Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.

An insight into the diagnosis and pathogenesis of hepatitis C virus infection

This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.

Multiplex qPCR for serodetection and serotyping of hepatitis viruses: A brief review

The present review describes the current status of multiplex quantitative real time polymerase chain reaction(q PCR) assays developed and used globally for detection and subtyping of hepatitis viruses in body fluids. Several studies have reported the use of multiplex q PCR for the detection of hepatitis viruses, including hepatitis A virus(HAV), hepatitis B virus(HBV), hepatitis C virus(HCV), hepatitis D virus(HDV), and hepatitis E virus(HEV). In addition, multiplex q PCR has also been developed for genotyping HBV, HCV, and HEV subtypes. Although a single step multiplex q PCR assay for all six hepatitis viruses, i.e., A to G viruses, is not yet reported, it may be available in the near future as the technologies continue to advance. All studies use a conserved region of the viral genome as the basis of amplification and hydrolysis probes as the preferred chemistries for improved detection. Based on a standard plot prepared using varying concentrations of template and the observed threshold cycle value, it is possible to determine the linear dynamic range and to calculate an exact copy number of virus in the specimen. Advantages of multiplex q PCR assay over singleplex or other molecular techniques in samples from patients with co-infection include fast results, low cost, and a single step investigation process.

Molecular basis of hepatocellular carcinoma induced by hepatitis C virus infection

Present study outlines a comprehensive view of published information about the underlying mechanisms operational for progression of chronic hepatitis C virus(HCV) infection to development of hepatocellular carcinoma(HCC). These reports are based on the results of animal experiments and human based studies. Although, the exact delineated mechanism is not yet established, there are evidences available to emphasize the involvement of HCV induced chronic inflammation, oxidative stress, insulin resistance, endoplasmic reticulum stress, hepato steatosis and liver fibrosis in the progression of HCV chronic disease to HCC. Persistent infection with replicating HCV not only initiates several liver alterations but also creates an environment for development of liver cancer. Various studies have reported that HCV acts both directly as well as indirectly in promoting this process. Whereas HCV related proteins, like HCV core, E1, E2, NS3 and NS5A, modulate signal pathways dysregulating cell cycle and cell metabolism, the chronic infection produces similar changes in an indirect way. HCV is an RNA virus and does not integrate with host genome and therefore, HCV induced hepatocarcinogenesis pursues a totally different mechanism causing imbalance between suppressors and proto-oncogenes and genomic integrity. However, the exact mechanism of HCC inducement still needs a full understanding of various steps involved in this process.

Torque teno virus:Its prevalence and isotypes in North India

AIM: To investigate the prevalence and genotype dis-tribution of Torque teno virus (TTV) in patients with different liver diseases and chronic renal failure treated at a referral hospital in North India. METHODS: Whereas prevalence of TTV was based on amplification of conserved region of ORF2 of TTV genome,the genotyping of TTV was carried out using restriction fragment length polymorphism (RFLP) procedure on the N22 region of ORF1. RESULTS: TTV-DNA was detected in 137 of 513 (26.7%) patients with liver diseases and 38 of 65 (58.5%) patients with chronic renal failure. TTV was also detected in 27% of healthy controls. The sequence analysis of the PCR product from 10 randomly selected cases failed to show a significant sequence divergence when compared with that of the TRM1 isolate of TTV genotype 1. The results of genotyping in 55 randomly selected patients showed the presence of genotype 1 (G1) in 53 (96.4%) and genotype 2 (G2) in 2 cases (3.6%),respectively. Other genotypes were not identified in this patient subgroup,suggesting that G1 is predominant in this area. The results of genotyping by RFLP were also supported by phylogenetic tree analysis,where G1 was found to be the major genotype. CONCLUSION: These results indicate that TTV is moderately present in Indian patients,with G1 to be the major genotype in North India. The pathogenicity and etiological role of TTV in different diseases is still a question mark and warrant further studies.

Transfusion transmitted virus: A review on its molecular characteristics and role in medicine

现在的评论给输送的更新的概述播送病毒(TTV ) ，一个新奇代理人在与它的分子的特征的关系，流行病学的特征，传播的模式，组织向性，致病，在各种各样的疾病的角色和它从身体的根除。TTV，一个 DNA 病毒，一个单身者被搁浅，非包，有包括 3852 的一个小、 covalently 关上的圆形的染色体的长 DNA 病毒基于的 3.8 kb。它是尝试性地指明的 Circinoviridae 病毒。TTV 染色体顺序是异构的并且揭示六不同遗传型和几种子类型的存在。TTV 被报导了不仅经由非肠道的线路，而且经由交替的线路播送。这个病毒也在不同非人类的首领被检测了。目前， TTV 被聚合酶链反应(PCR ) 没有另外的可得到的诊断试金检测。它全球性显示出它的存在并且在健康的人的高百分比人口以及在各种各样的疾病组被检测。开始，它应当与肝疾病有强壮的协会；然而，几乎没有小证据在引起肝疾病显示出它的肝向性和贡献。它在牙齿过敏细胞溶解病人显示出高流行，向它在肾的疾病的意义指。另外， TTV 与几传染、非传染的疾病被联系。不过，它的准确致病是还没清楚的， TTV 病毒可能住并且在骨髓房间和外部血乘单音的原子房间(PBMC ) 。最近，被尝试了根除有干扰素治疗的这个病毒。更多的信息仍然被需要解脱与 TTV 有关的各种各样的谜。

Transfusion-transmitted virus in association with hepatitis A-E viral infections in various forms of liver diseases in India

瞄准：描述播送输送的病毒(TTV ) 的流行与在在诺思 India.METHODS 的肝疾病的不同形式的肝炎 A-E 病毒的感染联合的感染：从一个总数的血清 137 个病人数，包括 37 有尖锐病毒的肝炎( AVH )的病人，有长期的病毒的肝炎( CVH )的 37 个病人，有肝硬变的 31 个病人和有暴发性的肝的失败( FHF )的 32 个病人，为 TTV-DNA 和肝炎 A-E 病毒的标记两个都被分析。肝炎 B (HBV ) 的存在，丙肝病毒(HCV ) 和肝炎 E 病毒(HEV ) 感染在不同的组在不同比例被检测。而且， TTV-DNA 同时在 100 健康供血者 also.RESULTS 被测试：任何一个都没病人有肝炎 A 病毒(HAV ) 和肝炎 D 病毒(HDV ) 感染。TTV-DNA 的全面流行与 FHF 与 AVH，有 CVH 的 18.9% 盒子，有肝硬化的 48.4% 盒子和 9.4% 盒子在 27.1% 情况中被检测。同时在 100 健康供血者测试的 TTV-DNA 显示出 27% 确实。在与另外的肝炎建立在 TTV 感染之间的一种关系上病毒的感染， TTV 在这些疾病组与 HBV， HCV 和 HEV 表明了合作感染。有中高音的 TTV 的关联在重量的单位铺平一没在感染 TTV 的病人表明高中高音水平，建议那 TTV 不引起严重的肝 damage.CONCLUSION：TTV 感染在印度在病人和健康个人两个都是流行的。然而，它没与另外的肝炎有任何重要关联病毒的感染，它也不与肝疾病在病人生产严重的肝损坏的一条证据。

Expression of TTV-ORF2 Protein for Detection of Anti-TTV IgG Antibodies in Human Sera

The present study describes the cloning and expression of ORF-2 region of TTV genome and the use of expressed peptide in developing immunoassay for detection of anti-TTV antibodies in serum. Presence of TTV-DNA in serum was detected by PCR amplifying N-22 region of ORF-1 of TTV genome. This was followed by genotyping of TTV by RFLP using N-22 amplicon. Using genotype-1 positive serum as the source of TTV, the ORF-2 region was amplified by PCR and subsequently cloned and expressed in pET-19b vector. The expressed protein, identified as 20 kDa protein on SDS-PAGE gel, was purified by affinity chromatography and then used as antigen to develop western blot assay for detection of anti-TTV antibodies in serum. Analysis of sera for anti-TTV antibodies and their comparison with presence of TTV-DNA, produced encouraging results. There was a good relation between presence of anti-TTV and TTV-DNA in these sera samples. Anti-TTV antibodies could be detected in all TTV-DNA positive sera irrespective of the presence of TTV-genotype. This investigation demonstrates that ORF-2 peptide may be used in developing immunoassay for identification of TTV infection.