Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis C infection

BACKGROUND AND AIM: Parvovirus B19 has been reported to be detected in the sera of patients with acute or chronic hepatitis. The prevalence and clinical significance of B19 DNA in serum samples from patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were investigated. METHODS: Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53 normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme-linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR), Southern blotting and direct nucleotide sequencing, respectively. RESULTS: Anti-B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51 serum samples from patients with HCV infection. B19 DNA was detected in serum samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51 patients with HCV infection, but not in 53 serum samples from normal controls. The occurrence of liver dysfunction was not affected by B19 infection in patients with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA from patients with chronic HBV infection and all of the 12 serum samples with B19 DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9 subtype, respectively. The variant subtypes of B19 were found to be distinctive in patients with HBV or HCV infection. CONCLUSIONS: These data revealed that human parvovirus B19 infection was frequently found in patients with chronic HBV or HCV infection. The variant genotypes were present in patients with different chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the frequency of liver dysfunction in patients with chronic hepatitis. Long-term longitudinal studies are required to determine the natural course of parvovirus B19 infection and whether its coinfection affects the natural history of chronic hepatitis B or hepatitis C.     

The prevalence of hepatitis B virus and hepatitis C virus infection among patients with chronic liver disease in South India.

OBJECTIVE: Determining the identity of hepatitis C virus (HCV) genotypes in liver disease has key implications for ascertaining the duration of antiviral therapy and disease prognosis. We investigated the presence of various genotypes of HCV among 69 chronic liver diseased (CLD) patients with chronic HCV infection. METHODS: Sixty-nine consecutive subjects with underlying chronic hepatitis (n=28), cirrhosis (n=35), and hepatocellular carcinoma (n=6), diagnosed by clinical, biochemical, and histological means, were studied. Hepatitis B virus (HBV) and HCV diagnostic markers were used. HCV-RNA was extracted from sera of HCV-infected subjects and subsequently the HCV genotypes were determined using a commercial line probe assay (Inno-LiPA HCV II). RESULTS: Of the 69 CLD cases screened for possible markers of HBV and HCV infection, 39 (57%) were positive for HBV and 30 (43%) were HCV infected. The overall HCV-RNA positivity was 77% (23/30). Of these, the majority were genotype 1b (13/23, 57%), followed by 1a (6/23, 26%), mixed genotypes 3 and 4(3/23, 13%), and mixed pattern of 1a, 1b, and 4 (1/23, 4.3%). The genotype 1b infected subjects demonstrated significantly elevated transaminase (ALT) levels (p<0.05) as compared with the other non-1b HCV genotypes. CONCLUSIONS: The predominance of HCV genotype 1b among CLD patients could pose a major challenge for the efficient management of HCV disease and the development of effective therapeutic interventions in peninsular India.     

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis(PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs(c DMARDs) or biological ones(b DMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus(HBV) and hepatitis C virus(HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen(anti-HBs Ag), HBs Ag, and antibody to HCV(anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a(Cy A) or b DMARDs(etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBs Ag and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV.In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.     

上海急慢性乙型肝炎患者病毒基因型分布概况比较

目的 了解上海急慢性乙型肝炎患者的病毒基因型分布概况.方法 2003至2007年入住上海长海医院的62例急性乙型肝炎(AHB)患者和随机抽取的73例同期住院的慢性乙型肝炎(CHB)患者被纳入本研究.对所有患者血清HBV S区基因应用直接基凶测序方法进行基因分型,同时收集肝功能、病毒学指标和相关流行病学资料.对组间均数差异应用t检验,频率差异用x2检验.结果 上海地区AHB和CHB的主要病毒基因型为B型、C型,分别为48.4%(30/62)、51.6%(32/62)和26.0%(19/73)、74.0%(54/73),B型在AHB比例明显高于CHB(P<0.05).在流行病学特征和临床转归方面,这两种病毒基囚型在AHB之间差异无统计学意义.C型在CHB中比例明显高于AHB(x2=7.25,P<0.01).AHB组的主要传播途径为多伴侣性接触,为18例,占29.0%;CHB组的主要传播途径为母婴传播,为38例,占52.1%.结论 上海地区AHB和CHB主要病毒基因型均为B型和C型,AHB组B型所占比例相对较高,CHB组C型所占比例相对较高,病毒基因型与AHB临床预后无关.     

Current therapy for hepatitis C or D or immunodeficiency virus concurrent infection with chronic hepatitis B

Concurrent hepatitis C virus (HCV), hepatitis delta virus (HDV), or human immunodeficiency virus (HIV) infection with chronic hepatitis B virus (HBV) appears to increase the risk of progressive liver disease including liver cirrhosis and hepatocellular carcinoma. There is a 10% prevalence of HCV infection in chronic HBV or HDV infection. Serological evidence of previous exposure to HBV is found in more than 80% of HIV-positive patients in the high risk group. Notably, the most recently acquired virus tends to suppress the pre-existing virus. In chronic HBV infection acquired perinatally or in early childhood, usually HCV is dominant and may suppress or even displace HBV and HDV. Less frequently, HBV or HDV suppresses HCV. It is generally agreed that the dominant virus should be identified in order to make appropriate treatment decisions. Studies with standard interferon (IFN) to treat patients with HCV dominantly dual HBV/HCV infection have showed only limited virological response. But high dose of IFN has been demonstrated with better response rate. Combined ribavirin with standard or pegylated IFN therapy could achieve a sustained HCV clearance rate comparable with those infected with HCV alone. On the contrary, patients with HBV dominantly dual viral infection might indicate more appropriate addition of lamivudine to IFN than ribavirin. Additionally, patients with concurrent infection of HBV and HDV, IFN seems to be the only effective agent. However, the efficacy of IFN is related to the dose. High dose of IFN [9 MU tiw (thrice per week)] and longer treatment duration (at least 2 years) have been shown to achieve adequate virological response. In patients with concurrently infected HBV and HIV, anti-HBV therapy should be considered for all patients with evidence of liver disease, irrespective of the CD4 cell count. In patients not requiring antiretroviral therapy, HBV therapy should be preferentially based on IFN, adefovir, or telbivudine. In contrast, in patients with CD4 cell counts <350 cells/μl or those already on antiretroviral therapy, agents with double anti-HBV and anti-HIV activity are preferred. At present, the evidence of therapeutic efficacy is not sufficient to make a recommendation in treating patients with dual HBV/HCV or HBV/HDV or HBV/HIV infection. Further studies of the well-designed, larger scale are needed to elucidate the role of different regimens or combination in the treatment of dual viral infection.     

Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C

The clinical manifestations of chronic hepatitis B (CH-B) and chronic hepatitis C (CH-C) are different. We previously reported differences in the gene expression profiles of liver tissue infected with CH-B or CH-C; however, the signaling pathways underlying each condition have yet to be clarified. Using a newly constructed cDNA microarray consisting of 9614 clones selected from 256,550 tags of hepatic serial analysis of gene expression (SAGE) libraries, we compared the gene expression profiles of liver tissue from 24 CH-B patients with those of 23 CH-C patients. Laser capture microdissection was used to isolate hepatocytes from liver lobules and infiltrating lymphoid cells from the portal area, from 16 patients, for gene expression analysis. Furthermore, the comprehensive gene network was analyzed using SAGE libraries of CH-B and CH-C. Supervised and nonsupervised learning methods revealed that gene expression was correlated more with the infecting virus than any other clinical parameters such as histological stage and disease activity. Pro-apoptotic and DNA repair responses were predominant in CH-B with p53 and 14-3-3 interacting genes having an important role. In contrast, inflammatory and anti-apoptotic phenotypes were predominant in CH-C. These differences would evoke different oncogenic factors in CH-B and CH-C. In conclusion, we describe the different signaling pathways induced in the livers of patients with CH-B or CH-C. The results might be useful in guiding therapeutic strategies to prevent the development of hepatocellular carcinoma in cases of CH-B and CH-C.     

慢性HBV/HCV感染人群伴随的免疫相关表现

慢性HBV/HCV感染者常常伴有自身免疫系统紊乱,在丙型肝炎中尤为常见。介绍了慢性丙型肝炎患者免疫状态紊乱的机制,出现非器官特异性自身抗体的比例,以及伴随的免疫相关疾病,如混合型冷球蛋白血症、肾小球肾炎、干燥综合征、甲状腺疾病、2型糖尿病的临床表现、诊断和治疗等。简述了慢性乙型肝炎患者免疫状态紊乱的机制、相关的免疫表现以及抗病毒治疗对其的影响。慢性乙型或丙型肝炎的抗病毒治疗可以减轻伴随的免疫系统疾病,但是不宜采用干扰素治疗,因此,乙型肝炎患者应采用核苷和核苷酸类药物治疗,丙型肝炎患者应采用直接抗病毒药物治疗。     

Treatment of chronic hepatitis B or C in HIV-infected patients with dual viral hepatitis

Dual chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are recognized in 3%-5% of human immunodeficiency virus (HIV)-infected individuals. More severe liver disease is seen in these patients. Viral interference may account for the fact that replication of one virus generally predominates over replication of the other. The impact that treatment of HBV or HCV infection has on this reciprocal inhibition is not well established. No evidence of reactivation of either HBV or HCV was seen when complete suppression of the other predominant virus was achieved with specific therapy in 21 subjects with HIV infection and dual HBV/HCV infections. This information has important pathogenic implications and may influence therapeutic decisions.     

Sicca complex among Egyptian patients with chronic hepatitis C virus infection

The objective of this study was to assess the prevalence of sicca complex (SC) in patients with chronic hepatitis C virus (HCV) infection and its association with clinical and laboratory features of liver disease. Subjective and objective criteria of xerophthalmia and xerostomia were investigated in 120 HCV Egyptian patients. The lacrimal gland function was assessed by: tear film break-up time and lid parallel conjunctival folds test (LIPCOF), dacroscintigraphy (DSG) for lacrimal drainage and that of salivary glands by sialoscintigraphy. Sixty six of 120 patients (55%) had SC; all (100%) were proved to have xerostomia by sialoscintigraphy and xerophthalmia detected by ophthalmologic tests. Using dacroscintigraphy all SC patients (100%) were positive for lacrimal drainage abnormalities. Only 10.1% were symptomatic for SC. None of our patients had anti-Ro or anti-La antibodies. The presence of SC was associated with older age (r = 0.28, p = 0.00), female gender (p = 0.001), cirrhosis (r = 0.34, p = 0.00), thrombocytopenia (r = −0.72, p = 0.00), and rheumatologic manifestation (p = 0.000), but not with viral load (r = 0.19, p = 0.06). DSG showed significant statistical correlation with ophthalmologic tests (r = 0.87, p = 0.00). High prevalence of SC in HCV Egyptian patients was detected. LIPCOF and DSG are objective and noninvasive methods for early diagnosis of xerophthalmia and assessment of the nasolacrimal drainage, respectively. Hindrance of lacrimal drainage proved by DSG was frequently encountered in HCV patients with SC (100%) and strongly correlated with xerophthalmia.     

Distribution of hepatitis B virus genotypes among patients with chronic infection.

Hepatitis B virus (HBV) can be classified into at least eight genotypes, A-H. We evaluated the distribution HBV genotypes among patients with chronic infection. METHODS: We consecutively evaluated adult patients with chronic HBV infection from Salvador, Brazil. Patients were classified according to HBV infection chronic phases based on HBV-DNA levels and presence of serum HBV markers. HBV-DNA was qualitatively and quantitatively detected in serum by polymerised chain reaction (PCR). Isolates were genotyped by comparison of amino acid mutations and phylogenetic analysis. RESULTS: One-hundred and fourteen patients were evaluated. HBV-DNA was positive in 96 samples. HBV genotype was done in 76. Mean age was 36 +/- 11.3. In 61 of 76 cases subjects were classified as inactive HBsAg carriers. Their mean HBV serum level was 1760 copies/ml and 53 of 61 were infected with HBV genotype A, seven with HBV genotype F and one with genotype B. Twelve of the 76 patients had detectable hepatitis B e-antigen (HBeAg) in serum. Ten were infected with HBV genotype A and two with genotype F; most had increased alanine aminotransferase and high HBV-DNA levels. Three patients were in the immunotolerant phase, two were infected with HBV genotype A and one with genotype F. HBV subtyping showed subtypes adw2 and adw4. CONCLUSIONS: HBV genotype A adw2 and genotype F adw4 were the most prevalent isolates found. We could not find differences in genotype distribution according to HBV clinical phases and DNA levels. We did not detect HBV genotype D in contrast to a previous study in our center with acute hepatitis B. All inactive HBsAg carriers had low HBV-DNA levels.     

Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection

BACKGROUND & AIMS: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. METHODS: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. RESULTS: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1-21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. CONCLUSIONS: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma.     

Evidence for hepatitis B virus infection in patients with chronic hepatitis C with and without serological markers of hepatitis B

To assess the influence of HBV infection on anti-HCV-positive chronic liver disease, we performed a prospective case-control study comparing 19 HBsAg-positive, anti-HCV-positive patients with 38 HBsAg-negative, anti-HCV-positive patients, pair-matched for age, sex, and ALT levels. HBV and HCV infections were investigated by standard serology and polymerase chain reaction. HCV RNA was found in all patients with CAH and in 90.0% with cirrhosis (33% HBsAg-positive). HBV DNA sequences were found, in the HBsAg-positive subjects, in 71.4% of CAH and in 83.3% of cirrhotics; in the HBsAg-negative ones, only 10% of CAH but 77.7% of cirrhotics had demonstrable HBV DNA sequences. Consequently, 80.0% of cirrhotics had evidence of both HBV and HCV infection. Conventional serology gives partial information on the true occurrence of HBV infection in HBsAg-negative patients, while PCR defines more accurately the HBV status. When the rate of double infection is defined in this way, it correlates with the presence of cirrhosis.This work was supported by grants 40% (Progetto Virus) of MURST (Ministero dell'Università e della Ricerca Scientifica) and AIRC (Associazione Italiana per la Ricerca sul Cancro). A.G. is a recipient of a fellowship from Wellcome Italia.