Detrusor Underactivity: The Current Concept of the Pathophysiology

Based on evidence from available literature, we review the pathophysiology of detrusor underactivity (DU). DU is likely to be multifactorial. Aging reduces detrusor activity, but other concomitant causes may aggravate this condition, resulting in decrease of detrusor contractility. Impaired detrusor contractility has been regarded as a major etiologic factor of DU. However, a more complex pathology has been proposed. As contributing factors to DU, we discuss disturbances of the sensory afferent side of the micturition reflex, the central nervous system (CNS) and the efferent side of the reflex, including nerves and the detrusor muscle. Particularly, dysfunction of afferent nerves in the bladder and urethra may play a crucial role in the pathogenesis of DU. In addition, recent studies suggest that chronic bladder ischemia and resultant oxidative stress cause detrusor overactivity progressing to DU and inability to empty the bladder.     

Treatment Options for Hepatitis Delta Virus Infection

The hepatitis D virus (HDV), the smallest virus known to infect man, causes the most severe form of chronic viral hepatitis, hepatitis delta. It is estimated that about 15 to 20 million people are suffering from chronic HDV infection. HDV is a defective satellite virus depending on the hepatitis B surface antigen (HBsAg) for transmission. Chronic hepatitis delta is associated with a rapid progression of liver fibrosis and a high prevalence of liver cirrhosis, even in younger patients. Immunization against hepatitis B virus (HBV) protects from HDV infection, but there is no specific vaccine against HDV available for HBsAg-positive individuals. Treatment options for hepatitis delta patients are limited. So far, only interferon-alpha has shown an antiviral efficacy against HDV. Recent trials showed sustained virological response rates concerning HDV in 25 %–30 % of patients treated with pegylated interferons. HDV is dominant over HBV in the majority of cases, but HBV DNA-positive subjects should be treated with HBV polymerase inhibitors. Combination therapy of pegylated interferon-alpha and adefovir showed a more pronounced HBsAg decline, but the exact role of combination therapies in hepatitis delta requires further investigation. Alternative future treatment strategies may include prenylation inhibitors and HBV entry inhibitors, which are in early clinical development.     

Clearance of Chronic HCV Infection During Acute Delta Hepatitis

Abstract   The course of chronic hepatitis C in acute HDV/HBV superinfection is unknown. Here, we report a patient with chronic hepatitis C who cleared HCV during acute self-limited hepatitis B/D superinfection. Recovery from HCV was associated with the appearance of a strong and multispecific HDV-specific memory CD4+ and CD8+ T cell response – but only weak HCV-specific CD4+ T cell responses. These data suggest that HCV can be cleared by bystander mechanisms during acute infections with other pathogens which may be considered in the development of immunotherapies for hepatitis C. *KD and SVP contributed equally.     

A Rapid Point-of-Care Test for the Serodiagnosis of Hepatitis Delta Virus Infection

Hepatitis Delta virus (HDV) is a satellite of the Hepatitis B virus (HBV) and causes severe liver disease. The estimated prevalence of 15–20 million infected people worldwide may be underestimated as international diagnostic guidelines are not routinely followed. Possible reasons for this include the limited awareness among healthcare providers, the requirement for costly equipment and specialized training, and a lack of access to reliable tests in regions with poor medical infrastructure. In this study, we developed an HDV rapid test for the detection of antibodies against the hepatitis delta antigen (anti-HDV) in serum and plasma. The test is based on a novel recombinant large hepatitis delta antigen that can detect anti-HDV in a concentration-dependent manner with pan-genotypic activity across all known HDV genotypes. We evaluated the performance of this test on a cohort of 474 patient samples and found that it has a sensitivity of 94.6% (314/332) and a specificity of 100% (142/142) when compared to a diagnostic gold-standard ELISA. It also works robustly for a broad range of anti-HDV titers. We anticipate this novel HDV rapid test to be an important tool for epidemiological studies and clinical diagnostics, especially in regions that currently lack access to reliable HDV testing.     

The Delta Agent in Acute and Chronic Hepatitis B Infection in Sweden

The occurrence of the delta (δ) agent was analyzed in 89 patients with acute hepatitis B infection during 1976-1979 in Gothenburg, Sweden, and in 46 patients (16 drug addicts) with chronic HBsAg-positive liver disease. Four of the patients with acute hepatitis B had transiently detectable anti-δ antibodies in serum. At least three of these four cases were associated with intravenous drug abuse. Eleven of the HBsAg carriers (24%) were anti-δ-positive, and all of them were drug addicts. One of the drug addicts transmitted hepatitis B infection without detectable anti-δ in serum to two other non-addicts via parenteral routes. Apparently, in Sweden today δ-infection is mostly restricted to drug addicts and seldom found in other groups of hepatitis B patients.     

Prevalence of Hepatitis Delta Virus (HDV) Infection in Chronic Hepatitis B Patients with Unusual Clinical Pictures

Background

Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone.

Objectives

The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates.

Patients and Methods

81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations.

Results

12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients.

Conclusions

HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group.     

Current Views on the Pathophysiology of GB Virus C Coinfection with HIV-1 Infection

GB virus C (GBV-C), a member of the Flaviviridae family of viruses, recently received considerable attention largely owing to its potential role in decelerating HIV-1 disease progression by interfering with HIV replication. With similar transmission features, GBV-C is parenterally transmitted, similar to the serum hepatitis viruses and HIV-1, and replicates in hemopoietic cells and T lymphocytes in particular, with no observable disease pathology. Progressive T-cell depletion and subsequent immune abrogation being the cardinal features of HIV-1 infection, accumulating evidence indicates that GBV-C effectively overturns HIV’s chances of exploiting the T-cell machinery and leads to enhanced survival rates of HIV-infected subjects. Much effort has been devoted to understanding the beneficial role of GBV-C in HIV disease. This review discusses recently proposed mechanisms underlying the pathophysiology of GBV-C coinfection in HIV disease.     

Determination of Hepatitis Delta Virus (HDV)-RNA in Asymptomatic Cases of HDV Infection

Objectives: To assess the frequency of hepatitis delta virus (HDV) viremia in asymptomatic cases of HDV infection and the clinical significance of the HDV viremia, we conducted a cross-sectional community-based study. Methods : Of 2207 examinees, 210 (9.5%) were found to be positive for hepatitis B surface antigen (HBsAg). Antibody to HDV was detected in 47 (22.4%) of the 210 examinees, and 43 of the 47 were further evaluated for serum HDV-RNA by polymerase chain reaction. Results : Twenty-one (48.8%) of the 43 had detectable levels of HDV-RNA in serum, and 22 (51.2%) were negative for serum HDV-RNA. The majority (61.9%) of the HDV-RNA-positive HBsAg carriers had high levels of serum ALT. In contrast, the frequency of an abnormally high level of serum ALT was only 9.1% in the HBsAg carriers positive for HDV antibody but negative for HDV-RNA and the frequency did not differ from that seen in the HBsAg-negative individuals. The semi-quantified HDV-RNA levels did not correlate with the serum ALT levels. Conclusion : Seropositivity of HDV-RNA was strongly associated with liver cell damage, even in asymptomatic cases. The absence of a detectable level of serum HDV-RNA might be related to previous HDV infection.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients: A Concept for Consideration

Hemodialysis patients potentially have an increased risk of infection with parenterally transmitted viral agents due to an impaired host immune response and multiple transfusion requirements. Viral hepatitis is considered as a problem for hemodialysis patients because 1.9% of all deaths among this population are related to the consequence of viral hepatitis. Hepatitis B virus (HBV) is one of the most important causes of transmitted infections by the parenteral route in hemodialysis patients. Occult HBV infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg), which harbors potential risk of HBV transmission through hemodialysis. There are conflicting reports on the prevalence of occult HBV infection (OBI) in hemodialysis patients. Considering the importance of occult HBV infection in hemodialysis patients and the growing evidence on this subject, the purpose of this review is to provide comprehensive information on OBI prevalence in hemodialysis patients and highlight the most important points in this issue.     

Pathophysiology of Chronic Bronchial Infection in Bronchiectasis

Bronchiectasis is a complex and heterogeneous disease. Its pathophysiology is poorly understood, but chronic bronchial infection plays an important role in its natural history, and is associated with poor quality of life, more exacerbations and increased mortality. Pseudomonas aeruginosa, Haemophilus influenzae and Staphylococcus aureus are the most common bacteria related to chronic bronchial infection. Non-tuberculous mycobacteria, fungi and respiratory viruses are also present during clinical stability, and may increase the risk of acute exacerbation. Chronic inflammation is present in bronchiectasis, especially neutrophilic inflammation. However, macrophages and eosinophils also play a key role in the disease. Finally, airway epithelium has innate mechanisms such as mucociliary clearance and antibacterial molecules like mucins and antimicrobial peptides that protect the airways from pathogens. This review addresses how the persistence of microorganisms in the airways and the imbalance of the immune system contribute to the development of chronic bronchial infection in bronchiectasis.     

Chronic Hepatitis C Infection in Children: Current Treatment and New Therapies

Viral hepatitis C is responsible for a large burden of disease worldwide. Treatment of hepatitis C infection is currently undergoing a revolution with the development of new direct acting antivirals that offer higher cure rates and fewer side effects than other medications currently available. Treatment options for children, although well-defined and evidence-based, are limited relative to adults as there are few trials regarding the use of these newly developed agents in children. With so much optimism in the development of novel therapeutic options for hepatitis C, it is timely to review and summarize the current standard of care treatment and indications for treatment of chronic hepatitis C in children. We provide here an overview of recent drug developments and their potential for use in children.     

Epidemiology of Hepatitis B Virus Infection in China: Current Status and Challenges

The prevalence of hepatitis B is high in China. Based on the National Disease Supervision Information Management System of China, the mean reported incidence of hepatitis B was 84.3 per 100,000 in China between 2005 and 2010. There are differences in population distribution based on region and ethnic group. Here, risk factors, virological characteristics, and prophylaxis of hepatitis B in China are reviewed. Although the prevalence of HBV infection is gradually declining, there are many challenges in HBV infection control, including higher prevalence in floating population, poor compliance of antiviral therapy, and high disease burden.     

Acute Delta Hepatitis: Serological Diagnosis with Particular Reference to Hepatitis Delta Virus RNA

To evaluate serologic diagnosis of hepatitis delta virus, we tested HDV RNA in stored sera from 48 patients with acute delta hepatitis who were identified with anti-HD antibodies. Initial sera were positive for HDV RNA in 27 of 48 (56%) patients. In comparison, isolated IgM anti-HD was present in 18 (38%) patients, although IgM and IgG anti-HD were present concurrently in 16 (33%) additional patients. Overall, either HDV RNA or IgM anti-HD was present in 69% of the initial sera. The HDV infection was self-limiting in all except two patients who died of fulminant hepatitis and nine others in whom chronic delta hepatitis ensued. Patterns of HDV seropositivity during progression to chronicity induced variable persistence, disappearance or recrudescence of either HDV RNA or IgM and IgG anti-HD. Results of HDV RNA and IgM anti-HD tests were concordant in only 40-50% of instances. Our results indicate that serological testing for HDV RNA is direct and will demonstrate HDV replication in a large number of cases with acute delta hepatitis. Testing for IgM anti-HD could provide supplemental evidence for HDV infection. Sequential testing for these markers will facilitate assessment of the outcome of acute HDV infection.     

各型病毒性肝炎患者庚型肝炎病毒感染状况

目的:了解武汉地区各型病毒性肝炎患者中庚型肝炎病毒(HGV)感染的情况。方法:用酶联免疫吸附试验(ELISA)及逆转录聚合酶链反应(RT-PCR)方法测定各型病毒性肝炎患者的抗HGV和HGV RNA,并对庚肝病毒感染者进行临床分析。结果:351例各型病毒性肝炎患者中抗HGV阳性者56例,占15.05％;此56例中HGV RNA阳性者21例,占37.50％。各型病毒性肝炎患者中抗HGV阳性率及庚肝抗体阳性者中HGV RNA阳性率分别为:甲肝14.29％(5/35)及20.00％(1/5);乙肝17.29％(37/214)及35.14％(13/37);丙肝14.52％(9/62)及55.56％(5/9);戊肝4.00％(1/25),0.00％(0/1);非甲～戊肝26.67％(4/15),50.00％(2/4)。56例抗HGV阳性者中43例有输血、使用血制品或静脉药癌史,占76.79％。HGV感染在肝炎各临床类型分布为急性、慢性和重型肝炎患者无明显差异,且无性别和年龄分布的差异。HBV重叠感染HGV患者的SALT及TBil水平明显高于单纯HBV感染者(P<0.05),而HGV和其它肝炎病毒((HAV、HCV、HEV)重叠感染患者与单纯其它肝炎病毒感染者的SALT及TBiL水平无明显差异(P>0.05)。结论:武汉地区各型病毒性肝炎患者均可存在HGV感染。HGV可单独感染或与其它病毒混合感染。血液传播是HGV感染的主要途径。乙型肝炎患者合并庚肝病毒重叠感染可加重病情,而甲、丙、戊型肝     

Occult Hepatitis C Virus Infection in Patients With Autoimmune Hepatitis

Background:

Occult hepatitis C virus infection (OCI) is recognized by finding hepatitis C virus (HCV) RNA in hepatocytes without detectable anti-HCV antibodies and viral RNA in plasma. Autoimmune hepatitis (AIH) is a chronic and generally progressive disease without exactly-identified etiology.

Objectives:

This study aimed to determine the prevalence of OCI among patients with AIH and to evaluate the tests used to rule out HCV infection in diagnosing AIH.

Patients and Methods:

Between July 2012 to February 2013, 35 Iranian patients with AIH who attended Tehran Hepatitis Center were investigated. For identifying OCI, detection of HCV RNA in both ultracentrifuged serum samples and peripheral blood mononuclear cells (PBMCs) was used. Data analysis was performed using SPSS.

Results:

Six males and 29 females with mean disease duration of 77.1 ± 39.5 month and mean age of 43.62 ± 12.67 years were investigated. All cases were negative for anti-HCV antibody and we could not find any HCV RNA in ultracentrifuged serum samples and PBMCs.

Conclusions:

With our laboratory diagnostic method, it seems that there are no cases of OCI in patients with AIH. However, we recommend further studies with more samples and more precise laboratory method.