Circulating levels of High-mobility group box 1 protein and nucleosomes are associated with outcomes after liver transplant.

BACKGROUND: Liver transplantation (LT) can be associated with early complications, such as allograft dysfunction and acute kidney injury, which contribute significantly to morbidity and mortality. High-mobility group box 1 protein (HMGB1) has been identified as mediator in ischemia-reperfusion injury. Nucleosomes are complexes formed by DNA and histone proteins, and histones contribute to organs failure and death during sepsis. METHODS: HMGB1 and nucleosome plasma levels were measured, by enzyme-linked immunosorbent assays, during LT and in the first 48 post-operative hours in 22 LT patients. The association between HMGB1 and nucleosome levels and the complications and survival within 6 months after LT were investigated. RESULTS: We observed peak HMGB1 and nucleosome levels after graft reperfusion. HMGB1 and nucleosome levels were associated with the occurrence of acute kidney injury, early allograft dysfunction, and early survival after LT. Nucleosome levels after graft reperfusion were associated with the occurrence of systemic inflammatory response syndrome. CONCLUSIONS: HMGB1 and nucleosome levels increased after liver reperfusion in human LT setting and were associated with early complications and survival. New studies are necessary to explore their role as early markers of hepatocellular injury in human LT and the risk of graft and organs dysfunction and death.

Sarcopenia, body composition and factors associated with variceal gastrointestinal bleeding and splenectomy in hepatosplenic schistosomiasis mansoni.

BACKGROUND: Sarcopenia is a common complication of cirrhosis and an important predictor of morbimortality. We aimed to determine the prevalence of sarcopenia and its associated factors in hepatosplenic schistosomiasis (HSS) as well as to evaluate whether muscle mass and function are associated with variceal upper gastrointestinal bleeding (VUGIB) and previous splenectomy in subjects without other liver diseases. METHODS: We conducted a cross-sectional study including adults with HSS who underwent clinical, biochemical, anthropometric, muscle strength and physical performance evaluations and were submitted to bioelectrical impedance analysis and abdominal ultrasound. Sarcopenia was diagnosed according to the 2019 European consensus criteria. RESULTS: A total of 66 patients with HSS (62.1% male; mean age 48.8±8.6 y) were included. Overall, six subjects (9.1%) were diagnosed with probable sarcopenia and none had confirmed sarcopenia. Fat-free body mass index (BMI) was independently associated with VUGIB (odds ratio 0.701 [95% confidence interval 0.51 to 0.96]; p=0.025). Compared with patients who did not undergo surgery, individuals who underwent esophagogastric devascularization combined with splenectomy (EGDS) had higher serum lipid levels, fat percentage and frequency of metabolic syndrome, with lower skeletal muscle mass index and hand grip strength. CONCLUSIONS: HSS mansoni seems not to cause sarcopenia. However, a lower fat-free BMI was associated with previous VUGIB and the subgroup of patients who underwent EGDS presented higher lipid levels, fat percentage and frequency of metabolic syndrome and lower muscle mass and function.

Liver stiffness is able to differentiate hepatosplenic Schistosomiasis mansoni from liver cirrhosis and spleen stiffness may be a predictor of variceal bleeding in hepatosplenic schistosomiasis.

BACKGROUND: Ultrasonography is limited for differentiating portal hypertension due to liver cirrhosis from that secondary to hepatosplenic schistosomiasis (HSS). We aimed to investigate the role of transient elastography (TE) in differentiating HSS mansoni from cirrhosis and the factors associated with liver and spleen stiffness (LS and SS) in HSS. METHOD: A cross-sectional study was conducted including patients with HSS mansoni (n=29) and liver cirrhosis due to non-alcoholic steatohepatitis (n=23). All patients underwent TE and those with HSS were assessed by the Niamey protocol. RESULTS: HSS subjects presented lower median LS (9.6 vs 21.3 Kpa, p<0.001) and liver controlled attenuation parameter (229 vs 274 dB/m, p=0.010) than cirrhosis subjects, in addition to higher SS (73.5 vs 42.2 Kpa, p=0.002). The area under the receiver operating characteristic curve for detecting cirrhosis by LS was 0.947 (95% CI 0.89 to 1.00, p<0.001), with an optimal cut-off of 11.75 Kpa. In HSS subjects, higher SS was associated with the presence of the following: diabetes mellitus (p=0.036), metabolic syndrome (p=0.043), esophageal varices (p=0.001), portal vein thrombosis (p=0.047) and previous variceal bleeding (p=0.011). In HSS patients without portal vein thrombosis, variceal bleeding was associated with higher SS (p=0.018). Niamey categories were not associated with LS (p=0.676) or SS (p=0.504). CONCLUSION: TE can play a role in differentiating HSS from cirrhosis, especially by LS. SS may be further investigated for predicting complications in HSS.

Are seizures associated with neuroschistosomiasis mansoni? An exploratory survey in an endemic area of Brazil.

BACKGROUND: Deposition of Schistosoma mansoni eggs in the brain of patients with hepatosplenic schistosomiasis (HS-SM) is frequent and usually asymptomatic. However, it is questioned whether it could cause seizures. Thus, we investigated the occurrence of seizures in these patients and also searched for parameters associated with this disorder. METHODS: In a cross-sectional survey, we compared 128 patients with HS-SM with 102 patients with portal hypertension due to compensated chronic hepatic disease of other etiologies. A standardized questionnaire, emphasizing epilepsy-related parameters, was applied to all participants. RESULTS: Eight (6.3%) patients with HS-SM had a history of seizures, whereas this condition was reported by three (2.9%) individuals from the comparison group (p=0.354). None of the variables were associated with the occurrence of seizures, either in univariate or in multivariate analysis. CONCLUSIONS: The frequency of seizures was similar in both study groups. However, it was higher than that described in population-based studies. Thus, we hypothesize that HS-SM individuals may have a higher frequency of seizure. The lack of difference between the two study groups may be explained by the inclusion of cases of HS-MS overlapping other chronic liver diseases in the comparison group, because this finding is relatively common in schistosome-endemic areas.

Portal vein thrombosis in patients with hepatosplenic schistosomiasis who underwent oesophagogastric devascularization combined with splenectomy.

BACKGROUND: Portal vein thrombosis (PVT) has been described in nearly 50% of patients who underwent oesophagogastric devascularization combined with splenectomy (EGDS), but no previous study has compared its occurrence in surgical and non-surgical groups. This study aimed to investigate PVT in hepatosplenic schistosomiasis (HSS) and its association with EGDS and upper variceal bleeding (UVB). METHODS: Retrospectively, 104 HSS individuals were enrolled. Following EGDS, the occurrence of PVT, mesenteric vein thrombosis (MVT), hospital admissions and UVB were recorded. RESULTS: EGDS was performed in 27 (26%) patients. PVT and MVT were detected in 30 (33%) and 8 (9.8%) patients, respectively. Patients who underwent EGDS were at greater risk of PVT (63% vs 19.7%; odds ratio [OR] 6.12 [95% confidence interval {CI} 2.3 to 16.1], p<0.001) when compared with a non-surgical approach. There was no significant difference in UVB occurrence and ß-blocker usage. PVT was associated with more hospital admissions (p=0.030) and higher alkaline phosphatase levels (p=0.008). UVB occurrence in patients with and without thrombosis was similar. In multivariate analysis, after adjustment, PVT was associated with the surgical approach (OR 4.56 [95% CI 1.55 to 13.38], p=0.006) and age at HSS diagnosis (OR 0.94 [95% CI 0.90 to 0.99], p=0.021). CONCLUSIONS: EGDS was not associated with a decreased frequency of UVB when compared with the non-surgical approach but was an independent risk factor for PVT.

Crosstalk Between Plasma Cytokines, Inflammation, and Liver Damage as a New Strategy to Monitoring NAFLD Progression.

Cytokines are involved in the immunopathogenesis of nonalcoholic fatty liver disease (NAFLD), but the relationship between them and clinical parameters of NAFLD progression is still unknown. Using flow cytometry, we evaluated the plasma levels of IL-1ß, IL-6, IL-12, TNF and IL-10 and their association with clinical and biochemical parameters of liver function during simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) in biopsy-proven patients. The NASH patients showed higher levels of IL-6 associated with a lower IL-10/IL-6 ratio. Besides heatmaps were similar in the NAFL and NASH groups, the same did not occur in signature curves, the NASH patients were high producers to IL-12 and IL-6 while the NAFL patients were not high producers of any cytokines evaluated. Integrative biomarker network analysis revealed that cytokines are differently correlated with clinical parameters, while IL-12, IL-10 presented moderate and negative correlations with glycemic and lipid profile in the NAFL group. The NASH group IL-12 and TNF revealed stronger and positive correlations with transient elastography parameters and NAFLD liver fibrosis score. These data suggest that IL-6 and IL-10 might act in chronic inflammation and insulin resistance whereas IL-12 and TNF may be involved in promoting liver damage and NAFLD progression. Plasma concentration analysis of these molecules and their association with clinical parameters can be used as new biomarkers to monitoring NAFLD progression and to reflect NASH development.

Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety.

Donor-derived tuberculosis (DD-TB) accounts for less than 5% of TB cases and is considered a rare event. In the transplant setting, the frequency of active TB is estimated to be 20 to 74 times higher than that in the general population, and it is associated with high mortality. In this context, the main strategy to minimize the risk of DD transmission is to identify high-risk donors. Despite screening recommendations, failures may result in a breakdown of safety that ends in the transmission of potentially fatal diseases. This report describes a case of DD-TB and emphasizes communication gaps that may occur between organ procurement organizations and transplant centers. Failure in reporting results, lack of exchanging information regarding recipients from the same donor, and inefficient communication between organ procurement organizations and transplant centers are lacks that may be prevented by a more efficient approach towards screening protocols and communication.

Expression of MAPK and PI3K/AKT/mTOR Proteins according to the Chronic Liver Disease Etiology in Hepatocellular Carcinoma.

AIMS: Chronic liver disease (CLD) of different etiologies leads to hepatocellular carcinoma (HCC) by multiple mechanisms that may be translated into clinicopathological differences. We evaluated the tissue expression of the MAPK and PI3K/Akt/mTOR pathway proteins and their association with long-term outcome and other parameters, according to the etiology of the CLD, in HCC patients. METHODS: Clinicopathological data from 80 patients who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were compared according to CLD etiology. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analyzed. Pathway protein expression was assessed by immunohistochemistry (IHQ) in both tumor and underlying cirrhosis and by RT-PCR in tumor tissue. RESULTS: Strong expression (SE) of KRAS was more frequent in tumors arising from viral (26.8%) than the nonviral group of liver disease (7.7%, p=0.024) and also than cirrhotic parenchyma (0%, p=0.004). SE of PI3K was more frequent in tumor than in cirrhosis (p=0.048, p < 0.01), without differences in its tumor expression among etiologic groups (p=0.111). mRNA of ERK, PI3K, and BRAF was expressed in the tumor, without differences between CLD etiologies, and there was no association with IHQ findings. Older age and microvascular invasion (MIV) were the only parameters independently associated with the event. MIV was also associated with shorter EFS. CONCLUSIONS: Hepatitis B and C virus can lead to HCC by different mechanisms compared with nonviral hepatopathy. KRAS and PI3K may have a role in carcinogenesis. The prognostic and therapeutic implications need to be investigated.

Nonalcoholic fatty liver disease in women with polycystic ovary syndrome: associated factors and noninvasive fibrosis staging in a single Brazilian center.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence and factors associated with NAFLD in women with PCOS and evaluate noninvasive indices of hepatic fibrosis in patients with PCOS and NAFLD. SUBJECTS AND METHODS: Patients with PCOS (n = 87) and women without PCOS (n = 40; controls) were included. NAFLD was diagnosed by abdominal ultrasonography after exclusion of alcohol consumption and viral or autoimmune liver disease. Anthropometric, clinical and metabolic variables, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid accumulation product (LAP), FIB-4 index, NAFLD score, and transient elastography (TE; FibroScan) were obtained in subsets of patients with PCOS and NAFLD. RESULTS: A total of 87 patients with PCOS were included (mean age: 34.4 ± 5.7 years, mean body mass index [BMI]: 34.7 ± 4.7 kg/m 2 ). NAFLD was present in 67 (77.0%) patients with PCOS versus 21 of 40 (52.5%) controls (p = 0.005). Women with PCOS and liver steatosis, compared with their NAFLD-free counterparts, had higher values of BMI, waist circumference, triglycerides, total cholesterol, alanine and aspartate aminotransferases, and γ-glutamyltransferase, along with higher frequencies of obesity, metabolic syndrome, and insulin resistance. NAFLD was independently associated with waist circumference, serum triglycerides, and alanine aminotransferase levels. The FIB-4 index was not compatible with advanced fibrosis in any of the evaluated patients, while NAFLD score and TE were compatible with advanced liver fibrosis in 1 of 26 (3.8%) and 3 of 25 (12%) patients, respectively. CONCLUSION: Women with PCOS had a high risk of NAFLD, and a combination of both was associated with central obesity, dyslipidemia, insulin resistance, and metabolic syndrome. Noninvasive methods suggested low rates of severe hepatic fibrosis in Brazilian women with PCOS. Arch Endocrinol Metab. 2020;64(3):235-42.

Hepatocellular carcinoma is associated with an increased risk of hepatitis B virus recurrence after liver transplantation.

BACKGROUND & AIMS: Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) is significantly reduced by prophylaxis with hyperimmune antibody to hepatitis B surface antigen (anti-HBs) globulins (HBIG) and antiviral drugs. The role of hepatocellular carcinoma (HCC) in HBV recurrence remains unclear. We investigated the association between HCC pre-OLT and HBV recurrence post-OLT. METHODS: We studied 99 hepatitis B surface antigen-positive patients who underwent OLT for cirrhosis. The median follow-up period was 43 months. All patients received HBIG, and 51 also received lamivudine and/or adefovir. Of these 99 patients, 31 had HCC before OLT. Total HBV DNA and covalently closed circular (ccc)-DNA were measured in tumor and nontumor tissues from the explanted livers of 16 of these 31 HCC patients and, also, in a context of tumor recurrence, in 3 patients who developed HBV/HCC recurrence. RESULTS: Fourteen patients (14.1%) developed HBV recurrence within a median period of 15 months post-OLT. HCC at OLT, a pre-OLT HBV DNA viral load > or = 100,000 copies/mL, and HBIG monoprophylaxis were independently associated with HBV recurrence post-OLT. Eleven out of the 31 patients with HCC at OLT presented with HBV recurrence and 3 out of the 68 patients without HCC had HBV recurrence (P < .0001). HBV recurrence was more frequent in patients who developed HCC recurrence (7/8 patients, 87.5%) than in those who did not (4/23 patients, 17.4%) (P < .0001). In the 16 explanted livers, cccDNA was detectable in HCC cells in 11 and in nontumor cells in 12. cccDNA was detected in a context of HCC recurrence in 2 of the 3 patients tested who developed HBV/HCC recurrence. CONCLUSIONS: The associations of HCC pre-OLT, and HCC recurrence with HBV recurrence post-OLT, and the detection of HBV DNA and cccDNA in HCC suggest that HBV replication in tumor cells may contribute to HBV recurrence post-OLT.

Laryngeal histoplasmosis in an immunocompetent patient from a non-endemic region: case report.

Histoplasma capsulatum infection involving the larynx is a rare manifestation, especially in immunocompetent individuals and a high index of suspicion is needed to establish the diagnosis correctly. We report a case of a 50-year-old Brazilian man who presented with progressive hoarseness and throat pain for 4 months. Laryngoscopy showed a supraglottic vegetant lesion, and the biopsies chronic granulomatous inflammation without any specific agent. A second laryngoscopy with biopsies was performed and after 17 days of incubation in specific medium, H. capsulatum was isolated. The patient was successfully treated with amphotericin B.

Nonalcoholic fatty liver disease in women with polycystic ovary syndrome: associated factors and noninvasive fibrosis staging in a single Brazilian center

ABSTRACT Objective Polycystic ovary syndrome (PCOS) is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence and factors associated with NAFLD in women with PCOS and evaluate noninvasive indices of hepatic fibrosis in patients with PCOS and NAFLD. Subjects and methods Patients with PCOS (n = 87) and women without PCOS (n = 40; controls) were included. NAFLD was diagnosed by abdominal ultrasonography after exclusion of alcohol consumption and viral or autoimmune liver disease. Anthropometric, clinical and metabolic variables, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid accumulation product (LAP), FIB-4 index, NAFLD score, and transient elastography (TE; FibroScan) were obtained in subsets of patients with PCOS and NAFLD. Results A total of 87 patients with PCOS were included (mean age: 34.4 ± 5.7 years, mean body mass index [BMI]: 34.7 ± 4.7 kg/m 2 ). NAFLD was present in 67 (77.0%) patients with PCOS versus 21 of 40 (52.5%) controls (p = 0.005). Women with PCOS and liver steatosis, compared with their NAFLD-free counterparts, had higher values of BMI, waist circumference, triglycerides, total cholesterol, alanine and aspartate aminotransferases, and γ-glutamyltransferase, along with higher frequencies of obesity, metabolic syndrome, and insulin resistance. NAFLD was independently associated with waist circumference, serum triglycerides, and alanine aminotransferase levels. The FIB-4 index was not compatible with advanced fibrosis in any of the evaluated patients, while NAFLD score and TE were compatible with advanced liver fibrosis in 1 of 26 (3.8%) and 3 of 25 (12%) patients, respectively. Conclusion Women with PCOS had a high risk of NAFLD, and a combination of both was associated with central obesity, dyslipidemia, insulin resistance, and metabolic syndrome. Noninvasive methods suggested low rates of severe hepatic fibrosis in Brazilian women with PCOS. Arch Endocrinol Metab. 2020;64(3):235-42

Identification and characterization of immune complexes in the cerebrospinal fluid of patients with spinal cord schistosomiasis.

The pathogenesis of neuroschistosomiasis is largely unknown. Available evidence suggests that it depends on the presence of parasite eggs in the nervous tissue and on the host's immune response. We investigated the presence of immune complexes (ICs) in the cerebrospinal fluid (CSF) of four patients with spinal cord schistosomiasis (SCS), and performed their characterization. ICs containing soluble egg antigen of Schistosoma mansoni (SEA) were found in the CSF of all the SCS patients. To our knowledge, this is the first evidence of ICs containing schistosomal antigens in the CSF of patients with SCS. Further studies are necessary to confirm our findings and investigate the possible roles of ICs in the pathogenesis of this disease.

Tuberculosis in liver transplant recipients: a single Brazilian center experience.

BACKGROUND: Tuberculosis (TB) is an important opportunistic infection in transplant recipients worldwide. The frequency of Mycobacterium tuberculosis disease varies among different regions, but the incidence of TB in adult liver transplant (LT) recipients is largely unknown. The estimated frequency ranges from 0.7% to 2.3%, with mortality rate up to 30%. However, these data are based on individual case reports or series with small samples. In LT recipients, therapy is generally associated with significant hepatotoxicity and interactions with immunosuppressive drugs. METHODS: This retrospective analysis included 319 patients who underwent LT at University Hospital, Federal University of Minas Gerais, Brazil, between September 1994 and July 2007 and survived more than 1 month. Among these, TB was diagnosed in five patients. No patients received chemoprophylaxis before or after LT. RESULTS: All five patients were women, mean age 39.6+/-16.5 years. Two patients had disseminated TB, two pulmonary involvement, and one extrapulmonary disease. Cultures were positive in four patients. Overall, four patients received isoniazid, rifampin, and pyrazinamide for 6 to 12 months, with good tolerance, but one patient presented recurrence. Another patient presented raised hepatic enzymes levels after initiating therapy. All patients are alive and well. CONCLUSIONS: In this series, the TB frequency after liver transplantation was 1.57%, with no confirmed hepatotoxicity with conventional treatment and an excellent survival rate (100%).