Investigation of saliva, faeces, urine or semen samples for the presence of GBV-C RNA

GBV-C/HGV has been demonstrated to be distributed worldwide with a prevalence in blood donors higher than HCV. This distribution in the general population probably requires an effective non-parenteral route of transmission. A previous study was performed to evaluate the presence of GBV-C/HGV in serum. Saliva, faeces and urine samples of 30 patients (15 males and 15 females) and 15 semen samples from patients whose serum gave a GBV-C/HGV RNA positive result were then tested by a sensitive polymerase chain reaction (PCR) test. Five semen supernatant samples (33.3%) tested positive – four of them belonged to HIV positive patients – and two saliva samples contained GBV-C/HGV sequences (6.6%) – one from a HIV-positive patient. An internal control was used to detect PCR non-specific inhibitors in the samples. The data suggest possible non-parenteral routes of transmission from this virus. Its presence in body fluids other than serum has clinical implications other than possible hepatic damage that remain to be investigated.     

GBV-C/HGV, a new virus as one possible cause of hepatitis of unknown etiology

For etiologically obscure (some 4%) viral hepatitis agents are sought and tested to make elucidation of their cause possible. One of the candidates is since 1995 the newly discovered virus GBV-C/HGV. Despite intense research its relationship to viral hepatitis of obscure origin (VHN) has not been elucidated so far. In the submitted paper the authors attempted to contribute to the elucidation of etiological associations of GBV-C/HGV infection and VHN by comparing the dynamics of markers of the infection in a group of 59 patients with VHN, two control groups exposed to a high risk of parenteral operations and a third comparative group. The first control group comprised 64 patients in a long-term haemodialyzation programme (HD), the second group was formed by 82 patients with haematooncological disease (BD). The third comparative group comprised 22 patients coinfected (CI) with virus of hepatitis C (VHC), or possibly hepatitis B (VHB). The patients with VHN were HBsAg, anti HCV and anti HEV negative. In the majority in the first blood sample transaminases were elevated which was one of the main reasons for examination of GBV-C/HGV RNA. Prevalence of GBV-C/HGV infection, proved by the presence of at least one of the two markers of current or past infection (GBV-C/HGV RNA, antiGBV-C/HGV) was in the compared VHN, HD and BD groups as follows: 88.1%, 59.4% and 43.9%. The frequency of GBV-C/HGV positivity was highest in VHN-76.3%. In control groups HD and BD GBV-C/HGV RNA positivity was substantially lower, 18.8% and 25.6% resp. Long-term continuous viraemia was recorded in patients with VHN in 18.6%. In groups HD and BD it was half that value: 9.3% and 9.18%. In patients with VHN surprisingly after 6.5 months a marked rise of negative findings occurred (5.6x) without the expected increase of antibodies. A similar finding was recorded also in the other groups (HD and BD), incl. CI patients. Disappearance of viraemia was observed most frequently in VHN (55.9%). In groups HD and BD GBV-C/HGV RNA disappeared only in 7.8% and 12.1% resp. In treated patients of the CI group viral RNA was present in 45.5% and it disappeared in 36.4%. On the other hand, seroconversion to antibodies was comparable in VHN, HD and BD (11.9%, 9.4%, 8.5%), only in group CI it was higher (18.2%), obviously in conjunction with treatment of concurrent HCV or HBV infection. Disappearance of viraemia without subsequent seroconversion occurs in GBV-C/HGV infection frequently, the highest rate was observed by the authors in patients with VHN. Disappearance of viraemia does not necessarily imply clearance of GBV-C/HGV but may be due to a change of GBV-C(HGV into a state of persistence without positive laboratory markers of the infection. Persistence of the virus could also be the reason of the assumed conditioned pathogenicity of the virus, and the effect of frequent disappearance of both markers could explain some controversial epidemiological observations when in studies only static data without dynamic associations were used.     

The prevalence of TT virus and GB virus C/hepatitis G virus infection in individuals with raised liver enzymes but without HBV or HCV infection in Taiwan

The prevalence of TT virus (TTV) and GB virus-C/hepatitis G virus (GBV-C/HGV) infection and the association with raised liver function tests in 546 Taiwanese with negative HBsAg, anti-HCV and HCV RNA was elucidated. They were tested for serum alanine aminotransferase (ALT), GBV-C/HGV RNA, anti-envelope protein 2 antibody (anti-E2) and TTV DNA. Direct sequencing and phylogenetic analyses were performed on 58 isolates for TTV genotype determination. The prevalence of TTV DNA, GBV-C/HGV RNA, anti-E2 and over all GBV-C/HGV exposure was 24.9, 3.4, 8.2 and 11.1%, respectively. Using uni- and multi-variate analyses, male gender and TTV viremia were associated significantly with raised ALT values. Sixty-nine percent of TTV isolates were deduced to be TTV genotype 1 and they had significantly lower mean age than genotype non-1 isolates. In the population, raised ALT may be related to male gender and be attributable to TTV infection but not to GBV-C/HGV among individuals with no evidence of current HBV and HCV infection. TTV genotype 1 is the most prevalent genotype and associated with younger age.     

HCV and GBV-c/HGV infection in HIV positive patients in southern Italy

Flaviviridae–hepatitis C virus (HCV) and GB virus C/hepatitis G virus (GBV-C/HGV) – and human immunodeficiency virus (HIV) frequently show similar modes of transmission. HCV and GBV-C/HGV infection was assessed in 134 consecutive patients with evidence of HIV infection, living in Campania, Italy. Data obtained from this cohort were compared with those obtained from 252 age- and sex-matched HCV infected patients without evidence of HIV infection (HCV control group). Following enzymatic immunoassays, samples were tested for the presence of HCV-RNA by RT-PCR. The HCV-RNA positive sera were genotyped by LiPA procedure. The prevalence of HCV infection in HIV patients was 19.40% and the largest group of HIV–HCV co-infected patients (84.62%) was represented by intravenous drug users (IVDU). The distribution of HCV genotypes in HIV–HCV patients was different, compared to that observed in HCV control group. HCV genotypes 1a (50%) and 3a (23.08%) were more frequently detected in HIV–HCV patients, compared to HCV control group (5.16 and 5.56% for 1a and 3a, respectively). Conversely, HCV genotypes 1b (55.70%) and 2a/2c (30.26%) were more represented in HCV control group, compared to HIV–HCV patients (15.38 and 0% for 1b and 2a/2c, respectively). GBV-C/HGV seroprevalence was 41.04% in HIV patients and 6.54% in healthy control individuals. Differently from HCV, GBV-C/HGV infection did not correlate to a preferential risk behaviour in the HIV cohort. Comparative analysis of HCV and GBV-C/HGV infection indicates that the use of injecting drugs might play a key role in the epidemiology of HCV and, in particular, of 1a and 3a HCV genotypes, in HIV patients.     

庚型肝炎病毒在肝炎及肝癌患者中感染情况

为研究庚型肝炎病毒在乙型肝炎、丙型肝炎、非甲—戊型肝炎及原发肝癌患者中的感染情况 ,选择临床肝炎患者血清及肝癌手术病人的术前血清、肝癌组织及癌旁组织。采用HGV RT PCR法检测标本中HGVRNA。结果 ,在临床乙型肝炎、丙型肝炎、非甲—戊型肝炎及肝癌手术病人中庚型肝炎感染率分别为 9% ( 12 / 130 )、10 % ( 3/ 30 )、17% ( 4 / 2 4 )、0 % ( 0 / 2 4 )。证明庚型肝炎是普遍存在的一种肝炎病毒 ,并与乙型肝炎、丙型肝炎有较高的重叠感染率 ,而与肝癌的相关性不大。     

Iatrogenic GB virus C/hepatitis G virus infection in an area endemic for hepatitis C virus

GB virus C/hepatitis G virus (GBV-C/HGV) is reported to be transmitted by blood products. This study reports infection with GBV-C/HGV from Area-O of town T, an area of high prevalence of antibody to hepatitis C virus (anti-HCV). Four hundred and thirty-five inhabitants of Area-O in town T were examined. Three hundred and forty-three inhabitants of Area-H in town T (where differences of age or sex are not markedly different to Area-O) were studied as controls. We investigated the virus markers and conducted a survey of life history in both areas. The seroprevalence of anti-HCV and GBV-C/HGV markers in Area-O was 17.7% and 11.7%, significantly higher than in Area-H (1.5% and 4.4%). The prevalence of GBV-C/HGV markers was significantly higher in the anti-HCV-positive group than in the sero-negative group. Anti-HCV- or GBV-C/HGV positive subjects tended to have a history of intravenous medications at hospital C in town T, suggesting iatrogenic infection through insufficient sterilization of needles and/or syringes.     

Ibrutinib,a Bruton's tyrosine kinase inhibitor,a new risk factor for cryptococcosis

PurposeInvasive fungal diseases and especially Cryptococcus neoformans infections are increasingly reported in patients with hematological malignancies receiving ibrutinib, a Bruton's tyrosine kinase inhibitor.Patients and methodWe reported three additional cases and reviewed 16 previous published cases together with cases from the international pharmacovigilance database.ResultsPatients were mainly treated for chronic lymphocytic leukemia. Cryptococcosis mostly occurred during the first six months (66%) and especially the first two months (44%) of treatment. Clinical presentation is often pulmonary (68%) and the outcome is usually favorable despite ibrutinib continuation.ConclusionClinicians must be aware of this infection in patients with hematological malignancies on ibrutinib.     

Global prevalence of occult hepatitis C virus: A systematic review and meta-analysis

BACKGROUNDOccult hepatitis C infection (OCI) is characterized by the presence of hepatitis C virus (HCV) RNA in the liver, peripheral blood mononuclear cells (PBMC) and/or ultracentrifuged serum in the absence of detectable HCV-RNA in serum. OCI has been described in several categories of populations including hemodialysis patients, patients with a sustained virological response, immunocompromised individuals, patients with abnormal hepatic function, and apparently healthy subjects.AIMTo highlight the global prevalence of OCI.METHODSWe performed a systematic and comprehensive literature search in the following 4 electronic databases PubMed, EMBASE, Global Index Medicus, and Web of Science up to 6th May 2021 to retrieve relevant studies published in the field. Included studies were unrestricted population categories with known RNA status in serum, PBMC, liver tissue and/or ultracentrifuged serum. Data were extracted independently by each author and the Hoy et al tool was used to assess the quality of the included studies. We used the random-effect meta-analysis model to estimate the proportions of OCI and their 95% confidence intervals (95%CI). The Cochran''s Q-test and the I² test statistics were used to assess heterogeneity between studies. Funnel plot and Egger test were used to examine publication bias. R software version 4.1.0 was used for all analyses.RESULTSThe electronic search resulted in 3950 articles. We obtained 102 prevalence data from 85 included studies. The pooled prevalence of seronegative OCI was estimated to be 9.61% (95%CI: 6.84-12.73) with substantial heterogeneity [I² = 94.7% (95%CI: 93.8%-95.4%), P < 0.0001]. Seropositive OCI prevalence was estimated to be 13.39% (95%CI: 7.85-19.99) with substantial heterogeneity [I² = 93.0% (90.8%-94.7%)]. Higher seronegative OCI prevalence was found in Southern Europe and Northern Africa, and in patients with abnormal liver function, hematological disorders, and kidney diseases. Higher seropositive OCI prevalence was found in Southern Europe, Northern America, and Northern Africa.CONCLUSIONIn conclusion, in the present study, it appears that the burden of OCI is high and variable across the different regions and population categories. Further studies on OCI are needed to assess the transmissibility, clinical significance, long-term outcome, and need for treatment.     

乙型、丙型、庚型肝炎病毒多重感染研究

目的探讨庚型肝炎感染患者是否存在双重感染和多重感染。方法应用庚型肝炎病毒（ＨＧＶ）ＮＳ３区逆转录聚合酶链反应技术检测了ＨＧＶ系列稀释的质控血清及ＡｂｂｏｔＧＢＶ－Ｃ参比样品中ＨＧＶＲＮＡ，并对９０例丙型肝炎病毒（ＨＣＶ）ＲＮＡ阳性和１２例乙型肝炎、丙型肝炎双重感染献血员进行了ＨＧＶＲＮＡ的检测。结果ＨＧＶ系列稀释质控血清１０－１～１０－５均为阳性；１０－６为阴性。２份ＡｂｂｏｔＧＢＶ－Ｃ样品均为ＨＧＶＲＮＡ阳性。９０例ＨＣＶＲＮＡ阳性样品中，８例ＨＧＶＲＮＡ阳性（１７．８％）；１２例乙、丙双重感染者中４例（４／１２）ＨＧＶＲＮＡ阳性。结论不仅存在ＨＣＶ及ＨＧＶ双重感染，也存在多重感染。     

乙型肝炎患者重叠感染丙型肝炎、庚型肝炎病毒的研究

[目的 ]了解乙型肝炎患者重叠感染丙型肝炎病毒 (HCV)、庚型肝炎病毒 (HGV)的情况。 [方法 ]应用 EL ISA法分别对 86 8例乙肝患者、5 17例乙肝病毒携带者检测血清抗 - HCV和抗 - HGV,应用逆转录聚合酶链反应法分别对HCV、HGV感染者进行血清 HCV- RNA、HGV- RNA检测 ,并与乙肝病毒携带者比较。 [结果 ]乙肝患者与乙肝病毒携带者 HCV感染率分别为 14.5 %、2 .3% ,HGV感染率分别为 15 .6 %、3.9% ,HCV和 HGV的重叠感染率分别为 2 .3%、0 .2 % ,两组间 HCV、HGV合并感染率均有非常显著性差异 (P<0 .0 1)。乙肝患者中 HCV感染者 HCV- RNA阳性率14.3% ,HGV感染者 HGV- RNA阳性率 11.9%。 [结论 ]乙型肝炎、丙型肝炎、庚型肝炎可以重叠感染。急慢性乙型肝炎患者的 HCV、HGV重叠感染率不同。     

Detection of HGV in serum and peripheral blood mononuclear cells of maintenance haemodialysis patients.

The aim of the present study was to investigate the prevalence of hepatitis G virus (HGV) and also hepatitis C virus (HCV) infections in maintenance haemodialysis patients, and to identify extrahepatic sites as HGV reservoirs. HGV RNA was detected in the serum of 6/61 (10%) patients and in the peripheral blood mononuclear cells of 2/61 (3%) patients (one of whom was serum negative). These findings suggest that lymphoid cells constitute an extrahepatic HGV reservoir. HCV RNA was detected in 7/61 (11%) patients. Five of these patients (71%) were identified as carrying HCV genotype 1b. Co-infection with HCV and HGV was detected only in one patient. Haemodialysis patients are at risk for HGV infection, by nosocomial routes or via transfusions. HGV itself does not seem to be an important cause of hepatitis since all six HGV RNA positive patients not co-infected by HCV or HBV showed normal ALT values.     

Viral co-infections in hepatitis C: HBV, HBV-C/HGV and TTV studies

BACKGROUND/AIMS: The prevalence of co-infections with hepatitis B virus (HBV) and novel hepatitis viruses GBV-C (Hepatitis G virus, HGV) and TT virus (TTV) in chronic hepatitis C (HCV) infection has been studied. In patients with chronic hepatitis C and in asymptomatic healthy HCV carriers, the influence of these agents on the course of HCV infection was assessed. METHODS: a total of 110 HCV-positive individuals, among them 77 patients with chronic hepatitis C--50 of them treated with interferon (IFN)--and 33 HCV carriers with normal alanine aminotransferase have been investigated. HBV-DNA, HGV RNA and TTV DNA were detected by PCR, to determine HBsAg and anti-HBc ELISA technic has been used. RESULTS: In the healthy population, the prevalence of anti-HCV was 0.3%, HBsAg 0.09%, anti-HBc 2.5%, HGV RNA 8.0% and TTV DNA 18.5%, respectively. In chronic hepatitis C HBsAg (accompanied with HBV-DNA) occurred in 1.29%, anti-HBc 25.97%, HGV RNA in 9.09% and TTV DNA in 40.25% of cases. In IFN-treated patients with sustained remission, the frequency of TTV was 20% vs. 45.7% found in non-responders. Among asymptomatic HCV-carriers, the prevalence of anti-HBc was 27.27%, HGV RNA 9.09% and TTV DNA 75.7% respectively. CONCLUSIONS: Neither previous HBV infection, nor HGV RNA and TTV DNA had apparent effect on the course of chronic HCV infection. TTV was detected with the lowest frequency in persons with sustained remission due to IFN, suggesting antiviral effect of IFN on TTV.     

Effects of Soy–Whey Protein Nutritional Supplementation on Hematopoiesis and Immune Reconstitution in an Allogeneic Transplanted Mice

Profound malnutrition and immunodeficiency are serious negative effects of radiotherapy and bone marrow transplantation for hematologic malignancy patients. This study aimed to evaluate the effects of nutritional supplementation with a soy–whey protein mixture on hematopoietic and immune reconstitution in an allogeneic transplant mouse model. Male BALB/c (H-2Kd) mice, 6–8 weeks-old, were divided randomly into five groups and then provided with different protein nutrition support. After 28 days, blood samples, bone marrow, spleen, and thymus were harvested to measure the effects. The results showed that soy–whey blended protein supplements promoted hematopoietic stem cell engraftment, body weight recovery, and the recovery of white blood cells, lymphocytes, and neutrophils; triggered the expansion of hematopoietic stem cells and progenitor cell pools by increasing the numbers of the c-kit⁺ progenitor, Lin-Sca1⁺c-kit⁺, short-term hematopoietic stem cells, and multipotent progenitors; enhanced thymus re-establishment and splenic subset recovery in both organ index and absolute number; improved overall nutritional status by increasing total serum protein, albumin, and globulin; protected the liver from radiation-induced injury, and increased antioxidant capacity as indicated by lower concentrations of alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and 4-hydroxynonenal. This study indicated that soy–whey blended protein as important nutrients, from both plant and animal sources, had a greater positive effect on patients with hematological malignancies to accelerate hematopoiesis and immune reconstitution after bone marrow transplantation.     

Hepatitis G virus infection from needle-stick injuries in hospital employees

A new RNA virus, hepatitis G virus (HGV) is known to be transmissible by blood transfusion. The aim of this study was to assess whether HGV is an occupational risk to hospital employees as a result of exposure to needle-stick injuries. Among 220 cases of needle-stick injuries, 21 employees were contaminated with HGV. Initially none of the 21 recipients were HGV positive. Fourteen of the 21 recipients were followed up and further tested for HGV RNA and serum antienvelope (E2) specific antibody. None of the 21 recipients exposed to HGV developed liver function abnormalities, but one of the 14 recipients became positive for HGV RNA after the injury. Anti-E2 was negative in all recipients tested. These findings suggest a low clinical risk of occupational exposure to HGV in hospital employees. Nevertheless, HGV is transmissible by needle-stick injury.     

HGV在HIV阳性人群的调查

目的：调查HIV流行地区庚型肝炎（HGV）在HIV阳性人群的感染率，并探讨其对HIV疾病进展的影响。方法：对某HIV流行地区人们作病史询问及血清实验室检测。结果：328名HIV－Ab阳性人群检测出210名（64％）合并感染HGV者；合并HGV的HIV感染人群艾滋病人或艾滋病死亡者所占比率较低（10．5％）。结论；合并感染瘐型肝炎似乎能延缓HIV感染者疾病的进展。     

Mucocutaneous infections in hematological malignancies

INTRODUCTION: Mucocutaneous infections of diverse etiology are frequent complications in patients with hematological malignancies. OBJECTIVE: To study the incidence, predisposing factors, microbiology, and primary clinical manifestations of these complications in oncohematological patients. MATERIAL AND METHODS: The study included 862 patients (394 females and 468 males) with hematological malignancies, treated in the Clinic of Hematology of the Higher Medical Institute, Plovdiv from 1990 to 1998. The patients were divided into three groups according to the primary disorder: lymphoproliferative disorders (541 patients), myeloproliferative disorders (296 patients), and bone marrow insufficiency (25 patients). RESULTS AND DISCUSSION: The mucocutaneous infections studied included most often abscesses and pyodermias. The predominant isolate was Staphylococcus aureus. Viral infections were caused mainly by herpes simplex virus type I and, less frequently, varicella zoster virus with intercostal localization. Candida species was isolated predominantly in oropharyngeal and esophageal mycoses. CONCLUSION: Prolonged cytostatic-induced neutropenia and suppressed cellular immune response are the principal factors for the infectious complications in hematological malignancies. The early clinical diagnosis and prompt etiological treatment of the mucocutaneous infections are crucial for the prophylaxis of the systemic infectious complications.     

替加环素治疗血液系统恶性肿瘤并发感染的疗效及其影响因素

目的 探讨替加环素治疗血液系统恶性肿瘤并发感染的疗效及其影响因素,为临床合理用药提供参考。 方法 回顾性分析某院血液系统恶性肿瘤并发感染且应用替加环素患者的临床资料,评价替加环素治疗的临床疗效,利用单因素分析和多因素logistic回归分析影响患者疗效的因素。 结果 共纳入182例患者,85例（46.7%）患者原发疾病为急性髓系白血病,粒细胞缺乏者116例（63.7%）,感染部位主要为肺部（72.0%）。分离病原菌62株,其中8株为耐碳青霉烯类肠杆菌目细菌。113例（62.1%）患者使用高剂量替加环素,疗程为（11.6±6.5）d,临床总有效率为55.5%。多因素分析结果显示,社区获得性肺炎、粒细胞缺乏时间>14 d和替加环素疗程 < 7 d是治疗失败的独立危险因素,治疗效果与患者性别、年龄、原发疾病、替加环素剂量、联合用药及感染病原菌无关。 结论 替加环素对血液恶性肿瘤并发感染患者有较好的疗效,但社区获得性肺炎、粒细胞缺乏时间>14 d和替加环素疗程 < 7 d会明显影响其疗效。     

Candidemia in the patient with malignancy

ABSTRACT

Invasive fungal infections are a common life-threatening disease and a major cause of morbidity, particularly in patients with malignancies, and Candida spp. is the most common isolated fungi in bloodstream. Candidemia is the focus of this review, which covers an approach to diagnosis and treatment, with an emphasis on patients with malignancies.

Acute leukemia, lymphoma, or myelodysplastic syndrome are the most common hematological malignancies associated with candidemia, while among solid tumors, gastrointestinal cancer has the majority of fungemia cases. Epidemiologic trends show there is a discrepancy between malignancies, where there is an important prevalence of non-albicans Candida in hematological malignancy patients.

Diagnosis is challenging, and a high index of suspicion is required to select at-risk patients for early empiric therapy with the goal of reducing mortality. There is an increased effort to improve understanding of individualized approaches to the patient based on precision medicine and to improve diagnosis in the future. The basis of treatment is prompt therapy with echinocandins and target therapy based on susceptibility and minimum inhibitory concentrations (MICs).     

Manifestations extrahépatiques au cours de l’infection par le GBV-C/HGV

The GBV-C/HGV virus has clearly established transmission modes, mainly blood contamination, and occasionally sexual transmission. It is frequently found among transfused patients, intravenous drug abusers, and hemodialysis patients and often associated with HCV. Its hepatic pathogenicity is very weak, marked by a moderate and transitory cytolysis. Chronic carriage is possible, but does not lead to chronic hepatitis. Carriage can be maintained before the virus disappears. The authors report the case of a patient presenting with pleuropericarditis after a blood transfusion without any other etiology than infection by GBV-C/HGV virus. The possible extrahepatic pathogenicity of the virus is suggested. This hypothesis was rarely put forward.     

输血传播庚型肝炎的前瞻性观察

目的了解庚型肝炎（ＨＧ）在我国输血后肝炎中的发生率及其与输血后乙型肝炎（ＨＢ）、丙型肝炎（ＨＣ）的关系。方法检测１３８例因手术输血病人在输血前后的ＨＢｓＡｇ、抗－ＨＢｓ，ＨＢｅＡｇ、抗－ＨＢｅ、抗－ＨＢｃ、抗－ＨＣＶ、ＨＣＶＲＮＡ和ＨＧＶＲＮＡ。结果５３例发生输血后肝炎病毒感染，其中丙型肝炎病毒感染４８例；乙型肝炎病毒感染２例（含１例两型混合感染）。７例输血后可用巢式ＲＴ－ＰＣＲ法查到庚型肝炎病毒感染，３例合并丙型肝炎病毒感染者均有ＡＬＴ增高。４例单纯ＨＧＶ感染者，ＡＬＴ均正常。ＨＧＶＲＮＡ持续１个月至半年不等。５例输血后ＨＧＶ感染的病人可查到供血，其中３例病人至少有１份供血ＨＧＶＲＮＡ阳性。结论单纯ＨＧＶ感染的献血员和输血后感染者均无病毒性肝炎的临床表现和ＡＬＴ改变，与ＨＧＶ作为一种重要肝炎病毒的观点不相符。