Cytomegalovirus viremia during Campath-1H therapy for relapsed and refractory chronic lymphocytic leukemia and prolymphocytic leukemia

Campath-1H is effective therapy for patients with relapsed and refractory chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (PLL), but it is associated with profound lymphopenia and deficiencies in cell-mediated immunity. We report the incidence of cytomegalovirus (CMV) viremia in 34 patients treated with Campath-1H for relapsed or refractory CLL and PLL. All patients received infection prophylaxis during therapy and continuing for at least 2 months following Campath-1H. Five patients (15%) developed CMV viremia at a median of 28 days (range, 20-30 days) after the first dose of Campath-1H. The median CMV viral load was 860/mL (range, 420-2100/mL), as determined by quantitative plasma polymerase chain reaction (PCR). All 5 patients had a temperature > 38.5 degrees C, normal chest radiographs, normal liver function tests, and negative bacterial blood cultures with no clinical evidence of CMV disease at the time of presentation with CMV viremia. The median absolute neutrophil count (ANC) was 740/ microL (range, 340-1600/ microL), and the median absolute lymphocyte count (ALC) was 16/microL (range, 11-169/ microL) for the 5 patients at the time of CMV viremia. All 5 patients received ganciclovir therapy followed by prompt fever resolution and clearance of CMV viremia by plasma PCR. By univariate regression analysis, the following were not risk factors for CMV viremia: age, number of prior regimens, prior rituximab therapy, prior splenectomy, modified Rai stage at Campath-1H therapy (low/intermediate vs. high), ANC, and ALC; although, there was a trend towards significance for prior rituximab therapy (P = 0.07). Cytomegalovirus viremia may be a significant infectious complication during Campath-1H therapy and should be investigated further in future studies.     

Studies on the antibodies to human herpesvirus type 6 among Hungarian patients with asymptomatic HIV infection

The occurrence and the possible role in promoting HIV infection by human herpesvirus type 6 (HHV-6) have not yet been revealed in Hungary. In different groups of patients, serum titre of IgM and IgG antibodies, as well as avidity of IgG were quantitated by indirect immunofluorescence and an enzyme-linked immunosorbent assay, using isolate U1102 of HHV-6 variant A as antigen. In 60% of HIV-seronegative adult controls, high avidity IgG antibodies were found in low titre suggesting childhood infection. In HIV-seronegative persons with high risk behaviour for HIV-infection, both IgM and low avidity IgG were frequently found in higher titre, representing either primary or frequent reinfections, or reactivation of latent HHV-6. In asymptomatic HIV-seropositive patients, high titre of high avidity IgG antibodies was predominant, proving virus infection in the near past. These results indicate the contribution of HHV-6 to immunosuppression prior to AIDS, predisposing the organism to HIV infection.     

Cytomegalovirus reactivation and its clinical impact in patients with solid tumors

Cytomegalovirus reactivation can be life threatening. However, little evidence on its incidence in solid cancers is available. Therefore our single center Cytomegalovirus polymerase chain reaction database with altogether 890 CMV positive blood serum samples of mainly hematological and oncological patients was retrospectively analyzed to examine the occurrence of Cytomegalovirus reactivation in patients with solid tumors, resulting in 107 patients tested positive for Cytomegalovirus reactivation. Seventeen patients with solid cancer and a positive CMV-PCR test were identified, of which eight patients had clinically relevant CMV disease and received prompt antiviral treatment. Five patients fully recovered, but despite prompt antiviral treatment three patients died. Among these three patients two had significant co-infections (in one case EBV and in the other case Aspergillus) indicating that that CMV reactivation was at least one factor contributing to sepsis. The patient with the EBV co-infection was treated in an adjuvant therapy setting for breast cancer and died due to Cytomegalovirus and Epstein-Barr virus associated pneumonia despite intensive therapy. The other two patients had progressive disease of an underlying pancreatic cancer at the time of CMV diagnosis. One patient died due to attendant uncontrollable Aspergillus pneumonia, the other patient most likely died independent from CMV disease because of massively progressive underlying disease.Cytomegalovirus reactivation and disease might be underestimated in routine clinical practice. In our retrospective analysis we show that approximately 50 % of our patients suffering from solid cancers with a positive Cytomegalovirus polymerase chain reaction also had clinically relevant Cytomegalovirus disease requiring antiviral therapy.     

Antibody status to HHV-6 in children with leukaemia.

Forty children with acute lymphoblastic (33) or myeloid leukaemia (seven) were studied for IgG and IgM antibodies and IgG avidity against human herpesvirus 6 (HHV-6) at the time of diagnosis, and compared with age-, sex- and season-matched children with various neurological diseases of suspected viral origin. Of the children with leukaemia, 97.5% had IgG antibodies and 40% IgM antibodies to HHV-6 compared with 92.3% and 7.7% of reference subjects (P = 0.005). A seronegative child with leukaemia seroconverted 3 weeks after the diagnosis. The avidity of IgG antibodies (based on the resistance to urea treatment) was high in all children with leukaemia. One reference child had HHV-6-specific IgG antibodies with low avidity, which together with his positive IgM indicated an acute infection. The presence of specific IgM antibodies in 40% of children with leukaemia and the high avidity of IgG suggest a reactivation or an inaproppriate primary response to HHV-6 infection. The results support the conclusion of the role of the HHV-6 infection at the onset of childhood leukaemia.     

Detection of Occult Hepatitis C Virus Infection in Egyptian Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents

Background: Occult hepatitis C virus (HCV) infection (OCI) is diagnosed based on the detection of HCV-RNA in non-serum reservoirs, such as peripheral blood mononuclear cells (PBMCs) and/or hepatocytes with undetectable HCV-RNA in the serum. The current study was designed to shed more light on the presence of occult HCV in a population of cases who achieved an SVR after receiving treatments for HCV-infection and its significance. Methods: This cross-sectional study evaluated 111 chronic HCV patients treated at Theodor Bilharz Research Institute, Egypt and achieved a sustained virological response (SVR) 12 -24 weeks after treatment with Direct acting antiviral drugs (DAAs). The treatment lasted 12 or 24 weeks using generic medications including Sofosbuvir (SOF) 400 mg/day and Daclatasvir (DCV) 60 mg/day ± weight-based Ribavirin (RBV) 600-1000 mg/day. After achieving the SVR 12 -24 weeks, all patients were subjected to clinical examination and full laboratory investigations. All the candidates were assessed for fibrosis pre/post-treatment by transient elastography (Fibroscan©). Eighty-seven patients (78.4%) received dual therapy (SOF/DCV) and 24 patients (21.6%) received triple therapy (SOF/DCV/RBV). One hundred and seven patients received the regimen for 12 weeks (96.4%) and only four patients received the regimen for 24 weeks (3.6%). All patients were examined in terms of HCV RNA in plasma and PBMCs. Results: Nine patients (8.1%) were positive for PBMCs HCV RNA. The presence of Occult HCV infection (OCI) was significantly correlated with age, level of AFP, and the degree of liver stiffness. Conclusion: The OCI was present in 8.1% of the patients who achieved an SVR 12 – 24 weeks. These patients were mostly aged and with elevated AFP and advanced fibrosis. Monitoring and follow-up of those patients may help to assess the outcomes.     

ADAM10 Gene Polymorphism and Its Relationship to Hepatocellular Carcinoma in Egyptian HCV Patients Receiving Direct-Acting Antiviral Therapies (DAAs)

Objective: The aim of this study was to investigate the ADAM 10 rs.653765 SNP genetic polymorphism in the hepatocellular carcinoma occurrence (de novo and post DAAs). Methods: This study was conducted on 360 participants divided to 4 groups. Group 1: 90 chronic adult patients infected with HCV received DAAs regimens and evolved HCC during the period of follow up. Group 2: Another 90 HCV patients received the same DAAs regimens and did not show HCC manifestations during the same follow up period. Group 3 included 90 de novo HCC patients (did not receive any DAAs). Finally, 90 apparently healthy participants as group 4. Clinical and laboratory data were evaluated, and ADAM 10 genotyping were performed using qPCR. Results: The study showed statistically significant between HCC de novo and HCC deterioration on top of DAAs according to three scoring systems (Child Pugh, BCLC and HKLC) with p- value <0.05. Regarding ADAM10 gene polymorphism, the study showed a significant difference between CC versus CT+TT genotypes of HCC groups according to Child Bugh, BCLC and HKLC staging systems. Yet, no significant difference was found when ADAM10 genotypes and allele frequencies were compared between the four different studied groups. No difference in the survival rate between HCC de novo and on the top of DAAs but more aggressive stages with HCC on top of DAAs. Conclusion: ADAM10 genotypes did not show any significant association with HCC. Also, no differences in the death rate recorded between the de novo HCC and HCC post DAAs treatment with statistical significant worse staging of HCC post DAAs and were noted. the study showed a significant difference between CC versus CT+TT genotypes of HCC groups according to Child Bugh, BCLC and HKLC staging systems.     

Low serum albumin level is associated with cytomegalovirus reactivation in patients with chronic lymphoproliferative diseases treated with alemtuzumab (Campath-1H)-based therapies

BACKGROUND: Alemtuzumab (Campath-1H), a monoclonal antibody that targets the CD52 antigen, has been approved for the treatment of fludarabine-refractory chronic lymphocytic leukemia. However, the profound immunosuppression caused by alemtuzumab has been associated with infectious complications. METHODS: The authors report on the incidence and risk factors for development of symptomatic cytomegalovirus reactivation in 113 patients with chronic lymphoproliferative disorders who received alemtuzumab-based therapy. Kaplan-Meier methods were applied to generate survival curves, and the log-rank test was used to assess the difference between groups; in addition, univariate and multivariate Cox proportional hazards models were used to estimate the hazard ratio of death including 95% confidence intervals. RESULTS: Cytomegalovirus reactivation was diagnosed in 25 patients (22%), and most of those patients responded to antiviral therapy. Nine additional patients had asymptomatic cytomegalovirus viremia. CONCLUSIONS: With appropriate therapy, most patients achieved clearance of cytomegalovirus viremia. Low serum albumin was the only factor associated significantly with symptomatic cytomegalovirus reactivation.     

Prospective Comparison of Hepatocellular Carcinoma Behavior and Survival of Patients who Did or Did not Receive HCV Direct-Acting Antivirals

Background & Aims: The safety and efficacy of hepatitis C (HCV) direct-acting antivirals (DAAs) have been established in several real-world trials; however, some reports have claimed an association between DAAs and hepatocellular carcinoma (HCC) occurrence or aggressive behavior. We aimed to prospectively examine differences in de-novo HCC tumor behavior and overall survival (OS) in DAAs-treated versus HCV-untreated patients as measured by BCLC progression during a two-year follow-up period. Methods: This multicenter cohort study recruited 523 patients with de-novo HCV-related HCC. After exclusion criteria were applied, 353 patients were placed into; Group 1, including 236 patients without a history of DAAs therapy, and Group 2 including 117 patients with de-novo HCC developed after receiving DAAs. Patients were then stratified in each group according to BCLC staging (Liver, 2018). All patients received standard of care management and were followed until death or a maximum of 2 years. Results: No statistically significant differences were observed between the two groups regarding tumor characteristics (number and size of lesions) and criteria for aggressiveness upon presentation. Among all BCLC stages, DAAs treated patients showed significantly lower baseline Fib4 values than DAA untreated patients in BCLC-0 stage (4.1 vs 7.7, p 0.019). No statistically significant differences were evident in HCC progression in the different BCLC stages at 12 and 24 months follow up periods (p 0.0718 and 0.279 respectively). Significantly better survival was recorded in Group 1 compared to Group 2 patients for BCLC stages C and D (p = 0.003 and 0.01, respectively). Conclusion: HCC may develop at an earlier stage of liver disease after DAAs therapy. No defensive role was found for DAAs treatment in delaying HCC progression that occurs after viral eradication.     

Cytomegalovirus colitis--a severe complication after standard chemotherapy

We report on a case of cytomegalovirus (CMV) enterocolitis occurring in a 65-year-old patient after a first course of standard chemotherapy for a small cell lung carcinoma (SCLC). Colonic biopsies showed typical inclusion bodies, CMV IgM and IgG antibodies were found in the serum, and polymerase chain reaction for CMV-DNA was positive. Lymphopenia and diminished CD4 T-cell counts were observed. Diarrhoea ceased under ganciclovir treatment, the patient recovered, but died several months later of metastatic lung cancer. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy.     

Cytomegalovirus Colitis--A Severe Complication after Standard Chemotherapy

We report on a case of cytomegalovirus (CMV) enterocolitis occurring in a 65-year-old patient after a first course of standard chemotherapy for a small cell lung carcinoma (SCLC). Colonic biopsies showed typical inclusion bodies, CMV IgM and IgG antibodies were found in the serum, and polymerase chain reaction for CMV-DNA was positive. Lymphopenia and diminished CD4 T-cell counts were observed. Diarrhoea ceased under ganciclovir treatment, the patient recovered, but died several months later of metastatic lung cancer. Significant immunosuppression leading to severe colitis by CMV infection or reactivation can occur after standard chemotherapy.     

Molecular Study of Parvovirus B19 Infection in Children with Acute Myeloid Leukemia

Background: Parvovirus B19 is a common viral infection in children. Nearby evidences are present about itsassociation with acute leukemia, especially acute lymphoblast leukemia. Nevertheless, scanty reports have discussedany role in acute myeloid leukemia (AML). Purpose: To evaluate the frequency of virological markers of B19 infectionincluding its DNA along with specific immunoglobulins G (IgG) and M (IgM) among children with newly diagnosedAML. Besides, describing the clinical importance of Parvovirus B19 infection in those patients. Patients and methods:A case-control retrospective study was conducted on 48 children recently diagnosed with AML before and duringchemotherapy induction and 60 healthy control. Specific serum IgM and IgG levels were determined by enzyme linkedimmunosorbant assay (ELISA) and DNA detection by polymerase chain reaction (PCR). Results: Parvovirus DNA wasdetected in 20 patients with AML. IgM was found in sera of four patients and one case had positive DNA and IgG (5%).Patients with recent parvovirus B19 infection had a significantly reduced hemoglobin levels, RBCs counts, plateletcounts, neutrophil counts and absolute lymphocytosis (p=0.01, p=0.0001, p=0.01, p=0.02, p=0.0003, respectively).There were no clinical findings with statistically significant association to recent infection. Half of the patients withAML had positive PCR and/or IgM for parvovirus B19. Among children with AML under chemotherapy, there werereduced hemoglobin levels (P=0.03), reduced platelet counts (P=0.0001) and absolute neutropenia (mean±SD, 1.200±1.00) in those with parvovirus B19 infection. More than half of patients with parvovirus B19 (72.2%) had positive PCRand/or IgM and 36.4% of them had positive IgG. Conclusion: This study highlights that parvovirus B19 is commonin children with AML either at diagnosis or under chemotherapy. There are no clinical manifestations that can be usedas markers for its presence, but hematological laboratory findings can provide evidence for infection in the presenceof anemia and neutropenia. Detection of parvovirus B19 by combined molecular and serological markers is requiredin such patients for accurate diagnosis.     

Distinctive natural history in hepatitis C virus positive diffuse large B-cell lymphoma: analysis of 156 patients from northern Italy.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) has been correlated to hepatitis C virus (HCV) infection in few series, but characteristics and outcome of these patients remain undefined. PATIENTS AND METHODS: We analyzed 156 previously untreated consecutive HCV-positive patients with DLBCL observed between 1994 and 2004 in three major institutions from northern Italy. RESULTS: Median age at presentation was 63 years and 8% of patients had DLBCL transformed from low-grade lymphomas. Spleen was the most frequently involved extranodal site, followed by liver and stomach. Treatment was delivered with cure-intent in 132 patients, while the remaining 24 patients received monochemotherapy or radiotherapy alone due to old age or seriously impaired hepatic function. Only five patients (4%) had to discontinue chemotherapy due to severe liver function impairment. The addition of rituximab did not seem to affect patients' tolerance to treatment. Five-year overall survival of the entire cohort was 72%, while 5-year progression-free survival (PFS) of the 132 patients treated with cure-intent was 51%. Hepatitis B virus co-infection, advanced Ann Arbor stage and nodal origin of the tumor resulted the strongest adverse prognostic factors. CONCLUSIONS: Patients with HCV-positive DLBCL share distinctive clinical features. Future studies should prospectively evaluate the association between HCV and aggressive lymphomas.     

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Cytomegalovirus (CMV) infection in clinical settings other than the allogeneic transplant represents a poorly explored issue. Thus, we performed a comprehensive review of the medical literature about CMV infection in patients undergoing autologous hematopoietic stem cell transplant and in other nontransplant‐related hematologic patients. In autologous hematopoietic stem cell transplant, a CMV reactivation is reported to occur in up to 41% of CMV seropositive patients, when a prospective monitoring of antigenemia and/or viremia by polymerase chain reaction was adopted. However, more contained frequencies, up to 12%, have been reported when the monitoring criteria were based on a clinically driven diagnostic strategy. The most relevant risk factors appear to be CD34 + selected autografts, total body irradiation, and prior treatment with Alemtuzumab, Fludarabine, or Bortezomib, respectively. Other possible risk factors (ie, prior treatment with Rituximab, T‐cell lymphomas, and pretransplant HBcIgG seropositivity) are still debated. In nontransplant settings, the data are very heterogeneous; thus, CMV infection incidence and risk factors are more difficult to establish. Overall, the rate of CMV infection/reactivation ranges between 2 and 67%. High‐dose steroids, advanced disease, poor performance status, and treatment with Alemtuzumab, Fludarabine, Bortezomib, and Rituximab appear as the most relevant, though putative, risk factors. Intravenous Ganciclovir represents the gold standard for first‐line treatment of CMV infection in these patients. Oral Valganciclovir and Foscarnet are other possible options. Extensive prophylaxis and preemptive therapy are not generally recommended, with the exception of high‐risk patients.     

Hepatitis B and C Seroprevalence in Solid Tumors - Necessity for Screening During Chemotherapy

Background: Hepatitis B and C are the leading causes of liver diseases worldwide. For hematological and solidmalignancy patients undergoing chemotherapy, increases in HBV DNA and HCV RNA levels can be detectedwhich may result in reactivation and hepatitis-related morbidity and mortality. The aim of this study was todetermine the seroprevalence of Hbs ag and Anti HCV positivity in patients with solid malignancies undergoingchemotherapy and consequences during follow-up. Materials and Methods: The files of 914 patients with solidmalignancies whose hepatitis markers were determined serologically at diagnosis were reviewed retrospectively.All underwent adjuvant/palliative chemotherapy. For the cases with HBV and/or HCV positivity, HBV DNAand HCV RNA levels, liver function tests at diagnosis and during follow-up and the treatment modalities thatwere chosen were determined. Results: Of 914 cases, Hbs Ag, anti Hbs and anti HCV positivity were detectedin 40 (4.4%), 336 (36.8%) and 26 (2.8%) of the cases respectively. All of the Hbs ag positive patients receivedprophylactic lamuvidine before the start of chemotherapy. In the Hbs ag and anti HCV positive cases, liverfailure was not detected during chemotherapy and a delay in chemotherapy courses because of hepatitis wasnot encountered. Conclusions: Just as with hematological malignancies, screening for HBV and HCV shouldalso be considered for patients with solid tumors undergoing chemotherapy. Prophylactic antiviral therapy forHBV reduces both the reactivation rates and HBV related mortality and morbidity. The clinical impact of HCVinfection on patients undergoing chemotherapy is still not well characterized.     

The impact of the revolution in hepatitis C treatment on hepatocellular carcinoma

Hepatitis C infection represents a global health problem affecting ∼200 million chronically infected patients worldwide. Owing to the development of a fibrogenic and inflammatory micromilieu in the liver, hepatitis C virus (HCV)-infected patients are at a high risk of developing fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral agents (DAAs), however, has spurred a revolution in the treatment of HCV patients with sustained viral response (SVR) rates exceeding 90% in real-life settings. Recent clinical trials suggest that these novel treatments will not only alter the epidemiology of HCV infection but also the incidence of HCV-induced complications including hepatic decompensation, liver transplantation and hepatocarcinogenesis. Here, we summarize data from clinical trials carried out in HCV patients with compensated and decompensated cirrhosis and analyze the impact of viral clearance on HCC development and treatment. Finally, we review and discuss current and future treatment options of HCV patients with HCC in pre- and post-transplantation settings.     

The Association of PNPLA3, COX-2 and DHCR7 Polymorphisms with Advanced Liver Fibrosis in Patients with HCV Mono-Infection and HCV/HIV Co-Infection

There is increasing evidence that host genetic variations may influence the natural history of chronic hepatitis C virus(HCV) infection. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs)of PNPLA3 (rs738409), COX-2 (rs689465) and DHCR7 (rs12785878) and advanced liver fibrosis in Thai patients. Atotal of 220 patients with HCV mono-infection, 200 patients with HCV/HIV co-infection and 200 healthy controls wereenrolled. The SNPs were detected by allelic discrimination using real-time PCR with TaqMan probes. Liver stiffnessmeasurement (LSM) was assessed by transient elastography. Our results showed that the distribution of the studiedSNPs were not significantly different between the HCV mono- and co-infected groups. The frequencies AG and GGgenotypes of rs689465 and GG genotype of rs12785878 were less commonly found in the HCV mono- and co-infectedgroups compare with healthy controls (P<0.01). Among patients with HCV infection, older age, HIV co-infection,GG genotype of rs738409 and GG genotype of rs689465 were independently associated with advanced liver fibrosis(LSM≥9.5 kPa) in multivariate analysis. Moreover, the percentage of patients with advanced liver fibrosis increasedsignificantly along with the accumulated numbers of these risk genotypes. In conclusion, PNPLA3 (rs738409) andCOX-2 (rs689465) polymorphisms were associated with advanced liver fibrosis in patients with HCV mono- andco-infection, suggesting that these variants might play an important role in progressive liver fibrosis in these patients.     

Molecular and Serological Prevalence of HCMV in Iranian Patients with Breast Cancer

Background: Human cytomegalovirus (HCMV) is prevalent viral infection involved in several human cancers including breast cancer. The presence of HCMV genome in breast cancer tissue and footprint of viral last exposure patient’s serum are considered as important factor in the process of breast cancer development. Objectives: This study aimed to investigate molecular and serological epidemiology of HCMV in patients with breast cancer in Iran for first time. Methods: In our case-control study, 98 samples of breast tissue, including 49 cancerous (case) and 49 adjacent non-cancerous tissue were collected (control). In addition, we collected sera samples from all patients (n=49) and healthy individual (n=49). Seroprevalence of HCMV was assessed by Enzyme-linked immunosorbent assay (ELISA) and detection of HCMV genome was performed using Nested-PCR method. Results: HCMV genome found in 16.3% (8/49) of cases tissue and 2% (1/49) of controls tissue. In patients group, the levels of anti-CMV IgG and IgM were 93.9% and 2% compared to 69.4% and 4.1% in healthy individuals, respectively. There was a statistically difference between the anti-CMV IgG in patients and healthy control (p= 0.002). We found 75% of (6/8) HCMV genome positive PCR samples were also positive for their anti-CMV IgG in cases which was statistically significant (p= 0.01).  Conclusions: Our result showed significant presence of HCMV genome and anti-CMV IgG in patients, supporting the role of HCMV in breast cancer.     

A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma

The aim of the study was to assess whether co-infection by hepatitis-B virus (HBV) and hepatitis-C virus (HCV) is associated with a higher risk of developing hepatocellular carcinoma (HCC) than each infection alone. A meta-analysis of data published up to June 1997 was performed. HBsAg and anti-HCV antibodies or HCV RNA (anti-HCV/HCV RNA) were considered as serological markers of current HBV and HCV infection respectively. A total of 32 case-control studies were suitable for a quantitative overview. The summary odds ratios (OR) were 13.7 for HBsAg positivity and 11.5 for anti-HCV/HCV RNA positivity. The OR for anti-HCV was lower among studies using second- or third-generation anti-HCV or HCV RNA (OR, 8.2) with respect to studies with first-generation anti-HCV test (OR, 19.1). When combining data from the studies with second- or third-generation anti-HCV or HCV RNA, the OR for HBsAg positivity and anti-HCV/HCV RNA negativity was 22.5 (95% confidence interval (CI), 19.5–26.0), the OR for anti-HCV/HCV RNA positivity and HBsAg negativity was 17.3 (95% CI, 13.9–21.6), and the OR for both markers positivity was 165 (95% CI: 81.2–374, based on 191 cases and 8 controls exposed). A synergism was found between HBV and HCV infections, the OR for co-infection being greater than the sum and lower than the product of those for each infection alone. The interaction was therefore negative according to the multiplicative model, providing epidemiological evidence both of an independent effect and of interference between the 2 viruses in the carcinogenic process. Int. J. Cancer 75:347–354, 1998. © 1998 Wiley-Liss, Inc.     

丙肝相关肝细胞癌患者肝动脉化疗栓塞术对丙肝病毒再激活、肝炎加重的影响

目的:探讨丙肝病毒相关肝细胞癌患者接受肝动脉化疗栓塞术（transcatheter arterial chemoembolization,TACE）对丙肝病毒再激活、肝炎加重的影响。方法:收集2013年1月1日至2017年10月31日期间,确诊为丙肝相关肝细胞癌患者的临床资料进行统计学分析。结果:纳入156例丙肝相关肝细胞癌患者资料,针对TACE术对丙肝病毒再激活风险的统计学研究显示,74例进行TACE患者有19例发生丙肝病毒再激活,82例未行TACE患者中发生丙肝病毒再激活6例,两者具有统计学差异（P=0.00）。针对TACE术后丙肝病毒再激活风险评估显示,HCV再激活组患者术前WBC计数较未激活组患者低,两者有统计学差异(P=0.02)。Lg（HCV RNA）在两组中有差异,且Lg（HCV RNA）≥4的患者发生丙肝病毒再激活的概率大于Lg（HCV RNA）＜4的患者,两者差异有统计学意义(Fisher确切检验 P=0.03)。肿瘤直径在两组中有差异,且肿瘤直径≥6 cm患者发生病毒再激活的概率大于肿瘤直径<6 cm的患者,两者差异有统计学意义(P=0.03)。Logstic多因素回归分析发现:治疗前WBC水平、Lg（HCV RNA）及肿瘤直径是丙肝病毒再激活的独立预测因素。最后,肝炎加重发生率与丙肝病毒再激活的关联性研究显示,HCV再激活组肝炎加重发生概率明显高于HCV未激活患者（P=0.01）。结论:丙肝相关肝细胞癌患者接受TACE术增加病毒再激活风险,且低WBC水平、Lg(HCV RNA)≥4、肿瘤直径≥6 cm是发生HCV病毒再激活的独立危险因素,并且可能通过HCV再激活增加肝炎加重的风险。