Hepatotropic Viral Infections Research Articles

Tissue Determinants of Antiviral Immunity in the Liver.

The liver is an organ bearing important metabolic and immune functions. Hepatocytes are the main metabolically active cells of the liver and are the target of infection by hepatotropic viruses. Virus-specific CD8 T cells are essential for the control of hepatocyte infection with hepatotropic viruses but may be subject to local regulation of their effector function. Here, we review our current knowledge of the tissue determinants of antiviral immunity in the liver. Liver Sinusoidal Endothelial Cells (LSECs) not only allow through their fenestrations the access of circulating virus-specific CD8 T cells to engage in direct contact with infected hepatocytes without the need for extravasation but also cross-present viral antigens released from infected hepatocytes to these CD8 T cells. Two important features of LSECs and hepatocytes contribute to antiviral immune surveillance and liver failure. First, CD8 T cell immunity targeting LSECs leads to widespread endothelial cell death and results in sinusoidal microcirculation failure, causing fulminant viral hepatitis, whereas immune-mediated loss of hepatocytes is rapidly compensated by the regenerative capacity of the liver. Second, virus-infected hepatocytes support clearance of infection by responding to TNF, which is released from virus-specific CD8 T cells, with the selective induction of apoptosis. This increased sensitivity for TNF-induced death is caused by reduced mitochondrial resilience in virus-infected hepatocytes and may assist antiviral immunity in preferential targeting of virus-infected hepatocytes. Thus, hepatocytes and LSECs actively contribute to the outcome of antiviral CD8 T cell immunity in the liver. The knowledge of the mechanisms determining CD8 T cell control of hepatotropic viral infection will help to improve strategies to increase antiviral immune surveillance.

Liver mechanosignaling as a natural anti-hepatitis B virus mechanism

The mechanisms underlying the natural control of hepatitis B virus (HBV) infection have long been an intriguing question. Given the wide physiological range of liver stiffness and the growing attention to the role of mechanical microenvironment in homeostasis and diseases, we investigated how physical matrix cues impact HBV replication. High matrix stiffness significantly inhibited HBV replication and activated YAP in primary hepatocyte culture system, a key molecule in mechanosignaling. YAP activation notably suppressed HBV transcription and antigen expression. Several YAP-induced genes exhibited strong anti-HBV effects. Single-cell analysis of liver tissue from male individuals with active HBV replication revealed a strong significant negative correlation between YAP signature activation and HBV transcript levels. Intraperitoneal administration of YAP small molecule agonist potently controls HBV in male mouse models. These findings unveil a mechanism that involves the mechanical environment of hepatocytes and YAP to clear hepatotropic viral infection in the liver, providing new perspectives for HBV cure studies and antiviral development.

A clinical case of diagnosis of autoimmune hepatitis at the stage of liver cirrhosis

The aim of the work is to analyze a clinical case of autoimmune hepatitis (АІН) diagnosis at the stage of cirrhosis in a 40-year-old female patient and to remind practicing doctors about the serious consequences of this disease. Materials and methods. A clinical case of AIH diagnosed according to the criteria of the International Autoimmune Hepatitis Group (2008) at the stage of cirrhosis in a 40-year-old female patient was analyzed. A puncture liver biopsy with a morphological study of the hepatobioptate was also performed to verify the diagnosis. Results. The analysis of the clinical case of AIH in a 40-year-old female patient revealed a delayed diagnosis of AIH at the cirrhosis stage. This was due to the absence of any clinical symptoms of the disease for a long period of time, and the lack of attention of practicing doctors in investigating the reasons for the long-term increase in transaminase activity. The trigger factor for the clinical manifestations of cirrhosis, which developed due to the long-term course of AIH, was emotional stress resulting from leaving the combat zone. The application of the International Autoimmune Hepatitis Group criteria in clinical practice was demonstrated, specifically the combination of elevated antinuclear antibodies and total IgG, characteristic histological changes in the liver, and exclusion of hepatotropic viral infections, which allowed for a reliable diagnosis of AIH. Medical treatment resulted in certain positive changes in clinical and laboratory indicators. However, according to the transplant doctor’s opinion, at this stage of the AIH course, the patient required a liver transplant and therefore was added to the waiting list. Conclusions. This clinical case highlights the late diagnosis of AIH at the cirrhosis stage in a 40-year-old female patient due to the absence of clinical manifestations over several years and the lack of vigilance among doctors, possibly primary care physicians or specialists, to investigate the persistent increase in transaminase activity. The application of the International Autoimmune Hepatitis Group criteria helped confirm the diagnosis of AIH.

Expression and functions of transient receptor potential channels in liver diseases.

Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults, to inflammation, subsequent fibrosis and hepatoma. We also explore expression levels of TRPs in liver tissues of ALD, NAFLD and HCC patients from Gene Expression Omnibus (GEO) or The Cancer Genome Atlas (TCGA) database and survival analysis estimated by Kaplan-Meier Plotter. At last, we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver diseases. The aim is to provide a better understanding of the implications of TRP channels in liver diseases, contributing to the discovery of novel therapeutic targets and efficient drugs.

Non-hepatotropic viral hepatitis and its causative pathogens: The ongoing need for monitoring in children with severe acute hepatitis of unknown etiology.

Non-hepatotropic viral hepatitis and its causative pathogens: The ongoing need for monitoring in children with severe acute hepatitis of unknown etiology.

Computational efforts to identify natural occurring compounds from phyllanthus niruri that target hepatitis B viral infections: DFT, docking and dynamics simulation study

Hepatitis B virus (HBV) is an enveloped hepatotropic virus responsible for nucleic acids replication. It causes chronic infection. Depending on the strain, mutations in the core protein of chronic hepatitis B virus (HBV) infections occur. Medicinal plants, the backbone of traditional medicine, are a potential source of lead molecules in drug discovery due to extensive pharmacological studies. In this study, we have screened twenty-nine phytochemicals. The ADME and drug-likeness of these phytochemicals were investigated. After screening, the binding affinity of ten phytochemicals was studied through molecular docking. Simulation studies were carried out for 100 ns to analyze the properties of RMSD, Rg, RMSF, average hydrogen bond number and SASA of hepatitis B virus capsid protein. As per the docking results phyllanthosterol, may be used as a potential inhibitors against HBV. The simulations findings revealed that, in case of mutant protein, the flexibility nature decreases as compared to wildtype protein. Our results may provide useful information for drug design and to lead the identification of novel inhibitor for hepatotropic viral infection.

Orthohepevirus C infection as an emerging cause of acute hepatitis in Spain: First report in Europe

Hepatitis E virus (HEV) was considered the only member of the Hepeviridae family with zoonotic potential. Nevertheless, this consideration has been reassessed owing to several reported cases of acute and chronic hepatitis linked to the Orthohepevirus C genus. Because the circulation of Orthohepevirus C in rodents has been described worldwide, the risk of zoonotic transmission is plausibly global. Orthohepevirus C RNA was retrospectively evaluated in 2 cohorts of patients in Spain. The first cohort included patients with acute hepatitis without etiological diagnosis after screening for hepatotropic virus infection. The second cohort included patients diagnosed with acute HEV infection, defined as positivity for anti-HEV-IgM antibodies and/or detectable HEV RNA in serum. Cohort 1 comprised 169 patients (64.4% male, median age 43 years) and cohort 2 comprised 98 individuals (68.3% male, median age 45 years). Of the individuals included in Cohort 1, two (1.18%; 95% CI 0.2-3.8) had detectable Orthohepevirus C RNA in serum. In Cohort 2, of the 98 included patients, 58 showed detectable HEV RNA, while 40 only showed positivity for IgM antibodies. Among those bearing only IgM antibodies, Orthohepevirus C RNA was detected in 1 (2.5%; 95% CI 0.06-13.1) individual. All strains were consistent with genotype C1. The infection resulted in mild self-limiting acute hepatitis in 2 patients. Infection caused severe acute hepatitis in the remaining patient who died as a result of liver and renal failure. We described 3 cases of Orthohepevirus C in patients with acute hepatitis, resulting in the first description of this infection in Europe. The prevalence obtained in our study suggests that Orthohepevirus C could be an emerging disease in Europe. We describe the first cases of acute hepatitis related to rat hepatitis E virus in Europe. The prevalence found in our study suggest that rat hepatitis E virus could be considered an emerging disease in Europe.

A review of alcohol-pathogen interactions: New insights into combined disease pathomechanisms.

Progression of chronic infections to end-stage diseases and poor treatment results are frequently associated with alcohol abuse. Alcohol metabolism suppresses innate and adaptive immunity leading to increased viral load and its spread. In case of hepatotropic infections, viruses accelerate alcohol-induced hepatitis and liver fibrosis, thereby promoting end-stage outcomes, including cirrhosis and hepatocellular carcinoma (HCC). In this review, we concentrate on several unexplored aspects of these phenomena, which illustrate the combined effects of viral/bacterial infections and alcohol in disease development. We review alcohol-induced alterations implicated in immunometabolism as a central mechanism impacting metabolic homeostasis and viral pathogenesis in Simian immunodeficiency virus/human immunodeficiency virus infection. Furthermore, in hepatocytes, both HIV infection and alcohol activate oxidative stress to cause lysosomal dysfunction and leakage and apoptotic cell death, thereby increasing hepatotoxicity. In addition, we discuss the mechanisms of hepatocellular carcinoma and tumor signaling in hepatitis C virus infection. Finally, we analyze studies that review and describe the immune derangements in hepatotropic viral infections focusing on the development of novel targets and strategies to restore effective immunocompetency in alcohol-associated liver disease. In conclusion, alcohol exacerbates the pathogenesis of viral infections, contributing to a chronic course and poor outcomes, but the mechanisms behind these events are virus specific and depend on virus-alcohol interactions, which differ among the various infections.

T cells protect against hepatitis A virus infection and limit infection-induced liver injury

Hepatitis A virus (HAV) is a common cause of enterically transmitted viral hepatitis. In non-immune individuals, infection results in typically transient but occasionally fulminant and fatal inflammatory liver injury. Virus-specific T cell frequencies peak when liver damage is at its zenith, leading to the prevalent notion that T cells exacerbate liver disease, as suspected for other hepatotropic virus infections. However, the overall contribution of T cells to the control of HAV and the pathogenesis of hepatitis A is unclear and has been impeded by a historic lack of small animal models. Ifnar1-/- mice are highly permissive for HAV and develop pathogenesis that recapitulates many features of hepatitis A. Using this model, we identified HAV-specific CD8+ and CD4+ T cells by epitope mapping, and then used tetramers andfunctional assays to quantify T cells in the liver at multiple times after infection. We assessed the relationships between HAV-specific T cell frequency, viral RNA amounts, and liver pathogenesis. A large population of virus-specific T cells accumulated within the livers of Ifnar1-/- mice during the first 1-2 weeks of infection and persisted over time. HAV replication was enhanced and liver disease exacerbated when mice were depleted of T cells. Conversely, immunization with a peptide vaccine increased virus-specific CD8+ T cell frequencies in the liver, reduced viral RNA abundance, and lessened liver injury. These data show that T cells protect against HAV-mediated liver injury and can be targeted to improve liver health. Hepatitis A virus is a leading cause of acute viral hepatitis worldwide. T cells were thought to contribute to liver injury during acute infection. We now show that virus-specific T cells protect against infection and limit liver injury.

Immune disorders and rheumatologic manifestations of viral hepatitis.

Infection with hepatotropic viruses is not limited to the liver and can lead to the development of various immunological disorders (the formation of cryoglobulins, rheumatoid factor, antinuclear antibodies, autoantibodies specific for autoimmune hepatitis and primary biliary cholangitis, and others), which can manifest as glomerulonephritis, arthritis, uveitis, vasculitis (cryoglobulinemic vasculitis, polyarteritis nodosa, Henoch-Schonlein purpura, isolated cutaneous necrotizing vasculitis), and other rheumatologic disorders, and be a trigger for the subsequent development of autoimmune hepatitis and primary biliary cholangitis. A further study of the association between autoimmune liver diseases and hepatotropic virus infection would be useful to assess the results of treatment of these associated diseases with antiviral drugs. The relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and C. Only isolated cases of these associations are described for hepatitis A. These links are least studied, and are often controversial for hepatitis E, possibly due to their relatively rare diagnoses. Patients with uveitis, glomerulonephritis, arthritis, vasculitis, autoimmune liver diseases should be tested for biomarkers of viral hepatitis, and if present, these patients should be treated with antiviral drugs.

Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation

Chronic hepatotropic viral infections are characterized by exhausted CD8+ T cells in the presence of cognate antigen in the liver. The impairment of T cell response limits the control of chronic hepatotropic viruses. Immune-modulatory strategies are attractive options to re-invigorate exhausted T cells. However, in hepatotropic viral infections, the knowledge about immune-modulatory effects on the in-situ regulation of exhausted intrahepatic CD8+ T cells is limited. In this study, we elucidated the functional heterogeneity in the pool of exhausted CD8+ T cells in the liver of mice expressing the model antigen Ova in a fraction of hepatocytes. We found a subpopulation of intrahepatic CXCR5+ Ova-specific CD8+ T cells, which are profoundly cytotoxic, exhibiting efficient metabolic functions as well as improved memory recall and self-maintenance. The intrahepatic Ova-specific CXCR5+ CD8+ T cells are possibly tissue resident cells, which may rely largely on OXPHOS and glycolysis to fuel their cellular processes. Importantly, host conditioning with CpG oligonucleotide reinvigorates and promotes exhausted T cell expansion, facilitating complete antigen eradication. The CpG oligonucleotide-mediated reinvigoration may support resident memory T cell formation and the maintenance of CXCR5+ Ova-specific CD8+ T cells in the liver. These findings suggest that CpG oligodinucleotide may preferentially target CXCR5+ CD8+ T cells for expansion to facilitate the revival of exhausted T cells. Thus, therapeutic strategies aiming to expand CXCR5+ CD8+ T cells might provide a novel approach against chronic liver infection.

A Study on Seroprevalence of Hepatotropic Viruses in Neonatal Cholestasis Patients at a Tertiary Care Hospital of Central India

Introduction: Neonatal Cholestasis (NC) is defined as conjugated hyperbilirubinaemia in infancy, Diverse aetiologies and several disorders are responsible for this hepatobiliary dysfunction. Hepatotropic viral infection may have an important role in the pathogenesis of NC and related clinical outcomes. Aim: This study was aimed to estimate the seroprevalence of the hepatotropic viruses and their possible role in neonates presenting with cholestatic jaundice. Materials and Methods: This retrospective study included 51 infants who presented with cholestatic jaundice. Serum samples were collected and screened for the hepatotropic viruses. The presence of serological markers to Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Hepatitis C (HCV), Hepatitis E (HEV), Herpes Simplex Virus (HSV) and Rubella were tested using enzyme-linked immunosorbent assays. Hepatitis B Virus (HBV) serostatus was determined by using rapid card tests. Results: Of the 51 cases, 4 (7.6%) patients presented with biliary atresia. Seroprevalence of CMV (23.5%) was found to be more predominant followed by EBV (13.7%), HCV (5.8%), HEV (5.8%), HSV (1.9%) and Rubella (1.9%). Co-infections were found in 7 (13.7%) cases and CMV-EBV co-infection being the most common. Conclusion: The presence of specific serological markers to hepatotropic viruses in the NC cases strongly suggests their aetiological role in this disorder. To the best of the knowledge, this is the first report documenting the seroprevalence of hepatotropic viruses in NC patients from Central India.

Diagnostic Performance of ElastPQ Point Shear Wave Elastography for Hepatic Fibrosis in Hepatitis B and Hepatitis C Patients

Introduction: Chronic viral hepatitis is a condition of hepatotropic viral infection associated with chronic inflammation, hepatocyte injury and progressive fibrosis. Non-invasive assessment of liver fibrosis in chronic hepatitis B and C patients has been increasing and used instead of liver biopsy. Aim: To assess the diagnostic performance of ElastPQ Point Shear Wave Elastography (ElastPQ PSWE) with liver biopsy as the gold standard and comparing these results with other serum fibrosis markers namely Aspartate to Platelet Ratio Index (APRI), Fibrosis-4 Score (FIB4). Materials and Methods: A cross-sectional study was carried out in which 73 patients underwent ElastPQ PSWE and Histopathological Examination (HPE) with METAVIR Scoring system staging. Serum fibrosis indices including APRI and FIB4 values were calculated. The diagnostic performance of ElastPQ PSWE, APRI and FIB4 was evaluated using Area Under Receiver Operating Characteristic (AUROCAUROC) curve analysis, correlations of ElastPQ PSWE, APRI and FIB4 ratio index with histopathological findings (as the reference standard) were determined using Spearman’s correlation coefficient. Results: Study included 73 patients with chronic hepatitis B and hepatitis C, of which 8 (10.96%) were no/early fibrosis (F0- F1); 20 (27.40%) were significant fibrosis (F2); 22 (30.13%) were severe fibrosis (F3), and 23 (31.51%) were cirrhosis (F4). There was a significant positive correlation between different stages of liver fibrosis by liver biopsy and liver stiffness detected by ElastPQ PSWE (r=0.912, p <0.0001). ElastPQ PSWE exhibited higher diagnostic accuracy than the APRI and FIB4 for the diagnosis of F0-F1 AUROC 0.980, 0.730, 0.710, respectively; F2 AUROC 0.840, 0.662, 0.669 respectively; F3 0.564, 0.528, 0.500 AUROC, respectively; and F4 0.967, 0.783, 0.751 AUROC, respectively. Using AUROC curve, the optimal cut-off of ElastPQ PSWE for stages F0-F1 is ≤3.9 kilopascals (kPa); F2 is ≤7.2kPa; F3 is ≥7.2kPa and F4 is≥10kPa. Conclusion: ElastPQ PSWE is a promising non-invasive method used for the evaluation of liver fibrosis, with high diagnostic performance, high Negative Predictive Value (NPV) and good specificity in evaluation of hepatitis B and hepatitis C patients.

Noncanonical NF-κB Signaling Pathway in Liver Diseases.

The noncanonical NF-κB signaling pathway is an important branch of NF-κB signaling. It is involved in regulating multiple important biological processes, including inflammation and host immune response. A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase (NIK), which activates the downstream kinase IKKα to process p100 to p52, thereby forming the RelB/p52 heterodimer to initiate the expression of target genes. Currently, many specific inhibitors and monoclonal antibodies targeting or triggering this pathway are being developed and tested for various diseases, including cancers, autoimmune diseases, and virus infection. Given that aberrant activation of the noncanonical NF-κB pathway is frequently observed in various liver diseases, targeting this pathway may be a promising therapeutic strategy to alleviate liver inflammation. Moreover, activation of this pathway may contribute to the antiviral immune response and promote the clearance of persistent hepatotropic virus infection. Here, we review the role of the noncanonical NF-κB pathway in the occurrence and development of different liver diseases, and discuss the potency and application of modulating the noncanonical NF-κB pathway for treatment of these liver diseases.

Prevalence of hepatitis C among haemodialysis patients in a tertiary care hospital in south India.

Background and Objectives:Hepatitis C is the most common hepatotropic viral infection that affects patients on maintenance hemodialysis. Most of the laboratories in India depend on HCV antibody detection by ELISA. PCR based studies on detection of HCV RNA among haemodialysis patients are very scanty in India. The current study was undertaken to find the prevalence of HCV among haemodialysis patients by ELISA and PCR.Materials and Methods:This prospective study was conducted from January to May 2018 in a total of 100 samples. Patients more than 18 years of age, who had undergone at least 15 sessions of dialysis were enrolled in the study. All samples were screened for HCV antibody by ELISA and HCV RNA by PCR. Data regarding age and gender of the patients, history of blood transfusion, duration of hemodialysis, total bilirubin levels were collected from medical records.Results:Among the 100 samples, only one was positive for HCV antibody by ELISA. Eight samples were positive for HCV RNA by PCR. In this study 62.5% of the HCV positives had a previous history of blood transfusion. Duration of dialysis was more among the HCV positive group but there was no statistical significance.Conclusion:This is the first study from the southern state of Kerala in India showing the prevalence of HCV among hemodialysis patients by PCR. Our study showed an overall HCV prevalence of 8% by PCR. All the PCR positive samples were negative by 3rd generation ELISA which is an alarming finding and further justifies the need for PCR for detecting HCV.

Polymorphisms rs231775 and rs5742909 CTLA-4 gene and their associative relations with chronic HBV infection in children

The study of the genetic polymorphism rs231775 (+ 49A > G) and rs5742909 (+ 3 18С > Т) of the CTLA-4 gene in 100 children with chronic HBV infection revealed associations only with the carriage of the + 49A/ G polymorphic variant. Moreover, the carriage of the G allele in the homozygous mutant + 49GG position suggested the development of pronounced forms with a progressive course and a high probability of the outcome of the disease in cirrhosis. The established gender differences — the boys' high expression of the minor G-allele of the CTLA-4 gene, especially in the homozygous mutant variation + 49GG — proves the phenomenon of a high incidence of hepatotropic viral infection in boys. Therefore, the carriage of mutant variation + 49GG can be considered among the HOST factors for predicting adverse outcomes of chronic HBV infection in children.

Second hits exacerbate alcohol-related organ damage: an update.

Chronic and excessive alcohol abuse cause direct and indirect detrimental effects on a wide range of body organs and systems and accounts for ~4% of deaths worldwide. Many factors influence the harmful effects of alcohol. This concise review presents newer insights into the role of select second hits in influencing the progression of alcohol-induced organ damage by synergistically acting to generate a more dramatic downstream biological defect. This review specifically addresses on how a lifestyle factor of high fat intake exacerbates alcoholic liver injury and its progression. This review also provides the mechanistic insights into how increasing matrix stiffness during liver injury promotes alcohol-induced fibrogenesis. It also discusses how hepatotropic viral (HCV, HBV) infections as well as HIV (which is traditionally not known to be hepatotropic), are potentiated by alcohol exposure to promote hepatotoxicity and fibrosis progression. Finally, this review highlights the impact of reactive aldehydes generated during alcohol and cigarette smoke coexposure impair innate antimicrobial defense and increased susceptibility to infections. This review was inspired by the symposium held at the 17th Congress of the European Society for Biomedical research on Alcoholism in Lille, France entitled 'Second hits in alcohol-related organ damage'.

Priming of Antiviral CD8 T Cells without Effector Function by a Persistently Replicating Hepatitis C-Like Virus.

Immune-competent animal models for the hepatitis C virus (HCV) are nonexistent, impeding studies of host-virus interactions and vaccine development. Experimental infection of laboratory rats with a rodent hepacivirus isolated from Rattus norvegicus (RHV) is a promising surrogate model due to its recapitulation of HCV-like chronicity. However, several aspects of rat RHV infection remain unclear, for instance, how RHV evades host adaptive immunity to establish persistent infection. Here, we analyzed the induction, differentiation, and functionality of RHV-specific CD8 T cell responses that are essential for protection against viral persistence. Virus-specific CD8 T cells targeting dominant and subdominant major histocompatibility complex class I epitopes proliferated considerably in liver after RHV infection. These populations endured long term yet never acquired antiviral effector functions or selected for viral escape mutations. This was accompanied by the persistent upregulation of programmed cell death-1 and absent memory cell formation, consistent with a dysfunctional phenotype. Remarkably, transient suppression of RHV viremia with a direct-acting antiviral led to the priming of CD8 T cells with partial effector function, driving the selection of a viral escape variant. These data demonstrate an intrinsic abnormality within CD8 T cells primed by rat RHV infection, an effect that is governed at least partially by the magnitude of early virus replication. Thus, this model could be useful in investigating mechanisms of CD8 T cell subversion, leading to the persistence of hepatotropic pathogens such as HCV.IMPORTANCE Development of vaccines against hepatitis C virus (HCV), a major cause of cirrhosis and cancer, has been stymied by a lack of animal models. The recent discovery of an HCV-like rodent hepacivirus (RHV) enabled the development of such a model in rats. This platform recapitulates HCV hepatotropism and viral chronicity necessary for vaccine testing. Currently, there are few descriptions of RHV-specific responses and why they fail to prevent persistent infection in this model. Here, we show that RHV-specific CD8 T cells, while induced early at high magnitude, do not develop into functional effectors capable of controlling virus. This defect was partially alleviated by short-term treatment with an HCV antiviral. Thus, like HCV, RHV triggers dysfunction of virus-specific CD8 T cells that are vital for infection resolution. Additional study of this evasion strategy and how to mitigate it could enhance our understanding of hepatotropic viral infections and lead to improved vaccines and therapeutics.

Role of Gamma Glutamyltransferase and Alkaline Phosphatase Assay in Enzymatic Panel for Hepatobiliary Function in Patients Attending Kibungo Hospital, Rwanda

Background: Liver complications show specific processes like hepatoxicity associated with drugs, primary neoplasm, or hepatotropic virus infections. Different markers based on laboratory testing help to diagnose and monitor liver related conditions. Mostly used tests are classed in a set known as hepatic panel or liver profile mainly consisting of body enzymes.Objective: The objective of the present study was to ascertain the role of gamma glutamyltransferase (GGT) and alkaline phosphatase (ALP) assay in enzymatic panel for hepatobiliary function assessment among patients attending Kibungo hospital.Methods: Two hundred twenty-five clients were included in the study. Demographic data were collected from December 2016 to March 2017. Blood sera were also collected and tested for serum GGT and ALP levels. Statistical package for social sciences (SPSS) was used in data analysis.Results: Seventy-four point seven per cent of clients had normal GGT whereas 63.1% had normal ALP. The 0.9% of clients comprised low levels of ALP. The means were 53 and 153 U/L for GGT and ALP, respectively. Fifty per cent of alcohol consumers’ population had elevated GGT and ALP. An increase of 69.2 and 61.5% for GGT and ALP, respectively was observed in smokers’ population. The subpopulation of hepatitis C virus (HCV) was the most with elevated GGT and ALP levels. In HIV population, serum GGT and ALP were raised at 31.1 and 37.8%, respectively. In fact, hepatitis B virus (HBV), HCV, and HIV patients are clinically considered as immuno-compromised people. Alcohol consumption and smoking were also found to increase GGT and ALP concentrations. In addition, GGT and ALP levels were simultaneously elevated in 19.6% of the clients, indicating the frequency of cholestatic liver disease.Conclusion: Elevated GGT and ALP revealed the occurrence of cholestasis among study participants due to factors that elevate serum GGT and ALP levels as a result of dysfunctional liver conditions. In hospital laboratories, GGT and ALP should always be included in the panel of tests for screening and bio-monitoring liver related conditions in Rwanda.

From the Editor’s Desk…

From the Editor’s Desk…