47 (22.4%, 27 NMO, 20 other NMOSD), single attack of myelitis 23 (11.0%), single attack of optic neuritis 21 (10.0%), relapsing myelitis 10 (4.8%), acute disseminated encephalomyelitis (ADEM) 9 (4.3%), relapsing optic neuritis in 6 (2.9%), opticospinal multiple sclerosis 3 (1.4%) and single attack of brainstem encephalitis 3 (1.4%). Compared to CMS, NMOSD patients had older onset age, lower frequencies of brain MRI abnormalities and CSF OCB, higher frequency of LETM, higher CNS inflammation attack frequency in the first 2years, worse clinical outcome with higher EDSS score and mortality rate. This hospital-based study suggests that CMS (41.9%) and NMOSD (22.4%) are the most common CNS IDD among Hong Kong Chinese. NMOSD has worse clinical outcome than CMS. Detection of AQP4 Ab facilitates early diagnosis and prompts immunotherapies of NMOSD.

Photochemical properties of CeO2-coated ZnO nanorods.

Well-aligned ZnO nanorods were deposited by a mild hydrothermal process and coated with nanosized CeO2 particles (approximately 5 nm) by an oxidative-soak-coating method at 45 degrees C. The low growth temperature proved useful in avoiding interfacial reaction between the two phases. Correlation of photoluminescence results indicated that the defects responsible for the deep level emission (DLE) from ZnO were largely located at the surface. The CeO2 coating reduced the DLE but also the photocatalytic activity as surficial hydroxyl groups were involved in the nucleation of the CeO2 phase and thus not available for absorption of the methylene blue species for degradation. Still, CeO2 coated ZnO nanorods retained their photocatalytic ability and could be useful as bifunctional catalyst to treat multiple contaminants simultaneously.

Intracellular levels of hepatitis B virus DNA and pregenomic RNA in peripheral blood mononuclear cells of chronically infected patients.

It remains uncertain whether hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and pregenomic RNA (pgRNA) can be detected in the serum or peripheral blood mononuclear cells (PBMC) of patients with chronic hepatitis B (CHB) infection. We examined HBV cccDNA and pgRNA in the serum and PBMC, and investigated the effect of lamivudine therapy on the viral loads in the PBMC of CHB patients. Paired serum and PBMC samples from 50 treatment-naïve CHB patients [25 hepatitis B e antigen (HBeAg) positive and 25 HBeAg negative] were quantified for total HBV DNA, cccDNA and pgRNA by real time polymerase chain reaction. HBV cccDNA and pgRNA were below the lower detection limit in all serum samples, and in 84% of PBMC. HBV DNA (r = 0.889, P < 0.001) and pgRNA (r = 0.696, P < 0.001) in PBMC correlated with the HBV DNA in serum. In the longitudinal study, 30 patients treated with lamivudine therapy for a median duration of 34 weeks (range 12-48 weeks) were examined. The median HBV DNA reduction in PBMC before and after treatment was 1.318 (range -0.471 to 3.846) log units, which was significantly lower than serum HBV DNA reduction [3.371 (range -0.883 to 9.454) log units, P < 0.05]. HBV cccDNA and pgRNA were undetectable in the serum of CHB patients. HBV viral loads in PBMC correlated with serum HBV DNA. Lamivudine therapy had less effect on the HBV viral loads in PBMC compared with the serum viral loads.

Clinical trial: a phase II, randomized study evaluating the safety, pharmacokinetics and anti-viral activity of clevudine for 12 weeks in patients with chronic hepatitis B.

BACKGROUND: Clevudine is a polymerase inhibitor that has the unusual feature of delayed viral rebound after therapy in some patients which may be related to its pharmacokinetics. AIM: To characterize pharmacokinetic and pharmacodynamic profile of clevudine, a potent hepatitis B polymerase inhibitor. METHODS: A multicenter, randomized study comparing 10, 30 and 50 mg clevudine once daily for 12 weeks with 24 weeks off-treatment follow-up. Patients had chronic HBV infection, were nucleoside-naïve without co-infection. HBV viral load (VL) was assayed using Digene Hybrid Capture II with a lower limit of detection of 4700 copies/mL (940 IU/mL). Clevudine levels were measured using a liquid chromatography/mass spectrometery method. RESULTS: A total of 31 patients were enrolled into the 10 mg (n = 10), 30 mg (n = 11) and 50 mg (n = 10) groups, respectively. At week 12, the median VL change was -3.2, -3.7 and -4.2 log(10) copies/mL (-0.64, -0.74 and -0.84 log(10) IU/mL) in the 10, 30 and 50 mg groups, respectively (P = 0.012). At week 12, one of 10, five of 11 and two of 10 patients had VL below the assay lower limit of detection. Clevudine was well tolerated with no severe/serious adverse events. The mean plasma half-life of clevudine was 70 h and consequently is not the cause of the delayed viral rebound seen in some patients. Through modelling, 97% of the maximal treatment effect was reached with a 30 mg daily dose. Six patients had genomic changes without viral rebound. CONCLUSION: Clevudine appears to be a potent and tolerable (over 12 weeks) anti-viral and the optimal dosage appears to be 30 mg once daily.

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.

Efficacy of a pre-S containing vaccine in patients receiving lamivudine prophylaxis after liver transplantation for chronic hepatitis B.

Lamivudine monoprophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants and second generation recombinant HBV vaccine is not effective. We studied the efficacy of two courses each of three double-doses (20 microg) of third-generation recombinant pre-S containing vaccine (Sci-B-Vac) in 20 patients on lamivudine prophylaxis at a median of 637 days (range, 390-2666 days) after transplantation. At enrollment, all patients were seronegative for HBsAg, anti-HBs and HBVDNA (by qPCR). Lamivudine (100 mg/day) was continued throughout the study. Five patients (25%) responded to the first course and five additional patients responded after the second course (overall response rate 50%). The response rate was 88% in patients younger than 50 years old and 25% in older patients (p = 0.02). The median peak anti-HBs titer was 153 mIU/mL with six responders having a titer >100 mIU/mL and seven sustained >6 months. Among seven previous nonresponders to second generation recombinant vaccine, three (44%) responded. At the end of the study, all patients remained seronegative for HBsAg. In conclusion, Sci-B-Vac is effective in about 50% of patients receiving lamividine prophylaxis and may prevent recurrence due to escape mutants.

Predicting response to peginterferon alpha-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B.

OBJECTIVE: In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24 week post-treatment biochemical and virological response rates with peginterferon alpha-2a with or without lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses was investigated. METHODS: Multivariate analyses were performed using available data from 518 patients treated with peginterferon alpha-2a with or without lamivudine, or with lamivudine alone. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA level of <20,000 copies/ml. RESULTS: In logistic regression analyses across all treatment arms, peginterferon alpha-2a (with or without lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response at 24 weeks post-treatment. In the peginterferon alpha-2a and lamivudine monotherapy arms, patients with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to the combination than to peginterferon alpha-2a monotherapy (p = 0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for the peginterferon alpha-2a, 19.0% for the combination, and 10.0% for the lamivudine groups, with genotypes B or C associated with a sustained combined response to peginterferon alpha-2a with or without lamivudine therapy. CONCLUSIONS: Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response at 24 weeks post-treatment, in patients treated with peginterferon alpha-2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon alpha-2a with or without lamivudine.

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.

48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection.

BACKGROUND/AIM: Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown. METHOD: We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated interferon alpha-2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL at week 72. RESULTS: Twenty-nine patients were treated with 48 weeks of pegylated-interferon-alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated-interferon-alpha-2a was independently associated with sustained virological response (P = 0.04 adjusted hazards-ratio 9.37). CONCLUSION: Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B.

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.

Pharmacokinetics of pitavastatin in subjects with Child-Pugh A and B cirrhosis.

AIM: Lipid lowering therapy with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors is increasingly used for the prevention of cardiovascular events, but they should be used with caution in patients with impaired liver function. We therefore studied the pharmacokinetics of pitavastatin in patients with liver cirrhosis. METHODS: Plasma concentrations of pitavastatin were determined after administration of 2 mg single-dose pitavastatin to 12 male patients with liver cirrhosis (six Child-Pugh grade A and six grade B). These results were compared with the single-dose pharmacokinetic results obtained from six male volunteers without liver disease. RESULTS: Administration of 2 mg single-dose pitavastatin to patients with Child-Pugh grade A and grade B cirrhosis resulted in a 1.19- and 2.47-fold increase in Cmax and 1.27- and 3.64-fold increase in AUCt, respectively, when compared with normal subjects. The geomean Cmax of pitavastatin was 59.5 ng ml(-1), 70.7 ng ml(-1) and 147.1 ng ml(-1) in the control, Child-Pugh grade A and Child-Pugh grade B groups, respectively. The geomean AUCt of pitavastatin in the three groups was 121.2 ng h(-1) ml(-1), 154.2 ng h(-1) ml(-1) and 441.7 ng h(-1) ml(-1), respectively. The geomean Cmax of pitavastatin lactone was 20.3 ng ml(-1), 19.1 ng ml(-1) and 9.9 ng ml(-1) in the control, Child-Pugh grade A and grade B groups, respectively. The AUCt of pitavastatin lactone was 120.2 h(-1) ml(-1), 108.8 h(-1) ml(-1) and 87.5 h(-1) ml(-1), respectively. CONCLUSION: The plasma concentration of pitavastatin is increased in patients with liver cirrhosis. In such patients, caution is required, although dose reduction may not be necessary in Child-Pugh A cirrhosis.

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.