Early Antiviral Therapy Research Articles

Hepatitis C Virus Recurrence Occurs Earlier in Patients Receiving Donation After Circulatory Death Liver Transplant Grafts Compared With Those Receiving Donation After Brainstem Death Grafts

IntroductionHepatitis C virus (HCV)-related cirrhosis remains the commonest indication for liver transplantation worldwide, yet few studies have investigated the impact of donation after circulatory death (DCD) graft use on HCV recurrence and patient outcomes. DCD grafts have augmented the limited donor organ pool and reduced wait-list mortality, although concerns regarding graft longevity and patient outcome persist. MethodsThis was a single-center study of all HCV + adults who underwent DCD liver transplantation between 2004 and 2014. 44 HCV+ patients received DCD grafts, and were matched with 44 HCV+ recipients of donation after brainstem death (DBD) grafts, and their outcomes examined. ResultsThe groups were matched for age, sex, and presence of hepatocellular carcinoma; no significant differences were found between the group's donor or recipient characteristics. Paired and unpaired analysis demonstrated that HCV recurrence was more rapid in recipients of DCD organs compared with DBD grafts (408 vs 657 days; P = .006). There were no significant differences in graft survival, patient survival, or rates of biliary complications between the cohorts despite DCD donors being 10 years older on average than those used in other published experience. ConclusionsIn an era of highly effective direct acting antiviral therapy, rapid HCV recrudescence in grafts from DCD donors should not compromise long-term morbidity or mortality. In the context of rising wait-list mortality, it is prudent to use all available sources to expand the pool of donor organs, and our data support the practice of using extended-criteria DCD grafts based on donor age. Notwithstanding that, clinicians should be aware that HCV recrudescence is more rapid in DCD recipients, and early post-transplant anti-viral therapy is indicated to prevent graft injury.

Disseminated herpes zoster causing acute respiratory distress syndrome in an immunocompetent patient

Disseminated cutaneous varicella herpes zoster with visceral involvement is rare and seen almost exclusively in immunocompromised patients. We describe an unusual case of fulminant herpes zoster (HZ) in a healthy,...

Clinical courses of herpes simplex virus-induced urethritis in men.

We retrieved clinical data of 13 men having herpes simplex virus (HSV)-induced non-gonococcal urethritis (NGU) without visible herpetic lesions. They visited a clinic in Sendai, Japan, between April 2013 and December 2015. All the men complained of dysuria. Meatitis was observed in 9 of the 13 men. Mononuclear cells were observed in the urethral smears from 9 men. The 13 men were treated with azithromycin or sitafloxacin regimen. First-voided urine (FVU) specimens became negative for HSV in 8 of the 10 men who returned to the clinic after antibacterial treatment, and urethritis symptoms were alleviated. However, herpetic lesions were observed at the follow-up visits in 3 men, and 2 of them were still positive for HSV in their FVU. HSV could be a cause of acute urethritis without causing visible herpetic lesions. The shedding of HSV from the urethra would spontaneously cease with alleviation of urethritis symptoms in most cases of HSV-induced NGU without antiviral therapy. However, new herpetic lesions could be developed in some cases. Early antiviral therapy is beneficial for patients with HSV infections. The development of meatitis and the mononuclear cell response in the urethral smear could be helpful to diagnose HSV-induced NGU. Therefore, we should presumptively initiate anti-HSV therapy for patients with signs and symptoms suggestive of HSV-induced NGU at their first presentation.

Eczema Herpeticum

Abstract Eczema herpeticum in immunocompromised cancer patients if not identified and treated early can be life threatening. It is commonly found in patients with skin integrity disorders, atopic dermatitis, or immunocompromised patients with herpes simplex type 1 infection. The trunk, head, and neck are regions that commonly are involved. Early antiviral therapy is crucial in immunocompromised hosts to prevent a rapid progression of infections. We present a case of adult generalized eczema herpeticum and a review of the differential diagnosis, and management options.

Factors predicting life-threatening infections with respiratory syncytial virus in adult patients

Background: Respiratory syncytial virus (RSV) is a significant cause of acute respiratory illness with a clinical spectrum ranging from self-limiting upper respiratory infection to severe lower respiratory infection in elderly persons as well as young children. However, there are limited data on risk factors for life-threatening infections that could guide the appropriate use of antiviral agents in adult patients with RSV.Methods: We conducted a retrospective cohort study from October 2013 to September 2015. Adult patients with RSV who visited the emergency department were enrolled. Primary outcome was life-threatening infection (admission to intensive care unit, need for ventilator care or in-hospital death).Results: A total of 227 patients were analysed. Thirty-four (15%) were classified as having life-threatening infections. By logistic regression, lower respiratory infection, chronic lung disease and bacterial co-infection were independent predictors of life-threatening infections. We developed a simple clinical scoring system using these variables (lower respiratory tract infection = score 4, chronic respiratory disease = score 3, bacterial co-infection = score 3 and fever ≥38 °C = score 2) to predict life-threatening infection. A score of >5 differentiated life-threatening RSV from non-life-threatening RSV with 82% sensitivity (95% CI, 66–93) and 72% specificity (95% CI, 65–78).Conclusions: The use of a clinical scoring system based on lower respiratory infection, chronic respiratory disease, bacterial co-infection and fever appears to be useful for outcome prediction and risk stratification in order to select patients who may need early antiviral therapy.

Virological, epidemiological, clinic, and molecular genetic features of the influenza epidemic in 2015-2016: prevailing of the influenza A(H1N1)09 pdm virus in Russia and countries of the Northern hemisphere.

This work describes the specific features of the influenza virus circulating in the period from October 2015 to March 2016 in 10 cities of Russia, the basic laboratories of CEEI at the D.I. Ivanovsky Institute of Virology "Federal Research Centre of Epidemilogy and Microbiology named after the honorary academician N.F. Gamaleya" of the Ministry of Health of the Russian Federation. The increase in the morbidity caused by influenza viruses was detected in January-February 2016. The duration of the morbidity peak was 4-5 weeks. The most vulnerable group included children at the age from 3 to 6; a high rate of hospitalization was also detected among people at the age of 15-64 (65%). In clinic symptoms there were middle and severe forms with high frequency of hospitalization as compared with the season of 2009-2010, but much higher in comparison with the season of 2014-2015. Some of the hospitalized patients had virus pneumonias, half of which were bilateral. Among these patients, 10% were children; 30%, adults. The mortality in the intensive care unit of the hospital was 46%. Almost all lethal cases were among unvaccinated patients in the case of late hospitalization and without early antiviral therapy. The predominance of the influenza A(H1N1)09pdm virus both in the Russian Federation and the major part of the countries in the Northern hemisphere was noted. The results of the study of the antigenic properties of influenza strains of A(H1N1)pdm09 virus did not reveal any differences with respect to the vaccine virus. The sequencing data showed the amino acid substitutions in hemagglutinin (receptor binding and Sa sites) and in genes encoding internal proteins (PA, NP, M1, NS1). Strains were sensitive to oseltamivir and zanamivir and maintained resistance to rimantadine. The participation of non-influenza ARI viruses was comparable to that in preliminary epidemic seasons.

Valós idejű polimeráz láncreakció alkalmazása cytomegalovirus-fertőzés és -reaktiváció nyomon követésére malignus hematológiai betegségek kemoterápiás kezelése során és autológ őssejt-transzplantációt követően

Because of the use of chemo-immunotherapeutic drugs, cytomegalovirus infection is one of the most important infectious complications among patients with haematological malignancies. The aim of the authors was to detect cytomegalovirus infection and reactivation using quantitative real-time polymerase chain reaction. Between 2012 and 2014, the authors retrospectively analysed 96 patient's medical history hospitalised in haematology Unit. Patients were grouped on the basis of their underlying diseases (lymphoprolipherative malignancies, acute leukaemias), and the following groups were created: autologous stem cell transplanted and non-transplanted groups. Eighty-three patients were treated with lymphoprolipherative disorders, and 63 (76%) of them underwent autologous stem cell transplantation. Out of the 604 plasma specimens 46 (7.6%) were positive for the cytomegalovirus desoxyribonucleic acid collected from 25 patients [6 non-transplanted (18%) and 19 from the transplanted group (30.2%)]. The frequency of cytomegalovirus positivity was doubled in the transplanted patient group, however, reactivation was asymptomatic in 68% of the cases. The routine use of cytomegalovirus monitoring is not necessary in this patient group. In case of suspected cytomegalovirus infection, molecular tests allow early preemptive antiviral therapy, which may decrease the mortality attributed to cytomegalovirus infection. Orv. Hetil., 2016, 157(35), 1403-1409.

Cytomegalovirus pneumonia after living-related donor kidney transplantation : the experiences of one single center within 10 years

Objective To report one-center experience on diagnosis and treatment of cytomegalovirus (CMV) pneumonia in recipients after living-related donor kidney transplantation (LDKT). Methods The clinical and follow-up data of 168 recipients after LDKT from April 2005 to September 2014 were analyzed retrospectively. We analyzed the general information, clinical manifestation, treatment and outcomes of 34 recipients who were diagnosed as CMV pneumonia. Of the 34 patients, 26 were male and 8 were female. The average age were 32.0 years old. Thirty-four patients developed CMV pneumonia between 12 to 402 days with an average of (91.7±60.8) days post-transplant. It was (6.4±3.7) d(range 1-14 d) from the onset of illness to seeking medical intervention. All cases presented with fever, 18 cases with dyspnea, 11 cases with cough and 6 cases with myalgia or fatigue. The highest temperature was (38.8±0.5)℃ (range 38.0-40.0℃). Leukocyte count was (10.5±4.4)×109/L, elevated in 18 cases, normal in 14 cases, reduced in 2 cases. Quantitative polymerase chain reaction(PCR) assay for CMV DNA was (9.3-15.8)×103 copies/ml for active CMV infection. Chest X ray or CT of all cases demonstrated patchy shadow or interstitial pneumonia. The etiological examination showed that 12 cases were complicated with other microorganism, including 8 cases with Pneumocystis carinii, 3 cases with Streptococcus A, 3 cases with Neisseria, 3 cases with candida albicans, 2 cases with klebsiella pneumoniae, Staphylococcus aureus, enterococcus faecium, Pseudomonas aeruginosa varied 1 case. Results In antiviral therapy, patients were treated by introvenous ganciclovir 5 mg/kg every 12 h for 14-21d and then 5 mg/kg every day. Glucocorticoid treatment included intravenous methylprednisolone 200 mg/kg for 3-5 d, then gradually reduced to 160 mg/kg for 3-5 d, 120 mg/kg for 3 d, 80 mg/kg for 3 d, 40 mg/kg for 3-5 d, until to the original oral dose. Early application of broad-spectrum antibiotics was to prevent bacterial infection, and routine application of compound sulfamethoxazole to prevent Pneumocystis carinii pneumonia. Treatment options were adjusted according to periodic bacteria and fungal culture in blood, urine or sputum, and effective anti bacterial, viral or fungal treatment was selected. After administration of antiviral therapy, methylprednisolone, treatment for other microorganism, as well as adjusted immunosuppressive drugs, 30 cases were cured. The total course of the pneumonia lasted for (28.5±9.4) days on average. However, 4 patients complicated with other microorganism died of severe pneumonia and acute respiratory distress syndrome(ARDS). Conclusion CMV infection was a common complication of living-related donor kidney transplantation. CMV infection often complicated with other microbial infections, and became one of the causes of death after renal transplantation. Early diagnosis, early antiviral therapy combined with effective anti bacterial, fungal treatment would improve the survival of kidney transplant recipients. Key words: Cytomegalovirus; Kidney transplantation; Living donors; Pneumonia

JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2.

JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2.

Outcomes and Prognostic Features of Patients With Influenza Requiring Hospitalization and Receiving Early Antiviral Therapy: A Prospective Multicenter Cohort Study

In Japan, the routine use of early antiviral therapy for patients with influenza is standard. This multicenter prospective cohort evaluation of hospitalized patients with laboratory-confirmed influenza identified prognostic factors among the patients receiving antiviral therapy. Of 1,345 patients with influenza (766 pediatric, 579 adult), excluding those aged < 1 year (who are not approved for antiviral therapy), 97.7% (1,224 of 1,253) received antiviral therapy. Among the adult patients, 24 (4.1%) died within 30 days, whereas none of the pediatric patients died. Five hundred twenty-eight (91.2%) adult patients had influenza A, 509 (87.9%) had a chronic underlying illness, and 211 (36.4%) had radiographically confirmed pneumonia. Twenty of the 24 patients who died had pneumonia of the following etiologies: Streptococcus pneumoniae (12.3%); Staphylococcus aureus (10.9%), including methicillin-resistant S aureus (MRSA) 3.3%; Enterobacteriaceae (8.1%); and Pseudomonas aeruginosa (3.3%). Of the adult patients, 151 were classified as having community-acquired pneumonia (CAP) and 60 as having health-care-associated pneumonia (HCAP). Inappropriate therapy was more common in HCAP than in CAP (15.2% vs 2%, P = .001). Potential multidrug-resistant (MDR) pathogens were more common (21.7% vs 2.6%, P < .001) in patients with HCAP, particularly MRSA (10% vs 0.7%, P = .002) and P aeruginosa (8.3% vs 1.3%, P = .021). Using Cox proportional hazards modeling with prescribed independent variables, male sex, severity score, serum albumin levels (malnutrition), and pneumonia were associated with survival 30 days from the onset of influenza. Among the prognostic factors, malnutrition and pneumonia are amenable to medical intervention. An opportunity exists to improve empirical therapy for patients with HCAP and influenza. Japan Medical Association Center for Clinical Trials; No.: JMA-IIA00123; URL: http://www.jmacct.med.or.jp/en/.

Clinical Characteristics and Treatment Experiences in 2 Serious Cases of Influenza A (H5N6) Virus Infection

Since April 2014, a fatal human infection with a novel reassortant H5N6 avian influenza virus was identified in China. Eight of 10 patients died from this virus. Two H5N6 patients were hospitalized in Shenzhen Third People’s Hospital in China, with one patient recovered. Here, we describe their clinical characteristics and treatment strategies. We suggest these strategies in the early stage may be important for severe avian influenza patients, including early combined antiviral therapy, oxygen therapy and ventilator support treatment, short-term usage of low-dose corticosteroid and appropriate immune globulin and keeping negative fluid balance in the progression period.

Outcomes of Influenza Infections in Hematopoietic Cell Transplant Recipients: Application of an Immunodeficiency Scoring Index

Hematopoietic cell transplant (HCT) recipients have lower immune response to influenza vaccination and are susceptible to lower respiratory tract infection (LRI) and death. We determined clinical characteristics and outcomes of laboratory-confirmed influenza, including 2014/H3N2 infection, in 146 HCT recipients. An immunodeficiency scoring index (ISI) was applied to identify patients at high risk for LRI and death. Thirty-three patients (23%) developed LRI and 7 (5%) died within 30 days of diagnosis. Most patients received antiviral therapy (83%); however, only 18% received it within 48 hours of symptom onset. The incidence of LRI was significantly higher in the ISI high-risk group than it was in the low-risk group (P < .001). Receiving early antiviral therapy was associated with a substantial reduction in LRI for all ISI risk groups with the greatest risk reduction observed in the high-risk group. When compared with previous seasons, no significant differences in patient outcomes were observed during the 2014/H3N2 season; however, antiviral therapy was more promptly initiated in the latter season. The ISI that was originally developed for respiratory syncytial virus may help identify HCT recipients at risk for progression to LRI and mortality after influenza infection. These patients should be monitored more closely. Early initiation of antiviral therapy for influenza in HCT recipients, regardless of the ISI risk group, may improve morbidity as well as mortality.

Predictive Symptoms and Signs of Laboratory-confirmed Influenza: A Prospective Surveillance Study of Two Metropolitan Areas in Taiwan.

Influenza infection poses annual threats and leads to significant morbidity and mortality. Early diagnosis is the key to successful treatment. Laboratory-based diagnosis has various limitations. Diagnosis based on symptoms or signs is still indispensable in clinical practice. We investigated the symptoms or signs associated with laboratory-confirmed influenza.A prospective study across 2 influenza seasons was performed from June 2010 to June 2012 at 2 branches (Taipei and Lin-Kou) of Chang Gung Memorial Hospital. Patients who visited outpatient clinics with suspected acute respiratory tract infection were sampled by throat swab or nasopharyngeal swab. RT-PCR and/or virus culture were used as a reference standard. We used logistic regression to identify the symptoms or signs associated with laboratory-confirmed influenza infection. We also evaluated the performance metrics of different influenza-like illness used in Taiwan, the USA, and WHO.A total of 158 patients were included in the study. The prevalence of influenza infection was 45% (71/158). Fever, cough, rhinorrhea, sneezing, and nasal congestion were significant predictors for influenza infection. Whereas fever + cough had a best sensitivity (86%; confidence interval [CI] 76%–93%), fever + cough and sneezing had a best specificity (77%; CI 62%–88%). Different case definitions of influenza-like illness had comparable accuracy in sensitivity and specificity.Clinical diagnosis based on symptoms and signs is useful for allocating resources, identifying those who may benefit from early antiviral therapy and providing valuable information for surveillance purpose.

人感染H7N9禽流感病毒的研究进展

新型甲型流感病毒的出现会导致流感大流行甚至暴发，2013年2月，新型甲型流感病毒H7N9在上海出现并蔓延至全国多省市。本篇文章对2013年2月以来有关H7N9病毒株的流行病学、临床表现、防治措施等相关文献进行综述，目前的数据显示，H7N9禽流感病毒通过基因突变获得人源受体，随候鸟迁徙传播给家禽。禽接触是主要传播途径。年龄、性别和基础疾患是影响预后的主要因素。对H7N9早期感染者多采取抑制剂奥司他韦和帕拉米韦治疗。目前针对H7N9的疫苗还处于实验阶段。做好持续监测和及时沟通，对于探索H7N9禽流感病毒的起源与传播途径并制定行之有效的控制措施是非常重要的。 Novel influenza A virus may cause epidemic and outbreak. In February 2013, a novel AIV (H7N9) strain was discovered in Shanghai and spreaded to several provinces. Here we reviewed the current knowledge of the virus about its epidemiology, clinical features, as well as prevention and cure measures. The data available so far indicated that H7N9 was originated by a reassortment process in birds and contained human-receptor and transmitted to humans through direct contact with live-bird markets. The severity of the respiratory disease caused by novel H7N9 virus in humans can be partly attributed to the age, sex, and underlying medical conditions of the patients. Early antiviral therapy with neuraminidase inhibitors was effective. A universal influenza vaccine is not available, constant surveillance and communication combined with novel research approaches to identify the source and mode of transmission of these viruses and develop alternative and effective anti-influenza strategies are needed to overcome influenza A (H7N9) virus.

Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: When and how to apply prophylaxis, with a special focus on corticosteroid therapy.

Currently immunosuppressive and biological agents are used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to pre-emptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.

Can we trust the guidelines? Comparison between the data presented and the recommendations of the International Antiviral Society-USA Panel.

IntroductionClinicians often do not have the time and possibilities to read all scientific evidence necessary to maintain high quality patient care. They rely on guidelines made by experts to help them in their daily work.MethodsWe compared the 2012 recommendations and the arguments of the IAS-USA Panel with the data referenced and presented with the original data of the studies. Special topic was the timing of antiretroviral therapy. Only studies included in the guideline text were analyzed.ResultsThere is a large discrepancy between the data and the recommendations concerning early antiviral therapy. The studies are either not designed to answer this question or the data is not sufficient to support the arguments. The authors highlight benefits without mention of side effects or other problems. Neither in transmission rates, nor mortality, AIDS events, co-morbidities (hepatitis B and C excluded) or decreasing the risk of malignancy, the data presented support early therapy.ConclusionsA large discrepancy between the underlining data and the recommendation made by the IAS-USA Panel exists concerning early antiviral therapy.

Herpes Simplex Virus Hepatitis: A Rare Case in an Immunocompetent Male

Introduction: Hepatitis is a rare manifestation of herpes simplex virus (HSV) infection, usually affecting immunosuppressed patients and females in the third trimester of pregnancy, often leading to fulminant hepatitis, acute liver failure, liver transplantation, and/or death. We present a rare case of herpetic hepatitis in an immunocompetent male. Case Report: A 26-year-old incarcerated male was brought to the hospital with nausea, vomiting, and altered mental status. The patient was awake on presentation, but did not respond to questions. His vital signs were stable. On physical examination, the patient did not follow commands, had scleral icterus, his abdomen was non-tender to palpation, and no organomegaly was appreciated; no skin, oral, or genital lesions were present, deep tendon reflexes were equal and symmetric. His labs revealed an AST of 247 u/l, ALT of 422 u/l, total bilirubin 6.6 mg/dL, direct bilirubin 2.8 mg/dL, ammonia level 59.3 umol/L (reference range 11-32 umol/L). He tested negative for HIV, hepatitis A, B, and C. Autoimmune studies and viral studies were ordered. Ultrasound of the abdomen showed unremarkable liver and pancreas with no biliary duct dilatation; magnetic resonance imaging (MRI) of the brain was normal and an electroencephalogram (EEG) revealed diffuse slowing consistent with mild encephalopathy. Over the next few days, although the patient’s liver enzymes continued to rise (ALT 1191 u/l, AST 416 u/l), his ammonia level normalized and his altered behavior had resolved. Autoimmune studies were negative, but his viral studies revealed markedly elevated IgM and IgG levels for HSV 1 and 2. Discussion: Hepatitis is an uncommon manifestation of HSV, usually rare in immunocompetent adults. When hepatitis does occur due to HSV, it is frequently fulminant. HSV Hepatitis is often overlooked in the differential diagnosis of severe hepatitis due to lack of specific symptoms or signs such as skin, mouth, and/or genital lesions, which are present in 57% of patients with HSV hepatitis. Further diagnostic challenges result from lack of rapid diagnostic modalities for HSV. The above factors lead to dangerous delays in early antiviral therapy, which is key to survival. HSV hepatitis carries high mortality (>80%), but is one of the few treatable causes of acute liver failure, reemphasizing the need for early diagnosis and treatment with acyclovir or vidarabine. This case highlights the rare manifestation of HSV infection as fulminant hepatitis in an immunocompetent adult. In light of his rapidly rising liver enzymes with no obvious etiology, a wide range of differentials were investigated with the most unlikely etiology emerging as the culprit.

Liver inflammation is a risk factor for prediabetes in at-risk latinos with and without hepatitis C infection.

Early recognition of prediabetes can lead to timely clinical interventions to prevent type 2 diabetes. Both Latino ethnicity and chronic hepatitis C (HCV) have been identified as diabetic risk factors. We aimed to investigate predictors of impaired fasting glucose (IFG), a common prediabetic state, among Latinos with and without HCV. One hundred Latino adults with no history of diabetes or cirrhosis underwent clinical, laboratory, and metabolic evaluation, including oral glucose tolerance testing (OGTT) and insulin suppression testing to quantify directly measured insulin resistance (IR). Isolated IFG was defined as fasting glucose ≥100 mg/dl and <140 mg/dl at 2 h during normal glucose tolerance during OGTT. Overall subject characteristics included median age 44 years, 64% male, 40% HCV-positive and 32% with isolated IFG. Factors associated with isolated IFG included subject age (OR 2.42 per decade, 95%CI 1.40-3.90, P = 0.001), HCV infection (OR 4.0, 95%CI 1.71-9.72, P = 0.002) and alanine aminotransferase (ALT) (OR 2.35 per doubling, 95%CI 1.46-3.77, P < 0.0001). Multipredictor logistic regression analysis identified ALT (OR 2.05 per doubling, P = 0.005, 95% CI 1.24-3.40) and age (OR 2.20 per 10 years, P = 0.005, 95%CI 1.27-3.80) as factors independently associated with IFG. While HCV was associated with 4-fold higher odds of IFG, this entire effect was mediated by ALT. We found strong evidence that liver inflammation is a risk factor for prediabetes among Latinos with and without HCV. Among HCV-infected individuals, early antiviral therapy could mitigate the effect of inflammation and represent an important intervention to prevent diabetes in this at-risk population.

A simple smart amplification assay for the rapid detection of human cytomegalovirus in the urine of neonates

Human cytomegalovirus (CMV) is the most common cause of infection-related congenital abnormalities in neonates and the leading cause of non-hereditary sensorineural hearing loss in childhood. In addition, the number of low-birth-weight infants has recently increased, especially in Japan, in association with an increasing frequency of postnatal CMV infections transferred through raw breast milk. The increase in the number of congenital CMV and postnatal CMV infections in low-birth-weight infants requires rapid detection at the bedside in order to ensure a correct diagnosis and provide early anti-viral therapy. In this report, a simplified smart amplification (SMAP) method was developed to detect CMV in the urine of neonates. This method does not require DNA extraction, and the DNA amplification procedure is performed under isothermal conditions. Therefore, it takes only 60min to detect CMV in a urine sample, and CMV DNA was rapidly detectable in symptomatic infants. In brief, this SMAP-based assay provides a simple, rapid and efficient method for detecting human CMV at the bedside.

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances.

Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.