Recurrent Intestinal Obstruction in a Patient with Selective IgA Deficiency.

A 32 year old woman presented with acute onset of abdominal pain and fever. An urgent computerised tomography (CT) of the whole abdomen showed dilated loop at the terminal ileum in the right lower abdomen with thickening of the wall and oedema. The CT was suggestive of distal small bowel obstruction at the ileum with surrounding wall oedema. Multiple biopsies taken from the terminal ileum and colon on colonoscopy were all unremarkable. She represented one-year later with a recurrence of intestinal obstruction. CT enteroclysis showed collapse at the distal 3 cm segment of the terminal ileum. There was no associated wall thickening, active inflammatory changes or ileitis. This was suspicious of post-inflammatory change or fibrosis. She was subsequently found to have selective IgA deficiency with recurrent infection in the terminal ileum resulting in intestinal obstruction. In conclusion, selective IgA deficiency should be considered in patients with recurrent intestinal obstruction without anatomical obstructions.

Tuberculous scar tumour detected by dual tracer positron emission-computerised tomography in a tuberculous endemic area.

Tuberculous scar tumour is difficult to diagnose as it does not present with any respiratory symptoms and has a negative chest X-ray. This is a case report on the use of dual tracer 11C-acetate and 18F-fluorodeoxyglucose (18FDG) whole body positron emission tomography-computerised tomography (PET-CT) for detection of tuberculous scar tumour. A 44-year-old Chinese female was incidentally found to have a raised serum Ca 19.9. Magnetic resonance imaging of the whole abdomen, upper endoscopy, and colonoscopy were all unremarkable. A low-dose computed tomography (CT) of the thorax showed bilateral upper lobe fibrosis. Bronchoalveolar lavage for culture and cytology was negative. A dual tracer 11C-acetate and 18FDG whole body PET-CT showed that the left upper lobe fibrosis was hypermetabolic in nature. It was more avid for 11C-acetate than for 18FDG. The left upper lobe lesion was subsequently confirmed on open lung biopsy to be a moderately differentiated adenocarcinoma. Therefore, in a tuberculous endemic region, dual tracer whole body PET-CT with 11C-acetate and 18FDG may have a role in the early detection of tuberculous scar tumour in the lung.

Hepatomegaly and periportal oedema of the liver in a patient with eosinophilic gastroenteritis.

Periportal halos are an uncommon finding on computerised tomography (CT) of the liver. Here, reported a case of periportal halos and hepatomegaly in a patient with eosinophilic gastroenteritis. A 49-year-old male presented with a six week history of right lower quadrant pain and diarrhoea. A CT of the abdomen showed hepatomegaly and multiple hypodense periportal halos around the patent portal veins consistent with periportal oedema. A colonoscopy showed normal looking mucosa in the colon and terminal ileum. Blind biopsies taken throughout the terminal ileum and colon showed increased numbers of eosinophils (more than 25 per high-power field) consistent with eosinophilic gastroenteritis. A liver biopsy showed minimal non-specific chronic inflammatory infiltrates and eosinophils in the portal tracts with ductular proliferation. In conclusion, eosinophilic gastroenteritis should be considered in patients presenting with periportal halos, hepatomegaly, and diarrhoea.

Retracted: outcome and immune reconstitution of HBV-specific immunity in patients with reactivation of occult HBV infection after alemtuzumab-containing chemotherapy regimen.

UNLABELLED: Whether preemptive anti- hepatitis B virus (HBV) therapy should be considered in all hepatitis B surface antigen (HBsAg)-negative patients with occult HBV infection receiving alemtuzumab containing chemotherapy is uncertain. We determined the outcome and effect on HBV-specific immunity of an alemtuzumab-containing chemotherapy regimen in occult HBV-infected patients. Twenty-one consecutive occult HBV-infected patients treated with an alemtuzumab containing chemotherapy regimen were studied. T cell reactivity to HBV antigens and -peptides were quantified by ELISpot and the T cell subset by flow cytometry. Six of the 21 patients (28.6%) developed HBsAg seroreversion. The median (range) time to development of HBsAg seroreversion after the end of chemotherapy was 1.8 months (0.2-2.3 months). Direct sequencing showed that the occult HBV infection of all six patients (100%) was reactivated. These six patients developed severe HBV-related hepatitis. At the end of follow-up, four of these six patients (66.7%) had become negative for HBsAg again. Recovery of CD4+ T cell count and CD4+T cell reactivity against hepatitis B core antigen (HBcAg) occurred 9 months after the end of chemotherapy. Loss of HBsAg occurred after recovery of the CD4+T cell count and increased CD4+T cell reactivity against HBcAg 9 months after the end of chemotherapy. CONCLUSION: An alemtuzumab-containing chemotherapy regimen is associated with a high risk of reactivation of occult HBV infection. Suppression of HBV immunity by an alemtuzumab-containing chemotherapy regimen would persist until 9 months after the end of chemotherapy. In occult HBV-infected patients receiving an alemtuzumab-containing chemotherapy regimen, preemptive anti-HBV therapy should be continued until 9 months after the end of chemotherapy, when recovery of HBV immunity has occurred.

Prevalence and time trend of intestinal metaplasia in Hong Kong.

BACKGROUND AND METHODS: Upper endoscopy records from 1998 to 2003 were reviewed. The demographic data, endoscopic diagnosis, results of rapid urease test and the absence or presence of intestinal metaplasia (IM) in histology were reviewed, to evaluate the prevalence of IM and Helicobacter pylori (Hp) infection over time in Hong Kong. RESULTS: Among 1805 endoscopies performed, 1751 had both rapid urease test and histology available. A significant drop in the prevalence of duodenal ulcers from 17.9% in 1998 to 9.8% in 2003 was found (P = 0.015). Prevalence of IM was 13.9%, 5.9% and 9.4% in Hp positive, Hp negative and overall respectively (P < 0.05). The prevalence of IM increased with age, and the patterns were similar amongst subjects in 1998-2000 and those in 2001-2003. There was progressive decrease in Hp prevalence from 58% in 1998 to 40% in 2001 (P = 0.014), but no further decrease was seen in 2002-3. There was no corresponding decrease in IM prevalence. Instead IM prevalence in 2002-2003 was significantly higher than the prevalence in previous few years (P = 0.04). CONCLUSION: The prevalence of IM did not change in the period from 1998 to 2003 despite a drop in the prevalence of Hp infection since 1994.

Silver nanoparticles inhibit hepatitis B virus replication.

BACKGROUND: Silver nanoparticles have been shown to exhibit promising cytoprotective activities towards HIV-infected T-cells; however, the effects of these nanoparticles towards other kinds of viruses remain largely unexplored. The aim of the present study was to investigate the effects of silver nanoparticles on hepatitis B virus (HBV). METHODS: Monodisperse silver nanoparticles with mean particle diameters of approximately 10 nm (Ag10Ns) and approximately 50 nm (Ag50Ns) were prepared from AgNO3 in HEPES buffer. The in vitro anti-HBV activities of these particles were determined using the HepAD38 cell line as infection model. RESULTS: Ag10Ns and Ag50Ns were able to reduce the extracellular HBV DNA formation of HepAD38 cells by >50% compared with the vehicle control (that is, HepAD38 cells in the absence of silver nanoparticles). Silver nanoparticles had little effect on the amount of HBV covalently closed circular DNA (cccDNA), but could inhibit the formation of intracellular HBV RNA. Gel mobility shift assays indicated that Ag10Ns bound HBV double-stranded DNA at a DNA:silver molar ratio of 1:50; an absorption titration assay showed that the nanoparticles have good binding affinity for HBV DNA with a binding constant (Kb) of (8.8 +/- 1.0)x10(5) dm(3)mol(-1). As both the viral and Ag10Ns systems are in the nanometer size range, we found that Ag10Ns could directly interact with the HBV viral particles as revealed by transmission electronic microscopy. CONCLUSIONS: Silver nanoparticles could inhibit the in vitro production of HBV RNA and extracellular virions. We hypothesize that the direct interaction between these nanoparticles and HBV double-stranded DNA or viral particles is responsible for their antiviral mechanism.

Impact of early viral kinetics on T-cell reactivity during antiviral therapy in chronic hepatitis B.

BACKGROUND: The patterns of hepatitis B viral dynamics during different antiviral therapies and the associated changes in HBV-specific T-cell reactivity are not well defined. METHODS: We investigated the impact of early viral load decline on virus-specific T-cell reactivity in 30 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B randomized to monotherapy with adefovir dipivoxil (ADV) or in combination with emtricitabine (ADV/FTC). Viral kinetics were analysed by mathematical modelling. T-cell reactivity to HBV core and/or surface antigens and natural killer T cell frequency were tested longitudinally, baseline to week 48, using EliSPOT assays and/or flow cytometry. RESULTS: Mathematical modelling of early HBV kinetics identified two subsets of patients: 11 fast responders (undetectable viraemia by week 12; eight on ADV/FTC three on ADV) and 19 slow responders who remained viremic (six on ADV/FTC 13 on ADV). The rate of infected hepatocyte loss was higher in fast than in slow responders (P = 0.0007), and correlated inversely with pre-treatment levels of intrahepatic covalently closed circular HBV DNA. The frequency of HBV core-specific CD4+ T-cells increased significantly only in fast responders, peaking between week 16 and 24, while the HBV surface-specific CD4+ T-cells increased in both subsets. These changes in CD4+ T-cell reactivity were transient however, and no increase in HBV-specific CD8+ T-cells was observed. By week 48, HBeAg seroconversion occurred only in 3/30 (10%) patients. CONCLUSIONS: Early viraemia clearance facilitates recovery of virus-specific CD4+ T-cell reactivity, but appears insufficient to establish clinically relevant antiviral immunity.

Trends for genetic variation of Hepatitis C Virus quasispecies in Human Immunodeficiency virus-1 coinfected patients.

Chronic infection by Hepatitis C Virus (HCV) causes liver fibrosis, which is accelerated by unknown mechanisms in patients with HIV-1 coinfection. The evolution of HCV quasispecies in this setting of coinfection is not fully understood. To compare HCV quasispecies between HIV-HCV coinfection and HCV monoinfection, we sequenced 340 HCV clones from the HVR-1 and NS3 regions at two different time points in two groups of treatment-naïve patients with HCV-1a infection: (1) HIV-HCV positive (n=6); and (2) HIV negative-HCV positive (n=3). In HCV/HIV coinfection, we found a trend for reduced HCV genetic complexity and diversity, and a trend towards reduced dN/dS ratios in the HVR-1 region, especially in those patients with CD4<200cells/mm(3), who lost positive selective immune pressure in the HVR-1 region. Differences in immune regulation of HCV quasispecies in HIV coinfected individuals deserve further exploration to clarify the different outcomes of chronic hepatitis C noted between the immunocompromised and the immunocompetent host.

Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant mRNA splicing of the liver intestine-cadherin gene CDH17 in liver tissues was triggered by the specific constellation of two CDH17 single nucleotide polymorphisms (651T and IVS6+35G). CDH17 aberrant splicing was highly associated with tumor dissemination and shorter survival of HCC patients. Consequently, it is highly relevant to assess whether the presence of these single nucleotide polymorphisms in the general population represents a risk to the development of HCC. EXPERIMENTAL DESIGN: We conducted a case-control study including 164 HCC and 99 cirrhosis patients and 293 healthy controls. Genotyping was done by PCR and direct sequencing. Odds ratio (OR) and chi2 analysis were used to analyze genotypes and haplotypes. RESULTS: Genotypes 651TT [OR, 2.62; 95% confidence interval (95% CI), 1.34-5.03] and IVS6+35 GG (OR, 1.95; 95% CI, 1.04-3.62) were highly associated with HCC disease. The 651T (C>T) and IVS6+35G (A>G) alleles were also overrepresented in HCC patients and, in particular, the T-G haplotype was the most prevalent in HCC patients when compared with healthy controls (OR, 1.57; 95% CI, 1.167-2.109; P=0.004), which was in agreement with the aberrant splicing observed in tumor tissues. There was no significant difference in genotype and allele frequencies between cirrhosis patients and controls. CONCLUSION: The functional T-G haplotype of CDH17 (651 C>T and IVS6+35A>G) is a genetic susceptibility factor for the development of HCC in a Chinese population.

Fibrosis progression in chronic hepatitis C patients with occult hepatitis B co-infection.

Occult hepatitis B virus (HBV) infection in individuals without hepatitis B surface antigen (HBsAg) can be identified in hepatitis C virus (HCV) infected patients. However, its role in fibrosis progression remains uncertain. This retrospective study compared the fibrosis progression (defined as fibrosis progression by at least one stage) and progression to severe fibrosis (fibrosis stage 3 or 4) in HCV patients with occult HBV infection. Occult HBV infection was diagnosed by the detection of HBV DNA in the serum of 74 consecutive anti-HCV positive patients by PCR. Thirty-one patients (41.9%) had occult HBV infection. All 74 patients had a median of 2 (range 2-3) liver biopsies. The median time between the first and last liver biopsy was 57.7 (range 15.0-132.8) months. Eleven of the 31 patients with occult HBV infection compared with 12 of the 43 patients without occult HBV infection had fibrosis progression (35.5% versus 27.9%, respectively, p=0.608). Six of the 31 patients with occult HBV infection compared with 8 of the 43 patients without occult HBV infection developed severe fibrosis (19.4% versus 18.6%, respectively, p=0.946). In conclusion, chronic HCV patients with occult HBV co-infection does not seem to progress more than patients without occult HBV infection. However, more large-scale studies are needed before a definite conclusion can be obtained.

Immune system and hepatitis B virus infection.

The immune system plays an important role in determining the outcome of hepatitis B virus (HBV) infection. This is because recovery from of acute HBV infection is associated with a clear division in the profile of adaptive immune response. Multispecific antiviral CD4 and CD8 responses with a type 1 cytokine production can be observed in patients who recover from acute HBV infection. On the other hand, those who develop chronic infection tend to have a weak virus specific T cell response. Therapeutic strategies aimed at correcting this defective T cell reactivity could represent a complementary approach to the cure of chronic HBV infection.

Sexual transmission of hepatitis B infection despite the presence of hepatitis B virus immunity in recipients of allogeneic bone marrow transplantation.

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.

Tumor necrosis factor-alpha-induced protein 1 and immunity to hepatitis B virus.

AIM: To compare the gene expression profile in a pair of HBV-infected twins. METHODS: The gene expression profile was compared in a pair of HBV-infected twins. RESULTS: The twins displayed different disease outcomes. One acquired natural immunity against HBV, whereas the other became a chronic HBV carrier. Eighty-eight and forty-six genes were found to be up- or down-regulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-alphaIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RT-PCR. However, upon HBV core antigen stimulation, TNF-alphaIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+ channel tetramerization domain in TNF-alphaIP1 that shares a significant homology with some human, mouse, and C elegan proteins. CONCLUSION: TNF-alphaIP1 may play a role in the innate immunity against HBV.

Advances in immunomodulating therapy of HBV infection.

Patients with chronic hepatitis B virus (HBV) infection have a higher risk of developing liver cirrhosis and hepatocellular carcinoma. Interferon-alpha, lamivudine and adefovir dipivoxil are the three approved treatment for chronic HBV infection and offers the only means of preventing the development of these complications. However, the efficacy of these agents, in terms of loss of Hepatitis B e antigen with or without seroconversion to Hepatitis B e antibody, normalization of serum alanine transaminase levels, loss of serum HBV DNA, and improvement in liver histology can only be achieved in 20-30% of those treated. Long-term treatment with either lamivudine or adefovir dipivoxil can result in the development of drug resistant mutants leading to an increased length of treatment with additional nucleoside analogues. These limitations of the current antiviral therapies underline the need for alternative therapies. Specific and nonspecific immunotherapeutic strategies to restore effective virus-specific T cell responses in those with chronic HBV infection offers an interesting alternative approach. These immunotherapeutic therapies include the adoptive transfer of HBV immunity, pegylated interferon and therapeutic vaccine therapies.

Lymphocytic colitis complicated by a mass in the terminal ileum.

Lymphocytic colitis is a chronic inflammatory disease affecting the bowel. The clinical course of lymphocytic colitis is believed to be benign with watery diarrhoea. We report herein what is, to the best of our knowledge, the first case of lymphocytic colitis complicated by a terminal ileal mass. A 23-year-old man presented with diarrhoea. Blind biopsies of samples taken from the terminal ileum, caecum and ascending colon showed features of lymphocytic colitis. He declined treatment with budesonide or 5-aminosalicylates. He presented 14 months later with pain over the right lumbar region and nausea. Computed tomographic enteroclysis showed a focal soft tissue enhancing mass at the terminal ileum. Excision of the soft tissue mass revealed that it was reactive nodular lymphoid hyperplasia with fibrous granulation tissue. In conclusion, an untreated lymphocytic colitis may result in the formation of an inflammatory mass lesion.

Prognostic factors in severe exacerbation of chronic hepatitis B.

Forty-seven patients with severe hepatitis B exacerbation were compared with patients who had mild exacerbation (n=96) or no exacerbation (n=96). Seventeen patients (36.2%) died or underwent liver transplantation. Preexisting cirrhosis and a prothrombin time (PT) of >30 s were associated with adverse outcome in 60.9% and 87.5% of patients, respectively. The rate of adverse outcome increased to 92.3% when albumin levels of < or =35 g/L and bilirubin levels of >200 microM were present. Other factors associated with adverse outcomes included peak bilirubin level, peak PT, time to reach peak PT, and the presence of encephalopathy and/or ascites. There was no difference in the frequency of precore mutations in patients with severe or mild exacerbation or without exacerbation. A significantly lower prevalence of core promoter mutants was found in patients with severe exacerbation (50%), compared with those who had mild exacerbation (81.3%; P=.004). Patients with severe exacerbation of hepatitis B with poor prognostic factors should be considered for early liver transplantation.

Effects of primary metronidazole and clarithromycin resistance to Helicobacter pylori on omeprazole, metronidazole, and clarithromycin triple-therapy regimen in a region with high rates of metronidazole resistance.

The aim of this study was to investigate the effect of metronidazole resistance (MtzR) and clarithromycin resistance (ClaR) on the eradication rate for omeprazole, clarithromycin, and metronidazole triple-therapy regimen and on the development of posttherapy drug resistance in a region of high rates of MtzR. One hundred ninety-six Helicobacter pylori isolates were recovered from patients with duodenal ulcer, gastric ulcer, or nonulcer dyspepsia during upper endoscopy. The prevalences of MtzR, ClaR, and dual resistance were 37.8%, 13.8%, and 8.7%, respectively. The intention-to-treat eradication rates for metronidazole-susceptible (87.2% vs. 67.6%; P=.001) and clarithromycin-susceptible (86.4% vs. 40.7%; P<.001) strains were significantly higher than the rates for resistant strains. Multiple logistic regression analysis implicated younger age (<40 years old), MtzR, ClaR, and the diagnosis of nonulcer dyspepsia as independent factors that predicted treatment failure. The rates of posttreatment MtzR, ClaR, and dual resistance were 88%, 88%, and 75%, respectively. MtxR and ClaR significantly affected the success of eradication therapy. Posttreatment rates of resistance were high and were related to the presence of pretreatment antibiotic resistance.

Hepatitis B virus genotypes B and C do not affect the antiviral response to lamivudine.

To date, there have been no studies examining the role of hepatitis B virus (HBV) genotypes on the response to lamivudine therapy and the development of YMDD mutations. The present study aimed at determining any differences in the antiviral response and risk of YMDD mutations between lamivudine-treated patients with HBV genotype B and genotype C. Eighty-two patients receiving lamivudine were recruited. HBV genotypes at baseline and YMDD mutations at week 52 were determined by line probe assays (LiPA). HBV DNA levels were determined by the Cobas Amplicor HBV Monitor Test. Seventeen (20.7%) and sixty-four (78%) patients had single genotypes of B and C, respectively. At both week 24 and 52 there were no differences in the median reduction of HBV DNA levels (median 4 logs drop), the median reduction of alanine aminotransferase (ALT) levels, and the proportion with normalization of ALT [8/8 (100%) vs 26/37 (70.3%), P=0.19] between patients with genotypes B and C. The rate of HBeAg seroconversion [3/17 (17.6%) vs 6/64 (9.4%), P=0.39] and the chance of YMDD mutation development [3/17 (17.6%) vs 12/64 (18.8%), P=1.0] at week 52 were also similar between patients with genotype B and C, respectively. In conclusion, there was no difference in the antiviral response and the rate of development of YMDD mutations in Chinese patients with genotype B and C after 1 year of lamivudine. Determination of HBV genotypes before lamivudine therapy was probably not an important pretreatment investigation to predict antiviral responses in Chinese patients.

Recurrent extended-spectrum beta-lactamase-producing Escherichia coli urinary tract infection due to an infected intrauterine device.

The use of intrauterine devices (IUDs) have been widespread since the 1960s. In 2002, the World Health Organization estimated that approximately 160 million women worldwide use IUDs. However, IUDs are associated with short-term complications such as vaginal bleeding, pelvic discomfort, dyspareunia and pelvic infection. Herein, we report the case of a woman who had recurrent urinary tract infection (UTI) due to the use of an IUD, even after treatment. The patient developed four episodes of UTI within a seven-month period after IUD insertion. During each episode of UTI, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) was cultured from the patient's midstream urine. The IUD was finally removed, and culture of the removed IUD was positive for ESBL-producing E. coli. An infected IUD as a source of recurrent UTI should be considered in women with IUD in situ who develop recurrent UTI even after treatment.

Endogenous lipoid pneumonia associated with Legionella pneumophila serogroup 1.

Endogenous lipoid pneumonia is an uncommon condition. This is a report of a 29-year-old woman diagnosed with endogenous lipoid pneumonia associated with Legionella pneumophila serogroup 1 infection. The patient's endogenous lipoid pneumonia resolved completely after treatment for Legionella pneumophila infection. This suggests that early diagnosis and aggressive treatment of the underlying infection may prevent any long-term sequelae of lipoid pneumonia.