Metastatic renal cell cancer is typically resistant to chemotherapy but does respond to vascular endothelial growth factor receptor signal transduction inhibition and to a variety of immunotherapies, including interleukin (IL)-2 and monoclonal antibodies that inhibit immune checkpoints. Enhanced immune recognition of tumor antigens may improve clinical outcomes. The objective of this study was to investigate the effects of a patient-specific approach utilizing autologous dendritic cell vaccines and self-renewing autologous tumor cells in patients with metastatic renal cell carcinoma.

Short-term cell lines were established from resected renal cell cancer specimens. Autologous dendritic cells were derived from peripheral blood mononuclear cells cultured in granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. Antigen loading was accomplished by incubating irradiated tumor cells with dendritic cells. The vaccine was admixed with GM-CSF and injected subcutaneously weekly for 3 weeks, then monthly for 5 months.

Short-term cell lines were established for 28 patients. Dendritic cells were produced for 11 patients. Nine patients were referred for treatment. The nine patients received 58 injections, and 6 received all 8 planned doses. Treatments were well-tolerated, other than mild to moderate injection site reactions. One patient experienced an anaphylactoid reaction attributed to microaggregates in GM-CSF. Three patients had conversion from negative to positive for a delayed-type hypersensitivity test to intradermal injection of one million autologous irradiated tumor cells. Two of seven patients had delayed complete regression of measurable oligometastatic disease. Three patients were still alive and disease-free after 5 years.

This patient-specific vaccine approach is feasible, well-tolerated, and associated with encouraging long-term survival in some patients. Larger trials of dendritic cells with autologous tumor antigens derived from self-renewing tumor cells, rather than bulk tumor, may be warranted.

Autophagy is a physiologic mechanism, which utilizes the self-digestion of cell organelles to promote cellular homeostasis, such as in the setting of dysfunctional cellular components, cellular stress or energy-deprived states. In vitro studies have pointed toward the key role of autophagy in colorectal cancer. However, in vivo studies from human colorectal cancer tissues are lacking.

We collected tissue samples from six patients with colon cancer who received curative surgery at Baylor College of Medicine. We also obtained normal colonic mucosa biopsy from five unrelated polyp-free individuals who were matched to cases individually by age, sex, ethnicity, and colon segment. Total RNA was successfully extracted from fresh frozen tissue biopsies of five tumor tissues and five unrelated normal tissues. We tested the expression levels of 84 genes in a predefined autophagy pathway using the RT2 Profiler PCR array. We compared differences using Student’s t-test. The false-discovery rate was used for multiple testing adjustment. We also used the TCGA dataset to validate our findings.

We observed significant differential expression between colon cancer tissue and normal colon mucosa for 29 genes in the autophagy pathway (p < 0.05). After multiple testing adjustment, the expression of 17 genes was significantly down-regulated, with fold-change greater than 2 in colon cancer; these included ATG4A, ATG4C, ATG4D, and CTSS (q < 0.10). The down-regulation was observed in both early and late stage colon cancer. We observed the same down-regulation of multiple autophagy-related genes using the TCGA data. The ATG9B gene was the only statistically non-significantly up-regulated gene after multiple testing adjustment.

This pilot study showed the down-regulation of multiple autophagy pathway genes in human colon cancer, corroborating the increasing clinical relevance of autophagy in human colorectal carcinogenesis. This preliminary finding should be validated in larger studies.

Background and Aims: Hepatitis C virus (HCV) infection results in hepatocytic injury with elevation of both alanine aminotransferase (ALT) and aspartate aminotransferase (AST). It remains to be determined if direct-acting antiviral treatment can terminate hepatocytic injury following virologic response. To this end, we evaluated the pattern and predicting factors of ALT and AST normalization during and after direct-acting antiviral treatment with sustained virologic response at 12 weeks (SVR12).

Methods: Single-center retrospective study on 115 HCV-infected patients who achieved SVR12 was performed.

Results: At treatment week 2, 100% and 45.9% showed decline in HCV RNA to <700 IU/mL and undetectable levels, respectively, and this was associated with 85.5%, 83.9% and 77.4% ALT normalization, AST normalization and ALT and AST normalization. At end of treatment, 85.6% of patients with baseline elevation of both ALT and AST had normalization of both ALT and AST. At posttreatment weeks 12 and 24, 90.8% and 94.8% had normalization of both ALT and AST. HCV clearance also resulted in further decline of both ALT and AST in those with baseline <40 IU. Univariate analysis showed baseline Child-Pugh score of <6, model for end-stage liver disease score of <10, HCV genotype 1, and HCV RNA of <500 IU/mL at treatment week 2 were associated with sustained normalization of both ALT and AST at posttreatment week 12. On multivariate analysis, baseline model for end-stage liver disease score of <10 was significantly associated with normalization of both ALT and AST at posttreatment week 12, independent of baseline Child-Pugh score <6, HCV genotype 1, and HCV RNA of <500 IU/mL at treatment week 2.

Conclusions: During direct-acting antiviral therapy, 85.5% and 83.9% had normalization of both ALT and AST as early as in week 2, providing biochemical evidence of hepatocytic injury resolution. Sustained normalization of both ALT and AST was seen in 90.8% at posttreatment weeks 12, and was independently associated with baseline model for end-stage liver disease score of <10.

Background and Aims: Recently, the World Health Organization adopted the first-ever global hepatitis strategy with the dream of eliminating viral hepatitis as a public health threat by 2030. However, the epidemiology and treatment rates of hepatitis C virus (HCV) infection in Western China are still unknown.

Methods: A total of 111,916 adult individuals (15–96 years) who underwent the HCV-antibody (HCV-Ab) test in the Second Affiliated Hospital of Chongqing Medical University between 2013 and 2015 were included in this study. We retrospectively analyzed the electronic medical records’ data for each, and the positivity of HCV-Ab and the treatment of HCV RNA-positive patients were evaluated.

Results: During 2013–2015, the crude prevalence of HCV-Ab was 1.4% (95%CI: 1.4–1.5; 1,611/111,916) and the adjusted prevalence of HCV-Ab was 1.7% (95%CI: 1.6–1.8), which was higher than in the 2006 national study (0.43%). The prevalence was 2-times higher in males than females (2.0% vs. 1.1%, p < 0.01). Notably, only 46% (434/951) of the HCV RNA-positive patients received standard peg-interferon plus ribavirin treatment, with 370 (82%) that completed treatment, of whom 272 (74%) achieved sustained virologic response (SVR). Particularly, 11% (32/292) of HCV RNA-positive patients were HBsAg-positive, and the SVR rate for them was lower than for the HBsAg-negative patients, but no significant difference was observed.

Conclusions: HCV infection may have increased since 2006 in Western China. The SVR rate of peg-interferon plus ribavirin treatment was high, but the proportion of untreated HCV patients was large. Thus, more efforts need to be made by the government to create a scientific-based policy for HCV treatment and prevention.

The transmembrane 6 superfamily member 2 (TM6SF2) gene E167K variant (rs58542926) was identified by exome-wide association study as a nonsynonymous single nucleotide polymorphism associated with nonalcoholic fatty liver disease. The TM6SF2 E167K variant features a C-to-T substitution at nucleotide 499, encoding a glutamate with lysine change at codon 167 (E167K). TM6SF2 is markedly expressed in the liver, small intestine and kidney, and has been proposed as an important risk factor for diseases associated with lipid metabolism. Subsequently, multifunctional studies of the TM6SF2 E167K variant have been carried out in a spectrum of liver diseases, such as nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, fibrosis, cirrhosis, and viral hepatitis. This review summarizes the research status of the TM6SF2 E167K variant in different liver diseases and specific populations, and discusses the potential mechanisms of the TM6SF2 E167K variant’s role in the progression of various liver diseases.

Luteolin is a flavonoid compound and exhibits antioxidant, antiinflammatory, antibacterial, antidiabetic and antiproliferative properties. Studies have shown that luteolin may inhibit cell proliferation, metastasis, and angiogenesis of numerous types of cancers, including breast cancer, through inducing cell cycle arrest and apoptosis and by modulating cell signaling. In this review, we have summarized the recent studies on inhibitory effects and underlying mechanisms of luteolin in breast cancer. These studies support that luteolin is a promising drug to treat breast cancer.

Recurrent acute bacterial cholangitis is a unique indication for liver transplantation in primary sclerosing cholangitis. We present the first report on utility of healthy donor fecal transplantation for management of recurrent acute bacterial cholangitis in a primary sclerosing cholangitis patient. We demonstrate the striking liver biochemistry, bile acid and bacterial community changes following intestinal microbiota transplantation associated with amelioration of recurrent cholangitis.

In parallel with the rising prevalence of metabolic syndrome globally, nonalcoholic fatty liver (NAFL) disease is the most common chronic liver disease in Western countries and nonalcoholic steatohepatitis (NASH) has become increasingly associated with hepatocellular carcinoma. Recent studies have identified NASH as the most rapidly growing indication for liver transplantation (LT). As a hepatic manifestation of the metabolic syndrome, NAFL disease can be histologically divided into NAFL and NASH. NAFL is considered a benign condition, with histological changes of hepatocyte steatosis but without evidence of hepatocellular injury or fibrosis. This is distinct from NASH, which is characterized by hepatocyte ballooning and inflammation, and which can progress to fibrosis and cirrhosis, hepatocellular carcinoma, and liver failure. As for any other end-stage liver disease, LT is a curative option for NASH after the onset of decompensated cirrhosis or hepatocellular carcinoma. Although some studies have suggested increased rates of sepsis and cardiovascular complications in the immediate postoperative period, the long-term posttransplant survival of NASH cases is similar to other indications for LT. Recurrence of NAFL following LT is common and can be challenging, although recurrence rates of NASH are lower. The persistence or progression of metabolic syndrome components after LT are likely responsible for NASH recurrence in transplanted liver. Therefore, while maintaining access to LT is important, concerted effort to address the modifiable risk factors and develop effective screening strategies to identify early stages of disease are paramount to effectively tackle this growing epidemic.

Background and Aims: The poor outcomes of hepatocellular carcinoma (HCC) patients may be due to not only malignant tumors but also limited liver function. Therefore, as stated in major guidelines, only patients with relatively normal liver function (Child-Pugh A) would be referred for curative hepatectomy. Even so, the postsurgery survival rate of patients is still extremely poor. Direct curative resection may benefit most patients. This study aimed to improve the prognosis predicting accuracy of the Child-Pugh scoring system.

Methods: This study included two cohorts: cohort A being composed of 613 HCC patients, with a 23-month median postsurgery follow-up time; and cohort B being composed of 554 tumor-free chronic liver disease patients. Kaplan–Meier test and Cox model were used for survival analysis. Independent-samples t test or one-way ANOVA was used to test the differences between different groups.

Results: Serum prealbumin levels were found inversely correlated with worsening of fibrotic scores (r = −0.482, p < 0.001). Lower levels of presurgery prealbumin was an independent factor of poor postsurgery prognosis in Child-Pugh A patients, with a hazard ratio of 0.731 (p = 0.001). By integrating prealbumin together with total bilirubin level, serum albumin concentration and prothrombin time, a modified liver disease prognosis scoring system was developed to define traditional Child-Pugh A HCC patients as Modified Child-Pugh MCP-1, MCP-2 and MCP-3, with median postsurgery overall survival times of 44.00, 28.00 and 11.00 months respectively.

Conclusions: Preoperative serum prealbumin is a valuable prognosis predicting biomarker for Child-Pugh A HCC patients who may be under consideration for curative resection. With serum prealbumin included as one of the parameters, the MCP scoring system might improve the postsurgery survival predicting accuracy for HCC patients.

Background and Aims: Spontaneous bacterial peritonitis (SBP) is a serious complication of liver cirrhosis and a prognostic model to predict it is needed. This study was designed to test the ability of different laboratory tests and the new scoring system by Wehmeyer and colleagues (consisting of age, C-reactive protein (CRP) and platelet count) to predict it.

Methods: Three-hundred patients admitted to the National Liver Institute, University of Menoufia, Egypt (2015–2016) with liver cirrhosis and ascites were included in our study. SBP was diagnosed if ascetic neutrophil count was ≥250/µL with no sign of secondary peritonitis.

Results: The patient population had age range of 29–81 years old, was 60% men and showed a majority (91.7%) with primary cause of liver disease being hepatitis C. By univariate analysis, associations with age, total bilirubin, aspartate aminotransferase level, creatinine level, international normalized ratio, model for end-stage liver disease score, total leucocytic count, platelet count and CRP level were significant. By multivariate analysis, independent predictors were age, platelet count and CRP level (p = 0.004, 0.013 and <0.001, respectively). CRP at a cut-off point ≥13.5 mg/L could predict SBP (sensitivity of 86.4% and specificity of 66.0%). Wehmeyer’s SBP scoring system was predictive (p < 0.001); only 4% of patients with 0 score developed SBP (CRP cut-off of 30 mg/L), while 92.8% with score of 3 or 4 developed SBP. By using our modified Wehmeyer score with CRP cut-off value of 13.5 mg/L, no patient with 0 score developed SBP.

Conclusions: Age, CRP level and platelet count are independent predictors for SBP and a scoring system including them could easily predict the condition. SBP diagnosis could be excluded in patients with 0 score, using CRP cut-off value of 13.5 mg/L.

Background and Aims: To report long-term results in treatment of intermediate hepatocellular carcinoma (HCC) in cirrhotics using new high-powered microwaves (MWS) ablation alone.

Methods: This multicenter study included 215 cirrhotics (age range: 67–84 years; 137 males; 149 Child A, 66 Child B) who underwent percutaneous ultrasound-guided high-powered MWS ablation instead of transarterial chemoembolization. Among the patient population, 109 had a single nodule (Ø 5.3–8 cm) [group A], 70 had 2 nodules (Ø 3–6 cm) [group B] and 36 had 3–5 nodules (Ø 1.5–6.8 cm) [group C]. MWS ablation efficacy was evaluated using enhanced-computed tomography and/or magnetic resonance imaging. Primary end-point was 5-year cumulative overall survival (OS).

Results: On enhanced-computed tomography and/or magnetic resonance imaging, complete ablation rates were 100% for 1.5–3.5 cm nodules. In nodules >3.5–5 cm, it was 89% for the first ablation and 100% for the second. For lesions >5–8 cm, ablation was up to 92%. Overall, 1-, 3- and 5-year survival rates were 89, 60, and 21%, respectively. The cumulative OS rate of group A was 89%, 66% and 34% at 1, 3 and 5 years. The cumulative OS rate of group B was 88%, 60% and 11% at 1, 3 and 5 years. The cumulative OS rate of group C was 86%, 55% and 0%. The 5-year survival rate was significantly different among the groups (p <0.001). One patient died from rupture of HCC. Upon multivariate analysis, preablation total bilirubin >1.5 mg/dL was an independent factor for predicting lower survival.

Conclusions: Percutaneous MWS ablation of intermediate HCC is safe and effective in inducing large volume of necrosis in intermediate HCC nodules, providing long-term survival rates similar to transarterial chemoembolization. Preablation total bilirubin >1.5 mg/dL as expression of liver function reserve is the main factor predicting a worse outcome.