Association between virus infection and periodontitis: Evidence from the National Health and Nutrition Examination Survey 2009-2014.

Periodontitis is a cumulative inflammatory disease associated with multiple health conditions and various systemic diseases. As a common disease, virus infection along with its consequences has become a serious health burden. The study aims to evaluate the relationship between common viruses including hepatitis virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), human papillomavirus (HPV), and periodontitis. The data from the US National Health and Nutrition Examination Survey (NHANES) 2009-2014 was adopted and screened through, including 10 714 participants. Generalized linear regression was conducted to verify the relationships between the virus infections and periodontitis. Moreover, we also performed analyses in age and gender subgroups. The results suggested that the infection of HCV, HSV-1, and HSV-2 was significantly associated with the prevalence of periodontitis (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.26-1.70; OR 1.09, 95% CI 1.05-1.13; OR 1.06, 95% CI 1.01 - 1.11, respectively) and risk of developing moderate or severe periodontitis (OR 1.51, 95% CI 1.29-1.77; OR 1.08, 95% CI 1.04-1.12; OR 1.05, 95% CI 1.01-1.10, respectively) after adjusting all relevant co-factors. Subgroup analyses revealed a steady association between periodontitis and hepatitis C virus (HCV) or HSV-1 infection, while the relationship between HSV-2 and HPV infection can also be found in some subgroups. The presence of HCV and HSV infection was found to be significantly associated with the prevalence of periodontitis, including moderate or severe cases. Moreover, the association of periodontitis and HPV infection can also be observed in people < 35 years.

Influence of genetic and environmental risk factors in the development of hepatocellular carcinoma in Mexico.

The latest studies on the epidemiology of diverse types of cancers have located in the scene the relevance of liver tumors, particularly hepatocellular carcinoma (HCC). HCC is a life-threatening malignancy triggered by chronic exposure to hepatitis B and C viruses, excessive alcohol intake, hepatic lipid droplet accumulation, and aflatoxins that lead to persistent liver damage. The occurrence of such etiological risk factors deeply marks the variability in the incidence of HCC worldwide reflected by geography, ethnicity, age, and lifestyle factors influenced by cultural aspects. New perspectives on the primary risk factors and their potential gene-environment interactions (GxE) have been well-addressed in some cancers; however, it continues to be a partially characterized issue in liver malignancies. In this review, the epidemiology of the risk factors for HCC are described enhancing the GxE interactions identified in Mexico, which could mark the risk of this liver malignancy among the population and the measures needed to revert them. Updated healthcare policies focusing on preventive care should be tailored based on the genetic and environmental risk factors, which may influence the effect of the etiological agents of HCC. Robust regional investigations related to epidemiological, clinical, and basic studies are warranted to understand this health problem complying with the rules of ethnic, genetic, environmental, and social diversity.

Micro-Players of Great Significance-Host microRNA Signature in Viral Infections in Humans and Animals.

Over time, more and more is becoming known about micro-players of great significance. This is particularly the case for microRNAs (miRNAs; miR), which have been found to participate in the regulation of many physiological and pathological processes in both humans and animals. One such process is viral infection in humans and animals, in which the host miRNAs-alone or in conjunction with the virus-interact on two levels: viruses may regulate the host's miRNAs to evade its immune system, while the host miRNAs can play anti- or pro-viral roles. The purpose of this comprehensive review is to present the key miRNAs involved in viral infections in humans and animals. We summarize the data in the available literature, indicating that the signature miRNAs in human viral infections mainly include 12 miRNAs (i.e., miR-155, miR-223, miR-146a, miR-122, miR-125b, miR-132, miR-34a, miR -21, miR-16, miR-181 family, let-7 family, and miR-10a), while 10 miRNAs are commonly found in animals (i.e., miR-155, miR-223, miR-146a, miR-145, miR-21, miR-15a/miR-16 cluster, miR-181 family, let-7 family, and miR-122) in this context. Knowledge of which miRNAs are involved in different viral infections and the biological functions that they play can help in understanding the pathogenesis of viral diseases, facilitating the future development of therapeutic agents for both humans and animals.

[Viral hepatitis A to E: prevalence, pathogen characteristics, and pathogenesis]. / Die Virushepatitiden A bis E: Prävalenz, Erregermerkmale und Pathogenese.

Viral hepatitis is characterized as an acute or chronic inflammation of the liver induced by an infection with certain viruses. At present, around 325 million humans suffer from the chronic form of the disease worldwide. Each year, about 1.6 million people die as a result of viral hepatitis. The causative agents, hepatitis viruses, are subdivided into five groups of pathogens, which are denoted with the letters A to E (HAV to HEV). These differ from each other with respect to phylogeny, transmission, epidemiology, host-specificity, life cycle, structure, and distinct aspects of pathogenesis.The strictly human-pathogenic HAV, a member of the Picornaviridae family, mostly induces acute hepatitis and displays a dominant spread over the Global South. The Hepeviridae-affiliated HEV shows a similar epidemiology, yet spreads further into industrialized countries due to its zoonotic potential. Furthermore, HEV is defined by the capability of inducing chronic hepatitis. This course of disease is also found in a more pronounced manner for the globally prevalent HBV (Hepadnaviridae) and its satellite virus HDV (Kolmioviridae), which further increases their carcinogenic potential. Lastly, a worldwide distribution is similarly described for HCV (Flaviviridae), which displays a high risk of chronifications and therefore a highly increased carcinogenic potential.The aforementioned pathogens differ with respect to their properties and life cycles. Thus, a differentiated look on epidemiology, diagnostic procedures, and disease prevention is required. Despite the presence of therapies, in some cases even a vaccine, there is an urgent need for advances in research on these aspects, especially for poverty-related pathogens.

Impact of hepatitis C virus on survival in patients undergoing resection of intrahepatic cholangiocarcinoma: Report of a Japanese nationwide survey.

AIM: We reviewed the data of a nationwide follow-up survey to determine the impact of hepatitis C virus (HCV) infection on the outcomes of hepatectomy for mass-forming (MF) type, and combined mass-forming and periductal infiltrating (MF + PI) type intrahepatic cholangiocarcinoma (ICC). METHODS: In total, 956 patients with ICC who underwent curative hepatic resection were included in this cohort study, and patients were classified according to virus status. Patients were classified according to virus status as follows: HCV-related ICC (n = 138, 14.4%), hepatitis B virus (HBV)-related ICC (n = 43, 4.5%) and non-virus-related ICC (n = 775, 81.1%). To control for variables, we used 1:1 propensity score-matching to compare outcomes after surgery between HCV-related (n = 102) and non-virus-related ICC cases (n = 102). RESULTS: We successfully matched HCV-related and non-virus-related ICC cases with similar liver function and tumor characteristics. Patients with HCV-related ICC had significantly shorter recurrence-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, p = 0.016) and overall survival (hazard ratio: 0.57, 95% confidence interval: 0.37-0.88, p = 0.011) than patients with non-virus-related ICC. Cox proportional hazard analysis showed that HCV-related ICC offered a worse prognosis than non-virus-related ICC. CONCLUSIONS: HCV infection increases the risk of recurrence and worsens overall survival in patients after curative resection for MF and combined MF + PI type ICC.

Association between serum liver enzymes and all-cause mortality: The Japan Public Health Center-based Prospective Study.

BACKGROUND & AIMS: The association of serum liver enzyme levels with all-cause mortality in individuals without hepatitis B virus or hepatitis C virus infection is inconsistent. We aimed to investigate all-cause and non-liver disease mortality according to levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) stratified by hepatitis virus infection status in a Japanese cohort. METHODS: Participants were 7243 men and 13 513 women aged 40-69 years at the baseline survey in 1993-1994. Multivariate-adjusted hazard ratios of death from the baseline health check-up to December 2012 were calculated with a Cox proportional hazards model controlling for potential confounding factors. RESULTS: During follow-up, 2235 deaths in men and 1901 deaths in women were identified. All serum liver enzymes were associated with all-cause mortality in each sex and hepatitis virus infection status. In participants without infection, those with more than twice the upper level of normal (ULN), which was defined as 30 IU/L for AST and ALT and 50 IU/L for GGT, had a higher risk of non-liver disease mortality compared to those below the ULN (HR 1.69; 95% confidence interval 1.13-2.53, 1.49; 1.02-2.18, 1.39; 1.11-1.73, 1.72; 1.08-2.74 and 1.72; 1.10-2.69 for AST, ALT, and GGT in men and AST and GGT in women, respectively), except for ALT in women. CONCLUSIONS: In participants without hepatitis virus infection, serum liver enzyme levels were positively associated with all-cause mortality. Similar associations were also found for non-liver disease mortality.

Estimates of the future burden of cancer attributable to infections in Canada.

More than 7000 incident cancers diagnosed in Canada in 2015 were attributable to infections. The future infection-associated cancer burden can be lowered by reducing the prevalence of major cancer-causing infections; hepatitis B virus (HBV), hepatitis C virus (HCV), Helicobacter pylori (H. pylori) and human papillomavirus (HPV). We modeled the future impact of (1) 10%, 25%, and 50% relative reductions in the prevalence of HBV, HCV and H. pylori and (2) different school-based HPV vaccination coverage levels (lower, current, higher) on Canadian cancer incidence by the year 2042. We modeled counterfactual reductions in HBV, HCV and H. pylori prevalence in 2018, assuming a latency period of 15-years, to estimate the impact on cancer incidence starting in 2033. The number of HPV-attributable cancers among vaccinated cohorts was a function of pre-2018 vaccine coverage levels and the 2018 counterfactuals. A 50% counterfactual reduction in the prevalence of HBV, HCV and H. pylori could prevent an estimated 10,585 cancers from 2018 to 2042; a 25% reduction could prevent 5293 cancers and a 10% reduction could prevent 2117 cancers. Assuming continuity of current estimated country-wide HPV vaccine coverage, 3977 anogenital and 1073 head and neck cancers could be prevented from 2018 to 2042, whereas vaccine coverage of 80% in girls and boys could prevent an additional 311 cancers. Almost 16,000 cancers could be prevented in Canada from 2018 to 2042 with a 50% relative reduction in HBV, HCV and H. pylori prevalence and 80% HPV vaccine coverage of girls and boys.

Cancers attributable to infections in Canada.

Infections are estimated to cause approximately 15% of the world's cancers with large geographic variations. Yet, Canadian estimates for specific cancer-causing infections are not available. To estimate the number of infection-associated cancers diagnosed among Canadian adults in 2015, we calculated population attributable risks (PARs) and the number of attributable cases for seven carcinogenic infections and their 20 associated cancers. A systematic literature search was performed for each infection to obtain data on infection prevalence in the population and the relative risk or odds ratio associated with the cancer it causes. When mechanistic evidence suggested that detection of a given infection within cancer tissue was sufficient to attribute the cancer to the infection, prevalence among cancer cases was used to approximate the PAR. Data from 61 studies formed the basis of our analyses. The estimated number of infection-attributable cancer cases for 2015 was: 3828 for human papillomavirus (HPV), 2052 for Helicobacter pylori, 578 for Epstein-Barr virus, 509 for hepatitis B and C viruses (HBV, HCV), 100 for human herpesvirus type 8, and 30 cases for human T-cell lymphotropic virus type 1. These seven infections were responsible for 3.7% of cancers diagnosed among Canadian adults in 2015; 3.5% among men and 4.0% among women. The infections with the highest number of attributable cases are largely preventable or treatable through vaccination (HBV and HPV), antibiotic therapy (H. pylori), or a combination of interventions (HCV), thereby representing an important target for reducing the infection-caused cancer burden among Canadians.

Enteric Viruses in Surface Waters from Argentina: Molecular and Viable-Virus Detection.

Water resources contaminated with wastewater are an important source for the dissemination of enteric viruses with an impact on the health of the population. The aim of the study was to assess the viral contamination of freshwater from a dam in Argentina by using infectious enterovirus detection, viral RNA amplification, and a genetic characterization of five enteric viruses associated with diarrhea and hepatitis. Enterovirus infectivity (iEV) was evaluated by cell culture and direct immunofluorescence. The detection of the viral genome of rotavirus (RV), human astrovirus (HAstV), norovirus (NoV), hepatitis A virus (HAV), and hepatitis E virus (HEV) was performed by reverse transcriptase PCR (RT-PCR). A total of 48 water samples from 4 monitoring points on the body of the dam from January to December 2012 and 66 water samples from 3 tourist beaches on the edge of the dam from October 2013 to October 2015 were collected monthly. During the first period, the overall viral frequency detection was 52.1% for group A RV, 50% for HAstV, 60.4% for NoV, 22.9% for HAV, 2.1% for HEV, and 64.6% for iEV. The overall frequency detection for the second sampling was 18.2% for RV and HAstV, 31.8% for NoV, 7.57% for HEV, and 66.7% for iEV. There was no detection of HAV during this period. The genotypes and genogroups detected through the study correlated with the most common genomic variants associated with human gastrointestinal and hepatitis illnesses. The results obtained could alert the health systems and environmental sanitation to make decisions for viral control and prevention in our environment.IMPORTANCE The study shows the impact of anthropic contamination of one of the most important tourist water resources in Argentina. This course of recreational water would be a favorable scenario for infection, as well as a reservoir for the enteric viruses, creating a risk for the population exposed to these waters. The results obtained could alert the health systems and environmental sanitation to make decisions for the control and prevention of viral diseases in this environment.

Full-length genomic sequence analysis of new subtype 3k hepatitis E virus isolates with 99.97% nucleotide identity obtained from two consecutive acute hepatitis patients in a city in northeast Japan.

Full-length genomic sequences of hepatitis E virus (HEV) obtained from two consecutive cases of acute self-limiting hepatitis E in a city in northeast Japan were determined. Interestingly, two HEV isolates from each patient shared nucleotide identity of 99.97% in 7 225 nucleotides, and a phylogenetic analysis showed that they formed a cluster of Japanese isolates that is considered as a new HEV subtype 3k. The high similarity of HEV sequences of two isolates from these patients in this study suggested that a subtype 3k HEV strain had spread via a commonly distributed food in the city, possibly pig liver.

[Specific infections in organ transplantation]. / Spezifische Infektionen bei Organtransplantationen.

This article is concerned with the important topic of infections associated with organ transplantation and includes a discussion on four subtopics. The first section describes the current options in the prevention and therapy of viral hepatitis in association with liver transplantation. Infections with hepatitis B, C, D (delta) and E are discussed with special emphasis on the interferon-free treatment of hepatitis C with the new antiviral drugs.The second section deals with Pseudomonas aeruginosa (PA) infections following lung transplantation (LuTx), which is one of the most frequently detected pathogens in the airway after LuTx. Patients with cystic fibrosis are particularly affected. This is important because studies have shown a clear correlation between chronic PA infections after LuTx and development of chronic transplant failure. Even if the data are still sparse, recommendations on prevention and therapeutic strategies are given. The theme of the third section is the high importance of viral infections after kidney transplantation. In addition to acquired infections, the transplanted organ as well as the recipient can be the source of the infection. The better the transplanted organ is tolerated under moderate immunosuppression, the less common and severe virus infections are. The focus of this section is on three common pathogens: cytomegalovirus, polyomavirus BK and hepatitis viruses.The final section deals with Aspergillus infections following transplantation of various organs. In this context Aspergillus spp. are one of the most commonly occurring fungal diseases. The epidemiology, risk factors, diagnostics, prophylaxis and therapy of invasive aspergillosis are presented.

Full genome analysis of a European-type genotype 3 hepatitis E virus variant obtained from a Japanese patient with autochthonous acute hepatitis E.

A unique European-type HEV strain (HE-JA12-0725) classifiable into subgenotype 3f was recovered from a 66-year-old Japanese female with autochthonous acute hepatitis E, and its entire genomic sequence was determined and characterized. The HE-JA12-0725 strain shared the highest identity of 92.7% with a Spanish swine isolate (EU723514) over the entire genome and possessed a long hypervariable region sequence of 111 amino acids, identical to the 3f strains of European origin. The patient had consumed pork liver obtained via home delivery in Japan approximately two months before the disease onset. These results suggest the circulation of rare 3f HEV strains in Japan.

Spontaneous reactivation of hepatitis B virus (HBV) infection in patients with resolved or occult HBV infection.

Reactivation of a former hepatitis B virus (HBV) infection can be triggered by immunosuppressive therapy, diseases associated with an immunocompromised state, organ transplantation or the withdrawal of antiviral drugs. Despite the absence of such risk factors, a spontaneous reactivation of HBV replication occurred in two elderly patients with resolved or occult HBV infection. A 73-year-old male underwent coronary artery bypass grafting in October 2008, and was negative for HBsAg but positive for anti-HBs. In July 2009, his serum became positive for HBsAg, HBeAg and HBV DNA (6.4 log copies/ml; genotype C), but negative for anti-HBc IgM, with abrupt elevation of the liver enzymes. The entire genomic sequence of HBV recovered from this patient revealed no mutations in the core promoter and precore regions that interfere with HBeAg production. A 76-year-old male with a history of endoscopic mucosal resection for esophageal cancer in 2002 and an initial diagnosis of diabetes mellitus in 2009, at which time he was negative for HBsAg. He was found to be positive for HBsAg in September 2012 during a laboratory examination performed prior to the resection of recurrent esophageal cancer, despite a low HBV load (2.1 log copies/ml). Three months later, without the administration of any anticancer drugs, the HBV DNA (genotype B) level increased to 5.1 log copies/ml. A precore G1896A variant with high quasispecies diversity was recovered from the patient. Aging, surgical stress and complication of disease(s) associated with compromised immunity, such as cancer, arteriosclerosis and diabetes mellitus may trigger spontaneous HBV reactivation.

Molecular analysis of the interspousal transmission of hepatitis B virus in two Japanese patients who acquired fulminant hepatitis B after 50 and 49 years of marriage.

A 71-year-old (C1I) and 69-year-old (C2I) Japanese female contracted fulminant hepatitis B after 50 and 49 years of marriage, respectively. Both index cases exhibited high levels of anti-HBc IgM antibodies (24.2 and 31.5 S/CO, respectively), suggestive of acute hepatitis B virus (HBV) infection, although they had no discernible risk factors for HBV infection, except for chronically HBV-infected spouses with detectable HBV DNA (3.3 log copies/ml [C1S: 72-year-old] and 7.2 log copies/ml [C2S: 71-year-old]). The HBV genotype/subgenotype was identical in each couple (B/B1 or C/C2). The HBV isolates from the index cases and spouses shared a nucleotide sequence identity of 99.5% and 99.7%, respectively, over the entire genome, and these four isolates had the highest nucleotide sequence identity of only 97% to HBV isolates deposited in DNA databases. Phylogenetic trees confirmed a close relationship of the HBV isolates between C1I and C1S and between C2I and C2S, supported by a high bootstrap value of 100% within each couple, indicating the transfer of HBV infection between spouses. These four isolates shared a precore mutation of G1896A known to be associated with fulminant hepatitis B. Although the history of sexual contact within a reasonable incubation period was obscure for one stable, monogamous couple (C1I and C1S), the other couple had a monogamous sexual relationship within six months prior to disease onset. This study indicates that two elderly Japanese patients with fulminant hepatitis B acquired HBV infection via interspousal (most likely sexual) transmission during long-lasting marriages.

m6A Methylation in Regulation of Antiviral Innate Immunity.

The epitranscriptomic modification m6A is a prevalent RNA modification that plays a crucial role in the regulation of various aspects of RNA metabolism. It has been found to be involved in a wide range of physiological processes and disease states. Of particular interest is the role of m6A machinery and modifications in viral infections, serving as an evolutionary marker for distinguishing between self and non-self entities. In this review article, we present a comprehensive overview of the epitranscriptomic modification m6A and its implications for the interplay between viruses and their host, focusing on immune responses and viral replication. We outline future research directions that highlight the role of m6A in viral nucleic acid recognition, initiation of antiviral immune responses, and modulation of antiviral signaling pathways. Additionally, we discuss the potential of m6A as a prognostic biomarker and a target for therapeutic interventions in viral infections.

Overview of acute liver failure in India.

Acute liver failure (ALF) is an infrequent, but serious complication subsequent to severe acute liver injury (sALI) due to various hepatotoxic agents such as hepatotropic virus(es) and drugs such as anti-tubercular medications, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and anti-cancer and anti-epileptic therapy and due to metabolic and autoimmune disease flares. ALF after sALI presents with encephalopathy associated with prolonged international normalized ratio (INR). Mortality in ALF is high and ranges between 50% and 80%. Due to severe liver damage, multiple sequels consequent to hepatic dysfunction result in complications such as hyperammonemia that culminates in encephalopathy associated with cerebral edema; innate immune paralysis resulting in increased frequency of infections and endotoxemia causing decrease in systemic vascular resistance (SVR) and tissue hypoperfusion and damage-associated molecular patterns (DAMPs) released from damaged hepatic parenchyma inducing pro-inflammatory cytokine storm, which may cause other organ dysfunctions. Certain etiologies such as hepatitis E virus and hepatitis A virus-related ALF or paracetamol-ALF (hyper-acute presentation) have better survival than remaining causes. In addition, if etiology-specific treatment (antivirals for ALF related to hepatitis B virus (HBV) or Herpes simplex virus (HSV) or N-acetylcysteine for paracetamol) is available, then the outcome with treatment is better. About half of the patients can be salvaged with medical therapy. All patients need intensive care and organ support to provide time for the liver to regenerate. Various prognostic models to predict high probability of mortality have been described, which should be used to select patient early during the disease for liver transplantation, which is associated with high long-term survival in these sick patients. The Indian National Association for Study of the Liver (INASL) recommends the ALF-Early Dynamic (ALFED) model as a preferred prognostic model in the Indian scenario, where hepatitis viruses are a dominant etiology of ALF and occur on a naïve liver with good regenerative capacity.

Liver immune-pathogenesis and therapy of human liver tropic virus infection in humanized mouse models.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate primarily in human hepatocytes. Few reliable and easy accessible animal models are available for studying the immune system's contribution to the liver disease progression during hepatitis virus infection. Humanized mouse models reconstituted with human hematopoietic stem cells (HSCs) have been developed to study human immunology, human immunodeficiency virus 1 infection, and immunopathogenesis. However, a humanized mouse model engrafted with both human immune and human liver cells is needed to study infection and immunopathogenesis of HBV/HCV infection in vivo. We have recently developed the humanized mouse model with both human immune and human liver cells (AFC8-hu HSC/Hep) to study immunopathogenesis and therapy of HCV infection in vivo. In this review, we summarize the current models of HBV/HCV infection and their limitations in immunopathogenesis. We will then present our recent findings of HCV infection and immunopathogenesis in the AFC8-hu HSC/Hep mouse, which supports HCV infection, human T-cell response and associated liver pathogenesis. Inoculation of humanized mice with primary HCV isolates resulted in long-term HCV infection. HCV infection induced elevated infiltration of human immune cells in the livers of HCV-infected humanized mice. HCV infection also induced HCV-specific T-cell immune response in lymphoid tissues of humanized mice. Additionally, HCV infection induced liver fibrosis in humanized mice. Anti-human alpha smooth muscle actin (αSMA) staining showed elevated human hepatic stellate cell activation in HCV-infected humanized mice. We discuss the limitation and future improvements of the AFC8-hu HSC/Hep mouse model and its application in evaluating novel therapeutics, as well as studying both HCV and HBV infection, human immune responses, and associated human liver fibrosis and cancer.

Novel single-step multiplex real-time polymerase chain reaction assay for simultaneous quantification of hepatitis virus A, B, C, and E in serum.

BACKGROUND AND AIM: Viral hepatitis needs an earliest diagnosis for its proper and timely treatment. Although serodiagnosis of viral hepatitis is in regular practice, however, it has certain limitations and points to alternate procedures of diagnosis. Present study was designed to develop a single-step multiplex real-time polymerase chain reaction (PCR) assay for detection of hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis E virus (HEV) related nucleic acids in sera from infected patients. METHODS: The PCR was standardized to detect HAV, HBV, HCV and HEV in serum using variables including annealing temperature, extension temperature, MgCl2 , and primer concentrations. The conserved regions of all viral genomes were used as targets for amplification. RESULTS: This novel assay was found to be a fast, sensitive, specific, and reproducible system for detection of HAV, HBV, HCV, and HEV in serum. The detection limit for different viral genomes at 100% level was found to be 280 copies/mL for HAV, 290 copies/mL for HBV, 30 copies/mL for HCV, and 300 copies/mL for HEV in a single-tube assay system. CONCLUSION: Present multiplex real-time PCR is the first report on single-step nucleic acid detection of HAV, HBV, HCV, and HEV in sera samples. It is an alternate diagnostic assay for common use in laboratories analyzing viral hepatitis cases.

Performance of Hepatitis Delta Virus (HDV) RNA Testing for the Diagnosis of Active HDV Infection: Systematic Review and Meta-analysis.

Background and Aims: Hepatitis delta virus (HDV) is a defective virus and causes severe liver disease. Several HDV RNA assays have been developed, however the diagnostic efficacy remains unclear.This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of HDV RNA assays to aid in the diagnosis of active hepatitis D. Methods: The PubMed, Embase, and Cochrane Library databases were systematically searched from the beginning to June 31, 2022. Information on the characteristics of the literature and data on sensitivity, specificity, and area under curve (AUC) of the receiver operating characteristic (ROC) were extracted. Stata 14.0 was used for meta-analysis of the combined sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Results: A total of 10 studies were included in the meta-analysis. The summary sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of HDV RNA assays for HDV diagnosis were 0.92 (95% CI: 0.87-0.95), 0.90 (95% CI: 0.86-0.93), 7.74 (95% CI: 5.31-11.29), 0.10 (95% CI: 0.06-0.18) and 99.90 (95% CI: 47.08-211.99), respectively. The AUC of the pooled ROC curve was 0.95 (95% CI: 0.92-0.96). Conclusions: The results show that HDV RNA assays had high diagnostic performance. However, that is limited by the number and quality of studies. Standard protocols for the development of assays by manufacturers and larger studies on the use of the assays are needed.

Al-Hijamah (Prophetic Wet Cupping Therapy) is a Novel Adjuvant Treatment for Viral Hepatitis That Excretes Viral Particles and Excess Ferritin Percutaneously, Synergizes Pharmacotherapy, Enhances Antiviral Immunity and Helps Better HCC Prevention and Treatment: A Novel Evidence-Based Combination with Prophetic Medicine Remedies.

Viral hepatitis progresses to liver cirrhosis and HCC. Several challenges are facing Sovaldi treatment to viral C hepatitis, eg, viral resistance, difficulty to treat all genotypes, and inability to access treatments in low-income countries. Also, current treatments to Hepatitis B are still challenging. Ideal treatments to viral hepatitis should decrease the viral load, enhance antiviral immunity and repair the viruses-induced tissue damage. That is still beyond reach. High serum ferritin in viral hepatitis correlates with chronicity, increased necro-inflammation, hepatotoxicity, progression to cirrhosis, progression to HCC, unresponsiveness to treatments and viremia. Previously, Al-hijamah (wet cupping therapy of prophetic medicine) significantly cleared thalassemic children of causative pathological substances (CPS), eg, excess ferritin, free radicals and serum lipids. Moreover, Al-hijamah significantly increased the antioxidant power and potentiated the natural antiviral immunity, eg, increasing CD4 count, CD8 count and CD4/CD8 ratio. Prophet Muhammad peace be upon him said: "If there is a benenvolence (benefit) in any of your medicines, benefit will be in shrtat mihjam (Al-hijamah), honey drink, and a stinge of fire compatible with disease and I do not like to cauterize". Likewise, the author suggests Al-hijamah as a novel promising adjuvant treatment for viral hepatitis (B and C) for percutaneous excretion of CPS as hepatitis viral particles, excess ferritin, inflammatory mediators, free radicals, and antigen-antibody complexes. Published reports proved that Al-hijamah exerted tissue-protective effects, and cleared blood through the fenestrated skin capillaries in a pressure-dependent and size-dependent manner (a kidney-like manner). That collectively may decrease the viral load for better HCC prevention and supports the evidence-based Taibah theory (Taibah mechanism). Same therapeutic benefits apply to other viral illnesses as AIDS. Even after HCC development, Al-hijamah is quite mandatory for excretion and clearance of CPS that favor malignancy, eg, lactate (Warburg effect), growth factors, metalloproteinases, and others. Al-hijamah-induced immune potentiation benefits HCC patients. Combining Al-hijamah with other natural antioxidant remedies of prophetic medicine, eg, nigella sativa, costus, natural honey, Zamzam water and others will maximize the therapeutic benefits. In conclusion, Al-hijamah and other prophetic medicine remedies are recommended adjuvants to current pharmacological treatments to viral hepatitis and HCC.