Hepatitis: Au WY

Au WY, Kwong YL. · Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China. · Acta Pharmacol Sin. · Pubmed #18298894 links to  free full text

Abstract: Arsenic trioxide (As2O3) has been used medicinally for thousands of years. Its therapeutic use in leukaemia was described a century ago. Recent rekindling in the interest of As2O3 is due to its high efficacy in acute promyelocytic leukaemia (APL). As2O3 has also been tested clinically in other blood and solid cancers. Most studies have used intravenous As2O3, although an oral As2O3 is equally efficacious. Side effects of As2O3 are usually minor, including skin reactions, gastrointestinal upset, and hepatitis. These respond to symptomatic treatment or temporary drug cessation, and do not compromise subsequent treatment with As2O3. During induction therapy in APL, a leucocytosis may occasionally occur, which can be associated with fluid accumulation and pulmonary infiltration. The condition is similar to the APL differentiation syndrome during treatment with all-trans retinoic acid, and responds to cytoreductive treatment and corticosteroids. Intravenous As2O3 treatment leads to QT prolongation. In the presence of underlying cardiopulmonary diseases or electrolyte disturbances, particularly hypokalaemia and hypomagnesaemia, serious arrhythmias may develop, with torsades du pointes reported in 1% of cases. This may be related to a dose-dependent arsenic-mediated inhibition of potassium ion channels that compromises cardiac repolarization. Because of slow intestinal absorption, oral-As2O3 gives a lower plasma arsenic concentration, which is associated with lesser QT prolongation and hence a more favorable cardiac safety profile. As2O3 does not appear to enter the central nervous system. However, if the blood brain barrier is breached, elemental arsenic may enter the cerebrospinal fluid. As2O3 is predominantly excreted in the kidneys, and dose adjustment is required when renal function is impaired.

Au WY, Leung WC. · Bone Marrow Transplant Unit, Department of Medicine, Queen Mary Hospital, Hong Kong. · Bone Marrow Transplant. · Pubmed #17310136 No free full text.

Abstract: Increasing numbers of successful pregnancies are reported in recipients of allogeneic hemopoietic stem cell transplantation (HSCT). These may occur naturally, or more commonly, through assisted reproduction. The pregnancy outcomes are usually normal. There are currently no guidelines on the prenatal management of pregnancies involving HSCT recipients. HSCT recipients are unique in that their red cells, lymphocytes and even the DNA in the circulation are donor derived. As a result, typical prenatal screening tests in parents, including mean cell volume (MCV), hemoglobin pattern, blood group, infective serology and DNA screening, are all affected. The MCV cannot be used as guide for iron and folate supplements, or for thalassemia and sickle cell anemia screening. Such screening must be based on pre-HSCT indices and pre-HSCT DNA samples. The risks for hemolytic disease of newborn and hepatitis B virus transmission have to be re-evaluated, based on both pre- and post-HSCT patient as well as donor blood group and serology results. Good communication between obstetricians and the HSCT physician is paramount to promote successful pregnancies in this distinct patient population.

Au WY, Kwong YL, Ma SK, Mak YK, Wong KF, Lei KI, Ng MH, Chan JC, Lin SY, Lee KK, Liang R. · Department of Medicine, Queen Mary Hospital, Hong Kong. · Hematol Oncol. · Pubmed #11135356 No free full text.

Abstract: BACKGROUND: Hairy cell leukemia (HCL) is a unique chronic B cell lymphoproliferative disease (B-LPD), with distinct clinical and pathological features, and excellent treatment response to 2-chlorodeoxyadenosine (2-CDA) and pentostatin. There have been few reports of HCL from oriental countries. PATIENTS AND METHODS: A retrospective survey of HCL in six major hematology units in Hong Kong over a 12-year period. RESULTS: There were 18 cases of HCL identified. Most patients presented with fever, splenomegaly and monocytopenia. Lymphadenopathy was present in three patients, and open biopsy revealed tuberculosis infection in two cases. Seven cases received interferon and 12 cases received 2-CDA. Four patients died from bronchogenic carcinoma, cerebral vascular accident, fulminant hepatitis B virus reactivation and malignant melanoma. The remaining 14 patients are in clinical remission at a median of 6 years' follow-up; two are also surviving from second malignancies (thyroid papillary carcinoma and renal cell carcinoma). CONCLUSIONS: Parallel to the low incidence of B-LPD in Chinese, the incidence of HCL (0.035/100000 population per year) is much lower than in Western series. Other clinical features such as male dominance, clinical presentation, response to 2-CDA treatment, and association with second malignancy are similar to Western reports. However, two common complications in the Chinese population are the fulminant reactivation of hepatitis B infection and disseminated tuberculosis infection.

Lau GK, Yiu HH, Fong DY, Cheng HC, Au WY, Lai LS, Cheung M, Zhang HY, Lie A, Ngan R, Liang R. · Division of Gastroenterology and Hepatology, University Department of Medicine, Queen Mary Hospital, Hong Kong Special Administrative Region, China. · Gastroenterology. · Pubmed #14724827 No free full text.

Abstract: BACKGROUND & AIMS: Hepatitis B virus reactivation is a serious cause of morbidity and mortality in hepatitis B surface antigen-positive patients treated with chemotherapy. We compared the efficacy of early and deferred preemptive lamivudine therapy in reducing the incidence of hepatitis due to hepatitis B virus reactivation in hepatitis B surface antigen-positive lymphoma patients treated with chemotherapy. METHODS: Thirty consecutive hepatitis B surface antigen-positive lymphoma patients undergoing intensive chemotherapy were randomized (1:1) to receive lamivudine 100 mg daily 1 week before chemotherapy (group 1) or to have this treatment deferred until there was serological evidence of hepatitis B virus reactivation on the basis of serial 2-week-interval serum hepatitis B virus DNA monitoring by a Digene Hybrid Capture II assay (group 2). RESULTS: Eight (53%) patients in group 2 and none in group 1 had hepatitis B virus virological reactivation after chemotherapy (P = 0.002). Seven patients in group 2 still had hepatitis (5 anicteric hepatitis, 1 icteric hepatitis, and 1 hepatic failure). Survival free from hepatitis due to hepatitis B virus reactivation in group 1 patients was significantly longer than that in group 2 (P = 0.002 on the log-rank test). The median onset of hepatitis B virus reactivation in these patients was 16 weeks (range, 4-36 weeks) after the initiation of chemotherapy. Three (13%) of the 23 patients treated with lamivudine had hepatitis B virus-related hepatitis after lamivudine withdrawal. CONCLUSIONS: Lamivudine should be considered preemptively before or at the initiation of chemotherapy for all hepatitis B surface antigen-positive lymphoma patients undergoing intense chemotherapy.

Lau GK, He ML, Fong DY, Bartholomeusz A, Au WY, Lie AK, Locarnini S, Liang R. · Division of Gastroenterology and Hepatology, University of Hong Kong, Hong Kong Special Administrative Region, China. · Hepatology. · Pubmed #12198664 No free full text.

Abstract: Exacerbation of hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface antigen (HBsAg)-positive patients undergoing transplantation. Our aim was to evaluate the effectiveness of lamivudine to prevent hepatitis due to exacerbation of HBV in HBsAg-positive patients treated with allogeneic hematopoietic cell transplantation. We studied 20 consecutive HBsAg-positive recipients of allogeneic hematopoietic cell transplantation who received lamivudine 100 mg daily starting one week before transplantation until week 52 after transplantation (group 1). Serial serum alanine aminotransferase and HBV DNA levels were measured before and after transplantation at 4- to 8-week intervals for the first year and then 4- to 12-week intervals. Their virologic and clinical outcomes were compared with 20 case-matched recipients who did not receive any antiviral therapy to HBV (anti-HBV) before and after hematopoietic cell transplantation (group 2). After transplantation, 9 patients (45%) in group 2 and one patient (5%) in group 1 had hepatitis due to exacerbation of HBV (P <.008), with 3 hepatic failures in group 2 and none in group 1. The one-year actuarial probability of survival without hepatitis due to exacerbation of HBV was higher in group 1 than group 2 (94.1% vs. 54.3%, P =.002). By multivariate Cox analysis, preemptive use of lamivudine effectively reduced hepatitis due to exacerbation of HBV (adjusted hazards ratio, 0.09; P =.021). In conclusion, preemptive lamivudine reduced HBV exacerbation. The use of lamivudine with other immunosuppressive regimens to prevent exacerbation of HBV should be further explored.

Au WY, Fung A, Liu CL, Fan ST, Ma SK, Liang R, Kwong YL. · Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong. · Am J Hematol. · Pubmed #16929538 No free full text.

Abstract: A 52-year-old man developed essential thrombocythemia (ET) with JAK2 V617F mutation after orthotopic liver transplantation (OLT). Retrospective analysis showed that, despite a low platelet count, the JAK2 mutation was already found at presentation 14 months before OLT. The high platelet count that would have been typical of ET might be masked by the cirrhosis-related hypersplenism. Thrombocythemia became obvious after OLT. The patient subsequently developed blastic transformation 12 months afterward, a process probably accelerated by the immunosuppression required for the OLT.

Hui CK, Cheung WW, Zhang HY, Au WY, Yueng YH, Leung AY, Leung N, Luk JM, Lie AK, Kwong YL, Liang R, Lau GK. · Centre For The Study of Liver Diseases, The University of Hong Kong, Hong Kong SAR, China. · Gastroenterology. · Pubmed #16831590 No free full text.

Abstract: BACKGROUND & AIMS: De novo hepatitis B virus (HBV)-related hepatitis after chemotherapy results in high morbidity and mortality. We evaluate the clinical course of de novo HBV-related hepatitis after chemotherapy. METHODS: Two hundred forty-four consecutive hepatitis B surface antigen (HBsAg)-negative lymphoma patients treated with chemotherapy were followed up for a median of 12.4 (range, 0.1-65.0) months. Serially collected serum samples were analyzed for hepatitis, serum HBV DNA, and HBsAg seroreversion. RESULTS: Eight of the 244 patients (3.3%) developed de novo HBV-related hepatitis. A 100-fold increase in serum HBV DNA preceded de novo HBV-related hepatitis by a median of 18.5 (range, 12-28) weeks. All 8 patients had normal serum alanine aminotransaminase level when the 100-fold increase in serum HBV DNA occurred. Patients with de novo HBV-related hepatitis were more likely to have occult HBV infection before chemotherapy. Direct sequencing results showed that these 8 patients had de novo HBV-related hepatitis from reactivation of occult HBV infection. Three of the 8 patients with de novo HBV-related hepatitis compared with 6 of the 236 patients without de novo HBV-related hepatitis developed fulminant hepatic failure (37.5% vs 2.5%, respectively, P < .001). On multivariate Cox analysis, de novo HBV-related hepatitis was independently associated with a higher risk of fulminant hepatic failure (relative risk, 29.854; 95% confidence interval: 4.844-183.980; P < .001). CONCLUSIONS: Close surveillance for a 100-fold increase in HBV DNA is recommended for HBsAg-negative patients treated with chemotherapy so that early commencement of antiviral therapy can be initiated before the occurrence of de novo HBV-related hepatitis.

Au WY, Lam CC, Liu CL, Yuen MF. · Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong. · Int J Hematol. · Pubmed #16207601 No free full text.

Abstract: Hepatitis C virus (HCV) eradication in hemophilia patients depends on viral and patient factors. We report the treatment results with interferon 3 (5 megaunits, 3 times per week) and ribavirin (1 g daily) for 1 year in 17 Chinese patients who were negative for the human immunodeficiency virus. The HCV genotype consisted of a mixture of Western (genotypes 1, 2, and 3) and Chinese (genotypes 1 and 6) patterns. Quasi species were common (29%). Seven patients (41%) stopped treatment because of complications. Sustained HCV eradication was achieved until the end of treatment or for 24 months in 7 of 17 patients, respectively. A sustained response occurred in 50% of the patients completing treatment and occurred only in patients with genotypes 1, 3, and 6 but not with quasi species.

Au WY, Liu CL, Lo CM, Fan ST, Lam CK. · Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China. · Haemophilia. · Pubmed #16011595 No free full text.

Abstract: We report the first case of unrelated living liver transplantation for hepatitis C related hepatocellular carcinoma (HCC) in a Chinese patient with haemophilia A. The development of cirrhosis and HCC was insidious in this patient, who has previously failed interferon treatment despite low viral load and genotype 6a. With factor VIII and novoseven support, there were no operative complications and there was no need for blood transfusion. Postoperative pegulated interferon treatment resulted in viral clearance with no increased cellular rejection. The use of living donors represent a potential life saving therapeutic options for hepatitis C virus related complications in haemophiliac, especially in countries of organ shortage. Careful patient and donor choice, meticulous surgical expertise and proper counselling, however, are prudent requirements.

Hui CK, Cheung WW, Au WY, Lie AK, Zhang HY, Yueng YH, Wong BC, Leung N, Kwong YL, Liang R, Lau GK. · Department of Medicine, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd, Hong Kong SAR, China. · Gut. · Pubmed #16000641 links to  free full text

Abstract: 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.

Hui CK, Lie A, Au WY, Ma SY, Leung YH, Zhang HY, Sun J, Cheung WW, Chim CS, Kwong YL, Liang R, Lau GK. · Division of Gastroenterology and Hepatology, The University of Hong Kong, China. · Am J Transplant. · Pubmed #15888052 No free full text.

Abstract: Use of hepatitis B surface antigen (HBsAg) positive donors for allogeneic hematopoietic stem cell transplantation (HSCT) causes serious hepatitis B virus (HBV)-related liver morbidity and mortality in the recipient. We compared the effectiveness of anti-HBV therapy in 29 recipients who underwent HSCT using HBsAg positive marrow (group I) against a historical control group of 25 patients who received HBsAg positive marrow without pre-HSCT prophylaxis (group II). Anti-HBV therapy consisted of lamivudine for HBsAg-positive donors and all recipients (n = 29) as well as HBV vaccination to all HBsAg-negative recipients (n = 10) before HSCT. After transplantation, HBV-related hepatitis was significantly higher in group II than group I recipients [12 of 25 recipients (48%) vs. 2 of 29 recipients (6.9%), p = 0.002] and in recipients whose donors had detectable serum HBV DNA by Digene Hybrid Capture II assay [8 of 14 recipients (57.1%) vs. 6 of 40 recipients (15.0%), p = 0.02]. Six recipients in group II and none in group I died of HBV-related hepatic failure (24.0% vs. 0%, p = 0.01). By multivariate Cox analysis, anti-HBV therapy effectively reduces post-HSCT HBV-related hepatitis (p = 0.01, adjusted hazards ratio 7.27, 95%CI 1.62-32.58). Our data support the use of prophylactic therapy in preventing HBV-related hepatitis after allogeneic HSCT from HBsAg-positive donor.

Hui CK, Sun J, Au WY, Lie AK, Yueng YH, Zhang HY, Lee NP, Hou JL, Liang R, Lau GK. · Department of Medicine, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong SAR, China. · J Hepatol. · Pubmed #15885351 No free full text.

Abstract: BACKGROUND/AIMS: The acquisition of hepatitis B virus (HBV) infection following organ transplantation from donors with occult HBV infection is an important cause of morbidity and mortality. The aim of this study is to determine the prevalence of occult HBV in allogeneic hematopoietic stem cell (HSC) transplantation donors. METHODS: We performed a retrospective study on 124 consecutive hepatitis B surface antigen negative HSC donors. Their serum samples were analyzed by PCR for the pre-S/S, pre-core/core and X regions of the virus. Samples reactive by at least two PCR assays were considered HBV-DNA positive. RESULTS: Nineteen of the 124 HSC donors (15.3%) had occult HBV infection. Sixteen of these 19 donors with occult HBV infection (84.2%) tested positive for hepatitis B core antibody while 78 of 105 subjects (74.3%) without occult HBV infection were also positive (P=0.56). Fourteen of the 19 donors (73.7%) with occult HBV infection tested positive for hepatitis B surface antibody while 67 of the 105 subjects without occult HBV infection were also positive (P=0.45). CONCLUSIONS: The prevalence of occult HBV infection among HSC donors in Hong Kong is high. Anti-HBc and anti-HBs status had no significant correlation with the presence of occult HBV infection.

Hui CK, Lie A, Au WY, Leung YH, Ma SY, Cheung WW, Zhang HY, Chim CS, Kwong YL, Liang R, Lau GK. · Division of Gastroenterology and Hepatology, The University of Hong Kong, SAR, China. · Blood. · Pubmed #15797991 links to  free full text

Abstract: The long-term hepatic complications after allogeneic hematopoietic stem cell transplantation (HSCT) in hepatitis B virus (HBV) endemic area are unknown. We examined the serological and liver-related outcome of 803 consecutive patients who received allogeneic HSCTs, with a median follow-up period of 83 months (range, 0.5-155 months). Late HBV-related hepatitis occurred in 2 of the 721 hepatitis B surface antigen-negative (HBsAg-) recipients compared with 16 of the 82 HBsAg+ recipients after HSCT (0.3% vs 19.5%; P < .001 by log-rank). Liver cirrhosis developed in 8 of the 82 HBsAg+ recipients compared with none of the 721 HBsAg- recipients (9.8% vs 0%; P < .001 by log-rank). Twenty of the 31 (64.5%) HBsAg+ recipients of hematopoietic stem cells from donors with natural immunity to HBV had sustained serologic clearance of HBsAg after HSCT. Eight of the 62 recipients without sustained HBsAg clearance compared with none of the 20 recipients with sustained HBsAg clearance developed liver cirrhosis (12.9% vs 0%; P = .02 by log-rank). Our study showed that long-term hepatic complications occur in a significant proportion of HBsAg+ patients after HSCT and the incidence of liver cirrhosis is reduced in those with sustained serologic clearance of HBsAg after HSCT.

Hui CK, Yu J, Au WY, Zhang HY, Bartholomeusz A, Locarnini S, Kwong YL, Liang R, Lau GK. · Division of Gastroenterology and Hepatology, University Department of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, SAR, China. · J Clin Virol. · Pubmed #15653422 No free full text.

Abstract: BACKGROUND: After hematopoietic cell transplantation (HCT), hepatitis due to hepatitis B virus (HBV) rarely occurred beyond the initial 12 months after transplantation. OBJECTIVES: We investigated the cause of "late" hepatitis due to HBV infection in two recipients after allogeneic HCT. STUDY DESIGN: Two male patients with acute myeloid leukemia and light chain myeloma, respectively, developed HBV-related hepatitis more than 2 years after HCT. All serum samples collected from the recipients, donors and their respective spouses were tested for HBV DNA by nested PCR, and if positive further quantified by Digene Hybrid Capture assay II. The HBV genotype was determined by PCR and sequencing. RESULTS: Genotypic analysis suggested that the cause of "late" hepatitis was due to acute HBV infection transmitted from their respective spouse. CONCLUSION: Our findings suggested that sexual precautions should be taken in these patients after HCT. Alternatively, or even additionally, active vaccination should be delivered to these patients once they have lost their HBV immunity.

Au WY, Kwok JS, Chu KM, Ma ES. · Department of Medicine, Queen Mary Hospital, Hong Kong, China. · Ann Hematol. · Pubmed #15503020 No free full text.

Abstract: Cryoglobulinemia is uncommon in Southern Chinese in Hong Kong, with tropical climates and low incidence of hepatitis C virus (HCV) infection. Eight positive cases were detected among 481 patients screened for cryoglobulins over a 10-year period. Three HCV carriers (38%) ran benign courses. The others included two carriers of hepatitis B virus (HBV), two patients with adenocarcinoma, and one with chronic lymphocytic lymphoma. Four of them (except one HBV carrier) ran fulminant courses and died of cryoglobulin-related complications. Interestingly, all four cases also had structural aortic abnormalities, including multiple dissections, aneurysms, and congenital aortic arch abnormalities, which were often life threatening. The association of aortic abnormality and cryoglobulinemia is hitherto unreported and may be peculiar to our ethnic group. Aggressive control of the cryoglobulin may help to reduce aortic intima damage.

Ma SY, Au WY, Ng IO, Lie AK, Leung AY, Liang R, Lau GK, Kwong YL. · Department of Medicine, Queen Mary Hospital, Hong Kong, China. · Transplantation. · Pubmed #15114094 No free full text.

Abstract: BACKGROUND: Graft-versus-host disease (GVHD) of the liver after allogeneic hematopoietic stem cell transplantation classically presents with increased bilirubin and alkaline phosphatase (ALP) levels. A hepatitic variant was recently recognized, with more than a 10-fold increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. This study defines the clinicopathologic features and prognostic implications of hepatitic GVHD compared with classic liver GVHD. METHOD: A total of 38 cases of hepatitic GVHD, 68 cases of classic liver GVHD, and 13 cases of hepatitis B virus (HBV)-related hepatitis after hematopoietic stem cell transplantation were analyzed. RESULTS: Hepatitic GVHD cases showed significantly higher ALT, AST, and ALP levels compared with classic liver GVHD cases (at onset, mean ALT: 154 vs. 58 U/L, P <0.001; AST: 167 vs. 77 U/L, P <0.001; at peak, ALT: 435 vs. 112 U/L, P <0.001; AST: 587 vs. 150 U/L, P <0.001; ALP: 416 vs. 238 U/L, P =0.001), persisted longer (74 vs. 32 days, P =0.006), and showed more lobular pathologic changes in biopsy (lobular changes: 16/26 vs. 4/19, P =0.007; hepatocyte necrosis: 16/26 vs. 6/19, P =0.008; acidophil bodies: 15/26 vs. 4/19, P =0.014) but less cholestasis (4/26 vs. 8/19, P =0.045). However, cumulative doses of immunosuppressants prescribed, response, and outcome were similar. Compared with hepatitic GVHD, HBV-related hepatitis occurred later (95 vs. 184 days, P =0.049), but clinical and biochemical profiles were similar, requiring liver biopsies for their distinction. CONCLUSIONS: Hepatitic and classic liver GVHD differed biochemically and pathologically, but these differences showed no obvious impact on outcome. The distinction of hepatitic GVHD from other hepatitis is mandatory.

Ma SY, Au WY, Ng IO, Lie AK, Leung AY, Liang RH, Lau GK, Kwong YL. · University Department of Medicine, Queen Mary Hospital, Hong Kong. · Transplantation. · Pubmed #12865805 No free full text.

Abstract: BACKGROUND: Derangement of liver function tests (LFT) is common after hematopoietic stem-cell transplantation (HSCT). The role of liver biopsy in such cases has not been defined in hepatitis B virus (HBV)-prevalent patients. The impact of liver biopsy in the management of LFT derangement after HSCT in an HBV-prevalent population was examined. METHODS: Seventy-five liver biopsies, performed for 323 patients with LFT derangement post-HSCT (263 allogeneic, 60 autologous), were analyzed. The HBV carrier rate was 13.6%. RESULTS: Significantly more LFT derangements and therefore liver biopsies occurred in allogeneic versus autologous HSCT. Before biopsy, graft-versus-host disease (GVHD) and HBV reactivation were clinically diagnosed in 70.6% and 25.3% of cases, respectively. A definite histopathologic diagnosis was obtained after biopsy in 53 cases, with GVHD, HBV hepatitis, and concomitant GVHD-HBV hepatitis found in 33%, 21%, and 8% of cases, respectively. The clinical and histopathologic diagnoses were concordant in 43 cases and discordant in 9 cases. Clinical management was altered in six of nine discordant cases, five of which were caused by HBV or hepatitis C virus (HCV) reactivation. Twenty-two biopsy specimens showed nondiagnostic histopathologic features. Twenty of these cases were successfully managed on the basis of clinical diagnoses. The clinical-biochemical features of patients clinically diagnosed to have GVHD did not differ significantly whether or not they were HBV-HCV carriers. However, liver biopsies in HBV-HCV carriers resulted in significantly more treatment alterations as compared with noncarriers. CONCLUSIONS: Clinical diagnoses of LFT derangements post-HSCT might be adequate for initiation of treatment, but liver biopsies in HBV-HCV carriers were needed, as this might impact on management.

Au WY, Lau GK, Lie AK, Liang R, Lo CM, Fan ST, Liu CL, Hawkins BR, Ng IO, Kwong YL. · Departments of Medicine, Surgery and Pathology, Queen Mary Hospital, Hong Kong, China. · Clin Transplant. · Pubmed #12709077 No free full text.

Abstract: 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.

Lau GK, Leung YH, Fong DY, Au WY, Kwong YL, Lie A, Hou JL, Wen YM, Nanj A, Liang R. · Division of Gastroenterology and Hepatology, University Department of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, People's Republic of China. · Blood. · Pubmed #11895763 links to  free full text

Abstract: The risk factors for hepatitis due to hepatitis B virus (HBV) reactivation in patients positive for hepatitis B surface antigen (HBsAg) treated with autologous hematopoietic cell transplantation (HCT) are unknown. We evaluated 137 consecutive patients (23 positive for HBsAg, 37 positive for hepatitis B surface antibody, and 77 negative for HBV) who underwent HCT. Serial serum ALT were measured before transplant and after transplant at 1 to 4 weekly intervals for the first year and then at 2 to 12 weekly intervals thereafter. Before HCT, basic core promoter (T(1762)/A(1764)) and precore (A(1896)) HBV variants were determined in HBsAg-positive and HBV DNA-positive (by polymerase chain reaction assay) patients by direct sequencing and serum HBV DNA quantitation using the Digene Hybrid Capture II assay. Cox proportional hazards analysis was used to assess the association between pretransplantation HBV virologic and host factors and occurrence of hepatitis due to HBV reactivation. After HCT, hepatitis due to HBV reactivation was more common in HBsAg-positive patients than in HBsAg-negative patients (hazard ratio, 33.3; 95% confidence interval [CI], 7.35-142.86; P <.0001). HBsAg-positive patients with detectable serum HBV DNA before HCT (on Digene assay) had a significantly higher risk of hepatitis due to HBV reactivation than HBsAg-positive patients with no detectable serum HBV DNA (adjusted hazard ratio, 9.35; 95% CI, 1.65-52.6; P =.012). Thus, we found that hepatitis due to HBV reactivation is common in HBsAg-positive patients undergoing autologous HCT. A high HBV DNA level (>10(5) copies/mL) was the most important risk factor for HBV reactivation, and its lowering by administration of nucleoside analogues before transplantation should be considered.

Au WY, Lie AK, Liang R, Liu CL, Shek TW, Lau GK. · Department of Medicine, Queen Mary Hospital, Hong Kong. · Bone Marrow Transplant. · Pubmed #11850714 links to  free full text

Abstract: 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.

Au WY, Lie AK, Lam CC, Fan ST, Liu CL, Young K, Lo CM. · Department of Medicine, Queen Mary Hospital, Hong Kong SAR, China. · Haematologica. · Pubmed #10870125 links to  free full text

Abstract: We report the course of thrombotic thrombocytopenic purpura (TTP) in a patient receiving tacrolimus (FK506) immunosuppression for an ABO mismatched second liver graft. A Chinese woman with fulminant hepatitis-B reactivation failed a living-related orthotopic liver transplantation (OLT) due to portal vein thrombosis. An ABO mismatched cadaveric OLT (group A to O) was performed, with peri-operative plasmapheresis to reduce anti-A hemagglutinin titers. On day 30, she developed fever, hemolysis, thrombocytopenia and neurologic dulling. Prominent microangiopathic features in peripheral blood film, and characteristic brain lesions on magnetic resonance imaging confirmed TTP. She responded initially to intensive plasmapheresis with cryosupernatant replacement, and withdrawal of FK506. An attempted reintroduction of FK506 for threatened rejection led to TTP exacerbation. This was controlled with prolonged plasmapheresis and a ten-day infusion of prostacyclin. Immunosuppression was changed to mycophenolate mofetil. By day 53, the peripheral film and lactate dehydrogenase level had returned to baseline and plasmapheresis was stopped.

Lau GK, Yuen ST, Au WY, Wu PC, Liang R. · Department of Medicine, Queen Mary Hospital, Hong Kong, China. · J Gastroenterol Hepatol. · Pubmed #10197497 No free full text.

Abstract: BACKGROUND: Serological clearance of hepatitis B surface antigen (HBsAg) has been described after reception of hepatitis B surface antibody positive marrow, via allogeneic bone marrow transplantation (BMT). Histological changes during the clearance of HBsAg are unknown. METHODS AND RESULTS: We described two chronic hepatitis B carriers (both hepatitis B e antigen negative), who cleared HBsAg after allogeneic bone marrow transplantation. Both received hepatitis B surface and core antibody positive human leucocyte antigen identical donors' marrow and had serological clearance of HBsAg 15 and 7 weeks after allogeneic BMT, respectively. Both events were preceded by hepatic flare. Both patients were also treated with famciclovir for the prevention of hepatitis B reactivation after BMT. Histological examination during the flare showed only mild necroinflammatory activity with multiple foci of confluent necrosis, associated with moderate lymphocytic infiltration. The majority of these lymphocytes were cluster of differentiation (CD) 8 positive. Using immunohistochemistry, there was no detectable hepatic expression of hepatitis B core antigen. However, HBsAg was positive, mainly in the area of confluent necrosis. Using in situ hybridization, hepatitis B virus (HBV) DNA was detected in the nucleus of 5% of hepatocytes, but not in the cytoplasm. CONCLUSIONS: At their last follow up, 22 and 16 months after BMT, the serum of both patients remained HBsAg negative, hepatitis B surface antibody positive and HBV-DNA negative by branched DNA assay.

Au WY, Liu CL, Tam S, Fong BM, Shek TW, Hui CK, Kwong YL. · No affiliation provided · Ann Hematol. · Pubmed #17571262 No free full text.

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Hui CK, Bowden S, Jackson K, Au WY, Fong DY, Lie AK, Chim CS, Liang R, Lau GK. · No affiliation provided · Blood. · Pubmed #15746088 links to  free full text

This publication has no abstract.

Au WY, Lie AK, Ma ES, Lau GK, Chan EC, Kwong YL. · No affiliation provided · Transfusion. · Pubmed #15157268 No free full text.

This publication has no abstract.