Diabetes-related foot disease(DFD)is a widely feared complication among people who live with diabetes.In Australia and globally,rates of disability,cardiovascular disease,lower extremity amputation,and mortality are s...Diabetes-related foot disease(DFD)is a widely feared complication among people who live with diabetes.In Australia and globally,rates of disability,cardiovascular disease,lower extremity amputation,and mortality are significantly increased in patients with DFD.In order to understand and prevent these outcomes,we analyse the common pathogenetic processes of neuropathy,arterial disease,and infection.The review then summarises important management considerations through the interdisciplinary lens.Using Australian and international guidelines,we offer a stepwise,evidence-based practical approach to the care of patients with DFD.展开更多
Introduction: The transmission of HIV from mother to child is reported from 30% to 40% without any intervention [1]. When all the measures for prevention are implemented, including treatment with HAART (Highly Active ...Introduction: The transmission of HIV from mother to child is reported from 30% to 40% without any intervention [1]. When all the measures for prevention are implemented, including treatment with HAART (Highly Active Antiretroviral Treatment), the rate of infection can be reduced between 1% and 2% [2]. In Guatemala, the statistics demonstrated an estimated of 20,000 women living with HIV virus infection during the period of 2009. In this scenario, mother to child HIV transmission is an important public health fact. In preliminary reports, there is strong evidence of the impact of preventing mother to child transmission with Lopinavir/Ritonavir in Guatemala is showing a small incidence of new HIV infections and good tolerance [3,4]. Objective: To evaluate the effect of HAART with Lopinavir/Ritonavir on the prevention of mother to child transmission (PMCT) in HIV-positive pregnant women at Roosevelt Hospital in Guatemala City. Methods: A retrospective cohort analysis study. The detection of pregnant HIV positive women and the follow up period was from January 2003 to December 2009, and a total of 219 women completed the follow up time. The HIV diagnosis and follow up for the child was made with molecular testing and antibody testing up to 18 months of age or until testing was negative. Adherence was quantified by pill counts. The interventions where offered to all the women in the cohort. Results: Regarding the pregnancy outcome, the study cohort gave a rate of abortion of 2.3%;10.6% of preterm births and 79.6% normal births. Of the 202/219 children born, there was a 1.4% rate of transmission (n = 3). The three infected children were born from mothers with high basal viral loads (xxx C/mL or higher). There were no serious adverse events related to antiretroviral therapy with Lopinavir/Ritonavir, with a 6.1% of non serious adverse events, most of them of gastrointestinal type, and anemia. Conclusions: The rate of transmission of HIV from mother to child was low in this population (1.4%), comparable to findings from similar studies [4]. Lopinavir/Ritonavir was well tolerated in this cohort and no serious adverse events in this population were reported.展开更多
BACKGROUND Ventilator-associated pneumonia(VAP)is defined as pneumonia that occurs two calendar days following endotracheal intubation or after that.It is the most common infection encountered among intubated patients...BACKGROUND Ventilator-associated pneumonia(VAP)is defined as pneumonia that occurs two calendar days following endotracheal intubation or after that.It is the most common infection encountered among intubated patients.VAP incidence showed wide variability between countries.AIM To define the VAP incidence in the intensive care unit(ICU)in the central gove-rnment hospital in Bahrain and review the risk factors and the predominant bacterial pathogens with their antimicrobial susceptibility pattern.METHODS The research was a prospective cross-sectional observational study over six months from November 2019 to June 2020.It included adult and adolescent patients(>14 years old)admitted to the ICU and required intubation and mechanical ventilation.VAP was diagnosed when it occurred after 48 h after endotracheal intubation using the clinical pulmonary infection score,which considers the clinical,laboratory,microbiological,and radiographic evidence.RESULTS The total number of adult patients admitted to the ICU who required intubation and mechanical ventilation during the study period was 155.Forty-six patients developed VAP during their ICU stay(29.7%).The calculated VAP rate was 22.14 events per 1000 ventilator days during the study period,with a mean age of 52 years±20.Most VAP cases had late-onset VAP with a mean number of ICU days before the development of VAP of 9.96±6.55.Gram-negative contributed to most VAP cases in our unit,with multidrug-resistant Acinetobacter being the most identified pathogen.CONCLUSION The reported VAP rate in our ICU was relatively high compared to the international benchmark,which should trigger a vital action plan for reinforcing the implementation of the VAP prevention bundle.展开更多
The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis w...The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.展开更多
Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living wit...Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living with HIV(PLWH)are six times greater affected by HCV,compared to HIV negative ones;the greater prevalence is encountered among people who inject drugs and men who have sex with men:the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection.These patients experience a high rate of chronic hepatitis,which if left untreated progresses to end-stage liver disease and hepato-cellular carcinoma(HCC)HIV infection increases the risk of mother to child vertical transmission of HCV.No vaccination against both infections is still available.There is an interplay between HIV and HCV infections.Treatment of HCV is nowadays based on direct acting antivirals(DAAs),HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono-and coinfected individuals,especially when used at an early stage of fibrosis,reducing liver disease mortality and morbidity.Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication,the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV.HCV eradication can determine dyslipidemia,since HCV promotes changes in serum lipid profiles and may influence lipid metabolism.In addition to these apparent detrimental effects on the lipid profile,the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function.The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.展开更多
Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phen...Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.展开更多
Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CD...Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of recurrence.However,it is still not clear whether C.difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment.The burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with IBD.IBD patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired infections.The clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often absent.Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for C.difficile.Treatment includes general measures such as supportive care and infection control measures.Antibiotic therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as possible.Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI.The aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.展开更多
Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of ...Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease(CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.展开更多
Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AID...Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus(HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.展开更多
Infectious agents causing aborted fetus problems in domestic pigs were investigated in this study. More than 10 different infectious agents were known to cause abortion in swine and the major eight viruses among them ...Infectious agents causing aborted fetus problems in domestic pigs were investigated in this study. More than 10 different infectious agents were known to cause abortion in swine and the major eight viruses among them were inspected. One hundred twelve samples of aborted fetuses from nine provinces in South Korea were collected during April to November, 2013 in this study for the diagnosis of infectious agents causing abortions in pigs. Eight major infection viruses were examined in this study mainly using various diagnostic kits and reverse transcriptase polymerase chain reaction (RT-PCR). Positive rate of the detection differed from each viruses. In this study, the main focus was the porcine reproductive and respiratory syndrome virus (PRRSV), which took the second large portion in the positive rate of detection, and then its ORF5 gene was compared with modified live virus (MLV) vaccine strain to figure out the influence of vaccine on disease. Between four positive samples' sequence, two of them were 99.9%-100% similar to MLV vaccine strain and two other samples were 88.6%-92.7% similar. Similarity rate of the sequences between the vaccine and virus from aborted fetuses are very crucial, because it implies that abortion in swine can be made due to the usage of vaccine not only by the infection of field virus, and if MLV vaccine actually do have an impact on the infection, usage of the vaccine should be reconsidered.展开更多
In July 2023,the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic.This report summarizes the rich discussion...In July 2023,the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic.This report summarizes the rich discussions that occurred during the workshop.The workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data,social media,and wastewater monitoring.Significant advancements were noted in the development of predictive models,with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease trends.The role of open collaboration between various stakeholders in modelling was stressed,advocating for the continuation of such partnerships beyond the pandemic.A major gap identified was the absence of a common international framework for data sharing,which is crucial for global pandemic preparedness.Overall,the workshop underscored the need for robust,adaptable modelling frameworks and the integration of different data sources and collaboration across sectors,as key elements in enhancing future pandemic response and preparedness.展开更多
Objective: Intracranial suppurations are a cosmopolitan pathology whose prevalence depend of the region of the world. They are mostly caused by otolaryngological infections. Despite the progress, they remain serious d...Objective: Intracranial suppurations are a cosmopolitan pathology whose prevalence depend of the region of the world. They are mostly caused by otolaryngological infections. Despite the progress, they remain serious diseases in Africa. The objective of this study was to report the epidemiology, clinical and etiological aspects of intracranial suppurations in Togo. Method: This was a retrospective and descriptive study carried out from January 1, 2012 to December 31, 2020 including all cases of intracranial suppuration treated in the neurosurgery unit of Sylvanus Olympio university hospital in Lomé. The evolution was evaluated at discharge, at 3 and 6 months after. Results: We collected 185 cases of intracranial suppuration. The average age of the patients was 12.6 years with a male predominance (72.4%). The main clinical signs were the infectious syndrome (92.4%), intracranial high pressure (51.4%), focal deficit (38.4%) and seizures (20.5%). An otolaryngological infections history was noted within 3 months in 72.4%. The brain CT scan noted a predominance of empyema (63.8%) mostly subdural (64.4%). Radiological sinusitis was found in 57.3%. We identified etiology in 69.2% predominated by otolaryngological causes. Patients received medical and surgical treatment in 77.3%. The bacteriology was positive only in 7 cases. The mortality rate was 15.1%, mostly no operated cases (78.6%). At 6 months 84% recovered without sequelae. The predictive prognostic factors for mortality were: coma (p 0.001), absence of surgical treatment (p 0.02). Conclusion: Intracranial suppuration remains frequent in our country, mainly due to otolaryngological pathologies. The clinical presentation is not always specific and Bergman’s triad is rarely complete. The results of treatment are good if it is early.展开更多
AIM: To investigate a possible association between serum vitamin D levels and spontaneous hepatitis B surface antigen (HBsAg) seroclearance. METHODS: Fifty-three patients diagnosed with chronic inactive hepatitis B an...AIM: To investigate a possible association between serum vitamin D levels and spontaneous hepatitis B surface antigen (HBsAg) seroclearance. METHODS: Fifty-three patients diagnosed with chronic inactive hepatitis B and spontaneous HBsAg seroclearance were followed up in two Israeli liver units between 2007 and 2012. This retrospective study reviewed medical charts of all the patients, extracting demographic, serological and vitamin D rates in the serum, as well as medical conditions and current medical therapy. Spontaneous HBsAg seroclearance was defined as the loss of serum HBsAg indefinitely. Vitamin D levels were compared to all patients who underwent spontaneousHBsAg seroclearance.HBsAg seroclearance. RESULTS: Out of the 53 patients who underwent hepatitis B antigen seroclearance, 44 patients (83%) had normal levels of 25-hydroxyvitamin vitamin D compared to 9 patients (17%) who had below normal levels. Multivariate analysis showed that age (>35 years) OR = 1.7 (95%CI: 1.25-2.8, P=0.05), serum vitamin D levels (>20 ng/mL) OR = 2.6 (95%CI: 2.4-3.2, P=0.02), hepatitis B e antigen negativity OR = 2.1 (95%CI: 2.2-3.1, P=0.02), low viral load (hepatitis B virus DNA < 100 IU/mL) OR = 3 (95%CI: 2.6-4.2, P = 0.01) and duration of HBsAg seropositivity (> 8 years) OR = 1.6 (95%CI: 1.15-2.6, P=0.04) were also associated with spontaneous HBsAg seroclearance. CONCLUSION: We found a strong correlation between normal vitamin D levels and spontaneous HBsAg seroclearance.展开更多
AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.METHODS: We selected studies published after year 2000, ...AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: "gastrointestinal infection AND antineoplastic chemotherapy AND children", "gastrointestinal infection AND oncology AND children", "liver infection AND antineoplastic chemotherapy AND children", "liver abscess AND chemotherapy AND child", "neutropenic enterocolitis AND chemotherapy AND children", "thyphlitis AND chemotherapy AND children", "infectious diarrhea AND children AND oncology", "abdominal pain AND infection AND children AND oncology", "perianal sepsis AND children AND oncology", "colonic pseudo-obstruction A N D o n c o l o g y A N D c h i l d A N D c h e m o t h e r a p y ", "microflora AND children AND malignancy", "microbiota AND children AND malignancy", "fungal flora AND children AND malignancy". We also analysed evidence from several articles and book references.RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infectionin those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available. CONCLUSION: The diagnostic work-up requires a multimodal approach and should be implemented(also by further studies on new biomarkers) for a prompt and individualized therapy.展开更多
Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest pa...Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.展开更多
Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholi...Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholic liver disease and its more severe form,non-alcoholic steatohepatitis and hepatocellular cancer.HIV can infect multiple cells in the liver,leading to enhanced intrahepatic apoptosis,activation and fibrosis.HIV can also alter gastro-intestinal tract permeability,leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function.This review focuses on recent changes in the epidemiology,pathogenesis and clinical presentation of liver disease in HIV-infected patients,in the absence of co-infection with hepatitis B virus or hepatitis C virus,with a specific focus on issues relevant to low and middle income countries.展开更多
AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred ...AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico Ⅱ". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis. CONCLUSION: Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that viruseradication following interferon treatment can last up to 20 years.展开更多
Hepatitis B virus(HBV)infection is the leading cause of severe chronic liver disease.This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes...Hepatitis B virus(HBV)infection is the leading cause of severe chronic liver disease.This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America.Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection.Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America;these strains have historically circulated among the indigenous population.Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans.In contrast,genotypes F,A and D are common in acute and chronic infections among mestizos with Caucasian ancestry.Hepatocellular carcinoma is rare in Mexicans,but it has been associated with genotype F1b among Argentineans.This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America,which contrast with those reported in other regions of the world.展开更多
Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonala...Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.展开更多
文摘Diabetes-related foot disease(DFD)is a widely feared complication among people who live with diabetes.In Australia and globally,rates of disability,cardiovascular disease,lower extremity amputation,and mortality are significantly increased in patients with DFD.In order to understand and prevent these outcomes,we analyse the common pathogenetic processes of neuropathy,arterial disease,and infection.The review then summarises important management considerations through the interdisciplinary lens.Using Australian and international guidelines,we offer a stepwise,evidence-based practical approach to the care of patients with DFD.
文摘Introduction: The transmission of HIV from mother to child is reported from 30% to 40% without any intervention [1]. When all the measures for prevention are implemented, including treatment with HAART (Highly Active Antiretroviral Treatment), the rate of infection can be reduced between 1% and 2% [2]. In Guatemala, the statistics demonstrated an estimated of 20,000 women living with HIV virus infection during the period of 2009. In this scenario, mother to child HIV transmission is an important public health fact. In preliminary reports, there is strong evidence of the impact of preventing mother to child transmission with Lopinavir/Ritonavir in Guatemala is showing a small incidence of new HIV infections and good tolerance [3,4]. Objective: To evaluate the effect of HAART with Lopinavir/Ritonavir on the prevention of mother to child transmission (PMCT) in HIV-positive pregnant women at Roosevelt Hospital in Guatemala City. Methods: A retrospective cohort analysis study. The detection of pregnant HIV positive women and the follow up period was from January 2003 to December 2009, and a total of 219 women completed the follow up time. The HIV diagnosis and follow up for the child was made with molecular testing and antibody testing up to 18 months of age or until testing was negative. Adherence was quantified by pill counts. The interventions where offered to all the women in the cohort. Results: Regarding the pregnancy outcome, the study cohort gave a rate of abortion of 2.3%;10.6% of preterm births and 79.6% normal births. Of the 202/219 children born, there was a 1.4% rate of transmission (n = 3). The three infected children were born from mothers with high basal viral loads (xxx C/mL or higher). There were no serious adverse events related to antiretroviral therapy with Lopinavir/Ritonavir, with a 6.1% of non serious adverse events, most of them of gastrointestinal type, and anemia. Conclusions: The rate of transmission of HIV from mother to child was low in this population (1.4%), comparable to findings from similar studies [4]. Lopinavir/Ritonavir was well tolerated in this cohort and no serious adverse events in this population were reported.
文摘BACKGROUND Ventilator-associated pneumonia(VAP)is defined as pneumonia that occurs two calendar days following endotracheal intubation or after that.It is the most common infection encountered among intubated patients.VAP incidence showed wide variability between countries.AIM To define the VAP incidence in the intensive care unit(ICU)in the central gove-rnment hospital in Bahrain and review the risk factors and the predominant bacterial pathogens with their antimicrobial susceptibility pattern.METHODS The research was a prospective cross-sectional observational study over six months from November 2019 to June 2020.It included adult and adolescent patients(>14 years old)admitted to the ICU and required intubation and mechanical ventilation.VAP was diagnosed when it occurred after 48 h after endotracheal intubation using the clinical pulmonary infection score,which considers the clinical,laboratory,microbiological,and radiographic evidence.RESULTS The total number of adult patients admitted to the ICU who required intubation and mechanical ventilation during the study period was 155.Forty-six patients developed VAP during their ICU stay(29.7%).The calculated VAP rate was 22.14 events per 1000 ventilator days during the study period,with a mean age of 52 years±20.Most VAP cases had late-onset VAP with a mean number of ICU days before the development of VAP of 9.96±6.55.Gram-negative contributed to most VAP cases in our unit,with multidrug-resistant Acinetobacter being the most identified pathogen.CONCLUSION The reported VAP rate in our ICU was relatively high compared to the international benchmark,which should trigger a vital action plan for reinforcing the implementation of the VAP prevention bundle.
文摘The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.
文摘Hepatitis C virus(HCV)/human immunodeficiency virus(HIV)co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,according to World Health Organization.People living with HIV(PLWH)are six times greater affected by HCV,compared to HIV negative ones;the greater prevalence is encountered among people who inject drugs and men who have sex with men:the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection.These patients experience a high rate of chronic hepatitis,which if left untreated progresses to end-stage liver disease and hepato-cellular carcinoma(HCC)HIV infection increases the risk of mother to child vertical transmission of HCV.No vaccination against both infections is still available.There is an interplay between HIV and HCV infections.Treatment of HCV is nowadays based on direct acting antivirals(DAAs),HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono-and coinfected individuals,especially when used at an early stage of fibrosis,reducing liver disease mortality and morbidity.Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication,the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV.HCV eradication can determine dyslipidemia,since HCV promotes changes in serum lipid profiles and may influence lipid metabolism.In addition to these apparent detrimental effects on the lipid profile,the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function.The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.
文摘Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.
文摘Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of recurrence.However,it is still not clear whether C.difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment.The burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with IBD.IBD patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired infections.The clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often absent.Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for C.difficile.Treatment includes general measures such as supportive care and infection control measures.Antibiotic therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as possible.Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI.The aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.
文摘Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn's disease(CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.
基金Supported by Instituto de Salud Carlos III,Plan Nacional de I+D+I 2008-2011No.PI11/00605 and Plan Estatal de I+D+I 2013-2016+1 种基金No.PI14/01779Co-financed by FEDER(Fondo Europeo de Desarrollo Regional)
文摘Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus(HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.
文摘Infectious agents causing aborted fetus problems in domestic pigs were investigated in this study. More than 10 different infectious agents were known to cause abortion in swine and the major eight viruses among them were inspected. One hundred twelve samples of aborted fetuses from nine provinces in South Korea were collected during April to November, 2013 in this study for the diagnosis of infectious agents causing abortions in pigs. Eight major infection viruses were examined in this study mainly using various diagnostic kits and reverse transcriptase polymerase chain reaction (RT-PCR). Positive rate of the detection differed from each viruses. In this study, the main focus was the porcine reproductive and respiratory syndrome virus (PRRSV), which took the second large portion in the positive rate of detection, and then its ORF5 gene was compared with modified live virus (MLV) vaccine strain to figure out the influence of vaccine on disease. Between four positive samples' sequence, two of them were 99.9%-100% similar to MLV vaccine strain and two other samples were 88.6%-92.7% similar. Similarity rate of the sequences between the vaccine and virus from aborted fetuses are very crucial, because it implies that abortion in swine can be made due to the usage of vaccine not only by the infection of field virus, and if MLV vaccine actually do have an impact on the infection, usage of the vaccine should be reconsidered.
文摘In July 2023,the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic.This report summarizes the rich discussions that occurred during the workshop.The workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data,social media,and wastewater monitoring.Significant advancements were noted in the development of predictive models,with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease trends.The role of open collaboration between various stakeholders in modelling was stressed,advocating for the continuation of such partnerships beyond the pandemic.A major gap identified was the absence of a common international framework for data sharing,which is crucial for global pandemic preparedness.Overall,the workshop underscored the need for robust,adaptable modelling frameworks and the integration of different data sources and collaboration across sectors,as key elements in enhancing future pandemic response and preparedness.
文摘Objective: Intracranial suppurations are a cosmopolitan pathology whose prevalence depend of the region of the world. They are mostly caused by otolaryngological infections. Despite the progress, they remain serious diseases in Africa. The objective of this study was to report the epidemiology, clinical and etiological aspects of intracranial suppurations in Togo. Method: This was a retrospective and descriptive study carried out from January 1, 2012 to December 31, 2020 including all cases of intracranial suppuration treated in the neurosurgery unit of Sylvanus Olympio university hospital in Lomé. The evolution was evaluated at discharge, at 3 and 6 months after. Results: We collected 185 cases of intracranial suppuration. The average age of the patients was 12.6 years with a male predominance (72.4%). The main clinical signs were the infectious syndrome (92.4%), intracranial high pressure (51.4%), focal deficit (38.4%) and seizures (20.5%). An otolaryngological infections history was noted within 3 months in 72.4%. The brain CT scan noted a predominance of empyema (63.8%) mostly subdural (64.4%). Radiological sinusitis was found in 57.3%. We identified etiology in 69.2% predominated by otolaryngological causes. Patients received medical and surgical treatment in 77.3%. The bacteriology was positive only in 7 cases. The mortality rate was 15.1%, mostly no operated cases (78.6%). At 6 months 84% recovered without sequelae. The predictive prognostic factors for mortality were: coma (p 0.001), absence of surgical treatment (p 0.02). Conclusion: Intracranial suppuration remains frequent in our country, mainly due to otolaryngological pathologies. The clinical presentation is not always specific and Bergman’s triad is rarely complete. The results of treatment are good if it is early.
文摘AIM: To investigate a possible association between serum vitamin D levels and spontaneous hepatitis B surface antigen (HBsAg) seroclearance. METHODS: Fifty-three patients diagnosed with chronic inactive hepatitis B and spontaneous HBsAg seroclearance were followed up in two Israeli liver units between 2007 and 2012. This retrospective study reviewed medical charts of all the patients, extracting demographic, serological and vitamin D rates in the serum, as well as medical conditions and current medical therapy. Spontaneous HBsAg seroclearance was defined as the loss of serum HBsAg indefinitely. Vitamin D levels were compared to all patients who underwent spontaneousHBsAg seroclearance.HBsAg seroclearance. RESULTS: Out of the 53 patients who underwent hepatitis B antigen seroclearance, 44 patients (83%) had normal levels of 25-hydroxyvitamin vitamin D compared to 9 patients (17%) who had below normal levels. Multivariate analysis showed that age (>35 years) OR = 1.7 (95%CI: 1.25-2.8, P=0.05), serum vitamin D levels (>20 ng/mL) OR = 2.6 (95%CI: 2.4-3.2, P=0.02), hepatitis B e antigen negativity OR = 2.1 (95%CI: 2.2-3.1, P=0.02), low viral load (hepatitis B virus DNA < 100 IU/mL) OR = 3 (95%CI: 2.6-4.2, P = 0.01) and duration of HBsAg seropositivity (> 8 years) OR = 1.6 (95%CI: 1.15-2.6, P=0.04) were also associated with spontaneous HBsAg seroclearance. CONCLUSION: We found a strong correlation between normal vitamin D levels and spontaneous HBsAg seroclearance.
文摘AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: "gastrointestinal infection AND antineoplastic chemotherapy AND children", "gastrointestinal infection AND oncology AND children", "liver infection AND antineoplastic chemotherapy AND children", "liver abscess AND chemotherapy AND child", "neutropenic enterocolitis AND chemotherapy AND children", "thyphlitis AND chemotherapy AND children", "infectious diarrhea AND children AND oncology", "abdominal pain AND infection AND children AND oncology", "perianal sepsis AND children AND oncology", "colonic pseudo-obstruction A N D o n c o l o g y A N D c h i l d A N D c h e m o t h e r a p y ", "microflora AND children AND malignancy", "microbiota AND children AND malignancy", "fungal flora AND children AND malignancy". We also analysed evidence from several articles and book references.RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infectionin those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available. CONCLUSION: The diagnostic work-up requires a multimodal approach and should be implemented(also by further studies on new biomarkers) for a prompt and individualized therapy.
文摘Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.
基金Supported by An NHMRC Practitioner Fellowship to Lewin SRan am FAR Mathilde Krim Fellowship in Basic Biomedical Science to Crane Man NHMRC postgraduate scholarship to Iser D
文摘Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholic liver disease and its more severe form,non-alcoholic steatohepatitis and hepatocellular cancer.HIV can infect multiple cells in the liver,leading to enhanced intrahepatic apoptosis,activation and fibrosis.HIV can also alter gastro-intestinal tract permeability,leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function.This review focuses on recent changes in the epidemiology,pathogenesis and clinical presentation of liver disease in HIV-infected patients,in the absence of co-infection with hepatitis B virus or hepatitis C virus,with a specific focus on issues relevant to low and middle income countries.
文摘AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico Ⅱ". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis. CONCLUSION: Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that viruseradication following interferon treatment can last up to 20 years.
基金Supported by The National Council of Science and Technology,Fondo Sectorial Salud-2010-1-139085the Jalisco State Council of Science and Technology,COECYTJAL-Universidad de Guadalajara 5-2010-1-1041 to Roman S,Guadalajara,Jalisco,Mexico
文摘Hepatitis B virus(HBV)infection is the leading cause of severe chronic liver disease.This article provides a critical view of the importance of genomic medicine for the study of HBV infection and its clinical outcomes in Latin America.Three levels of evolutionary adaptation may correlate with the clinical outcomes of HBV infection.Infections in Latin America are predominantly of genotype H in Mexico and genotype F in Central and South America;these strains have historically circulated among the indigenous population.Both genotypes appear to be linked to a benign course of disease among the native and mestizo Mexicans and native South Americans.In contrast,genotypes F,A and D are common in acute and chronic infections among mestizos with Caucasian ancestry.Hepatocellular carcinoma is rare in Mexicans,but it has been associated with genotype F1b among Argentineans.This observation illustrates the significance of ascertaining the genetic and environmental factors involved in the development of HBV-related liver disease in Latin America,which contrast with those reported in other regions of the world.
文摘Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.