Background & Aims: HIV-seropositivity shortens survival in patients with hepatocellular carcinoma (HCC). Although risk factors for HCC including HCV infection can influence T cell phenotype, it is unknown whether HIV can influence functional characteristics of the T cell infiltrate. Methods: From the Liver Cancer in HIV biorepository, we derived 129 samples of transplanted (76%) or resected (20%) HCC in eight European and North American centres. We profiled intra-and peritumoural tissue to evaluate regulatory CD4+/FOXP3+ and immune-exhausted CD8+/PD1+ T cells in HIV+ (n = 66) and HIV-(n = 63) samples. We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples evaluated in relationship with HIV status. We correlated immunopathologic features with patients' characteristics including markers of HIV infection. Results: Of the 66 HIV+ patients, 83% were HCV coinfected with an undetectable HIV viral load (51%) and a median blood CD4+ cell count of 430 cells/mm3 (range 15-908). Patients who were HIV+ were compared with HIV-controls with similar staging characteristics including Barcelona Clinic Liver Cancer (BCLC) stage A-B (86% vs. 83%, p = 0.16), <3 nodules (90% vs. 83%, p = 0.3) and median alpha-foetoprotein values (10.9 vs. 12.8 ng/ml, p = 0.72). HIV+ samples had higher PD-L1 expression rates in tumour tissue (51% vs. 8% p <0.0001) and displayed denser intratumoural CD4+/FOXP3+ (p <0.0001), CD8+/PD1+ (p <0.0001), with lower total peritumoural CD4+ (p <0.0001) and higher peritumoural CD8+/PD1+ (p <0.0001). Gene set analysis revealed HIV+ cases to have evidence of dysregulated adaptive and innate immunity. Tumour-infiltrating lymphocyte clonality was not influenced by HIV status. Conclusions: HIV-associated HCC harbours a profoundly immune-exhausted tumour microenvironment, warranting pro-spective testing of immunotherapy in this treatment-deprived patient population. Impact and Implications: Hepatocellular carcinoma is a non-AIDS defining malignancy characterised by poor survival. The programmed cell death (PD-1) pathway governs antiviral and anticancer immune exhaustion and is a therapeutic target in HCC. This study highlights how HIV infection is associated with significantly higher PD-L1 expression in HCC cells and in the surrounding microenvironment, leading to changes in cytotoxic and regulatory T cell function and dysregulation of proin-flammatory pathways. Taken together, our results suggest dysfunctional T cell immunity as a mechanism of worse outcome in these patients and suggest clinical testing of checkpoint inhibitors in HIV-associated HCC.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Tumour mutational burden (TMB) predicts improved response and survival to immunotherapy. In this pilot study, we optimized targeted next-generation sequencing (tNGS) to estimate TMB in hepatocellular carcinoma (HCC). We sequenced 48 non-paired samples (21 fresh-frozen [FF] and 27 paraffin-embedded [FFPE]), among which 11 FFPE samples were pretreated with uracil-DNA glycosylase (UDG). Thirty samples satisfied post-sequencing quality control. High/low TMB was defined by median number of mutations/Mb (Mut/Mb), across different minimum allele frequency (MAF) thresholds (≥0.05, ≥0.1 and ≥0.2). Eligible patients (n = 29) were cirrhotic (84%) with TNM stage I-II HCC (75%). FFPE samples had higher TMB (median 958.39 vs 2.51 Mut/Mb, P < .0001), estimated deamination counts (median 1335.50 vs 0, P < .0001) and C > T transitions at CpG sites (median 60.3% vs 9.1%, P = .002) compared to FF. UDG-treated samples had lower TMB (median 4019.92 vs 353 Mut/Mb, P = .041) and deamination counts (median 6393.5 vs 328.5, P = .041) vs untreated FFPE. At 0.2 MAF threshold with UDG treatment, median TMB was 5.48 (range 1.68-16.07) and did not correlate with salient pathologic features of HCC, including survival. While tNGS on fresh HCC samples appears to be the optimal source of tumour DNA, the low median TMB values observed may limit the role of TMB as a predictor of response to immunotherapy in HCC.

Acid sphingomyelinase deficiency (ASMD) is a rare metabolic disorder due to biallelic mutation in the SMPD1 gene. The defect leads to the accumulation of sphingomyelin within the cells of the reticulo-endothelial system, particularly in the spleen, liver, lungs, and bone marrow causing hepato-splenomegaly, lung disease and hematological abnormalities. At present, data on abdominal imaging in ASMD are limited. Here we describe the characteristics of focal liver lesions observed in a 30 years old female. During the Magnetic Resonance follow up an increase in number and size of the lesions, showing T1 hypointensity and T2 hyperintensity with contrast enhancement, was observed. Contrast enhanced ultrasound evidenced rapid wash-in and steady isoecogenicity without appreciable wash-out at 80 seconds. The main lesion was biopsied to rule out the presence of a hepatocellular carcinoma, and showed to be a benign foamy macrophages aggregate. In this report, we discuss the possible pathogenesis of focal hepatic lesions in ASMD and their differential diagnosis.

BackgroundModulation of adaptive immunity may underscore the efficacy of trans-arterial chemoembolization (TACE). We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment.MethodsWe profiled intratumoral (IT), peritumoral (PT) and non-tumoral (NT) background tissue to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD-1+ T-cells across T+ (n=58) and T− (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, indoleamine 2,3 dehydrogenase (IDO-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), Lag-3, Tim-3 and CD163.ResultsWe analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) hepatocellular carcinoma. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD-1+ and NT CD8+/PD-1+ (p<0.001) compared with T−. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed upregulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T−.ConclusionsTACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant upregulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumor microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.

Background & Aims Tumour mutational burden (TMB) predicts improved response and survival to immunotherapy. In this pilot study, we optimized targeted next-generation sequencing (tNGS) to estimate TMB in hepatocellular carcinoma (HCC). Methods We sequenced 48 non-paired samples (21 fresh-frozen [FF] and 27 paraffin-embedded [FFPE]), among which 11 FFPE samples were pretreated with uracil-DNA glycosylase (UDG). Thirty samples satisfied post-sequencing quality control. High/low TMB was defined by median number of mutations/Mb (Mut/Mb), across different minimum allele frequency (MAF) thresholds (>= 0.05, >= 0.1 and >= 0.2). Results Eligible patients (n = 29) were cirrhotic (84%) with TNM stage I-II HCC (75%). FFPE samples had higher TMB (median 958.39 vs 2.51 Mut/Mb, P < .0001), estimated deamination counts (median 1335.50 vs 0, P < .0001) and C > T transitions at CpG sites (median 60.3% vs 9.1%, P = .002) compared to FF. UDG-treated samples had lower TMB (median 4019.92 vs 353 Mut/Mb, P = .041) and deamination counts (median 6393.5 vs 328.5, P = .041) vs untreated FFPE. At 0.2 MAF threshold with UDG treatment, median TMB was 5.48 (range 1.68-16.07) and did not correlate with salient pathologic features of HCC, including survival. Conclusion While tNGS on fresh HCC samples appears to be the optimal source of tumour DNA, the low median TMB values observed may limit the role of TMB as a predictor of response to immunotherapy in HCC.

Hyaluronic acid (HA) is a glycosaminoglycan of extracellular matrix related to cell surface which interacts with various cell types. To understand the role of HA during hepatocarcinogenesis, we assessed the effect of the inhibition of HA deposition and its association with heterogeneous hepatocellular carcinoma (HCC) cells. In this study, we used transgenic mice C57BL/6J-Tg(Alb1HBV)44Bri/J (HBV-TG) and normal C57BL/6 J (WT) for in vivo study, while HCC cells Huh7 and JHH6 as in vitro models. Both models were treated with an HA inhibitor 4-methylumbelliferone (4MU). We observed that 4MU treatments in animal model down-regulated the mRNA expressions of HA-related genes Has3 and Hyal2 only in HBV-TG but not in normal WT. As observed in vivo , in HCC cell lines, the HAS2 mRNA expression was down-regulated in Huh7 while HAS3 in JHH6, both with or without the presence of extrinsic HA. Interestingly, in both models, the expressions of various cancer stem cells (CD44, CD90, CD133, and EpCAM) were also decreased. Further, histological analysis showed that 4MU treatment with dose 25 mg/kg/day reduced fibrosis, inflammation, and steatosis in vivo , in addition to be pro-apoptotic. We concluded that the inhibition of HA reduced the expressions of HA-related genes and stem cells markers in both models, indicating a possible modulation of cells-to-cells and cells-to-matrix interaction.

Chronic HCV liver infection is considered one of the main causes of liver cirrhosis and hepatocellular carcinoma (HCC). For a selected group of patients, orthotopic liver transplantation (OLTx) is the most effective option to cure both liver diseases. After liver transplantation, patients may be at risk of viral infection reactivation and HCC recurrence. HCV recurrence on the transplanted organ can lead to graft cirrhosis and therefore the clearance of virus with antiviral therapies has a pivotal role on the prevention of graft damage. Nowadays, direct antiviral agents (DAAs) represent the choice treatment for HCV recurrence in liver transplanted patients, ensuring high eradication rates. We present the case of a liver transplant recipient who developed, 7 years after OLTx and immediately after a DAAs treatment, a subcutaneous abdominal mass with histological characteristics of HCC.

Background. Gastrointestinal perforation (GIP) is a rare complication after adult liver transplant (LT) associated with high morbidity and mortality. Limited data are available about clinical risk factors and underlying pathogenic mechanisms. Methods. The retrospective study included all GIP cases from a consecutive cohort of 361 LT recipients during the period 2005-2017. Clinical variables were investigated as potential risk factors for GIP, and radiologic and histopathologic evaluations were undertaken to identify any causative mechanism. Results. A total of 22 patients developed at least 1 episode of GIP (prevalence 6.1%) at a median time of 18.5 [interquartile range, 12.5-28.5] days after LT. The perforations occurred in the small bowel (63.6%), transverse colon (27.3%), right colon (22.7%), left colon (9.1%), and stomach (9.1%). A total of 27.3% of patients developed multiple sites of GIP, and in 31% GIP recurred after curative surgery. The 30-day mortality rate after relaparotomy was 40%. A history of previous abdominal surgery (odds ratio, 2.5) and early post-LT relaparotomy due to other complications (odds ratio, 2.6) were significant risk factors for GIP. No thromboembolic or steno-occlusive complications of any splanchnic vessel were detected at computed tomography scan, while histopathology examination on perforated gastrointestinal segments excluded cytomegalovirus infection, graft-vs-host disease, and inflammatory bowel disease. In all the cases, ischemic necrosis with aspecific microangiopathy and microembolization were the pathologic features detected. Conclusions. GIP is a severe complication after LT with frequent multiple gastrointes-tinal involvement and recurrence after curative surgery. The pathologic underlying mechanism is usually microvascular ischemia. Clinical risk factors are history of previous abdominal surgery and early post-LT relaparotomy.

Chronic infection of Hepatitis BVirus (HBV) is one of the highest risk factors of hepatocellular carcinoma (HCC). The accumulation of HBV surface antigen (HBsAg) into hepatocytes induces inflammation and oxidative stress, impairing their replicative ability and allowing the activation of the hepatic stem cells (SC) compartment. This study aimed to understand the involvement of SC during hepatocarcinogenesis in HBsAg-related liver damage, from early injury until HCC. HBsAg-transgenic (TG) and wild type (WT) mouse were followed at several stages of the liver damage: inflammation, early hepatocytes damage, dysplasia, and HCC. Serum transaminases, liver histology, and diagnostic data were collected. The expressions of SC and cancer stem cells (CSC) markers was analyzed by RT-qPCR, immunohistochemistry and Western blot. Starting from 3 months, TG animals showed a progressive liver damage characterized by transaminases increase. The up-regulations of SCs markers Cd34 and Sca-1 started from the beginning of the inflammatory stage while progressive increase of Krt19 and Sox9 and CSCs markers Epcam and Cd133 from early hepatic injury. The expressions of Cd133, Cd34, and Afp were significantly higher in HCC compared to paired non-HCC tissue, in contrast to Epcam and Krt19. Western blot and IHC confirmed the positivity of Cd34 and Cd133 in small cells subpopulation.

Background The altered composition of the gastrointestinal (GI) microbiota, known as dysbiosis, can induce and modulate the systemic inflammation, through microbial translocation and T-cell activation, in several immuno-mediated diseases, such as inflammatory bowel disease (IBD), HIV infection, and ankylosing spondylitis. Objectives In a cohort of 85 patients with inflammatory bowel disease-associated spondyloarthritis (SpA/IBD), we assessed gut bacterial infiltration and intestinal damage. In systemic circulation, GI epithelial damage, microbial translocation and immune system activation were assessed with intestinal-fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), soluble CD14 (sCD14), respectively. Moreover, the in vitro activity of the latter two was evaluated on osteoblast cells. Methods I-FABP, LPS, sCD14, sclerostin (SOST) and anti-SOST antibodies (anti-SOST-IgG) were assayed with ELISAs. LPS and sCD14 were used in vitro to stimulate the MG63 human osteoblast-like cell line. Occludin, claudin-1, claudin-4, and the presence of bacteria were assessed, respectively, by real-time-PCR analysis and immunohystochemical staining of the ileum. Results Bacteria were detectable in the ileal epithelium of IBD patients, but only in SpA/IBD they were associated with epithelial damage and downregulation of occludin, claudin-1 and claudin-4 (figure 1A-B). The serum levels of I-FABP, LPS and sCD14 resulted significantly higher in axial (187.9, 14.03, and 26.97, respectively) and peripheral SpA/IBD (130.3, 11.55, and 18, respectively) than in IBD patients (IFABP 43.65, p<0.0001 for both patients’ groups; LPS 9.625, p<0.0001 vs Ax-SpA/IBD and=0.007 vs Per-SpA/IBD; sCD14 12.34, p<0.0001 for both patients’ groups) (figure 1C). In the SpA/IBD cohort, SOST was weakly correlated with I-FABP (r=-0.2683), LPS (r=-0.3063) and sCD14 (r=-0.3075), and anti-SOST-IgG with LPS (r=- 0.3959) and sCD14 (r=-0.3414). Moreover, sCD14 showed significant correlation with I-FABP (r=0.3316) and LPS (r=0.5649). In vitro, LPS, but not sCD14, significantly induced SOST expression through the upregulation of both Wnt3a and Wnt5a and the downregulation of the b-catenin proteins (figure 1D). On the opposite, the combination of LPS and sCD14 downregulated SOST expression through the upregulation of ERK1/2 and b-catenin protein (figure 1D).Abstract OP0271 – Figure 1 A. immunoistochemical staining of ileal bacteria. Ten ileal samples of patients affected by SpA/IBD or IBD were stained for bacteria infiltration (upper panel). Lower (from left to right): Gram and LPS staining of the same samples. B. Analysis of ¡leal tight-junctions proteins expression. From the left to the right: Ten ileal samples of patients affected by SpA/IBD or IBD were stained for occludin (and claudin-1 and -4, data not shown); count of occludin positive cells and quantitative real-time-PCR of occludin (and claudin-1 and -4, data not shown) expression in the same ¡leal samples. C. analysls of I-FABP, LPS and sCD14 serum levels in SpA/IBD and IBD patients. ELISAs assays were carried out in 45 patients with axial and 40 patients with peripheral SpA/IBD, and compared with IBD or HC. D. Western-blot analysis of MG-63 osteoblast-cells. The MG-63 osteoblast-like cell line was stimulated with LPS ± sCD14 in vitro and then cells were harvested for western blot analisys. Semi-quantitative densitometric analysis of the protein bands was carried out on the blot (data not shown). Statistical analysis: Kruskal-Wallis analysis. ••p<0.01; ••••p<0.0001; if not reported: p non significant. Abbreviations. SpA/IBD: inflammatory bowel disease-associated spondyloarthritis; ax-SpA/IBD: axial SpA/IBD: peripheral SpA/IBD; IBD: Inflammatory bowel disease; HC: healthy controls; I-FABP: intestinal fatty acid binding protein; LPS: bacterial lypopolysaccaride; sCD14: solubie CD14; ERK 1/2: extracellular Signal-regulated Kinase-1/2. Wnt: wingless protein family: SOST: sclerostin. Conclusions The role of gut inflammation and microbial translocation in the onset of arthritis in IBD patients are still under investigation. We have demonstrated that in SpA/IBD there is a significant bacterial infiltration of the ileal tract, associated with the downregulation of tight-junctions’ proteins (occludin, claudin-1 and claudin-4) and epithelial damage, that cause microbial translocation and higher plasma levels of I-FABP, LPS, and sCD14. LPS and sCD14, thus, could trigger a complex systemic inflammatory response acting on several biochemical pathways, linking the immune system (anti-SOST-IgG) and the bone (SOST). Disclosure of Interest None declared

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents is challenging the global care system. No therapeutic strategies have been defined so far, and changes in the lifestyle remain the only alternative. In this study, we assessed the protective effects of silymarin in a juvenile non-alcoholic steatohepatitis (NASH) model and the in vitro effects on fat-laden human hepatocytes. C57Bl/6 mice were exposed to HFHC diet immediately after weaning. After eight weeks, animals showed histological signs of NASH. Silymarin was added to the HFHC diet, the treatment continued for additional 12 weeks and the effects on BMI, hepatomegaly, visceral fat, lipid profile, transaminases, HOMA-IR, steatosis, inflammation, fibrosis, oxidative stress, and apoptosis were determined. The switch from HFHC to control diet was used to mimic life style changes. In vitro experiments were performed in parallel in human hepatocytes. HFHC diet supplemented with silymarin showed a significant improvement in glycemia, visceral fat, lipid profile, and liver fibrosis. Moreover, it reduced (both in vitro and in vivo) ALT, hepatic inflammation, oxidative stress, and apoptosis. Lifestyle changes restored the control group parameters. The data presented show the beneficial effects of the oral administration of silymarin in the absence of changes in the dietary habits in a juvenile model of NASH.

High temperature requirement A1 (HtrA1) is a secreted protease involved in placental development. Fibronectin (FN) is involved in important process such as wound healing, cell adhesion and spreading, growth, migration, and differentiation. The purpose of this study was to analyse the expression patterns of HtrA1 in relationship to FN and to the key growth zones of placenta such as mesenchymal villi as well as cell islands and cell columns. We demonstrated that FN and HtrA1 are localized in the placental key growth zones suggesting a pivotal role in maintaining the balance among the molecules involved in the placental development and differentiation.

Extraintestinal manifestations are common in inflammatory bowel disease; however, muscular involvement in Crohn disease is rarely reported. We present a case of a 26-year-old male with ileocolonic Crohn disease who developed sudden tenderness in both calves. Doppler ultrasound was negative for deep vein thrombosis. Magnetic resonance imaging of the gastrocnemius muscle showed high intensity signal in the muscle fibers, and muscle biopsy demonstrated nonspecific lymphocytic myositis. Other relevant laboratory results included normal antineutrophil cytoplasmic antibodies and creatine kinase as well as elevated C-reactive protein, erythrocyte sedimentation rate, and anti-Saccharomyces cerevisiae IgG titer. The patient was in clinical remission, being treated with azathioprine 2.5 mg/kg. Prednisone 60 mg/day was initiated with rapid resolution of calf tenderness; however, tenderness soon returned when the dose was tapered to 10 mg/day. Subsequently, prednisone and azathioprine were discontinued, and adalimumab was started at standard induction and maintenance doses. The patient’s symptoms resolved shortly after the first induction dose. A repeat magnetic resonance imaging of the calves – 3 months after starting adalimumab – showed complete resolution of muscle inflammation. To our knowledge, this is the first case of gastrocnemius myositis – a rare extraintestinal manifestation of Crohn disease – successfully treated with anti-tumor necrosis factor agents.

A 3-year-old boy presented with right lower abdominal pain and vomiting for 24 hours. On examination, he was febrile with guarding and rebound tenderness in the right lower abdomen. Laboratory investigations showed leukocytosis of 28.5 × 109/L and a C-reactive protein over 300 mg/L. The child underwent an urgent laparotomy for suspected acute appendicitis. Intraoperatively, a serosanguineous peritoneal effusion and a wide infarction of 5 × 3 cm in the right-inferior greater omentum were identified (Figures 1 and 2). The appendix, gallbladder, and pelvic organs were normal. The affected omentum was removed. Postoperatively, the recovery was uneventful. A thrombophilia screening was negative.Figure 2Histology showing congested vessels, hemorrhage, focal fat necrosis, and fibrinous exudates.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Omental infarction is a rare cause of acute abdominal pain in children. It is caused by a compromise in the blood supply by either torsion of the greater omentum or spontaneous venous thrombosis.1van Breda Vriesman A.C. de Mol van Otterloo A.J. Puylaert J.B. Epiploic appendagitis and omental infarction.Eur J Surg. 2001; 167: 723-727Crossref PubMed Scopus (40) Google Scholar Right epiploic vessels generally are involved, explaining the tipical predilection for right-sided omental infarctions.2Rimon A. Daneman A. Gerstle J.T. Ratnapalan S. Omental infarction in children.J Pediatr. 2009; 155: 427-431Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar A greater incidence in obese, pre-adolescent boys has been reported.3Helmrath M.A. Dorfman S.R. Minifee P.K. Bloss R.S. Brandt M.L. DeBakey M.E. Right lower quadrant pain in children caused by omental infarction.Am J Surg. 2001; 182: 729-732Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar The presentation often mimics acute appendicitis, and most cases are identified only intraoperatively.3Helmrath M.A. Dorfman S.R. Minifee P.K. Bloss R.S. Brandt M.L. DeBakey M.E. Right lower quadrant pain in children caused by omental infarction.Am J Surg. 2001; 182: 729-732Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Leukocytosis and low-grade fever may be present in a minority of cases.2Rimon A. Daneman A. Gerstle J.T. Ratnapalan S. Omental infarction in children.J Pediatr. 2009; 155: 427-431Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar On ultrasonography scans, the infarct area usually appears as a hyperechoic mass located in the omental fat.4Bachar G.N. Shafir G. Postnikov V. Belenky A. Benjaminov O. Sonographic diagnosis of right segmental omental infarction.J Clin Ultrasound. 2005; 33: 76-79Crossref PubMed Scopus (30) Google Scholar Characteristic computed tomography findings include a heterogeneous fatty mass with hyperintense strikes between the ascending or transverse colon and the abdominal wall.5Grattan-Smith J.D. Blews D.E. Brand T. Omental infarction in pediatric patients: sonographic and CT findings.AJR Am J Roentgenol. 2002; 178: 1537-1539Crossref PubMed Scopus (63) Google Scholar When the diagnosis is obtained preoperatively, conservative management is feasible because the condition usually is benign and self-limiting within 10-15 days.2Rimon A. Daneman A. Gerstle J.T. Ratnapalan S. Omental infarction in children.J Pediatr. 2009; 155: 427-431Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Otherwise, some authors advocate for the surgical resection of the affected omentum to expedite clinical recovery and to reduce the risk of secondary abscess formation.6Loh M.H. Chui H.C. Yap T.L. Sundfor A. Tan C.E. Omental infarction–a mimicker of acute appendicitis in children.J Pediatr Surg. 2005; 40: 1224-1226Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 7Balthazar E.J. Lefkowitz R.A. Left-sided omental infarction with associated omental abscess: CT diagnosis.J Comput Assist Tomogr. 1993; 17: 379-381Crossref PubMed Scopus (70) Google Scholar

Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

TO THE EDITORS: We read with interest the article by Goel et al.1 that was recently published in Liver Transplantation. The aim of this retrospective 2‐center cohort study was to compare hepatic artery (HA) and biliary complications in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) before LT and recipients with HCC who did not receive TACE. Of the 456 HCC patients who were analyzed, 328 (72%) received TACE before LT. The overall prevalence of HA complications and thrombosis was 4.7% and 3.9%, respectively, in the no‐TACE group and 7.9% and 3.7%, respectively, in the TACE group (P = 0.22). All HA stenosis complications (4.3%) occurred in the TACE group (P = 0.018). There was a nonstatistically significant increased chance (odds ratio = 2.02, P = 0.14) of HA complications in the TACE group versus the no‐TACE group. The authors concluded that TACE was not associated with higher odds of overall HA complications but was associated with a higher prevalence of HA stenosis. The results, limited to HA complications, from our single‐center experience comparing 68 HCC patients who received TACE before transplantation with 194 recipients without HCC who did not have TACE before LT are in accordance with the findings of Goel et al., and they showed no difference in the overall prevalence of HA complications (5.9% for the TACE group versus 8.2% for the no‐TACE group, P = 0.52) or HA thrombosis (1.5% versus 3%, P = 0.47). However, unlike the findings of Goel et al., we did not experience a higher prevalence of HA stenosis that was statistically significant because our data showed a 2.9% prevalence in the TACE group versus 3.6% in the no‐TACE group (P = 0.79). Moreover, to support those data, we did not register any statistically significant difference in the HA resistive index of the color Doppler ultrasound at different time points after transplantation between the TACE and no‐TACE groups: 0.63 ± 0.08 and 0.64 ± 0.08 (P = 0.60) at 1 month, 0.64 ± 0.06 and 0.65 ± 0.07 (P = 0.55) at 6 months, and 0.65 ± 0.04 and 0.64 ± 0.07 (P = 0.63) at 12 months, respectively. Therefore, on the basis of our experience, we would support the conclusion of Goel et al. that pre‐LT TACE is not associated with an increased prevalence of HA complications.