Cryptococcal peritonitis in patients on the liver transplant waitlist: Reporting two cases with opposite outcomes.

Cryptococcus neoformans is rarely associated with peritonitis in cirrhotic patients; nevertheless, it has a high mortality rate. Early diagnosis and prompt treatment may be the determining prognostic factors. This is a report of two patients awaiting a liver transplant who had opposite outcomes after the diagnosis of spontaneous cryptococcal peritonitis. In Patient 1, the fungal culture was positive in the blood and ascites. She had a poor evolution and died, which was likely caused by the delayed diagnosis and concomitant bacterial infections. In Patient 2, the fungus was found in the ascites, urine, and cerebrospinal fluid cultures. Antifungal treatment was effective. He underwent a liver transplant on the 83rd day of antifungal therapy and is still alive 1 year later. It is important to suspect fungal etiology when there is a lack of response to antibiotics in patients with decompensated cirrhosis and spontaneous peritonitis, and physicians must be aware of leukocyte count in the ascitic fluid, which is not so high in these cases. This report also emphasizes the need for the routine use of blood culture bottles for microbiological analysis of the ascitic fluid, as it was helpful to diagnose fungal peritonitis in both cases.

Direct-Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait-List Progression or Posttransplant Recurrence.

The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre- or post-LT DAA effect). From 994 included patients, 50.6% were HCV-, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alpha-fetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre- or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT.

Yellow fever disease in a renal transplant recipient: Case report and literature review.

Yellow fever (YF) is a viral disease, with clinical presentation among immunosuppressed patients not fully understood. YF vaccination (YFV), a live vaccine, is contraindicated in patients receiving immunosuppressive treatment due to the risk of developing the disease after vaccination. We report a case of a 50-year-old male recipient who presented wild-type YF five years after a deceased donor kidney transplant. He lived in a YF endemic area and inadvertently received YFV. One day after YFV, the patient presented nausea, vomiting, fever, diarrhea, polyarthralgia, thrombocytopenia, and increased levels of liver function enzymes. The serological test was compatible with YF disease, and quantitative viral load confirmed the diagnosis of wild-type YF. The patient received supportive care for twelve days, with hospital discharge in good clinical condition and stable renal function. One month after discharge, the patient developed de novo donor-specific anti-HLA antibodies (DSA) and histological evidence of endothelial lesion, with a diagnosis of acute antibody-mediated rejection (AMR), treated with plasmapheresis and human IVIg therapy. Six months after therapy, he presented normal renal function with a reduction of DSA MFI. In the reported case, we observed a clinical wild-type YF diagnosed even after YF vaccine administration, with good clinical outcome. De novo DSA and AMR occurred after the recovering of disease, with an adequate response to therapy and preserved allograft function. We reviewed the published literature on YF and YFV in solid organ transplantation.

Immunization in end stage renal disease: The perception of waiting list patients.

BACKGROUND: The number of patients with chronic kidney disease is increasing worldwide, as well as the number of patients in kidney transplant waiting lists. In order to prevent infections related to immunosuppressive therapy, immunization guidelines for CKD patients before transplantation have been proposed. The aim of the present study was to evaluate adherence to immunization in a cohort of CKD patients in transplant waiting list and their renal replacement therapy clinics. METHODS: CKD patients older than 18 years old, receiving renal replacement therapy longer than 12 months and included in kidney transplant waiting list at University of Campinas (Unicamp) were enrolled. RESULTS: From February 2014 to December 2015, 105 patients fulfilled the inclusion criteria. Complete hepatitis B vaccination was observed in 73% and influenza vaccine in 67%. None of the other vaccine protocols reached 50% of coverage. Patients receiving immunization at primary health units presented higher coverage for diphtheria, tetanus (dT), measles, mumps, rubella (MMR), and hepatitis B vaccines, while patients immunized at renal replacement therapy clinics showed higher prevalence of pneumococcus (pneumo23). CONCLUSION: The low rates of immunization could reflect the RRT's clinics knowledge about the vaccines guidelines and its application on daily care. We suggest an integration between transplant center and RRT clinics, through lectures, periodic checking of vaccination cards, and easy to follow guidelines in order to provide a better vaccine coverage and to obtain higher immunization rates.

Probable transfusion-transmitted Zika virus in Brazil.

BACKGROUND: Zika virus (ZIKV) is an emerging arthropod-borne flavivirus transmitted by Aedes mosquitoes. Recent commentaries regarding ZIKV routes of transmission describe a potential transmission by transfusion. Herein, we report a probable case of transfusion-transmitted ZIKV infection through a platelet transfusion that was detected from postdonation information. CASE REPORT: A blood donor made a voluntary telephone report to the blood donor facility 3 days after donation and informed the facility of a febrile illness (fever, malaise, and headaches). Due to the ongoing dengue epidemic, the initial clinical investigation included dengue among other possible diagnoses. The serology and molecular laboratory results excluded dengue infection. However, stored samples from the donation were positive for ZIKV on reverse transcription-polymerase chain reaction (RT-PCR) analysis. A retrospective investigation demonstrated that the platelet concentrate, which was part of a pool, had been transfused after a liver transplantation. A physician had evaluated the patient 4 days after surgery. Laboratory investigation showed enzyme-linked immunosorbent assay results that were negative for dengue immunoglobulin M antibodies; however, the results were positive for hemagglutination inhibition antibodies against flavivirus. ZIKV RT-PCR and virus isolation analyses in cell cultures from recipient serum were both positive. The sequencing confirmed ZIKV in the donor and patient samples. Ten partial nucleotide sequences from the ZIKV strain that were detected in the donor were aligned and compared with the ZIKV genome detected in the recipient, revealing a 99.8% homology between the two strains. CONCLUSIONS: This is a case of probable transmission of ZIKV through blood transfusion. The patient had been transfused with the blood product from an infected donor, most likely in the incubation period after ZIKV infection but prior to clinical disease onset. This report emphasizes the importance of postdonation information and recipient investigations during outbreaks of potentially blood-borne infections.

Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19.

COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

Understanding the Elevated Lethality of COVID-19 in Liver Transplant Recipients: Does Immunosuppression Management Matter? Results from a Brazilian Multicentric Historical Cohort.

BACKGROUND: Infections by SARS-CoV-2 in liver transplant recipients (LT) patients are of particular concern, notably due to perceived added risks related to immunosuppression and comorbidity burden. Current literature on this topic often relies on small, non-standardized, and geographically limited studies. This manuscript describes COVID-19 presentations and causes for elevated mortality in a large cohort of LT recipients. METHODS: This study was designed as a multicentric historical cohort, including LT recipient patients with COVID-19 in 25 study centers, with the primary endpoint being COVID-related death. We also collected demographic, clinical, and laboratory data regarding presentation and disease progression. RESULTS: Two hundred and thirty-four cases were included. The study population was predominantly male and White and had a median age of 60 years. The median time from transplantation was 2.6 years (IQR 1-6). Most patients had at least one comorbidity (189, 80.8%). Patient age (P = .04), dyspnea (P < .001), intensive care unit admission (P < .001), and mechanical ventilation (P < .001) were associated with increased mortality. Modifications of immunosuppressive therapy (P < .001), specifically the suspension of tacrolimus, maintained significance in multivariable analysis. CONCLUSIONS: Attention to risk factors and the individualization of patient care, especially regarding immunosuppression management, is crucial for delivering more precise interventions to these individuals.

Cryptogenic hepatitis patients have a higher Bartonella sp.-DNA detection in blood and skin samples than patients with non-viral hepatitis of known cause.

BACKGROUND: This study aimed to assess the prevalence of Bartonella sp.-DNA detection in blood and skin samples from patients with non-viral end-stage liver disease awaiting liver transplantation. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples and healthy skin fragments from 50 patients were tested using microbiological and molecular methods. Fifteen patients had cryptogenic hepatitis (CH) and 35 had alcoholic, drug-induced or autoimmune liver disease. DNA was extracted from whole blood and liquid culture samples, isolates, and skin fragments. Thirteen of the 50 patients (26%) had Bartonella henselae DNA detection in their blood (9/50) and/or skin (5/50) samples. Colonies were isolated in 3/50 (6%) and infection was detected in 7/50 (14%) of the 50 patients. B. henselae-DNA detection was more prevalent in patients with CH than in other patients (p = 0.040). Of 39 patients followed-up for at least two years, a higher mortality rate was observed among patients with CH infected with B. henselae (p = 0.039). CONCLUSIONS/SIGNIFICANCE: Further studies assessing the role of B. henselae infection in the pathogenesis of hepatitis patients must be urgently conducted.

Incidence and Impact of COVID-19 Cases in Brazilian Liver Transplant Recipients: An Academic, Single-center Experience.

BACKGROUND: Current literature reports diverge on the impact of COVID-19 in liver transplant (LT) recipients. Literature findings often report conflicting results, relying on small sample sizes, limited ethnic variability, and nonstandardized methodologies. Notably, there are no studies on this topic regarding Latin American populations. This study seeks to report the impact of COVID-19, disease characteristics, and progression in LT recipients in a Latin American academic center environment. METHODS: The study design was a historic cohort, including adult LT recipient patients with suspected or confirmed COVID-19 who sought care between December 2019 to October 2021. The primary end point was defined as COVID-19-related death. Demographic, clinical, and laboratory data was also collected. RESULTS: Twenty-seven patients were included, representing a 3.5% incidence within 752 patients in the follow-up. The mean age and years from transplantation were 54 (SD ± 11) and 6.3 years (SD ± 5.4), respectively. Most patients were white (23 - 85.2%) and male (21 - 25.2%). The hospitalization rate was 55.6%, and 5 patients (18.5%), all of whom subsequently died, were admitted to the intensive care unit. Neither the presence of comorbidities nor advanced age were related to lethality. Patients with immunosuppression modifications (P = 0.039) or isolated tacrolimus suspension (P = 0.006) were associated with increased mortality. CONCLUSIONS: This study described COVID-19 infections in LT recipients in Latin American populations. This group was not affected by common factors associated with higher lethality, and displayed a tendency toward lower hospitalization rates. Our study concurred with previously reported evidence of a protective association of tacrolimus maintenance during treatment in LT recipients affected by COVID-19.

Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report.

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

COVID-19 and isolation: Risks and implications in the scenario of new variants.

With the emergence of new variants of SARS-CoV-2, questions about transmissibility, vaccine efficacy, and impact on mortality are important to support decision-making in public health measures. Modifications related to transmissibility combined with the fact that much of the population has already been partially exposed to infection and/or vaccination, have stimulated recommendations to reduce the isolation period for COVID-19. However, these new guidelines have raised questions about their effectiveness in reducing contamination and minimizing impact in work environments. Therefore, a collaborative task force was developed to review the subject in a non-systematic manner, answering questions about SARS-CoV-2 variants, COVID-19 vaccines, isolation/quarantine periods, testing to end the isolation period, and the use of masks as mitigation procedures. Overall, COVID-19 vaccines are effective in preventing severe illness and death but are less effective in preventing infection in the case of the Omicron variant. Any strategy that is adopted to reduce the isolation period should take into consideration the epidemiological situation of the geographical region, individual clinical characteristics, and mask for source control. The use of tests for isolation withdrawal should be evaluated with caution, due to results depending on various conditions and may not be reliable.

Recommendations from the Brazilian Society of Nephrology for approaching Covid-19 Diagnostic Testing in Dialysis Units.

The Covid-19 pandemic brought several challenges to the healthcare system: diagnosis, treatment and measures to prevent the spread of the disease. With the greater availability and variety of diagnostic tests, it is essential to properly interpret them. This paper intends to help dialysis units concerning the use of clinical criteria and diagnostic tests for decision making regarding the discontinuation of isolation of patients with suspected or confirmed Covid-19, as well as the return to work activities for employees with suspected or confirmed Covid-19.

Bloodstream Infections in Early Postsurgery Liver Transplant: An Analysis of 401 Patients Over 10 Years.

Bloodstream infections are a major factor contributing to morbidity and mortality following liver transplantation. The increasing occurrence of multidrug-resistant bloodstream infections represents a challenge for the prevention and treatment of those infections. The aim of this study was to evaluate the occurrence and microbiological profile of bloodstream infections during the early postoperative period (from day 0 to day 60) in patients undergoing liver transplantation from January 2005 to June 2016 at the State University of Campinas General Hospital. A total of 401 patients who underwent liver transplantation during this period were included in the study. The most common cause of liver disease was hepatitis C virus cirrhosis (34.01%), followed by alcoholic disease (16.24%). A total of 103 patients had 139 microbiologically proven bloodstream infections. Gram-negative bacteria were isolated in 63.31% of the cases, gram-positive bacteria in 28.78%, and fungi in 7.91%. Fifty-six infections (43.75%) were multidrug-resistant bacteria, and 72 (56.25%) were not. There was no linear trend concerning the occurrence of multidrug-resistant organisms throughout the study period. Patients with multidrug-resistant bloodstream infections had a significantly lower survival rate than those with no bloodstream infections and those with non-multidrug-resistant bloodstream infections. In conclusion, the occurrence of bloodstream infections during the early postoperative period was still high compared with other profile patients, as well as the rates of multidrug-resistant organisms. Even though the occurrence of multidrug resistance has been stable for the past decade, the lower survival rates associated with that condition and the challenge related to its treatment are of major concern.

Cost-utility analysis of outpatient parenteral antimicrobial therapy (OPAT) in the Brazilian national health system.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) has been used for decades in different countries to reduce hospitalization rates, with favorable clinical and economic outcomes. This study assesses the cost-utility of OPAT compared to inpatient parenteral antimicrobial therapy (IPAT) from the perspective of a public university hospital and the Brazilian National Health System (Unified Health System -SUS). METHODS: Prospective study with adult patients undergoing OPAT at an infusion center, compared to IPAT. Clinical outcomes and quality-adjusted life year (QALY) were assessed, as well as a micro-costing. Cost-utility analysis from the hospital and SUS perspectives were conducted by means of a decision tree, within a 30-day horizon time. RESULTS: Forty cases of OPAT (1112 days) were included and monitored, with a favorable outcome in 97.50%. OPAT compared to IPAT generated overall savings of 31.86% from the hospital perspective and 26.53% from the SUS perspective. The intervention reduced costs, with an incremental cost-utility ratio of -44,395.68/QALY for the hospital and -48,466.70/QALY for the SUS, with better cost-utility for treatment times greater than 14 days. Sensitivity analysis confirmed the stability of the model. CONCLUSION: Our economic assessment demonstrated that, in the Brazilian context, OPAT is a cost-saving strategy both for hospitals and for the SUS.

Diagnosis and staging of fibrosis in patients with chronic hepatitis C: comparison and critical overview of current strategies.

In the past years, what has always been considered undisputed true in liver fibrosis staging has been challenged. Diagnostic performance of histological evaluation has proven to be significantly influenced by sample- and observer-related variabilities. Differentiation between lower levels of fibrosis remains difficult for many, if not all, test modalities, including liver biopsy but, perhaps, such a distinction is not indispensable in light of current therapeutic approaches. Biomarkers and elastography offer, nonetheless, high predictive values for advanced fibrosis and cirrhosis and correlate well with liver-related outcomes. Necroinflammation, steatosis, and hemodynamic changes may significantly interfere with elastography-based techniques, and longitudinal follow-up strategies must be tailored in light of these findings. Knowledge of different test modalities and diagnostic performance indicators can allow for better clinical decision-making and resource allocation.

All-oral direct antiviral treatment for hepatitis C chronic infection in a real-life cohort: The role of cirrhosis and comorbidities in treatment response.

BACKGROUND: Hepatitis C virus (HCV) infection is the major cause of end-stage liver disease (LD) worldwide. The aim of this study was to assess sustained virological response (SVR) rates in a real-world cohort of patients with HCV infection treated with interferon-free direct antiviral agents (DAA). PATIENTS AND METHODS: All patients with genotypes 1, 2 or 3 HCV infection who started interferon-free treatment at a university hospital from December 2015 through July 2017 were included. The primary outcome was SVR at post-treatment week 12 by intention-to-treat (ITT) and modified ITT (mITT) analysis. RESULTS: Five hundred twenty seven patients were enrolled, 51.6% with cirrhosis. Most patients received sofosbuvir + daclatasvir + ribavirin (60.7%) and sofosbuvir + simeprevir (25.6%). Overall SVR rates were 90.5% for ITT and 96% for mITT. SVR rates were higher in non-cirrhotic (94.2% in ITT and 96.8% in mITT) versus cirrhotic patients (87.1% in ITT and 95.2% in mITT). In ITT and mITT assessments, SVR rates were higher in patients with Child-Pugh A (n = 222, 88.7% and 95.7%, respectively) versus Child-Pugh B or C (n = 40, 80% and 90%, respectively); SVR rates were higher in patients with genotype 1 (n = 405, 92.1% and 98.2%), followed by genotype 2 (n = 13, 84.6% and 92.7%) and genotype 3 (n = 109, 84.4% and 88.4%). Lower comorbidity index (p = 0.0014) and absence of cirrhosis (p = 0.0071) were associated with SVR. Among cirrhotic patients, lower Model for End-Stage Liver Disease (p = 0.0258), higher albumin (p = 0.0015), and higher glomerular filtration rate (p = 0.0366) were related to SVR. Twenty-two cirrhotic patients (8%) had clinical liver decompensation during treatment. Complications of advanced LD were responsible for discontinuation of treatment and death in 12 and 7 patients, respectively. CONCLUSION: Treatment with all-oral DAA achieved high SVR rates, particularly in patients without cirrhosis and few comorbidities. Advanced LD is associated to poor outcome, such as treatment failure and death.

Controlled attenuation parameter for steatosis grading in chronic hepatitis C compared with digital morphometric analysis of liver biopsy: impact of individual elastography measurement quality.

BACKGROUND AND OBJECTIVE: Controlled attenuation parameter (CAP) diagnostic performance for steatosis grading has been controversial and considerable observer-related variability in liver biopsy has been reported. This is a subanalysis of a larger chronic hepatitis C study on noninvasive fibrosis staging. MATERIALS AND METHODS: Patients were prospectively enrolled for paired liver biopsy and transient elastography. Biopsy fragments were subjected to digital morphometric steatosis quantification. Associated patient and technical factors, including a newly described elastogram quality score, were evaluated. RESULTS: A total of 312 patients were included in the final analysis. The mean liver stiffness was 8.7±2.1 kPa. Morphometry showed S0 in 19.2% of patients, S1 in 28.5%, S2 in 31.1%, and S3 in 21.2%. CAP showed S0 in 11.2% of patients, S1 in 26.6%, S2 in 56.7%, and S3 in 5.4%. Spearman coefficient showed a positive and independent correlation between CAP and morphometric analysis (r=0.48, P<0.05), except for distinguishing S1 and S2 (P=0.11). Area under the receiver operating characteristic curves for the presence or absence of steatosis was 0.944; differentiation between levels I, II, and III were 0.776, 0.812, and 0.879. Elastogram quality independently predicted accuracy [odds ratio (OR): 6.95, 95% confidence interval (95%CI): 4.45-9.06 as well as CAP interquartile range OR: 2.81, 95%CI: 1.67-3.99] and liver stiffness (OR: 0.78, 95%CI: 0.51-0.80). CONCLUSION: We present an external validation for CAP against the objective steatosis quantification provided by digital morphometry. Fairly good performance indicators were found, except for S1 versus S2 differentiation. Variability and higher liver stiffness were associated with lower performance. Achieving higher quality measurements, however, overcame such limitations with excellent accuracy.

Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19

ABSTRACT COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America.

The Recommendations for Management of Endemic Diseases and Travel Medicine in Solid-Organ Transplant Recipients and Donors: Latin America clinical practice guideline is intended to guide clinicians caring for solid-organ transplant (SOT) donors, candidates and recipients regarding infectious diseases (ID) issues related to this geographical region, mostly located in the tropics. These recommendations are based on both systematic reviews of relevant literature and expert opinion from both transplant ID and travel medicine specialists. The guidelines provide recommendations for risk evaluation and laboratory investigation, as well as management and prevention of infection of the most relevant endemic diseases of Latin America. This summary includes a brief description of the guideline recommendations but does not include the complete rationale and references for each recommendation, which is available in the online version of the article, published in this journal as a supplement. The supplement contains 10 reviews referring to endemic or travel diseases (eg, tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections, viral hepatitis, and vaccines) and an illustrative section with maps (http://www.pmourao.com/map/). Contributors included experts from 13 countries (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey, United Kingdom, United States, and Uruguay) representing four continents (Asia, the Americas and Europe), along with scientific and medical societies.

Predictors of early discontinuation of interferon-free direct antiviral agents in patients with hepatitis C virus and advanced liver fibrosis: results of a real-life cohort.

AIM: The aim of this study was to determine risk factors for premature treatment discontinuation among patients with hepatitis C and advanced fibrosis with advanced fibrosis treated with interferon (IFN)-free direct antiviral agents (DAA)-based therapy. PATIENTS AND METHODS: We included all patients with chronic hepatitis C virus infection and advanced liver fibrosis in whom treatment was initiated with IFN-free DAA therapy at a university hospital from December 2015 through June 2016. We prospectively collected data from medical records using standardized questionnaires and evaluated them using Epi Info 7.1.2.0. The primary outcome was treatment interruption and associated factors. RESULTS: In total, 214 patients were included in this study; 180 patients were treated with sofosbuvir (SOF)+daclatasvir±ribavirin (RBV), 31 received SOF+simeprevir±RBV, and three were treated with SOF+RBV. Treatment discontinuation rate was 8.9% (19 patients) and cirrhotic decompensation was the main reason [8 (42.1%)]. Among patients with Child B or C cirrhosis (31), 10 (32.2%) prematurely interrupted treatment. The risk factors for treatment discontinuation in univariate analysis were older age (P=0.0252), higher comorbidity index (P=0.0078), higher model for end-stage liver disease (P<0.0001), higher fibrosis index based on the 4 factores (P=0.0122), and lower hemoglobin (P=0.0185) at baseline. Multivariate analysis showed that older age (odds ratio: 1.1, 95% confidence interval: 1.02-1.19) and higher model for end-stage liver disease (odds ratio: 1.27, 95% confidence interval: 1.03-1.56) were associated with premature treatment interruption. CONCLUSION: Older age and advanced liver disease were related to treatment interruption. Identification of risk factors associated with treatment discontinuation is important to recognize patients who should be followed up closely during treatment, ando those whom possibly may not benefit from immediate DAA treatment or should be followed up closely during treatment.