Human Herpesvirus Type 8 Infection Research Articles

Seroprevalence of human herpesvirus type 8 (HHV-8) in blood donors at Laquintinie Hospital of Douala (LHD), Cameroon

Background: The Human Herpesvirus type 8 (HHV-8), also called Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic virus. Its prevalence is high in many sub-Saharan African countries and some Asian areas. HHV-8 is transmitted through saliva and is acquired in early childhood. HHV-8 can also be transmitted sexually and by organ transplant or blood transfusion. Cameroon is an endemic area. That is why, for improving transfusion safety purpose, we assessed the HHV-8 infection rate in blood donors since the risk of transmission by blood transfusion was shown. Material and methods: Blood samples were collected from blood donors at Laquintinie Hospital of Douala (Cameroon) blood bank for 5 months. Participants were from different ages. Collected samples were tested for detection of antibodies against HHV-8 using enzyme-linked immunosorbent assay (ELISA). Data analysis was perform and P-value of 0.05 was statistical significance threshold. Results: Our result showed 2.2 % (2/91) seroprevalence rate of HHV-8 in blood donors. The two positive results were single and male-gendered. These observations were not statistically significant (P=0.6959 and P=0.851 respectively). Males were the most represented of our participants (92.31%). The mean age of our subject was 29±7 years. None of the studied population were at risk of HHV-8 infection. However, young adults aged between 18 to 28 years (54.94%) were the most represented. No evident association with socio-demographic data such as age, sex, level of education, and marital status was observed. Though, the high the educational level was the fewer we had volunteers for blood donation. Also, the number of blood donors decreased in an age-depending manner. Conclusion: Thus in our study, the HHV-8 infection rate was low in blood donors. Even though the potential risk of transmission might be low, we should consider HHV-8 infection check in some special cases such as immunodeficiency.

Seroepidemiology of the human herpesvirus 8 infection among people living with HIV in Taiwan, 2014-2018.

Human herpesvirus type 8 (HHV-8) can be transmitted through unprotected sex as HIV. We aimed to investigate the seroincidence of HHV-8 and associated factors among people living with HIV (PLWH). From 2014 to 2018, blood samples of PLWH on the first date of HIV care were determined for antibodies against HHV-8. Individuals testing HHV-8-seronegative at baseline were followed for at least four months to estimate the annual seroconversion rate. To identify the factors associated with HHV-8 seroconversion, we compared the clinical characteristics between seroconverters and non-seroconverters who were matched for observation duration. The HHV-8 seroprevalence increased from 8.1% in 2014 to 20.0% in 2018. HHV-8 seroconversion occurred in 154 (14.7%) PLWH after a total of 2652.16 person-years of follow-up (PYFU), resulting in an overall incidence rate of 5.62 per 100 PYFU, which increased from 3.20 to 6.84 per 100 PYFU during the study period. HHV-8 seroconverters were less likely to have chronic hepatitis B virus (HBV) infection (1.9% vs 10.6%) and more likely to be antiretroviral-naïve on entry into care (87.7% vs 75.4%) (both p<0.05). In multivariate logistic analysis, men who have sex with men (MSM) (adjusted odds ratio [aOR], 2.22; 95% CI, 1.01-4.86), being antiretroviral-naïve (aOR, 2.91; 95% CI, 1.27-6.67), and chronic HBV infection (aOR, 0.13; 95% CI, 0.03-0.61) at baseline were associated with HHV-8 seroconversion. An increasing trend of HHV-8 infection was observed among PLWH in Taiwan between 2014 and 2018. MSM and being antiretroviral-naïve were associated with higher risk for HHV-8 seroconversion.

Prevalence and Risk Factors of Human Herpes Virus Type 8 (HHV-8), Human Immunodeficiency Virus-1 (HIV-1), and Syphilis among Female Sex Workers in Malindi, Kenya.

The prevalence of Human Herpes Virus type 8 (HHV-8), Human Immunodeficiency virus (HIV), and syphilis is high in Sub-Saharan Africa. Studies on HHV-8 in Kenya are few and data on its coinfection with HIV and syphilis scanty. This cross-sectional study among female sex workers (FSWs) in Malindi, Kenya, aimed to determine the prevalence of HHV-8, HIV, and syphilis mono/coinfections and identify associated risk factors. A total of 268 FSWs consented and were administered a structured questionnaire and screened for antibodies against HHV-8, HIV, and syphilis following the National Guidelines. FSWs positive for HHV-8 were 67/268 (25%), HIV 44/268 (16.4%), and 6/268 (2.24%) for syphilis. Eight out of 67 (12%) tested positive for HHV-8/HIV and 2/67 (3%) for HHV-8/syphilis coinfections. Married FSWs had higher odds of HHV-8 infection (OR 2.90, 95%, and P=0.043). Single marital status was inversely associated (OR 0.46, 95% CI 0.23-0.94, and P=0.034) with HIV infection. HIV was associated with increasing age (OR 14.79, P<0.001), inconsistent condom use (OR 2.69, P=0.004), increased duration as sex worker ≥6 (OR 3.0, P=0.002) and clients ≥4 (OR 4.0, P<0.001), intravenous drug use (OR 2.5, P=0.043), and early sex debut (P=0.049) unlike HHV-8 which was not associated with high risk sexual behavior. HHV-8/HIV coinfection was associated with increasing age (OR 11.21, P=0.027). Infection by HHV-8 was not significantly associated with HIV (OR 0.62; P=0.257) or syphilis (OR 1.52; P=0.636). There was a high likelihood of infection with HHV-8 compared to HIV (OR 8.6, P=0.014) and syphilis (OR 14.6, P<0.001). The lack of association of HHV-8 with high risk sexual behavior suggests that sexual transmission may not play a significant role in transmission of HHV-8 among FSWs in Malindi.

Detection of Human Herpesvirus 8 Antibodies in Women with Breast Cancer in Kirkuk city

The aim of the study is to evaluate the seroprevalence of human herpes virus type 8 (HHV-8) in women with breast cancer. The study has been conduct in Kirkuk city for the period from January 1, 2019 to April 1, 2019 on 50 breast cancer women with age group 21-70 years. The study has also included 40 healthy women as control group. The study included the collection of 3 ml of venous blood for identification and measurement of IgG antibodies towards the HHV-8 by using ELISA technique (KomaBiotech, Co, USA). The study also included taking of full information from cases like living situation, age. The study showed that the maximum frequency of HHV-8 infection (34%) recorded among breast cancer women comparing with the control group (10%), with highly significant relation. The majority of breast cancer women with positive IgG were within the age group 51-60 (41.18%) and the lowest rate was in the age group 21-3 years. The study showed that the maximum frequency of HHV-8 infection in breast cancer women was found in women with 2nd stage of breast cancer (58.83%) and the lowest rate was in the 1st stage. The highest rate of HHV-8 infection in breast cancer women (76.47%) were with metastasis to neighbor lymph nodes while compared with 23.53% without metastasis while all breast\t cancer women with HHV-8 negative were without metastasis. It has concluded that there was significant association between HHV-8 infection and occurrence of breast cancer and high rate of this infection has related to metastasis.

A high seroprevalence of human herpesvirus type 8 already present in patients with chronic hepatitis before the development of cirrhosis

A high seroprevalence of human herpesvirus type 8 (HHV-8) in mild cirrhotics is significantly associated with hepatitis activity. Cirrhosis is always derived from chronic hepatitis. We aimed to evaluate the prevalence of HHV-8 infection in patients with chronic hepatitis. Blood samples collected from 129 patients with chronic hepatitis and 129 age- and sex-matched healthy controls were analysed for monocyte and platelet counts, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), HHV-8 antibody and DNA, and alanine aminotransferase (ALT). Mean monocyte and platelet counts were significantly higher and lower in patients than in healthy controls (p= 0.02 and < 0.0001, respectively). Seropositive rate for HHV-8 antibodies was significantly greater in patients (32.6%) than in controls (20.9%, p= 0.04), particularly in patients with HCV infection, or higher plasma ALT levels, or both (p= 0.004, 0.01, and 0.0009, respectively). Antibody titres for HHV-8 in patients also exceeded those in controls (p= 0.02). The mean age of HHV-8 seropositive patients (60.3 years) was significantly older than that of seronegatives (52.3 years) (p= 0.0007). Patients aged 55 or older had higher seropositive rate and titres for HHV-8 antibodies than those younger (p= 0.005 and 0.007, respectively). A significantly high HHV-8 seroprevalence is already present in patients with chronic hepatitis before the development of cirrhosis, particularly in patients with HCV infection and/or higher plasma ALT levels. Advancing age seems to play an important role in HHV-8 seroprevalence in patients with chronic hepatitis.

HHV-8 Seroprevalence and Genotype Distribution in Africa, 1998⁻2017: A Systematic Review.

Human herpes virus type 8 (HHV-8) is the causative agent of Kaposi’s sarcoma (KS). We systematically reviewed literature published between 1998 and 2017, according to the PRISMA guidelines, to understand the distribution of HHV-8 infection in Africa. More than two-thirds (64%) of studies reported on seroprevalence and 29.3% on genotypes; 9.5% were on both seroprevalence and genotypes. About 45% of African countries had data on HHV-8 seroprevalence exclusively, and more than half (53%) had data on either seroprevalence or genotypes. Almost half (47%) of the countries had no data on HHV-8 infection. There was high heterogeneity in the types of tests and interpretation algorithms used in determining HHV-8 seropositivity across the different studies. Generally, seroprevalence ranged from 2.0% in a group of young children in Eritrea to 100% in a small group of individuals with KS in Central African Republic, and in a larger group of individuals with KS in Morocco. Approximately 16% of studies reported on children. Difference in seroprevalence across the African regions was not significant (95% CI, χ2 = 0.86; p = 0.35), although specifically a relatively significant level of infection was observed in HIV-infected children. About 38% of the countries had data on K1 genotypes. K1 genotypes A, A5, B, C, F and Z occurred at frequencies of 5.3%, 26.3%, 42.1%, 18.4%, 5.3% and 2.6%, respectively. Twenty-three percent of the countries had data for K15 genotypes, and genotypes P, M and N occurred at frequencies of 52.2%, 39.1%, and 8.7%, respectively. Data on HHV-8 inter-genotype recombinants in Africa are scanty. HHV-8 may be endemic in the entire Africa continent but there is need for a harmonized testing protocol for a better understanding of HHV-8 seropositivity. K1 genotypes A5 and B, and K15 genotypes P and M, from Africa, should be considered in vaccine design efforts.

Primary effusion lymphoma: current perspectives.

Primary effusion lymphoma (PEL) is a rare and aggressive disease, affecting a unique population of patients who are often elderly or immunocompromised. PEL is associated with human herpesvirus type-8 infection and most commonly presents as malignant effusions of the body cavities. Patients diagnosed with PEL often have a compromised immune system from secondary conditions such as HIV. Chemotherapy has traditionally been the cornerstone of treatment for patients with a good performance status and no significant comorbidities. However, an optimal regimen does not exist. Most patients with PEL experience a relapse after frontline therapy within 6–8 months and subsequently require further treatment. In recent years, our understanding of the molecular drivers and environmental factors affecting the pathogenesis of PEL has expanded. This review will discuss the pathogenesis of PEL and various management approaches available in the frontline and relapsed setting as well as targeted agents that have shown promise in this disease.

Human Papilloma Virus-Type 16 (HPV-16) & Human Herpes Virus-Type 8 (HHV-8) infections were found to be co-existing major cancer-contributing factors. Individualized, safe, effective treatment of hopelessly advanced cancer patients with metastasis by combining 4 methods of effective treatment: 1) Optimal dose of Vitamin D3 using its 10 unique beneficial effects, 2) Selective Drug Uptake Enhancement Method, 3) Stimulation of newly

Previous study indicated Human Papilloma Virus-Type 16 (HPV-16) has important role in genesis of ovarian cancer, uterus cancer, &amp; breast cancer. Omura, Y. noticed HPV-16 virus co-exists with single-cell parasite Toxoplasma Gondii (T.G.) infection in most of the cancer tissues he examined. Therefore, he thought some unknown virus must exist in the T.G. In early 2018, he found there is strong Human Herpes Virus-Type 8 (HHV-8) infection in every cell of Toxoplasma Gondii he examined. Thus, we found in every cancer cells there are co-existing cancer-promoting factors of HPV-16 &amp; HHV-8 infection associated with Toxoplasma Gondii. As a common source of these infections in human cancer patients, we found most egg yolk has co-existing HPV-16, HHV-8 &amp; Toxoplasma Gondii, but egg whites are free of these infections &amp; can be eaten safely as protein supply. Many cats and dogs also have these infections. As most important, safe treatment of cancer, we found repeated optimal dose of Vitamin D3 with optimal interval of about 8 hours is ideal because of 10 unique, beneficial effects discovered by him. Individually determined one optimal dose of Vitamin D3 has most effective anti-cancer effects in hopeless, advanced, cancer patients by reducing extremely high Integrin α5β1 of over 1500ng to normal value of 0.002∼0.004ng and 8-OH-dG (proportional to DNA mutation which is required for cancer growth) of over 60∼80ng to normal value of 0.1∼0.25ng for average 8 hours and 6000∼9000ng of strong pathogenic infection of HPV-16 &amp; HHV-8 in cancer tissue reduced to safe range of less than 500ng by markedly increased urinary excretion. Concerning beneficial effect of optimal dose of Vitamin D3, all the previous studies failed to use individualized optimal dose. As a result, they could not properly evaluate beneficial effects &amp; side effects and many reports claimed there were no significant beneficial effects including anti-cancer effects. Although optimal dose of Vitamin D3 can eliminate these viral infections very significantly but not less than 500∼300ng. Cancer incidence is only significant when these viruses are above 6000ng inside the body. Thus, we can keep potentially serious patients with strong cancer-contributing virus infections at relatively safe low degree of infection of much less than 3000ng. Our ideal treatment for advanced cancer patients is a combination of 1) Individually determined Optimal dose of Vitamin D3 with optimal interval of about 8 hours, 2) Selective Drug Uptake Enhancement Method by manual stimulation organ representation area of pathological organs at hands, 3) Stimulation of Thymus gland representation area of the back of the hand which was discovered by Omura, Y. in 2017, &amp; 4) Identification &amp; removal of multiple co-existing cancer-promoting factors. This combination of 4 new methods of treatment was found to be most effective &amp; safe treatment for not only hopelessly advanced cancer patients but also many other difficult medical problems.

Predictors of seropositivity for human herpesvirus type 8 in patients with mild cirrhosis

The high seroprevalence of human herpesvirus type 8 (HHV-8) in moderate or severe cirrhotics appears to be associated with male sex, hepatitis B virus (HBV) infection, alcoholism, and disease severity. The status of HHV-8 infection in mild cirrhotics remains unclear. Plasma samples collected from 93 mild cirrhotics and 93 age- and sex-matched healthy controls were analyzed for HHV-8 antibody and HHV-8 DNA. Mild cirrhotics had higher seropositivity for HHV-8 antibodies than healthy controls (P=0.0001). Univariate logistic regression analysis revealed that an age ≥55 years (odds ratio (OR) 2.88, P=0.02), hepatitis C virus (HCV) infection (OR 3.42, P=0.01), and hepatitis activity (OR 4.10, P=0.004) were associated with HHV-8 seropositivity in cirrhotics. Stepwise multivariate logistic regression analysis confirmed that age ≥55 years (adjusted OR (aOR) 1.92, P=0.04) and hepatitis activity (aOR 3.55, P=0.005) were independent factors. The rate of hepatitis activity was higher in HCV-infected than in HBV-infected patients (P<0.0001) and in women than in men (P=0.0001). Cirrhotics who were seropositive for HHV-8 or HCV or had hepatitis activity were significantly older (P=0.02, <0.0001 and <0.0001, respectively). Plasma samples from all participants were negative for HHV-8 DNA. HHV-8 antibody titers in mild cirrhotics also markedly exceeded those in controls (P<0.0001), as did those in patients ≥55 years old vs. younger patients (P=0.01), those in patients with vs. without HCV infection (P=0.0008), and those in patients with vs. without hepatitis activity (P=0.0005). Mild cirrhotics had high HHV-8 seroprevalence and HCV infection, and, in particular, old age and hepatitis activity were predictors.Emerging Microbes & Infections (2017) 6, e45; doi:10.1038/emi.2017.32; published online 7 June 2017

Increased prevalence of human herpesvirus type 8 (HHV-8) genome among blood donors from North-Western Argentina.

The prevalence of HHV-8 infection varies widely in South American populations, displaying geographical variations in its distribution. The heterogeneous genetic contributions provided by the transatlantic parental populations that modified the Native American genomes may explain this epidemiological observation. Aiming to determine the prevalence of HHV-8 genome among healthy South American blood donors and its potential association with genetic ancestry, 772 individuals were screened by a highly sensitive PCR protocol and ancestry was assessed in 414 samples. HHV-8 DNA was significantly more prevalent among North-western Argentines than among those from the metropolitan region (P = 0.001) and Bolivians (P = 0.0008), but no differences were found when compared with Peruvians and Paraguayans. Although significant differences were observed in the ancestry components of the studied populations, no association was found in the genetic admixture between HHV-8 [+] and HHV-8 [-] samples from the same place. These results support the hypothesis of the existence of geographical factors related to HHV-8 prevalence which could be explained by the presence of specific risk factors, cultural characteristics or behaviors, probably related to contaminated saliva and/or sexual transmission. The presence of HHV-8 in South American blood units available for transfusion and an increased risk of infection in some provinces of North-western Argentina represent a hazard for immunosuppressed recipients. J. Med. Virol. 89:518-527, 2017. © 2016 Wiley Periodicals, Inc.

Expressions of Kaposi's sarcoma-associated herpesvirus type 8-associated microRNAs k12-1 and k12-12 in Kaposi's sarcoma and their significance

Objective To measure the expressions of Kaposi's sarcoma-associated herpesvirus type 8 associated-microRNAs k12-1 (kshv-miR-k12-1) and k12-12 (kshv-miR-k12-12) in Kaposi's sarcoma tissue, and to assess their relationship with pathological stage and lesion area of Kaposi's sarcoma, HIV infection, and human herpesvirus type 8 (HPV-8) infection. Methods Totally, 18 paired tissue specimens stored in liquid nitrogen from Kaposi's sarcoma lesions and paralesional skin were collected. Total RNAs were extracted from these specimens by using Trizol reagent, and reversely transcribed into cDNA. SYBR Green real-time fluorescence-based quantitative PCR was performed to measure the expressions of kshv-miR-k12-1 and kshv-miR-k12-12 in these specimens. The relationship of kshv-miR-k12-1 and kshv-miR-k12-12 expressions with the pathological stage and lesion area of Kaposi's sarcoma, HIV and HPV-8 infections was analyzed. Results Compared with paralesional normal skin, Kaposi's sarcoma lesions showed significantly increased expressions of kshv-miR-k12-1 (2-ΔΔCt: 1.016 ± 1.645 vs. 0.029 ± 0.019, t= 2.542, P= 0.016) and kshv-miR-k12-12 (2-ΔΔCt: 2.104 ± 1.973 vs. 0.102 ± 0.093, t= 4.301, P= 0.000). There were no significant differences in the expressions of kshv-miR-k12-1 or kshv-miR-k12-12 between patients with HIV or HPV-8 infection and those without, among patients with different pathological stages of Kaposi's sarcoma, or among patients with different lesion areas (all P> 0.05). Conclusion Both kshv-miR-k12-1 and kshv-miR-k12-12 are highly expressed in Kaposi's sarcoma, but neither of their expressions is related to HIV or HPV-8 infection, pathological stage or lesion area of Kaposi's sarcoma. Key words: Sarcoma, Kaposi; Herpesvirus 8, human; kshv-miR-k12-1; kshv-miR-k12-12

Clinical and morphological features of different types of Castleman's disease

To study the clinical features of Castleman's disease (CD) and to elaborate therapeutic approaches in its different morphological types. The clinical and laboratory data were studied in 59 prospectively examined patients and 17 retrospectively examined ones with CD who had been treated at the Outpatient Department, Hematology Research Centre, in 1996 to 2014. There were a total of 37 men (median age, 36 years) and 39 women (median age, 34 years). The diagnosis was established from the results of histological and immunohistochemical examinations of removed lymph nodes (LN) or tumors in all the cases. A hyaline vascular variant (HVV) with local LN involvement was diagnosed in 38 (50%) patients; a plasma cell variant (PCV) was in 38 (50%); among the latter, 17 (22%) patients were found to have local involvement and 21 (28%) had generalized (multicentriC) involvement (multicentric Castleman's diseases (MCD)). Five (24%) patients with MCD were established to be infected with human herpesvirus type 8 (HHV-8). HVV was more frequently diagnosed in women (4%) than in men (29%); PCV was equally common in both men (47%) and women (53%); MCD was statistically significantly more frequently encountered in men (86%) than in women (14%) (p=0.05). The basic involvement areas in local HVV and PCV were peripheral (38%), mediastinal (29), retroperitoneal (18%), abdominal (9%), and small pelvic (6%) LNs. HVV and local PCV were benign and these were cured by surgical removal of LNs involved in the pathological process. MCD took its aggressive course with obvious constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, hypergammaglobulinemia, autoimmune hemolysis, thrombocytopenia, and involvement of extranodal foci in the pathological process. MCD transformation to plasmablastic lymphoma was observed in 4 of the 5 HHV8-positive patients and followed by a poor outcome. The prognosis of untreated MCD was unfavorable. In a number of cases prednisolone monotherapy worsened prognosis and the MCD patients receiving timely multiple-drug R-CHOP or R-VD chemotherapy could achieve sustained remission (the 5-year overall survival was 55%). CD must be included into the differential diagnosis of lymphadenopathies. When specific treatment is performed, the prognosis of HVV and local PCV is favorable: the disease is surgically cured in 95% of cases. Multidrug chemotherapy according to the B-cell lymphoproliferative disease program is indicated for the treatment of MCD: sustained remission can be achieved by the use of R-CHOP or R-VD programs. The HHV-8-positive variants of MCD increase the probability of transforming the disease to incurable plasmablastic lymphoma. Overall, prognosis and therapy choice in HIV-negative patients with CD depend on the histological variant of the disease, the extent of a tumor, and HHV-8 infection.

Prospective study of human herpesvirus type 8 serostatus and prostate cancer risk in the placebo arm of the Prostate Cancer Prevention Trial.

Human herpesvirus type 8 (HHV-8), a gamma herpesvirus associated with Kaposi's sarcoma, has been proposed as a candidate risk factor for prostate cancer (PCa) because of its detection in benign and malignant prostate specimens, and its relation with histologic prostatic inflammation. We investigated the possible relation between pre-diagnostic HHV-8 infection and PCa risk in a case-control study sampled from the placebo arm of the Prostate Cancer Prevention Trial. We defined cases as men with a confirmed diagnosis of PCa after visit 2 (n = 315) and controls as men not diagnosed with PCa during the trial who also had a negative end-of-study prostate biopsy (n = 315). We tested sera from visit 2 for IgG antibodies against HHV-8 using a monoclonal antibody-enhanced immunofluorescence assay against multiple lytic HHV-8 antigens. The adjusted seroprevalence of HHV-8 infection was 11.6 % for cases and 11.0 % for controls (p = 0.81). No association was observed between HHV-8 seropositivity and PCa risk (OR 1.06, 95 % CI 0.65-1.76). Our findings of a null association between HHV-8 seropositivity and PCa risk do not support an association between HHV-8 infection and PCa development, consistent with the general tendency of the epidemiologic literature to date.

High seroprevalence of human herpesvirus type 8 infection in males with advanced lung carcinoma.

Human herpesvirus type 8 (HHV-8) DNA is consistently found in all types of Kaposi's sarcoma, which is prevalent in immunocompromised patients. Patients with advanced lung carcinoma often showed immunologic abnormalities, and prevalence of HHV-8 infection is unclear. In this study, blood samples from 109 lung carcinoma patients and 109 age- and sex-matched healthy controls were analyzed for lymphocyte and monocyte counts, and for antibody, DNA, and genotype of HHV-8. Lung carcinoma patients had significantly lower lymphocyte and higher monocyte counts than healthy controls (p < 0.0001, both). HHV-8 seropositivity was more prevalent in lung carcinoma patients (41.3%), particularly in male patients (50.8%), than in controls (24.8%) (p = 0.01 and 0.002, respectively). The seropositivity was also significantly higher in male (50.8%) than female patients (27.3%, p = 0.01). Titers of HHV-8 antibody in patients also significantly exceeded those in controls (p = 0.004). Under a higher threshold (antibody titer ≥1:160) which is equivalent to that of enzyme-linked immunosorbent assay, lung carcinoma patients still had higher HHV-8 seropositivity than controls (p = 0.006). Three patients with stage IV lung carcinoma were positive for HHV-8 DNA with K1 gene subtype C3, D1, and E, respectively; they had much lower lymphocyte counts (658 ± 132 µL) than patients positive for HHV-8 antibodies only (1,449 ± 873 µL). The study indicates that lung carcinoma patients, particularly males, have a high seroprevalence of HHV-8. HHV-8 DNA detected in the patients with advanced lung carcinoma may be a result of virus reactivation in the immunocompromised status.

Post renal transplantation Kaposi's sarcoma: a review of its epidemiology, pathogenesis, diagnosis, clinical aspects, and therapy

Kaposi's sarcoma (KS) is a vascular malignancy primarily involving the skin. This neoplasm occurs commonly in acquired immunodeficiency syndrome (AIDS) and post solid organ transplantation. Human herpesvirus type 8 (HHV-8) has been shown to play a causative role in AIDS-associated KS and in post renal transplantation KS. Based on a MEDLINE search, we present a review of the current information on the epidemiology, pathogenesis, diagnosis and treatment of post-transplantation KS (PT-KS) with an emphasis on renal transplantation. The different frequencies of PT-KS in different parts of the world seem to be related to seroprevalence of HHV-8 infection. Following renal transplantation and the administration of immunosuppressive therapy, HHV-8 may reactivate. The renal tubular epithelium is a site for HHV-8 latency. Rates of PT-KS in seropositive recipients and anti-HHV-8 mismatched recipients (donor+/recipient-) are approximately 13% and 4.6%, respectively. Additional risk factors for the development of PT-KS include skin color, country of birth, age at the time of transplantation, and different induction regimens including anti-thymocyte globulin, steroid, or anti-interleukin 2-receptor antagonists. Skin is the major site of involvement. Surprisingly, involvement of the transplanted organ has been reported to be extremely rare. Reduction in immunosuppressive therapy and switching to mammalian targets of rapamycin inhibitors, such as sirolimus, are effective treatments for PT-KS. In patients with no response to reduction in immunosuppressive therapy, systemic chemotherapy with different regimens has been reported to be successful. PT-KS in renal transplant patients is an important problem specifically in southern Europe and the Middle East. In the majority of patients, the diagnosis based on clinical suspicion is always essential. Clinicians should bear in mind that PT-KS may threaten graft function and hence result in rejection complications. Appropriate management increases patient survival.

Hepatitis C–Related Primary Effusion Lymphoma of the Pleura and Peritoneum, Imaged With F-18 FDG PET/CT

Primary Effusion Lymphoma (PEL) is a rare form of Non-Hodgkin lymphoma that involves serous body cavities (pleural, pericardial, or peritoneal) with lymphomatous effusions in the absence of lymphadenopathy or organomegaly. Although it was seen mostly in HIV-positive patients, it has recently been reported in HIV-negative patients with chronic Hepatitis B or C infections. PEL is associated with human herpes virus type-8 infection, often presents with rapidly progressive effusions and generally has a poor prognosis. This is a case of a 65-year-old HIV-negative man with Hepatitis C cirrhosis, who presented with abdominal pain. An F-18 FDG PET/CT showed marked ascites and pleural effusions with increased F-18 FDG uptake in the pleura and peritoneum on the left side. Analysis of the cells in the peritoneal fluid revealed a human herpes virus 8-positive PEL of the peritoneum. As a result the patient was no longer considered a liver transplant candidate and died 2 weeks after the diagnosis.

Castleman's disease—a two compartment model of HHV8 infection

Castleman's disease is a primary infectious disease of the lymph node that causes local symptoms or a systemic inflammatory syndrome. Histopathology reveals a destroyed lymph node architecture that can range from hyaline-vascular disease to plasma-cell disease. Viral interleukin 6 (vIL-6) produced during the replication of human herpesvirus type 8 (HHV8) is the key driver of systemic inflammation and cellular proliferation. Stage progression of Castleman's disease results from switches between viral latency and lytic replication, and lymphatic and hematogenous spread. Multicentric plasma-cell disease in HIV-1 patients is associated with HHV8 infection. Polyclonal plasmablast proliferation escapes control in the germinal center with eventual malignant transformation into non-Hodgkin lymphoma. Surgery produces excellent results in unicentric disease, while multicentric disease responds to anti-CD20 therapy or IL-6 and chemotherapy. Lymphovascular endothelium and naive B cells are infectious reservoir-opening options for antiangiogenic and anti-CD19 strategies to enhance outcomes in patients with systemic disease.

Evaluation of coexistence of the Human Herpesvirus type 8 (HHV‐8) infection and pemphigus

Human Herpesvirus type 8 (HHV-8) is a new member of the herpes virus family, first found in the tissue of acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma. Environmental factors including viral infection may play a role in the onset and/or development of pemphigus. Some studies based on polymerase chain reaction findings suggest an association between HHV-8 and pemphigus. The aim of this study is investigation of the association of pemphigus with HHV-8 and the relationship between inflammatory and acantholytic cells with HHV-8 infection. Tissue-extracted DNA from 41 paraffin-embedded skin tissues from patients first presenting with pemphigus was tested using nested PCR for the presence of HHV-8. A total of 37 cases had pemphigus vulgaris (PV) and 4 patients had pemphigus foliaceus (PF). For our control group, normal skin of 21 cosmetic surgery patients were included. Furthermore, microscopic slides with H&E staining were evaluated for the number of inflammatory and acantholytic cells per microscopic field. Skin lesions from 13 of 37 patients (35.1%) with PV and 2 of 4 cases (50%) with PF were positive for HHV-8 DNA. All specimens in our control group were negative for this virus. HHV-8 infection might be a contributing factor in the initiation or development of pemphigus.

Epidemiology of Human Herpesvirus Type 8 Infection in Cardiopathic Patients

Problem statement: The possible contribution of viruses to vascular pathology is still a controversial issue. Human herpesvirus type 8 (HHV-8) has been suggested to participate to the pathogenetic events associated with atherosclerotic lesion establishment and progression. Recently, a high incidence of infection of HHV-8 (11%) has been verified in the island of Sardinia. The aim of this study was to evaluate a possible relationship between the HHV-8 infection and cardiovascular diseases in the South of Sardinia. Approach: The presence of HHV-8 genome was detected in DNA extracted from peripheral leucocytes, by nested-PCR and Southern blotting, in either acute or chronic cardiopathic patients (n = 180); healthy blood donors were examined as controls (n = 108). Results: The results demonstrated a significant increase (p = 0.035) in HHV-8 DNA isolation from cardiopathic patients (22.8%) in comparison to healthy controls (12.0%). Conclusion: HHV8 infection can be considered, among others, as an additional risk factor for cardiovascular disease development, although it was not necessarily the starting cause. More extensive studies were needed to define the exact role of HHV-8 infection in cardiopathic patients.

Human Herpesvirus Type 8 in Patients With Cirrhosis

Immunologic abnormalities in patients with cirrhosis strongly correlate with severity of liver cirrhosis. The association between cirrhosis and human herpesvirus type 8 (HHV-8) infection is unclear. Plasma samples were obtained from 74 healthy control subjects and 59 patients with cirrhosis. The seropositive rates for HHV-8 antibodies in patients with cirrhosis (25/59 [42%]) were significantly higher than that in healthy control subjects (18/74 [24%]; P = .027), particularly in men (P = .027), patients with alcohol-related cirrhosis (P = .032), and patients with thrombocytopenia (P = .019) or Child-Pugh class C cirrhosis (P = .018) or both (P = .015), or hepatitis B virus (HBV) infection (P = .003). Antibody titers in seropositive patients also significantly exceeded those in healthy control subjects (P = .008). All subjects were negative for anti-HIV. In Taiwan, cirrhosis is associated with HHV-8 infection, particularly in men, patients with Child-Pugh class C cirrhosis and/or thrombocytopenia, and patients with alcohol- or HBV-related cirrhosis.