This study aimed to investigate the survival outcomes of antiviral agents (direct-acting antivirals DAAs or interferon IFN) in patients with hepatitis C virus who underwent liver resection for ...primary hepatocellular carcinoma.
This retrospective single-center study included 247 patients, between 2013 and 2020, being treated with DAAs (n = 93), IFN (n = 73), or no treatment (n = 81). Overall survival (OS), recurrence-free survival (RFS), and risk factors were analyzed.
After a median follow-up time of 50.4 months, the rates of 5-year OS and RFS in the IFN, DAA, and no treatment groups were 91.5% and 55.4%, 87.2% and 39.8%, and 60.9% and 26.7%, respectively. One hundred and twenty-eight (51.6%) patients developed recurrence; recurrence was mostly (86.7%) intrahepatic, and 58 (23.4%) developed early recurrence, most of which received no antiviral treatment. The OS and RFS were similar between patients who received antiviral treatment before (50.0%) and after surgery, but longer survival was observed in patients achieving sustained virologic response. In multivariate analysis, antiviral treatment was protective for OS (hazard ratio HR 0.475, 95% confidence interval CI: 0.242-0.933) with significance but not RFS, in contrast to microvascular invasion (OS HR 3.389, 95% CI: 1.637-7.017; RFS HR 2.594, 95% CI: 1.520-4.008). In competing risk analysis, DAAs (subdistribution HR 0.086, 95% CI: 0.007-0.991) were protective against hepatic decompensation events but not recurrence events.
In patients with hepatitis C virus, antiviral treatment suggested OS benefit for primary hepatocellular carcinoma after resection, and DAAs might be protective against hepatic decompensation. Following adjustment for oncological factors, IFN and DAA treatment was not significantly advantageous relative to the other.
Human studies on the use of metformin as host-directed therapy (HDT) for tuberculosis (TB) are rare. We performed a nationwide cohort study to evaluate the effect of metformin on mitigating the risk ...of active TB among patients with diabetes mellitus (DM). Among newly diagnosed DM patients identified in the Taiwan National Health Insurance Research Database, metformin users, defined on the basis of >90 cumulative defined daily doses within 1 year, and propensity-score-matched metformin nonusers were selected. The primary outcome was incident TB, identified using diagnostic criteria validated by real patient data at a medical center. Independent predictors were investigated using Cox regression analysis. Similar analysis was performed in a subpopulation without a history of hypertensive nephropathy and renal replacement therapy. A total of 88,866 metformin users and 88,866 propensity-score-matched nonusers were selected. Validation results showed that the TB diagnostic criteria had a sensitivity of 99.13% and specificity of 99.90%. During follow-up, 707 metformin users and 807 nonusers developed active TB. Metformin use was independently associated with a lower risk of incident TB (hazard ratio HR: 0.84 0.74-0.96). TB risk was lower in high-dose metformin users than in low-dose users (HR: 0.83 0.72-0.97). The effect of metformin remained when analysis was restricted in the subpopulation without renal function impairment. Newly diagnosed diabetic patients without contraindication should receive metformin as an anti-diabetic medication, with potential additional benefit against TB.
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•Most HCC tumors displayed similar tumor immune microenvironments among different regions within each tumor.•A single-region sample might be reliable to evaluate the tumor immune ...microenvironment of the entire HCC tumor.•Most HCC tumors displayed uniform expression of PD-L1 in different regions within each tumor.•Intratumor tertiary lymphoid structures are rare in HCC, and are prone to spatial heterogeneity.
Intratumor heterogeneity has frequently been reported in patients with hepatocellular carcinoma (HCC). Thus, the reliability of single-region tumor samples for evaluation of the tumor immune microenvironment is also debatable. We conducted a prospective study to analyze the similarity in tumor immune microenvironments among different regions of a single tumor.
Multi-region sampling was performed on newly resected tumors. The tumor immune microenvironment was evaluated by immunohistochemical staining of PD-L1, CD4, CD8, CD20, FoxP3, DC-LAMP (or LAMP3), CD68, MPO, and tertiary lymphoid structures (TLSs). PD-L1 expression was manually quantified according to the percentage of PD-L1-stained tumor or stromal cells. The densities (number/mm2) of immune cells and the number of TLSs per sample were determined by whole-section counting. RNA-sequencing was applied in selected samples. Similarities in tumor immune microenvironments within each tumor were evaluated by multivariate Mahalanobis distance analyses.
Thirteen tumors were collected from 12 patients. The median diameter of tumors was 9 cm (range 3–16 cm). A median of 6 samples (range 3–12) were obtained from each tumor. Nine (69.2%) tumors exhibited uniform expression of PD-L1 in all regions of the tumor. Out of 13 tumors analyzed by immunohistochemical staining, 8 (61.5%) tumors displayed a narrow Mahalanobis distance for all regions within the tumor; while 8 (66.7%) of the 12 tumors analyzed by RNA-sequencing displayed a narrow Mahalanobis distance. Immunohistochemistry and RNA-sequencing had a high concordance rate (83.3%; 10 of 12 tumors) for the evaluation of similarities between tumor immune microenvironments within a tumor.
A single-region tumor sample might be reliable for the evaluation of tumor immune microenvironments in approximately 60–70% of patients with HCC.
Heterogeneity in the regional immune microenvironments of tumors has been reported in patients with hepatocellular carcinoma. This heterogeneity could be an obstacle when trying to reliably evaluate the immune microenvironment of an entire tumor using only a single-region tumor sample, which may be the only option in patients with more advanced disease. Our study utilized both immunohistochemical and transcriptomic analyses to demonstrate that a single-region sample is reliable for evaluation of tumor immune microenvironments in 60–70% of patients with hepatocellular carcinoma.
Macrophages engulf oxidized-LDL (oxLDL) leading to accumulation of cellular cholesterol and formation of foam cells, which is a hallmark of atherosclerosis. Moreover, recent studies showed that ...accumulation of free cholesterol in macrophages leading to activation of NLRP3 inflammasome and production of interleukin-1β (IL-1β) has been linked to atherosclerosis-associated inflammation. However, it is not clear if cholesterol accumulation is associated with hepatic inflammation and fibrosis in the liver. In this study, we investigated the association of free cholesterol and oxLDL accumulation in portal vein with the inflammation, atherosclerosis, and fibrosis in human nonalcoholic fatty liver disease (NAFLD).
Serial sections derived from surgical specimens of NAFLD were stained with filipin and antibodies against IL-1β, CD68, α-smooth muscle actin (α-SMA), oxLDL and lectin-like oxLDL receptor-1 (LOX-1).
We show that free cholesterol was colocalized with oxLDL in the wall of portal vein, and which was associated with lumen narrowing, plaque formation, endothelium deformation, and portal venous inflammation. The inflammation was evidenced by the colocalization of Kupffer cells and IL-1β and the expression of LOX-1. Notably, ruptured plaque was closely associated with portal venous inflammation. Moreover, free cholesterol and oxLDL accumulation in periportal and sinusoidal fibrosis, which was associated with regional stellate cell activation and chicken-wire fibrosis.
These findings reveal a direct association between cholesterol accumulation, portal venous inflammation and fibrosis in NAFLD.
Right hepatectomy for a living liver donor via a pure minimally invasive approach is a challenging procedure and only a few cases have been reported. Between May 2013 and August 2015, 13 patients ...underwent robotic living donor right hepatectomy in our institute, and 54 patients received open surgery. In this series, no conversion was conducted for robotic donor right hepatectomy. The 2 groups shared similar blood loss (169 versus 146 mL), complication rates (7.7% versus 9.3%), and recovery of donor liver function (peak alanine aminotransferase, 269 versus 252 IU/mL). The robotic group needed longer operation time (596 versus 383 minutes) but less postoperative patient‐controlled analgesia (0.58 versus 0.84 ng/kg) and a shorter period before returning to work/school (52.9 versus 100.0 days) and sex (100.0 versus 156.0 days). For recipient outcomes regarding the donor procedure, the robotic group shared similar experiences in early allograft dysfunction, complications, and 1‐year recipient liver function with the open group. With respect to documented benefits of minimally invasive left‐sided liver donor procedure, the development of right donor hepatectomy is slow. In conclusion, with substantial improvements in patient recovery after the minimally invasive approach, the robotic platform would be a big step toward completing pure minimally invasive liver donor surgery. Liver Transplantation 22 1509–1518 2016 AASLD.
Background
Robotic liver resection has emerged as a new modality in the field of minimally invasive surgery. However, the effectiveness of this approach for liver resection is not yet known.
Methods
...A literature survey was performed using specific search phrases in PubMed. Case series that focused on biliary reconstruction were excluded. Characteristics, such as patient demographics, perioperative outcomes, and oncological results for colorectal liver metastasis and hepatocellular carcinoma were analyzed.
Results
Nineteen series that described the cases of 217 eligible patients were reviewed. The most commonly performed procedures were wedge resection and segmentectomy. Right hepatectomy was performed in a few specialized centers. The conversion and complication rates were 4.6 and 20.3 %, respectively. The most common reason for conversion was unclear tumor margin. Intra-abdominal fluid collection was the most frequently occurring morbidity. Mean operation time was 200–507 min. Mean intraoperative blood loss was 50–660 mL, with a tendency toward increased blood loss observed in series that included major hepatectomies. Mean postoperative hospital stay was 5.5–11.7 days. The longest mean follow-up time was 36 months for colorectal liver metastasis and 25.1 months in hepatocellular carcinoma. Disease-free survival for mixed malignancies was comparable to that after laparoscopic procedures. Overall survival was not reported.
Conclusions
Robotic liver resection is safe and feasible for experienced surgeons with advanced laparoscopic skills. Long-term oncologic outcomes are unclear, but short-term perioperative results seem comparable to those of conventional laparoscopic liver resection.
Insulin-like growth factor, (IGF)-1, is produced mainly by the liver and plays important roles in promoting growth and regulating metabolism. Previous study reported that development of ...hepatocellular carcinoma (HCC) was accompanied by a significant reduction in serum IGF-1 levels. Here, we hypothesized that dysregulation of microRNAs (miRNA) in HCC can modulate IGF-1 expression post-transcriptionally.
The miRNAs expression profiles in a dataset of 29 HCC patients were examined using illumina BeadArray. Specific miRNA (miR)-190b, which was significantly up-regulated in HCC tumor tissues when compared with paired non-tumor tissues, was among those predicted to interact with 3'-untranslated region (UTR) of IGF-1. In order to explore the regulatory effects of miR-190b on IGF-1 expression, luciferase reporter assay, quantitative real-time PCR, western blotting and immunofluorecence analysis were performed in HCC cells.
Overexpression of miR-190b in Huh7 cells attenuated the expression of IGF-1, whereas inhibition of miR-190b resulted in up-regulation of IGF-1. Restoration of IGF-1 expression reversed miR-190b-mediated impaired insulin signaling in Huh7 cells, supporting that IGF-1 was a direct and functional target of miR-190b. Additionally, low serum IGF-1 level was associated with insulin resistance and poor overall survival in HCC patients.
Increased expression of miR-190 may cause decreased IGF-1 in HCC development. Insulin resistance appears to be a part of the physiopathologic significance of decreased IGF-1 levels in HCC progression. This study provides a novel miRNA-mediated regulatory mechanism for controlling IGF-1 expression in HCC and elucidates the biological relevance of this interaction in HCC.
We aimed to compare long-term outcomes of surgical resection (SR) and percutaneous radiofrequency ablation (RFA) for Barcelona Clinic Liver Cancer (BCLC) very early stage hepatocellular carcinoma ...(HCC).
Total of 387 patients (SR group, 156; RFA group, 231) with well-preserved liver function (Child-Pugh A) diagnosed with a solitary HCC less than 2 cm were included. The overall survival (OS) and recurrence-free survival (RFS) rates were compared.
The median follow-up period was 39 months. The overall tumor recurrence rate was 16.7% in the SR group and 27.7% in the RFA group. The 1-, 3-, and 5-year OS rates were 100%, 97.2%, and 93.4%, respectively, in the SR group, compared with 100%, 88.6%, and 73.5%, respectively, in the RFA group (P < 0.001). The 1-, 3-, and 5-year RFS rates were 94.6%, 84.1%, and 78.3%, respectively, in the SR group, and 87.7%, 62.1%, and 46.8%, respectively, in the RFA group (P < 0.001).
Surgical resection provides better OS and RFS compared with percutaneous RFA for patients with BCLC very early HCC in long-term follow-up.
•Resection and local ablation are treatment options for early hepatocellular carcinoma.•Surgical resection appears to provide better long-term outcomes.•Tumor recurrence had significant survival impact in long-term follow-ups.•Survival rate from the time of tumor recurrence was similar between both treatment.
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