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BACKGROUND: Radical changes to clinical and endoscopy practice have been rapidly introduced following the spread of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Urgent endoscopies are, however, intended to proceed as normal with additional personal protective procedures. A perceived reduction in hospital attendances may suggest a number of urgently indicated endoscopic retrograde cholangio-pancreatographies (ERCPs) are being missed. Objectives and Methods: A review of all ERCPs carried out in a large tertiary referral endoscopy unit under healthcare restrictions was compared to the same time period in previous years. The intention was to determine if ERCPs are proceeding as normal or if there is a difference in referral characteristics. RESULTS: Under service restrictions (13 March to the end of April 2020), 55 ERCPs were performed compared with 87 ERCPs in 2019. Similar numbers to 2019 were also recorded in the preceding years. One case of coronavirus disease 2019 (COVID-19) was reported in a patient in the days following ERCP, with no cases notified among staff related to endoscopy. CONCLUSIONS: A reduction in ERCP referrals raises concern that a cohort of patients with significant biliary disease remain undetected. Whether this results in later, and more severe, presentation remains to be seen but a potential surge in such cases could significantly burden all future endoscopy planning services.

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Perinatal transmission is the most common mode of hepatitis B virus (HBV) transmission and is a leading cause of chronic infection worldwide. Maternal treatment with lamivudine (LAM) can result in a rapid and significant reduction in HBV viral load (VL) and, thus, mitigate the risk of mother-to-child transmission (MTCT). The aim of this study was to retrospectively evaluate the safety of LAM treatment administered in the third trimester of pregnancy and determine the influence, if any, on infant outcome. The medical charts of all HBV surface antigen (HBsAg)-positive women eligible for treatment with LAM and who registered for antenatal care between 2007 and 2012 were retrospectively reviewed. During the 6-year period, 45 women met the criteria for LAM treatment. Thirty-six women (80 %) accepted treatment; the remaining women declined treatment (5), defaulted from care (3) or transferred to another maternity unit (1). The median duration of treatment was 11.4 weeks (range 5.3-17.4) and the median baseline VL was 1.4 × 10(8) IU/mL (range 1.8 × 10(7)-1.7 × 10(8)). The median VL at delivery was 2.3 × 10(5) IU/mL and 60 % of women achieved a VL reduction >2 log10 IU/mL before delivery. No cases of perinatal transmission occurred in the infants born to mothers who received treatment; however, one infant, born to a mother who defaulted from care, was HBV-infected at 8 months. The results suggest that LAM therapy in highly viraemic HBV-infected pregnant women could lower the rate of vertical transmission.

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The aims of this study were to pilot universal antenatal HCV screening and to determine the true seroprevalence of HCV infection in an unselected antenatal population. A risk assessment questionnaire for HCV infection was applied to all women booking for antenatal care over a 1-year period. In addition the prevalence of anti-HCV antibody positive serology in this population was determined. Over the course of the year, 9121 women booked for antenatal care at the Rotunda and 8976 women agreed to take part in the study, representing an uptake of 98.4%. 78 (0.9%) women were diagnosed as anti-HCV positive, the majority of whom were Irish (60.3%) or from Eastern Europe (24.4%). 73% of anti-HCV positive women reported one or more known risk factor with tattooing and a history of drug abuse the most commonly reported. 27% (n = 21) of anti-HCV positive women had no identifiable risk factors. Due to selective screening, seroprevalence of HCV is impossible to accurately calculate. However the universal screening applied here and the high uptake of testing has allowed the prevalence of anti-HCV among our antenatal population to be calculated at 0.9%. A significant proportion (27%) of anti-HCV positive women in this study reported no epidemiological risk factors at the time

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BACKGROUND: Covered self-expandable metallic stents (SEMSs) are designed to prevent tumor ingrowth and can be removed if necessary. Only limited comparative data are available on the performance of covered SEMSs after primary placement versus reintervention. OBJECTIVE: To assess the effectiveness and safety of covered SEMS placement either as primary treatment or reintervention in patients requiring palliation of malignant biliary obstruction. DESIGN: Retrospective clinical cohort study. SETTING: Tertiary referral center. PATIENTS: This study involved 104 patients with unresectable malignant biliary strictures. INTERVENTION: Covered biliary SEMS placement. MAIN OUTCOME MEASUREMENTS: Stent patency, technical success, and patient survival. RESULTS: Covered SEMSs were placed as primary treatment in 48 patients (46%), and reintervention was performed in 56 patients (54%). At 3, 6, and 12 months thereafter, the Kaplan-Meier estimated fractions of all patients with patent stents were 94%, 84%, and 58%, respectively. Covered SEMSs remained patent until the patient's death in 75 of 89 nonsurvivors (84%). Although patency rates 3, 6, and 12 months after primary placement (100%, 93%, and 82%, respectively) were higher than those after reintervention (90%, 78%, and 48%, respectively), the differences were not statistically significant (P = .057). Overall, the most frequent adverse events were cholangitis (7%) and stent migration (4%). LIMITATIONS: The distribution of stricture locations differed among the groups, and survival data suggested the presence of more extensive disease in the primary treatment group at baseline. CONCLUSION: The clinical utility and safety of primary covered SEMS placement were confirmed. This study provides the most extensive evidence to date that reintervention with a covered SEMS can provide a useful palliative option.

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The evaluation of liver injury in HIV patients co-infected with HBV and HCV should follow the same principles as the evaluation of any patient with chronic liver disease. The initial clinical evaluation should include documentation of risk factors for progressive disease. HIV history is important particularly with respect to a past history of significant or prolonged immunosuppression as this has been clinically correlated with more advanced liver disease. Liver transaminases are an important predictor of disease severity and progression in HIV patients. Liver biopsy has remained the 'gold standard' for the grading of inflammation and staging of disease. We would still recommend liver biopsy in HIV patients particularly those with HCV because recent community-based studies in the HAART era have suggested slower rates of progression for HIV/HCV than studies from tertiary care centres and older cohorts. Since, liver biopsy is invasive and expensive, non-invasive techniques including serological tests and novel imaging techniques have evolved to stage liver fibrosis. A novel technique for measuring hepatic elasticity has recently been validated alone and in combination with serum markers for HCV mono-infection. Future trends for staging liver disease must not only focus on cross sectional diagnosis but on utilizing novel techniques to stratify risk for disease progression over time.

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Understanding of the pathogenesis of hepatic fibrosis on a molecular level has led to the identification of several putative serum markers of hepatic fibrosis. Either individually or in combination, these serum markers appear capable of determining early and advanced hepatic fibrosis. Radiological determination of hepatic fibrosis has insufficient sensitivity and specificity other than for detection of features of portal hypertension or features of end-stage cirrhosis. Transient hepatic elastography is a novel technology demonstrating promise as a noninvasive means of fibrosis determination. This article outlines the accuracy of all these modalities in the diagnosis of hepatic fibrosis and discusses how they may be incorporated into clinical practice.

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Major progress has been made in the treatment of chronic hepatitis C virus (HCV) infection over the 18 years since Hoofnagle et al. initially documented response of non-A non-B hepatitis to interferon alfa. Current optimal therapy with pegylated interferon alfa (PEG-IFN) and ribavirin results in sustained virologic response rates of just over 50%. With an estimated 2.7 million Americans with active HCV infection, we can anticipate a large number of potential treatment failures with the current standard of care. At this time, no therapy is approved by the US Food and Drug Administration for treatment failures of PEG-IFN and ribavirin. Maintenance interferon therapy with the goal of prevention of disease progression rather than viral eradication appears to offer an option for HCV treatment failures with advanced disease. Alternative medical strategies to reduce hepatic fibrosis are also under investigation. With the relatively static number of available organs for transplantation, prevention of disease progression and decompensation is essential for an impact to be made upon the predicted rates of HCV morbidity and mortality in the next 10 to 20 years.

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Intramedullary capillary haemangioma is extremely rare and only four cases have been previously reported. We describe a further case, outlining the clinical, radiological, surgical and pathological features.

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BACKGROUND AND AIMS: While upregulation of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (IREG1) within duodenal enterocytes is reported in patients with hereditary haemochromatosis (HH), these findings are controversial. Furthermore, the effect of HFE, the gene mutated in HH, on expression of these molecules is unclear. This study examines duodenal expression of these three molecules in HH patients (prior to and following phlebotomy), in patients with iron deficiency (ID), and in controls. METHODS: DMT1, IREG1, and HFE mRNA were measured in duodenal tissue of C282Y homozygous HH patients, in ID patients negative for the C282Y mutation with a serum ferritin concentration less than 20 microg/l, and in controls negative for C282Y and H63D mutations with normal iron indices, using real time polymerase chain reaction. RESULTS: DMT1 and IREG1 mRNA levels were not significantly different in non-phlebotomised (untreated) HH patients compared with controls. DMT1 expression was significantly increased in HH patients who had undergone phlebotomy therapy (treated) and in patients with ID compared with controls. IREG1 was significantly increased in ID patients relative to controls, and while IREG1 expression was 1.8-fold greater in treated HH patients, this was not statistically significant. HFE mRNA expression was not significantly different in any of the groups investigated relative to controls. CONCLUSIONS: These findings demonstrate that untreated HH patients do not have increased duodenal DMT1 and IREG mRNA, but rather phlebotomy increases expression of these molecules, reflecting the effect of phlebotomy induced erythropoiesis. Finally, HFE appears to play a minor role in the regulation of iron absorption by the duodenal enterocyte.

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Patients with cirrhosis and portal hypertension often have abnormal extracellular fluid volume regulation, resulting in accumulation of fluid as ascites, oedema or pleural effusion. These complications carry a poor prognosis with nearly half of the patients with ascites dying in the ensuing 2-3 years. In contrast to what happens in the abdominal cavity where large amounts of fluid (5-8 L) accumulate with the patient only experiencing only mild symptoms, in the thoracic cavity smaller amounts of fluid (1-2 L) cause severe symptoms such as shortness of breath, cough and hypoxaemia. Hepatic hydrothorax is defined as a pleural effusion, usually >500 mL, in patients with cirrhosis without cardiopulmonary disease. The pathophysiology involves the direct movement of ascitic fluid from the peritoneal cavity into the pleural space through diaphragmatic defects. The estimated prevalence among cirrhotic patients is 5-10%. The effusion, which is a transudate, most commonly occurs in the right hemithorax. The mainstay of therapy is similar to that of portal hypertensive ascites and includes sodium restriction and administration of diuretics. Refractory hydrothorax can be managed with transjugular intrahepatic portosystemic shunt in selected cases. Pleurodesis is not routinely recommended. Suitable patients with hepatic hydrothorax should be considered candidates for liver transplantation.

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HFE-associated hereditary hemochromatosis is characterized by imbalances of iron homeostasis and alterations in intestinal iron absorption. The identification of the HFE gene and the apical iron transporter divalent metal transporter-1, DMT-1, provide a direct method to address the mechanisms of iron overload in this disease. The aim of this study was to evaluate the regulation of duodenal HFE and DMT-1 gene expression in HFE-associated hereditary hemochromatosis. Small bowel biopsies and serum iron indices were obtained from a total of 33 patients. The study population comprised 13 patients with hereditary hemochromatosis (C282Y homozygous), 10 patients with iron deficiency anemia, and 10 apparently healthy controls, all of whom were genotyped for the two common mutations in the HFE gene (C282Y and H63D). Total RNA was isolated from tissue and amplified via RT-PCR for HFE, DMT-1, and the internal control GAPDH. DMT-1 protein expression was additionally assessed by immunohistochemistry. Levels of HFE mRNA did not differ significantly between patient groups (P = 0.09), specifically between C282Y homozygotes and iron deficiency anemic patients, when compared to controls (P = 0.09, P = 0.9, respectively). In contrast, DMT-1 mRNA levels were at least twofold greater in patients with hereditary hemochromatosis and iron deficiency anemia when compared to controls (P = 0.02, P = 0.01, respectively). Heightened DMT-1 protein expression correlated with mRNA levels in all patients. Loss of HFE function in hereditary hemochromatosis is not derived from inhibition of its gene expression. DMT-1 expression in C282Y homozygote subjects is consistent with the hypothesis of a "paradoxical" duodenal iron deficiency in hereditary hemochromatosis. The observed twofold upregulation of the DMT-1 is consistent with the slow but steady increase in body iron stores observed in those presenting with clinical features of hereditary hemochromatosis.

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Cytotoxic T lymphocytes (CTLs) play a central role in the control of persistent HIV infection in humans. The kinetics and general features of the CTL response are similar to those found during other persisting virus infections in humans. During chronic infection there are commonly between 0.1 and 1.0% of all CD8+ T cells in the blood that are specific for immunodominant virus epitopes, as measured by HLA class I peptide tetramers. These figures are greatly in excess of the numbers found by limiting dilution assays; the discrepancy may arise because in the latter assay, CTLs have to divide many times to be detected and many of the HIV-specific CD8+ T cells circulating in infected persons may be incapable of further division. Many tetramer-positive T cells make interferon-gamma, beta-chemokines and perforin, so are probably functional. It is not known how fast these T cells turn over, but in the absence of antigen they decay in number. Impairment of CTL replacement, because CD4+ T helper cells are depleted by HIV infection, may play a major role in the development of AIDS.

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OBJECTIVE: To compare the antiviral activity of once-daily didanosine (ddI) and twice-daily ddI in combination with stavudine (d4T). DESIGN: Randomized, double-blind, multicenter study. SETTING: Twenty-one sites in the United States. PATIENTS: Eighty-seven antiretroviral-naive, HIV-1-infected adults with baseline plasma HIV RNA counts of > or = 10,000 copies/ml and CD4 cell counts of > or = 100 cells/mm3 started study therapy. INTERVENTIONS: Patients received once-daily ddI or twice-daily ddI, each combined with twice-daily d4T. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA levels, CD4 cell counts, and adverse events were regularly monitored. The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens in change from baseline plasma HIV-1 RNA levels over the first 12 weeks of therapy. RESULTS: At week 12, median log10 HIV-1 RNA changes were -1.83 log10 copies/ml in the once-daily ddI/d4T group and -1.80 log10 copies/ml in the twice-daily ddI/d4T group, and 18 out of 44 patients (41%) and 17 out of 43 patients (40%), respectively, had HIV-1 RNA levels below 400 copies/ml. Similar results were seen at week 24. The TAD between the two treatment groups (once-daily ddI/d4T minus twice-daily ddI/d4T) in change from baseline plasma HIV RNA levels over the first 12 weeks was 0.14 log10 copies/ml (95% CI: -0.11, 0.40). At week 12, subjects averaged an increase in CD4 cell count of over 140 cells/mm3. The TAD between the two treatment groups in change from baseline CD4 cell counts over the first 12 weeks was 2 cells/mm3 (95% CI: -40, 45). CONCLUSION: Once-daily ddI plus d4T and twice-daily ddI plus d4T were similarly effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts over 12-24 weeks of therapy.

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Peripheral neuropathy has been recognized as a dose-limiting adverse effect in Phase I studies of didanosine (ddI) therapy for HIV infection. To study the effect of the currently recommended lower dose of ddI, the databases of 4 randomized, controlled trials were used to assess the frequency of dose-limiting peripheral neuropathy during treatment with ddI 500 or 750 mg/d, compared with zidovudine (ZDV) monotherapy or combination therapy with ddI/ZDV or zalcitabine/ZDV. No between-group differences in risk factors for neuropathy (eg, infectious and metabolic factors, malignancy, concurrent medications) were observed in the individual trials, and the presence of these risk factors appeared to have no increased treatment effect on the occurrence of neuropathy. No significant between-group differences were observed in the individual studies with regard to the incidence or time to onset of peripheral neuropathy. Analysis of the combined results by treatment regimen showed no significant difference in the incidence of neuropathy between recipients of ddI 500 mg/d, ddI 750 mg/d, or ZDV and no significant difference in the cumulative dose received until the onset of neuropathy between the ddI 500- and 750-mg regimens. Entry CD4+ cell counts were significantly predictive of neuropathy, with each 100-cell/microL decrement associated with a 17% increase in risk (P = 0.002); a CD4+ cell count of <50 cells/microL was highly predictive of neuropathy (P = 0.0001). In summary, the risk for peripheral neuropathy was not increased by treatment with ddI versus comparator regimens or by treatment with ddI at the dosages used in studies conducted more recently than the Phase I trials. Peripheral neuropathy seems more likely to be associated with advanced HIV infection and lower CD4+ cell counts (particularly counts <50 cells/microL) than with ddI therapy at the currently recommended dose.

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We assessed the safety profile, tolerability, and antiviral effect of 12 weeks of triple combination therapy with stavudine (d4T), didanosine (ddI), and nelfinavir in patients who had not previously received therapy with d4T, ddI, or a protease inhibitor. We also assessed the effect of the buffered tablet formulation of ddI on the pharmacokinetics of nelfinavir. The study had a single-arm, open-label design and enrolled patients aged > or =18 years who had HIV infection and > or =10,000 plasma HIV RNA copies/mL. Patients received the full recommended doses of oral d4T, ddI, and nelfinavir. Efficacy was assessed in terms of change from baseline in plasma HIV RNA and CD4+ cell counts, as well as in terms of the proportion of patients achieving HIV RNA levels <400 copies/mL. The first 10 patients enrolled in the study were included in a substudy to determine the effects of the buffered tablet formulation of ddI on the pharmacokinetic profile of nelfinavir. A dose of ddI was given 1 hour before nelfinavir, after which the maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the concentration-time curve (AUC) of nelfinavir were determined. A total of 22 patients entered the trial, of whom 1 (5%) had AIDS, 12 (55%) had symptomatic HIV infection, and 9 (41%) were asymptomatic. The median baseline CD4+ cell count was 315 cells/microL (range, 70-709 cells/microL), and the median plasma viral load was 4.8 log10 copies/mL (range, 4.0-5.6 log10 copies/mL). ddI had no clinically significant effects on the plasma pharmacokinetics of nelfinavir. At the end of 12 weeks of treatment, the mean (+/- SE) decrease in plasma viral load was 1.36+/-0.24 log10 copies/mL, and 8 of 16 patients (50%) achieved plasma HIV RNA levels <400 copies/mL; the mean (+/- SE) increase in CD4+ cell count was 111.4+/-31.7 cells/microL. Patients who were judged to be compliant with antiretroviral therapy (ie, who missed <7 days of all 3 study drugs during 12 weeks of treatment) experienced mean decreases in viral load exceeding 2.0 log10 copies/mL, and 6 of 7 patients achieved HIV RNA levels <400 copies/mL after 12 weeks of therapy. Although 95% of patients reported an adverse event of grade 1 or higher, only 1 patient experienced a grade 3 or 4 adverse event (maculopapular rash) related to nelfinavir. As reflected in the Cmax, Tmax, and AUC, administration of ddI 1 hour before nelfinavir did not influence the pharmacokinetic profile of the protease inhibitor. Triple drug therapy with d4T, ddI, and nelfinavir was well tolerated and associated with few clinically significant toxicities. This treatment resulted in substantial reductions in viral load and improvements in CD4+ cell count over 12 weeks.

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The course of naturally acquired infection with feline immunodeficiency virus was monitored in a cat over an 18-month period after diagnosis. The cat was admitted with diarrhea, poor body condition, a bite wound abscess, gingivitis, chronic fever, and splenomegaly. The cat's condition improved after splenectomy and remained stable for approximately 15 months, then began to deteriorate, as gingivitis, polyuria, polydipsia, pyrexia, multiple cutaneous masses, and hind limb paresis developed. The in vitro response of the cat's lymphocytes to mitogens was suppressed, and absolute lymphocyte counts were low. Spinal lymphosarcoma, disseminated mastocytoma, and presumptive diabetes mellitus were diagnosed after euthanasia. Decreased immune surveillance associated with feline immunodeficiency virus-related immunosuppression possibly played a role in the development of neoplastic disease in this cat.

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