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Background and Aims: Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Methods: Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. Results: SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Conclusion: Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

Growing evidence suggests that cholestatic and fatty liver disease share common pathophysiological mechanisms. Rare loss-of-function variants in the ATP binding cassette subfamily B member 4 (ABCB4) gene have been associated with gallstone disease and with a spectrum of cholestatic liver diseases, ranging from progressive familial intrahepatic cholestasis to less severe conditions, like low phospholipid-associated cholelithiasis or intrahepatic cholestasis during pregnancy. Whole-genome sequencing of Icelanders revealed the common variant rs2109505 T>A in ABCB4 , conferring protection against gallstone disease and being associated with lower transaminases. To identify common variants in ABCB4 associated with severe liver disease. We examined the association of missense and nonsense common variants (minor allele frequency >1%) at the ABCB4 locus with ALT in 412,912 Europeans from the UK Biobank using a whole-genome regression model. Next, we tested the association of the lead variant in the region with liver-related traits and incident severe liver disease in a subset of 365,449 unrelated Europeans by multiple linear/logistic regression models and Cox proportional hazards models, respectively. Analyses were adjusted for age, gender, BMI, type 2 diabetes, alcohol intake, and first 10 PCs of ancestry. We identified the ABCB4 rs1468615 T>C as the lead variant independently associated with ALT (P = 2.26 × 10−34). The rs1468615 is an intronic variant in high linkage disequilibrium with the rs2109505 (r2 = 0.94). The rs1468615 was associated with lower risk of gallstone disease (P = 8.56 × 10−12) and with lower liver enzymes (P = 2.28 × 10−30, P = 8.31 × 10−09, and P = 8.08 × 10−04 for ALT, AST, and GGT respectively). No association was found with liver cirrhosis, liver cancer, and gallbladder/biliary tract cancer. No association was found with incident severe liver disease. The rs1468615 T>C in ABCB4 confers protection against gallstone disease but not against the development of severe liver disease. [ABSTRACT FROM AUTHOR]

Programmed cell death 1/programmed cell death-ligand 1 (PD-1/PDL-1) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the PDCD1 variation associates with NAFLD severity in individuals with liver biopsy. We examined the impact of PDCD1 gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G>C variation was subsequently tested for association with liver damage in 2,889 individuals who underwent liver biopsy for suspected nonalcoholic steatohepatitis (NASH). Hepatic transcriptome was examined by RNASeq in a subset of NAFLD individuals (n=121). Transcriptomic and deconvolution analyses were performed to identify biological pathways modulated by the risk allele. The rs13023138 C>G showed the most robust association with HCC in UK Biobank (P = 5.28E-4, OR=1.32, 95% CI [1.1, 1.5]). In the liver biopsy cohort, rs13023138 G allele was independently associated with severe steatosis (OR 1.17, 95%C.I. 1.02-1.34; p=0.01), NASH (OR 1.22, 95%C.I. 1.09-1.37; p<0.001) and advanced fibrosis (OR 1.26, 95%C.I. 1.06-1.50; p=0.07). At deconvolution analysis, rs13023138 G>C allele was linked to higher hepatic representation of M1 macrophages, paralleled by upregulation of pathways related to inflammation and higher expression of CXCR6. The PDCD1 rs13023138 G allele was associated with HCC development in general population and with liver disease severity in patients at high risk of NASH. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of our study is to assess the incidence of prosthetic joint infection (PJI) after total Knee arthroplasty (TKA), total Hip arthroplasty (THA) and total Shoulder arthroplasty (TSA), to identify risk factors, determine the microbial spectrum and management’s outcome. PATIENTS AND METHODS: A case-control, retrospective observational study was performed analyzing patients who developed a PJI after TKA, THA, and TSA from 2000 to 2017 at our hospital. The patient’s risk profile was defined extracting from clinical records the following data: sex, age, BMI, type of implant, comorbidity, year of surgery, year of infection, previous intra-articular injection, microbial isolation, medical and surgical management outcome. We include in the “control group” for each “case” at least 3 patients who didn’t have a PJI after TJA. RESULTS: 28 patients met all inclusion and exclusion criteria. Comparing the “cases” with “controls” demographics parameters, medical comorbidities and previous intra-articular injection were not associated with an increased risk of PJI. Comparing the “early/delayed group” with “late group”, BMI was associated with an increased risk of early/delayed PJI, while demographics parameters, medical comorbidities, and previous intra-articular injection did not significantly increase the risk of PJI. Logistic regression showed that for each BMI unit there was a 20-fold increased risk of early prosthetic infection (OR 1.19, IC 1.03-1.38, p=0.01). Staphylococci were isolated most frequently from pre-operative and intra-operative cultures. Twostage arthroplasty exchange and surgical debridement resulted in the most performed surgical treatment with a success rate of 88 and 87%. CONCLUSIONS: Obesity is a risk factor for “early/delayed infection” of TJA. Two-stage arthroplasty exchange, debridement, antibiotics, and implant retention in patients are treatments with a high rate of success in terms of reinfection. [ABSTRACT FROM AUTHOR]

Background To investigate serum concentrations of high-sensitive C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP) in patients with T1DM, at diagnosis and after 12 months of intensive insulin therapy (T12). Methods CRP and AGP were measured in 44 recent onset T1DM patients (26M/18F, mean age 14.9 ± 9.1 years), and 44 age- and sex-matched controls, using a highly sensitive immunonephelometric assay. Results There were no significant differences in the concentrations of high-sensitive C-reactive protein (hs-CRP) and AGP between patients and controls. hs-CRP levels significantly increased in patients at T12 compared to the levels at diagnosis [0.69 (0.14-15.5) versus 0.43 (0.14-7.47) mg/L, p < 0.05; for males: 0.77 (0.14-15.5) versus 0.35 (0.14-7.47) mg/L, p < 0.05; for females the increase was not significant]. AGP levels were not different at T12 compared to diagnosis. No significant correlations were found between hs-CRP and body mass index (BMI), C-peptide, glycosylated haemoglobin, or insulin dose. A strong correlation was found between hs-CRP values at diagnosis and those at T12 (ρ = 0.73, p < 0.001); indeed, patients with hs-CRP levels above the 50th percentile at diagnosis showed significantly increased hs-CRP values at T12 compared to patients with baseline hs-CRP levels under the 50th percentile [1.61 (0.18-15.5) versus 0.16 (0.14-1.92) mg/L, p < 0.0001)], and to controls [0.55 (0.14-6.50), p = 0.001]. Conclusions This is the first report showing that, despite good metabolic control, 1 year of overt T1DM is sufficient to increase hs-CRP levels, especially in males. hs-CRP levels at diagnosis is a predictor for the values observed at 12 months, suggesting the possibility to select a subgroup of patients requiring strict follow-up for cardiovascular complications. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims : To evaluate the cytoplasmic and nuclear expression of hepatic growth hormone receptor (GHR) in different stages (S0, S1, S3 and S4, according to Knodell's classification) of chronic liver disease (CLD) and in hepatocellular carcinoma (HCC). Methods and results : Liver specimens from 31 patients with hepatitis C virus-related CLD, five patients with HCC and nine controls were examined for expression of hepatic GHR by immunohistochemistry with MAb 263. Cytoplasmic and nuclear staining were evaluated as a percentage of positively stained cells. The cytoplasmic expression of GHR was comparable between normal liver and S0 hepatitis, while it progressively decreased in S1, S3 and S4 CLD ( P < 0.01). Conversely, nuclear GHR showed increased expression in S3 and S4 CLD ( P < 0.05). No differences were observed between HCC and normal liver in terms of GHR immunoreactivity. Conclusions : This is the first study to show that the subcellular expression of hepatic GHR changes with the progression of CLD. The increase in nuclear expression of GHR with advanced stages of CLD suggests that GH may act directly at the nuclear level to promote hepatocyte proliferation/regeneration. [ABSTRACT FROM AUTHOR]