Special Issue:
Challenges and Opportunities in Hepatitis
Gisele B L Menezes
Universidade Federal da Bahia, Brasil; Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Brasil
Delvone Almeida
Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Brasil
Sidelcina Rugieri Pacheco
Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Brasil
Maurício Souza Campos
Universidade Federal da Bahia, Brasil
Michele Gomes Gouvea
Laboratório de Gastroenterologia e Hepatologia Tropical, Instituto de Medicina Tropical e Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
Joao Renato Rebello Pinho
Laboratório de Gastroenterologia e Hepatologia Tropical, Instituto de Medicina Tropical e Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
Roberto Meyer Nascimento
Laboratório de Imunologia do Instituto de Ciências e Saúde- Universidade Federal da Bahia
Songeli Menezes Freire
Laboratório de Imunologia do Instituto de Ciências e Saúde- Universidade Federal da Bahia
Robert Schaer
Laboratório de Imunologia do Instituto de Ciências e Saúde- Universidade Federal da Bahia
Maria Isabel Schinoni
Universidade Federal da Bahia, Brasil; Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Brasil
Abstract
Introduction: Hepatitis E virus infection can lead to severe liver disease and unregulated hepatitis in patients with a history of previous chronic liver disease of different etiologies.
Objective: To determine the seroprevalence of hepatitis E in untreated carriers of hepatitis C virus, hepatitis B virus, autoimmune hepatitis and in patients with drug-induced liver disease.
Materials and Methods: This is a cross-sectional study with a total sample of 301 outpatient hepatology volunteers. The detection of anti-HEV IgM and IgG antibodies was determined using the ELISA (RecomWell anti-HEV IgG and IgM, Mikrogen®, Germany), One-step real-time PCR was used for the detection of HEV-RNA (Taqman, Life Technologies TM, Foster City, CA, USA).
Results: The overall prevalence of anti-HEV IgG and IgM in the population studied was 12.95% and 2.3%, respectively. The prevalence by group were: anti-HEV IgG: hepatitis C virus with 13.2%, hepatitis B virus with 13%, autoimmune hepatitis with 8.1 and drug-induced liver disease with 21.1. Patients with HCV chronic hepatitis and positive HCV IgG serology showed an increase in transaminase levels in 66.7% (10/15) of the cases, while in the seronegative patients this increase was present in 42.4% (42/99) of the cases (p<0.05).
Conclusions: A high seroprevalence of HEV was observed. Among the patients with serology concomitantly positive for anti HEV IgG and IgM, 57.1% (4/7) had higher levels of TGO and TGP, suggesting acute HEV infection. A relationship between hepatitis C and E virus co-infection and elevated transaminase levels has been demonstrated. Future studies with evaluation of several clinical parameters are necessary.
Kristen Anne Salava, MD
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Ruchi Patel, DO
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Eric Newman, MD
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
P. Daniel Nicoholas, DO
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Dante M. Grassi, PharmD, BCPS
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Swana Thomas, PharmD, MPH
Pennsylvania Presbyterian Medical Center 3737 Market Street 11th Fl, Philadelphia, PA 19115
Joseph Chronowski, MBA
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
David Pugliese, DO
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Jonida Cote, DO
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Abstract
Objective: To close laboratory screening care gaps via rheumatology-pharmacy co-management in patients starting disease-modifying antirheumatic drugs.
Methods: Laboratory data were obtained from patients who started disease-modifying antirheumatic drugs (DMARDs) during the pre-and post-intervention periods. The intervention consisted of a rheumatology-pharmacy collaborative screening with guideline-driven DMARD protocol for hepatitis B, hepatitis C, and tuberculosis. The care gap closure for patients starting any type of DMARDs such as a conventional synthetic disease-modifying antirheumatic drug (csDMARD), a biologic disease-modifying antirheumatic drug (bDMARD), or a targeted synthetic disease-modifying antirheumatic drug (tsDMARD), was defined as meeting hepatitis screening completion. The care gap closure for patients starting a bDMARD or tsDMARD alone was defined as meeting both the hepatitis and tuberculosis screening completion. The Chi square method was used for the statistical analysis of the data comparing laboratory screening rates of rheumatologists’ pre-intervention versus rheumatologist-pharmacist co-management post-intervention. Post-intervention, subgroup analysis of laboratory screening rates among rheumatologists alone versus rheumatologist-pharmacist co-management was also performed.
Results: During the 30-month period 6/1/2019 to 11/30/2021, hepatitis screening for patients on DMARDs improved from 77% with rheumatologists alone to 82% with co-management post-intervention (P=0.005), whereas hepatitis/tuberculosis screening for patients on bDMARDs/tsDMARDs improved from 75% to 85% respectively (P=0.005). In post-intervention subgroup analysis, hepatitis screening for patients on DMARDs improved from 80% with rheumatologists alone to 95% with co-management(P=0.00), whereas hepatitis/tuberculosis screening for patients on bDMARDs/tsDMARDs improved from 83% to 94% respectively (P=0.033).
Conclusion: By integrating clinical pharmacists into our rheumatology clinic, we significantly improved hepatitis and tuberculosis laboratory screening in our immunosuppressed rheumatic population.
Implications: Rheumatologists can consider integrating clinical pharmacists into their practices to improve patient safety by closing laboratory screening care gaps in the immunosuppressed rheumatic population.
Phillip Huang Chen
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
Steven-Huy Han
Pfleger Liver Institute, UCLA Medical Center, Los Angeles, CA; Greater Los Angeles VA Healthcare System, Los Angeles, CA
Abstract
Hepatitis B (HBV) in special populations within this article is considered as acute on chronic liver failure due to HBV, coinfection with Hepatitis C (HCV), Hepatitis D (HDV), or Human Immunodeficiency Virus (HIV), and HBV infection in patients who are in immunosuppressive states due to specific therapies and liver transplant recipients. Patients within these special populations are at higher risk of liver-related complications such as fibrosis, accelerated cirrhosis, acute on chronic liver failure, and/or development of hepatocellular carcinoma (HCC). Given their respective complex pathophysiology, specific treatment approaches are required for each population. With the introduction of effective antiviral HBV therapies over the past decade and the respective treatment options for the special population diseases, patient outcomes have seen improvement. With the advent of HCV direct antivirals, treatment of HBV-HCV coinfection has been more successful and consistently shown high rates of sustained virologic response. Treatment of HBV-HDV coinfection remains primarily as interferon-based, though new promising therapies have shown greater improvement in viral suppression. HBV-HIV coinfection has also shown promising results given overlapping mechanisms for treatment and specific regimens should be chosen to decrease risk of resistance. HBV reactivation in patients undergoing immunosuppressive therapies have been reported and guidelines recommend close monitoring and in certain cases, HBV antiviral therapy prophylaxis. With the effective HBV therapies, the perception of HBV as a contraindication for liver transplant has been diminishing and prolonged graft survival with effective antiviral therapies have shown promising outcomes.
Tougar S
Department of Intensive Care Medicine, Ibn Rochd University Hospital, Faculty of medicine and Pharmacy of Casablanca, Hassan 2 University, Casablanca, Morocco
Maghrabi O
Department of Intensive Care Medicine, Ibn Rochd University Hospital, Faculty of medicine and Pharmacy of Casablanca, Hassan 2 University, Casablanca, Morocco
Elkhaouri I
Department of Intensive Care Medicine, Ibn Rochd University Hospital, Faculty of medicine and Pharmacy of Casablanca, Hassan 2 University, Casablanca, Morocco
Machrouh W
Department of Intensive Care Medicine, Ibn Rochd University Hospital, Faculty of medicine and Pharmacy of Casablanca, Hassan 2 University, Casablanca, Morocco
Mabchour M
Department of Intensive Care Medicine, Ibn Rochd University Hospital, Faculty of medicine and Pharmacy of Casablanca, Hassan 2 University, Casablanca, Morocco
Charra B
Department of Intensive Care Medicine, Ibn Rochd University Hospital, Faculty of medicine and Pharmacy of Casablanca, Hassan 2 University, Casablanca, Morocco
Abstract
Cytomegalovirus (CMV)is a member of the Herpes viridae family, its seroprevalence is high in the general population. CMV infection in the immunocompromised is a serious, sometimes fatal complication that can affect several organs. For immunocompetent patients, this infection is usually pauci- or asymptomatic, which evolves spontaneously favorably and does not require specific treatment. However, the primary infection can be exceptionally serious with multivisceral involvement, for which antiviral treatment is indicated with generally a quickly favorable response. In this article, we present an unusual case of hepatitis and pancreatitis due to CMV in an immunocompetent patient. The diagnosis was retained after excluding the most frequent and potential causes of acute hepatitis, with a brief review of the literature.
Sidelcina Rugieri Pacheco
Centro de Pesquisa Gonçalo Moniz- Fundação Oswaldo Cruz- Laboratório de Patologia e Biologia Molecular Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia-Brasil CEP: 40296-710; Universidade Federal da Bahia
Maria Isabel Schinoni
Universidade Federal da Bahia
Andreas Stocker
Universidade Federal da Bahia
Raymundo Paraná
Universidade Federal da Bahia
Mitermayer Galvão dos Reis
Centro de Pesquisa Gonçalo Moniz- Fundação Oswaldo Cruz- Laboratório de Patologia e Biologia Molecular Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia-Brasil CEP: 40296-710
Luciano Kalabric Silva
Centro de Pesquisa Gonçalo Moniz- Fundação Oswaldo Cruz- Laboratório de Patologia e Biologia Molecular Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia-Brasil CEP: 40296-710
Abstract
Mutations of genotypic resistance to nucleotide analogues Entecavirand Tenofovirhave been described in patients undergoing treatment and virgins for hepatitis B virus. The present study demonstrated in a sample of 263 patients with chronic HBV from the North and Northeast of Brazil, a mutation rate of resistance to nucleotide analogues of 3.8% (10). Of the 10 patients who had genotypic resistance mutations, only 1 had no genotypic resistance mutation for the first line treatment for hepatitis B, entecavir and tenofovir.Due to the emergence of vaccine escape mutations and resistance mutations to antiviral treatment, and the severity of liver disease caused by HBV, screening for genetic mutations is important due to the impact on therapeutic management.
Laurens Holmes, Jr
Global Epigenomic Research Analytics, Wilmington, DE 19802
Kerti Deepika
Global Epigenomic Research Analytics, Wilmington, DE 19802; 2 Fellow of Translational Health Disparities Science (FTHDS), Wilmington, DE 19803, USA
Janille Williams
Global Epigenomic Research Analytics, Wilmington, DE 19802 ; Fellow of Translational Health Disparities Science (FTHDS), Wilmington, DE 19803, USA
Benjamin Ogundele
Global Health Services Initiatives Inc, Arlington, TX, 76014; 2 Fellow of Translational Health Disparities Science (FTHDS), Wilmington, DE 19803, USA
Glen Philipcien
Emergency Department, Victoria Hospital, Castries, St. Lucia
Michael Enwere
Global Epigenomic Research Analytics, Wilmington, DE 19802; Fellow of Translational Health Disparities Science (FTHDS), Wilmington, DE 19803, USA; Public Health Department, Walden University, Minneapolis, MN 55401, USA
Shikha Jain
MVJ Medical College, Hoskote, Karnataka, India
Naresh Dasari
Medicine and Long-term care Associates, Cranston, RI 02920
Ram Sanjiv Alur
Marion Veterans affairs medical center, IL
Ramesh Adhikari
Franciscan Health, Lafayette, IN 47909
Gbadebo Ogungbade
Global Health Services Initiatives Incorporated, Arlington, TX 76014 USA
Abstract
Purpose: Viral infections had been historically observed in chronic disease development and complications including although not limited to hepatitis C, influenza A, cytomegalovirus (CMV), Epstein bar virus (EBV), HIV and herpes simplex. Epidemiologic data had implicated CMV, herpes simplex and hepatitis C in type II diabetes (T2D). With the observed increased incidence T2D in COVID-19 among children and adults, this review aimed to examine scientific literature on immune and endocrine systems dysregulation in T2D and pancreatic neoplasm.
Materials & Method: A qualitative systematic review (QSR) was utilized in assessing the immune system deregulation and endocrine system involvement in chronic disease development such as T2D. The PubMed was the main search engine in studies identification with several search terms such as “SARS-CoV-2 and T2D”, “COVID-19 and T2D”, SARS-CoV-2 and insulin resistant”, etc.
Results: Viral pathogens such as CMV, influenza A, and herpes simplex and hepatitis C infections have been implicated in decreased insulin sensitivity (IS) and increased insulin resistant (IR). Similarly, these pathogenic microbes increased the T2D incidence and complications. SARS-CoV-2 a COVID-19 causative pathogen had been observed in increased risk and incidence of T2D among children and adults. While data are not currently available on the precise mechanistic process, SARS-CoV-2 viral infection in T2D incidence may be explained by excess pro-inflammatory cytokines elaboration (cytokine storm) resulting in increased IR and decreased IS, leading to glucose intolerance and T2D. Further COVID-19 may increase pancreatic neoplasm in populations with increased incidence of COVID-19, due to pancreatic beta cells and insulin receptors dysregulation and cellular dysfunctionality as abnormal cellular proliferation.
Conclusions/Recommendation: SARS-CoV-2 a causative pathogen in COVID-19 morbidity is associated with increased incidence of T2D, which is explained in part by immune and endocrine system integration dysregulation, resulting in cytokine storm, decreased IS and increased IR, implying glucose intolerance and T2D. Additionally this pathogenic microbe may result in increasing incidence of pancreatic neoplasm, a malignant neoplasm with the worst prognosis and excess mortality due to late stage at diagnosis and marginalized biomarkers of susceptibility and morbidity.
Yutaka Kishida, M.D., Ph.D.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Osaka Kaisei Hospital, Osaka, Japan
Abstract
Background: Persistent hepatitis C virus (HCV) infection results from inefficient innate and adaptive immune responses and exhausted virus-specific T-cell responses. Host cytokines and innate immune responses play important roles in controlling HCV infection. Innate immune responses modulate adaptive immune responses. These responses have recently been shown to have roles in antiviral therapy for chronic HCV infection. My previous study has indicated that viral clearance early in the course of therapy is associated with the restoration of innate and adaptive immune responses, and thus has potential as a novel therapeutic strategy for chronic hepatitis C (CHC).
Methods: The efficacy and safety of induction therapy (IT) with natural (n)-interferon (IFN)-beta followed by pegylated-IFN-alpha and ribavirin (PR) alone (group A, n = 30) were compared with those of IT with a protease inhibitor (PI) (Simeprevir or Vaniprevir) plus PR (group B, n = 13) in patients with CHC with genotype 1b and high viral load.
Results: During IT with n-IFN-beta, the virologic response rates in group A and group B were 10% and 8% (p = 0.6792) at week 4; 30% and 16% (p = 0.6989) at week 12; and 47% and 20% (p = 0.0887) at week 24. During and after treatment with PR alone, or PI plus PR, the virologic response rates in groups A and B were 50% and 82% (p = 0.01535) at week 4: 53% and 91% (p = 0.006745) at week 8; 57% and 91% (p = 0.001126) at week 12; 57% and 100% (p = 0.001845) at the end of the treatment; and 57% and 80% (p = 0.005166) after treatment cessation.
Conclusion: IT with PI plus PR restored the innate immune response, was tolerated well, overcame virological breakthrough, enhanced early virologic responses, and resulted in a sustained virologic response in patients with intractable CHC. Thus, IT with PI plus PR is beneficial for patients with intractable CHC. Steps for augmenting immune responses must be identified.
Ajitava Dutta
Department of Neuromedicine, Bangur Institute of Neurosciences, Institute of Post Graduate Medical Education and Research & SSKM Hospital, Kolkata, West Bengal, India
Ritwik Ghosh
Department of General Medicine, Burdwan Medical College and Hospital, Burdwan, West Bengal, India
Alak Pandit
Department of Neuromedicine, Bangur Institute of Neurosciences, Institute of Post Graduate Medical Education and Research & SSKM Hospital, Kolkata, West Bengal, India
Adrija Ray
Department of General Medicine, RG Kar Medical College, and Hospital, Kolkata, West Bengal, India
Dwaipayan Bhattacharya
Department of Neuromedicine, Bangur Institute of Neurosciences, Institute of Post Graduate Medical Education and Research & SSKM Hospital, Kolkata, West Bengal, India
Arkaprava Chakraborty
Department of Neuromedicine, Bangur Institute of Neurosciences, Institute of Post Graduate Medical Education and Research & SSKM Hospital, Kolkata, West Bengal, India
Uddalok Chakraborty
Department of Neuromedicine, Bangur Institute of Neurosciences, Institute of Post Graduate Medical Education and Research & SSKM Hospital, Kolkata, West Bengal, India
Souvik Dubey
Department of Neuromedicine, Bangur Institute of Neurosciences, Institute of Post Graduate Medical Education and Research & SSKM Hospital, Kolkata, West Bengal, India
Julián Benito-León
Department of Neurology, University Hospital “12 de Octubre”, Madrid, Spain; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Department of Medicine, Complutense University, Madrid, Spain
Abstract
Background: Cerebral venous thrombosis (CVT) following either human immunodeficiency virus (HIV) infection or hepatitis B virus (HBV) infection is a very rare condition. Moreover, it has never been reported as the presenting manifestation of HIV and HBV co-infection, even more so when the patient had a normal CD4 count and no demonstrable opportunistic infections. We aimed to report the first case of an adult Indian male, an intravenous drug abuser who developed CVT as the presenting manifestation of HIV-HBV co-infection.
Methods: Patient data were obtained from medical records from the Bangur Institute of Neurosciences, Institute of Post Graduate Medical Education and Research & SSKM Hospital, Kolkata, West Bengal, India.
Results: A 25-year-old male with a history of intravenous drug abuse and a normal CD4 count developed CVT as the presenting manifestation of HIV-HBV co-infection. His CD4 count was normal, and he had no demonstrable opportunistic infections. He had an uneventful recovery of the condition (CVT) following the institution of conventional anticoagulation therapy alongside anti-retroviral therapy.
Conclusion: Whether illicit drug abuse or HIV/HBV infection itself or all in combination led to this thrombotic event cannot be precisely established. Notwithstanding, we recommend serologic testing for HIV and HBV in patients suffering from CVT with high-risk behavior.
Mark E. Fraser
Department of Pulmonology, Critical Care, Sleep, and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN 46202
Cheryl Kucharski
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556
Zoe Loh
Department of Pathology, Duke University School of Medicine, Durham, NC 27710
Erin Hanahoe
Moderna, 200 Technology Square, Cambridge MA 02139
Malcolm J. Fraser, Jr
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556
Abstract
Chikungunya virus is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates following the introduction of its major vector, Aedes albopictus. Recent cases have been documented in Europe, the Caribbean, and the Americas. Chikungunya virus causes a disease frequently misdiagnosed as Dengue fever, with potentially life-threatening symptoms that can result in long term debilitating arthritis. There have been ongoing investigations of possible therapeutic interventions for both acute and chronic symptoms, but to date none have proven effective in reducing the severity or lasting effects of this disease. Recently, a promising vaccine candidate has received accelerated approval, indicating the importance of remedies to this emerging worldwide health threat. Nonetheless, therapeutic interventions for Chikungunya and other mosquito borne virus diseases are urgently needed yet remain elusive. The increasing risk of spread from endemic regions via human travel and commerce, coupled with the absence of a vaccine or approved therapeutic, puts a significant proportion of the world population at risk for this disease. In this report we explore the possibility of using Specific On/oFf Adapter Hepatitis Delta Virus Ribozymes as antivirals in cells infected with Chikungunya virus. The results we obtained suggest there could be some role in using these ribozyme molecules as antiviral therapies for not only Chikungunya virus, but potentially other viruses as well.
Gabriela Riter Martins de Matos
School of Medicine Hospital de Clínicas, Federal University of Paraná, General Carneiro, 181, Curitiba, PR 80060‑900, Brazil
Franciane Pavloski Kühl
School of Medicine Hospital de Clínicas, Federal University of Paraná, General Carneiro, 181, Curitiba, PR 80060‑900, Brazil
Guilherme Cecchetti
Department of Internal Medicine, Hospital de Clínicas, Federal University of Paraná, General Carneiro, 181, Curitiba, PR 80060‑900, Brazil
Carolina Chaves Hahnemann
Department of Internal Medicine, Hospital de Clínicas, Federal University of Paraná, General Carneiro, 181, Curitiba, PR 80060‑900, Brazil
Gustavo Lenci Marques
Department of Internal Medicine, Hospital de Clínicas, Federal University of Paraná, General Carneiro, 181, Curitiba, PR 80060‑900, Brazil
Jean Rodrigo Tafarel
Doctor of Health Sciences – Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição, 1155, Curitiba, PR, CEP 80215901
Abstract
Cystic Fibrosis is an autosomal dominant disease that affects the CFTR gene, which is responsible for producing a protein that regulates the transport of chloride ions across the cell membrane. This alteration results in obstruction in the body’s ducts and channels, primarily affecting the pulmonary system. Additionally, other systems can be affected. Cystic Fibrosis-related liver disease is a common complication that can lead to steatosis, fibrosis, and multifocal biliary cirrhosis; however, there are no well-established diagnostic criteria yet. The present study was conducted at the Cystic Fibrosis Outpatient Clinic of the Hospital de Clínicas, Federal University of Paraná, examining 98 medical records of patients with cystic fibrosis for at least 10 years. Patients with hepatitis B, hepatitis C, alcohol consumption, or pregnancy were excluded. The objective was to determine the best predictor for the outcome of cirrhosis, and for this purpose, demographic parameters, laboratory tests, and imaging were collected. The statistical analysis was performed using SPSS® software, with quantitative variables described as mean ± standard deviation and categorical variables presented as the number of observations and percentage. ROC curves were adjusted to determine the best predictor, using the Youden index to establish the optimal cutoff point and the corresponding area under the curve to determine the model’s efficacy. The study included 80 patients, and 10 of them (12.5%) were diagnosed with Cystic Fibrosis-related cirrhosis. The average age of the cirrhosis group was 21.6 years, with a predominance of males. The most accurate parameter for predisposition to cirrhosis was the APRI score, with a cutoff value of 0.27. Univariate analysis showed that gender, hepatic changes on ultrasound, splenomegaly, increased portal vein diameter, presence of vomiting, levels of alanine transaminase, aspartate transaminase, platelet count, and FIB-4 score were significantly associated with an APRI score value greater than 0.27. This study suggests the hypothesis that the APRI score is the most sensitive and specific tool for defining cirrhosis in patients with cystic fibrosis.
Katsutoshi Miura
Department of Regenerative & Infectious Pathology, Hamamatsu University School of Medicine
Toshihide Iwashita
Department of Regenerative & Infectious Pathology, Hamamatsu University School of Medicine
Abstract
Background: Chronic liver damage, such as viral hepatitis, causes liver fibrosis. Recently, the advent of interferon (INF) and antiviral drugs has reduced hepatitis viruses, enabling liver function recovery and fibrosis improvement. A quantitative assessment of liver fibrosis is mandatory to identify treatment efficacy.
Aim: We aimed to apply speed-of-sound (SOS) values for the objective assessment of fibrosis in liver biopsy because SOS values correlate with stiffness.
Methods: We differentiated SOS images of pre- and post-treatment INF liver. We then compared the SOS values with the fibrosis score and magnetic resonance elastography (MRE) values. We tried to digest sections with collagenase to clarify the process of fibrosis deletion.
Results: After INF therapy, SOS images demonstrated a marked reduction in fibrosis in the lobules. SOS values were well correlated with the fibrosis score and slightly corresponded to MRE values. Perisinusoidal fibrosis was susceptible to collagenase digestion. Portal areas were minimal.
Conclusion: The SOS value, which objectively evaluates fibrosis in tissue sections, is an excellent indicator. It assesses fibrosis progression and reduction post-treatment.
Linda Fryklund, PhD
Ex Pfizer retired independent consultant in biopharmaceuticals
Abstract
Forty years ago, recombinant DNA technology caused a revolution in the way growth disorders and diabetes could be treated. Bacteria or human cells were modified so as to be able to produce human hormones instead of relying on cadaveric material in the case of growth disorders and porcine insulin in the case of diabetics. The new technology also removed the risk of contracted hepatitis or fatal Creutzfeldt Jacob disease.
A signal peptide was used to transport the new protein into the periplasmic space giving rise to an exact, correctly folded version of monomeric human growth hormone.
More eligible patients could be treated, resulting not only in a large number of clinical trials. Daily tiny subcutaneous injections were found to be much more effective than twice or thrice weekly in the treatment of children and adults,
The progress for recombinant human insulin turned out to be somewhat different. Insulin is a more complicated protein, with an Alpha and Beta chain joined by two disulphide bridges, but is produced in the human pancreas as a single chain, proinsulin, the C peptide is removed to make the active molecule.
Recombinant insulin development was in a way the opposite to growth hormone since human insulin acts faster than porcine. Short fast and long-acting analogues have been developed all to improve the treatment regimens for both type 1 and type 2 diabetics,
A similar development is now taking place in the growth hormone field. Depot preparations for weekly administration are under development to achieve better compliance. One recently approved depot uses an analogue, modified in one amino acid of the peptide chain to permit acylation and albumin binding. In a way this is a retrograde step and it remains to be seen if the patient’s growth and metabolic responses are comparable to the daily administration of tiny amount of recombinant natural sequence hormone over several years of treatment.
Dhanya Mohan
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates
Amna Khalifa Alhadari
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates
Dileep Kumar
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates
Sima Abdolla Nejad
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates
Rahaf Mohamad Wardeh
Department of Internal Medicine, Dubai hospital, Dubai, United Arab Emirates
Batool Khan
Dubai Medical College for Girls, Dubai, United Arab Emirates
Madheeha Mahmood
Dubai Medical College for Girls, Dubai, United Arab Emirates
Zuha Fathima
Dubai Medical College for Girls, Dubai, United Arab Emirates
Mohammed Railey
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates
Abstract
Cryoglobulinemic vasculitis presents with systemic vasculitis including vasculitic rash, fever, peripheral neuropathy, and, in rare cases renal involvement. This could be secondary to infections like hepatitis C, malignancies like myeloma, Non Hodgkin’s lymphoma and chronic lymphocytic leukemia. We encountered a patient who presented with fever, anemia, purpuric skin rash and acute kidney injury due to acute glomerulonephritis with nephritic picture and fluid overload that required hemodialysis.Investigations revealed hemolytic anemia, cryoglobulinemia, proliferative glomerulonephritis with Ig M intra-capillary deposits and hyaline thrombi. Bone marrow biopsy clinched the diagnosis of Chronic lymphocytic B cell lymphoma with CD 20 positivity. Treatment was instituted with Rituximab and Bendamustine. Plasmapheresis was done for hyperviscosity syndrome. With treatment, hemodialysis could be discontinued after 10 weeks and renal functions recovered partially with serum creatinine settling at 1.5 mg/dl. We present this case to highlight the presentation of chronic lymphocytic leukemia with cryoglobulinemic vasculitis that presented with purpura and rapidly progressive renal failure that required dialysis.
Oscar Cobar
Pharmacogenomics and Nutrigenomics Research Laboratory, School of Chemical Sciences and Pharmacy, University of San Carlos, Guatemala.; Biomedical Sciences, Ph.D. Program, School of Medical Sciences, University of San Carlos, Guatemala.
Stella Cobar
School of Chemical Sciences and Pharmacy, University of San Carlos, Guatemala.
Abstract
Background: One of the major problems in drug design is to enhance the drug’s potency against genetic variants, for which adding a suitable pharmacophore to a newly designed molecule is preferred.
RNA-dependent RNA polymerase (RdRp) is the SARS-CoV-2 enzyme responsible for genome replication and gene transcription into the human cell. Cryogenic Electron Microscopy resolved the first structure of the RdRp complex of SARS-CoV-2 in April 2020, followed by two other studies that reported similar structures that same year. The RdRp complex is built up from several nonstructural proteins included nsp12, nsp7, and nsp8.
The protein nsp12 represents the core component and the catalytic subunit of RdRp, while nsp7 and nsp8 are accessory factors that increase the binding and processivity of the RdRp template. The nsp12 subunit contains an N-terminal nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain, an interface domain and a C-terminal RdRp domain. Subunits nsp7 and nsp8 bind to the thumb, and an additional copy of nsp8 binds to the fingers domain.
During replication, the active site of RdRp is responsible for incorporating free nucleotides into the daughter RNA strand of the replication complex. RdRp inhibitors, once metabolized, compete with the viral ATP molecules for incorporation into the nascent RNA strand. Once the RdRp drug replaces ATP in the new strand, the RNA synthesis process is terminated, thereby preventing further replication of the virus from occurring. In several studies reviewed in this manuscript, Molecular Docking simulations was employed to screen inhibitors that showed binding interaction with the conserved residues of RdRp.
Aim: The purpose of the Review is to present a literature review from January 1, 2023, to April 30, 2024, on the advances in SARS-CoV-2 RdRp inhibitors as a therapeutic approach against the virus, emphasizing on the structure of the enzime, the non-structural proteins that comprises, in particular nsp12, nsp 8 and nsp 7, the mechanisms that underlie the antiviral activity of RdRp inhibitory substances, the structure of the nucleoside analogs that have demonstrated RdRp inhibition in structural biology and computational research studies, and examine the current understanding of the molecular mechanisms underlying the action of these nucleoside analogs.
Materials and Methods: Original scientific articles published in Medline, Pubmed, Science Direct, Web of Science, Scopus, EBSCO and BioMed Central databases, official health organizations (World Health Organization, U.S. Centers for Disease Control and Prevention, European Centre for Disease Prevention and Control) electronic publications, and specialized media in the subject, were electronically searched to accomplish the aim of the study. Articles published in any language were included from January 1, 2023, to April 30, 2024, using a variety of keywords in combination. The studies relevant to our review were analyzed and compared.
Results and Discussion:Inhibition of RdRp´s has been an integral approach for managing various viral infections such as dengue, influenza, Hepatitis C (HCV), Bovine Viral Diarrhea Virus (BVDV), among others. Inhibition of the SARS-CoV-2 RdRp is currently rigorously explored for the treatment of COVID-19. Consequently, the importance of RdRp in developing anti-viral agents against this viral disease, has been discussed by the scientific community in the last four years. The structure activity relationship profile and binding conformations of the reported inhibitors are essential features to elucidate some hypothesis for the designing of further SARS-CoV-2 RdRp inhibitors. The search on scientific literature on these inhibitors, the analyses of the interaction characteristics, together with the examination of the inhibitors chemical structure, it would guide the rational design of antiviral medications and research into viral transcriptional mechanisms.
Conclusions: Several RdRp inhibitors have shown promising results for their use in treating the SARS-CoV-2 virus. While work must still be conducted to fully understand the mechanisms responsible for reducing the antiviral activity of SARS-CoV-2, their potential in healing infected individuals is extremely valuable. The development of SARS-CoV-2 RdRp inhibitors, to relieve the severity of an infection for a SARS-CoV-2 variants that could emerge in the near future, it is an essential task for the scientific community. The analyses of inhibitors chemical structure-RdRp, besides the analyses of the inhibitors-RdRp interactions, it would guide the rational design of antiviral medications and research into SARS-CoV-2 transcriptional mechanisms. This review summarizes recent progress in studies of RdRp inhibitors, 87 compounds was tested, focusing on the chemical structure of the inhibitors and the interactions between these inhibitors and the enzyme complex.
HuiTing Cheng
Department of Cell Biology, SUNY Downstate Medical Center 450 Clarkson, Avenue, Brooklyn, NY 11203.; Miriums Laboratories, 760 Parkside Avenue. Brooklyn, NY 11203.
Prem Premsrirut
Department of Cell Biology, SUNY Downstate Medical Center 450 Clarkson, Avenue, Brooklyn, NY 11203.; Miriums Laboratories, 760 Parkside Avenue. Brooklyn, NY 11203.
Lilly Tennyson
Department of Cell Biology, SUNY Downstate Medical Center 450 Clarkson, Avenue, Brooklyn, NY 11203.; Miriums Laboratories, 760 Parkside Avenue. Brooklyn, NY 11203.
Philip Mo
Department of Cell Biology, SUNY Downstate Medical Center 450 Clarkson, Avenue, Brooklyn, NY 11203.; Miriums Laboratories, 760 Parkside Avenue. Brooklyn, NY 11203.
XiaoHong Wang
Veterans Affairs New York Harbor Healthcare System – Manhattan Campus
Miriam Silberstein
Department of Pathology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203.
Matthew R. Pincus
Miriums Laboratories, 760 Parkside Avenue. Brooklyn, NY 11203; Department of Pathology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203.
Abstract
This communication takes note of unexpected factors that can influence the results of RT-PCR in quantitation of copy numbers such as in determination of viral loads and in viral identification. We show that the presence of serum separator gel in authorized collection tubes for hepatitis C (HCV) viral load determinations causes underestimation of viral loads by blocking viral diffusion into plasma and that the presence of more than one targeted virus in a multiplex RT-PCR viral assay, while not affecting analytical specificity, results in raising of the minimal detectable viral titer and therefore a decreased analytical sensitivity. Our results suggest the possibility that HCV samples should be placed in cell lysis buffer for full viral load determination and that multiplex assays should be carefully validated and modified if necessary to minimize loss of sensitivity.
Remy André-Jean
Mobile Hepatits Team, Perpignan Hospital, Perpignan, France
Bouchkira Hakim
Mobile Hepatits Team, Perpignan Hospital, Perpignan, France
Happiette Arnaud
Mobile Hepatits Team, Perpignan Hospital, Perpignan, France
Hervet Jeremy
Mobile Hepatits Team, Perpignan Hospital, Perpignan, France
Roy Berengere
Mobile Hepatits Team, Perpignan Hospital, Perpignan, France
Wenger Hugues
Mobile Hepatits Team, Perpignan Hospital, Perpignan, France
Abstract
Introduction and objective: HCV treatment for all was effective in France since 2017. HCV testing, diagnosis and treatment of drugs users and precarious people remain low. Lost follow-up was too important since several stages are necessary. Pangenotypic direct antiviral agents were available. Point-of-care HCV RNA testing offers advantage over antibody testing, enabling diagnosis of active infection with real time measure in a single visit. It is missing link between HCV RDT, liver fibrosis evaluation by FIBROSCAN and treatment. Validated Xpert HCV Viral Load assay CEPHEID, fast training technique, allow developing projects of diagnosis to treatment session. Our objective was to evaluate test to cure session allowing the access in 5 hours to an antiviral treatment to vulnerable and precarious populations (drug users, migrants, psychiatric patients).
Materials and methods: Eligible patients had to have known positive serology or risk behavior, an unknown or unchecked viral load after antiviral treatment; 5 to 7 patients were recruited per each session by social or nursing interview. Between 9 am and 2 pm these patients had access to measure of the hepatic fibrosis by FIBROSCAN, HCV viral load in real time by CEPHEID Xpert HCV Viral load finger-stick samples, social interview, shared educational evaluation, collective workshops, especially harm reduction, depiction of results by hepatologist and prescription of DAA (sofosbuvir velpastasvir combination) allowed delivery of 1st month of treatment. Specific social and nursing follow-up was made during and after treatment. Compliance and sustained virological rate were determinate at week 12.
Results: From October 2019 to December 2021, 223 sessions were realized on 27 sites: 9 drug units, one prison, 17 social units; 1602 patients with drug using history were screened; 427 patients had HCV positive serology and 24 patients did not come; 403 FIBROSCAN measures and 403 measures of viral load in real time were realized. Mean value of liver stiffness was 8.2 and 29% of patients were F3 or F4: 229 patients were HCV RNA positive (56.8%), 57 declared knew their HCV status; 228 treatments began same day, only 1 was delayed due to default social rights; 120 patients had a negative viral load spontaneously and 54 following prior treatment; 399 social interviews and 405 collective workshops were realized. On 31st January 2022, 207 antiviral treatments were completed and 199 patients were cured; 12 patients interrupted treatment; 3 patients relapsed and 5 reinfections; 89% of patients were satisfied with this program.
Conclusions: Despite 3 months interruption by COVID 19 pandemic lockdown and sanitary restrictions, 94% of positive participants were linked to care and cure with this mobile clinic model, by screening and RNA real time measure in unity of place adapted to precarious public, patients distant from system of care had access immediately to treatment.
Charles S. Wilcox, Ph.D., M.P.A., M.B.A.
Praxis Research Consulting, 1400 Quail Street, Suite #285, Newport Beach, California 92660 (USA); Alzheimer’s Association (Orange County); Alzheimer’s Impact Movement
Abstract
The 2021 approval of aducanumab in the United States, was not followed by approvals in Europe, Canada, Australia or elsewhere; nonetheless, the initial pricing of $56,00.00/year created a firestorm of controversy. The 2023 Food and Drug Administration approval of lecanemab has been followed by approvals in Japan and China. The current (2024) costs are $26,500 in USA, $20,438 (National Health Insurance) in Japan and $28,180 (private market) in China. In Europe, a health technology assessment will drive coverage decisions and set single-payer prices for each health system for lecanemab and subsequently approved new treatments. For comparison, 2024 average pricing for the top five selling drugs for cancer [$198,273], arthritis [$83,666], hepatitis C [$75,118] and multiple sclerosis [$86,765] far exceed lecanemab’s annual cost. Could there be an anti-brain-health bias?
The International Consortium for Health Outcomes Measurement notes that patient-centered outcome measures represent the ultimate measure of quality and they are always multi-dimensional. Quality-adjusted life-years (QALY) seem to be absent from the computation of pricing for anti-dementia treatments. Although global consensus on QALY calculations remains elusive, currently extant data are compelling. The QALY calculation is the change in utility value induced by the treatment, which is then multiplied by the duration of treatment effect to provide the number of QALYs gained. QALY ranges differ quite significantly, even amongst the most industrialized nations. Value-based pricing from double-blind, placebo-controlled trial results, demonstrating statistically significant beneficial effects on cognition and/or global function, would reward manufacturers for innovation whilst also enabling payer systems to remain solvent.
Now that the first truly disease-modifying treatment for Alzheimer’s (lecanemab) has been approved, a second disease-modifying treatment (donanemab) appears to be heading for regulatory approval as well. The full value of these newest anti-dementia treatments may be understated when quantified under older pricing models and, hence, could unwittingly be a disincentive to further innovation. We now have disease-modifying and symptomatic relief treatments for Alzheimer’s disease to be included within the treating clinicians’ armamentarium and, when priced appropriately, access should be widely available whilst also encouraging further innovative anti-Alzheimer’s clinical research.
Annarosa Floreani
Senior Scholar, University of Padova, Padova, Italy; Scientific Consultant IRCCS Negrar, Verona, Italy
Daniela Gabbia
Dept. of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
Sara De Martin
Dept. of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
Abstract
IgG4-related disease (IgG4-RD) is a rare condition characterized by an immune-mediated fibro-inflammation affecting various organs (liver, pancreas, heart, kidney, brain among others) with peculiar histopathologic feature. Few epidemiological data have been published so far, although a dramatic increase in the number of patients diagnosed with IgG4-RD has been recorded in the last years. The clinical manifestations of IgG4-RD involve frequently liver and pancreas. Specifically, a crucial challenge in differential diagnosis is IgG4-related sclerosing cholangitis which is frequently accompanied by pancreatic involvement. Inflammatory alterations of liver parenchyma have also been described, with a new nosology of IgG4-autoimmune hepatitis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-RD. The first-ever epidemiological study to estimate the point prevalence of IgG4-related sclerosing cholangitis has been recently conducted in Japan. Moreover, several demographic studies on IgG4-RD involving liver and pancreas have been published in other countries, although the majority of them are cohort studies and data on incidence/prevalence are lacking. This review aims to update the recent epidemiological and clinical knowledge of IgG4-RD involving liver and pancreas, focusing also on the risk of malignancy.
Mukund Tinguria
Department of Pathology and Laboratory Medicine Brantford General Hospital 200 Terrace Hill Street Brantford, Ontario Postal Code – N3R 1G9 Canada
Abstract
Celiac disease (CD) is an immune mediated disorder characterised by intolerance to glutens in certain grains like whet, barley, and rye. The exposure to gliadin protein component in the susceptible individuals leads to an inflammatory reaction damaging small bowel mucosa with progressive disappearance of intestinal villi. The damaged intestinal mucosa leads to malabsorption. The usual symptoms of celiac disease include diarrhea, steatorrhea, weight loss, fatigue, and abdominal pain. Diagnosis is based on clinical features, duodenal biopsy, elevated levels of anti-gliadin antibodies and response to gluten free diet. Contrary to common belief, celiac disease is a protein systemic disease rather than merely a pure digestive alteration. Celiac disease is closely associated with genes that code HLA -II antigens mainly of DQ2 and DQ8 classes, production of disease specific antibodies (i.e., endomysial antibodies), multiorgan involvement, comorbidity with other autoimmune diseases (shared autoimmunity), familial aggregation, and immune system dysregulation.
The clinical presentation of celiac disease can be variable. In mild form, patients can be almost asymptomatic whereas in the most severe form, the patients are at increased risk of life-threatening complications. Celiac disease has a well-known association with other autoimmune diseases such as autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), diabetes mellitus, autoimmune thyroid diseases, skin diseases such as dermatitis herpetiformis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, psoriasis, sarcoidosis, immune thrombocytopenic purpura, and pancreatitis. In addition, celiac disease may be associated with rare but potentially serious complications such as, collagenous sprue, ulcerative jejunoileitis, refractory celiac disease (RCD), enteropathy associated T-cell lymphoma, small bowel adenocarcinoma (SBA), hyposplenism, and cavitating mesenteric lymph node syndrome (CMLNS). The present article describes clinicopathologic features of these rare but serious complications of celiac disease.
Dhineshreddy Gurala, MD
Gastroenterology and Hepatology, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA
Ravindran Nishal, MD
Gastroenterology and Hepatology, Staten Island University Hospital, Northwell Health, Staten Island, New York, USA
Jobin Philipose, MD
Gastroenterology and Hepatology, Mountain View Medical Center, Las Cruces, New Mexico, USA
Abstract
Obesity is a chronic, preventable condition, and has a significant public health concern. Its implications extend beyond metabolic syndrome, casting a shadow over the development and prognosis of various cancers, with a particularly strong tie to hepatocellular carcinoma (HCC) among all cancer types. Non-Alcoholic Fatty Liver Disease (NAFLD) is now a leading cause of liver cancer, along with the treatment of hepatitis B and C. Liver cancer is the fourth most common cause of cancer related deaths worldwide, with obesity, exacerbating the risk especially two times higher in Body Mass Index (BMI) above 30 and four times higher in BMI above 35. Visceral adiposity, measured by waist circumference, is considered more important risk factor than general adiposity. Several mechanisms have been proposed to explain the pathophysiology of how obesity can trigger HCC, but the precise mechanisms that control the progression from steatosis to steatohepatitis and tumor initiation remain unclear. Hepatocellular cancer may occur in patients with NAFLD without cirrhosis. The diagnosis of HCC in NAFLD can be challenging due to an increase in poor-quality ultrasound in obese individuals, which necessitates a more accurate and cost-effective surveillance strategy for early detection. The delay in diagnosis, older age, and the presence of relevant comorbidities limit the possibility of therapeutic intervention. Weight management through lifestyle changes and surgical interventions like bariatric surgery offers promise in mitigating both metabolic syndrome and the risk of HCC. Diagnosis hinges on advanced imaging techniques like multiphase Magnetic Resonance Imaging or Computed Tomography scan using specific criteria. Treatment modalities for HCC are multifaceted, depends upon tumor characteristics, metastasis, cirrhosis, and overall liver function. However, despite advancements, there remains a pressing need for more efficacious interventions to combat obesity and curb the trajectory of HCC, given its persistently high mortality rate. Surveillance protocols for HCC in cirrhotic patients entail regular abdominal ultrasounds with or without Alpha Fetoprotein testing at six-month intervals. However, there is a need for cost effective surveillance strategies for HCC in non-cirrhotic NAFLD.
Isabel Fonseca Silva, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Ana Aguiar, M.D.
EPIUnit – Instituto De Saúde Pública, Universidade do Porto, Porto, Portugal; Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal; ICBAS-UP, Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto
Arlindo Guimas, M.D. Ana Oliveira, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Arlindo Guimas, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Pedro Vita, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Rute Alves, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Ana Luísa Rego, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Álvaro Ferreira, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Alexandre Pinto
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Miguel Ricardo, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Graziela Carvalheiras, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Ana Novo, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Ana Vigário, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Ana Rita Costa, M.D.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Diana Valadares
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal
Filipe Nery, M.D. PhD.
Unidade de Cuidados Intermédios Médicos, Serviço de Cuidados Intensivos, Centro Hospitalar Universitário Do Porto, Porto, Portugal; EPIUnit – Instituto De Saúde Pública, Universidade do Porto, Porto, Portugal; Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR), Universidade do Porto, Porto, Portugal; ICBAS-UP, Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto
Abstract
Background & Aims: Severe acute liver injury (ALI) precedes acute liver failure (ALF). Risk factors related to ALI progression to ALF or death, are not well-known. We aimed to investigate which predictors of poor outcomes can be identified in patients with ALI.
Methods: We retrospectively analyzed 59 patients with ALI diagnosis, admitted from 2010 to 2021 in our Intermediate Medical Care Unit, and checked for clinical, biochemical and imagiological data, in order to explore their relationship with progression to ALF or death.
Results: From the 59 patients with ALI, 11 (18.6%) evolved to ALF and 9 (15.3%) died during the hospital staying or within the first month after discharge. Not having drug-induced liver injury or ischemic hepatitis as etiological factors was associated to increased progression to ALF (hazard ratio [HR] 0.17; 95% confidence interval [CI]: 0.03-0.96; P=0.041). In univariate analysis, ascites related to development to ALF (HR 0.25; 95% CI: 0.06-0.97; P=0.037) and death (HR 7.09; 95% CI: 1.55-33.04; P=0.006), while renal dysfunction, was only allied to death (HR 0.99; 95% CI: 0.97-1.00; P=0.035). Inflammatory markers at admission were not linked to progression to ALF. Yet, increased C reactive-protein levels were commonly found in patients who died (HR 1.01; 95% CI: 1.00-1.03; P=0.035). In multivariate analysis, only ascites remained significant (P=0.005) as predictor of death.
Conclusions: In patients with ALI, ascites at presentation is the only marker of poor prognosis (mainly to death). Still, those who are more inflamed or have renal dysfunction at baseline are more willing to die.
Omar Zardain Medlich Ducoulombier
University of Monterrey, Health Sciences Vice-Rectorate, School of Medicine. Avenida Ignacio Morones Prieto 4500 Pte., Jesús M. Garza, 66238, San Pedro Garza García, Nuevo León, México
Sofía Teresa Lozano Díaz
University of Monterrey, Health Sciences Vice-Rectorate, School of Medicine. Avenida Ignacio Morones Prieto 4500 Pte., Jesús M. Garza, 66238, San Pedro Garza García, Nuevo León, México
Erick Roberto Santaella Sosa
University of Monterrey, Health Sciences Vice-Rectorate, School of Medicine. Avenida Ignacio Morones Prieto 4500 Pte., Jesús M. Garza, 66238, San Pedro Garza García, Nuevo León, México
Félix Adolfo Sánchez Chávez
Mexican Social Security Institute, Traumatology and Orthopedics High Specialty Medical Unit No. 21, Pathology, Education, Research and Orthopedics Department. Juan Ignacio Ramón 350, Centro, 64000, Monterrey, Nuevo León, México
Arnulfo Miramontes Morales
Mexican Social Security Institute, Traumatology and Orthopedics High Specialty Medical Unit No. 21, Pathology, Education, Research and Orthopedics Department. Juan Ignacio Ramón 350, Centro, 64000, Monterrey, Nuevo León, México
Manuel Torres Nájera
Mexican Social Security Institute, Traumatology and Orthopedics High Specialty Medical Unit No. 21, Pathology, Education, Research and Orthopedics Department. Juan Ignacio Ramón 350, Centro, 64000, Monterrey, Nuevo León, México
Francisco González Salazar
University of Monterrey, Health Sciences Vice-Rectorate, School of Medicine. Avenida Ignacio Morones Prieto 4500 Pte., Jesús M. Garza, 66238, San Pedro Garza García, Nuevo León, México; Mexican Social Security Institute, Northeast Biomedical Research Center. Calle 2 de Abril – Jesús Dionisio González 501, Independencia, 64720, Monterrey, Nuevo León, México
Abstract
Introduction: Osteoarticular tuberculosis poses a significant diagnostic and therapeutic challenge in developing countries, where the absence of molecular tools demands reliance on clinical suspicion and histopathological findings for diagnoses. Here, we present a compilation of case studies on osteoarticular tuberculosis for academic reference and support to aid primary care physicians in providing the best possible patient care.
Methods: Retrospective analysis of cases diagnosed with osteoarticular tuberculosis through biopsy from 2010 to 2020 at a Mexican Traumatology and Orthopedics Hospital, examined using descriptive statistics.
Results: Thirty-three patients were registered: 23 men (70%) and 10 women (30%). The most affected regions included the spine in 28 cases (84%), the hip in 3 (9%), and the elbow and sternoclavicular joints in 1 case each. The main clinical manifestations were paravertebral abscesses in 16 patients (48%), discitis in 12 (36%) and arthritis in 5 (15%), while the primary associated diseases were immunosuppression in 8 cases (24%), 2 cases with hepatitis (6%) and 3 with hypertension (9%).
Discussion: Tuberculosis is endemic in Mexico, similar to other developing countries, with numerous reported cases of osteoarticular tuberculosis. This study highlights the importance of using alternative diagnostic tools when molecular tests and cultures are not accessible to general practitioners and orthopedic physicians who treat patients with clinical suspicion of osteoarticular tuberculosis.
Bruno Mozzanega, MD
Department SDB Woman’s and Child’s Health, University of Padua, Padova, Italy
Abstract
After recalling that Levonorgestrel Emergency Contraceptive Pills never delay or suppress ovulation, but impair the luteal body functions, and, consequently, the embryo-implantation, we focus on the mechanism of action (MOA) of ellaOne®: micronized UPA (Ulipristal Acetate) 30mg and on UPA- toxicity.
EMA and, after it, the National Drug Regulatory Institutions and the most renowned International Gynecological Societies present ellaOne® as an anti-ovulatory drug which is safe even in repeated assumption, also during the same menstrual cycle. We’ll try to understand whether this dogma is supported by experimental data in literature.
As to the MOA, EMA reports (EMEA-261787-2009) that Ulipristal blocks the synthesis of the proteins necessary to begin and maintain pregnancy, and that Ulipristal and mifepristone were approximately equipotent as to their ability to terminate pregnancy. Besides, EMA further evidences (EMA/73099/2015) that it is unknown whether it is possible to use ellaOne® for abortion.
Data in Literature evidence that ellaOne® can delay ovulation only when is taken in the very first fertile days of the cycle. In the pre-ovulatory, most fertile, days – when most intercourses do occur and over 70% fertilizations ensue – it never prevents ovulation, like placebo. On the contrary, whenever it is taken in the cycle, it consistently impairs the endometrium that becomes an inhospitable ground for the embryo: endometrial gene expression is completely subverted compared with that of the normal luteal phase.
Recently, an UPA-based drug used for uterine fibroids-treatment (Esmya®) was withdrawn from the market because it caused fulminant hepatitis requiring transplantation (EMA/455818/2020). It was prescribed by the hospital for 3-6 months and carefully followed-up. The strict post-marketing surveillance allowed to link UPA-administration and tissue-accumulation to liver-failure. Surprisingly EMA, while revoking Esmya®, warranted for the safety of ellaOne®, though it is taken by millions of women unaware of the risk, repeatedly without prescription, without medical supervision and any possibility of post-marketing surveillance, in UPA-cumulating doses even greater than with Esmya.
Finally, we criticize the attempt to propose UPA in daily contraceptive pills, at doses even double than in Esmya® and for much longer periods, to fertile women aiming at preserving their fertility and health.
