DAA treatment is not associated with a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the short term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, given that DAA regimens were used to treat persons at higher risk for developing HCC. (Hepatology 2018;67:2244-2253).

Purpose. To determine the immune response after dendritic cell (DC) vaccine and cytokine-induced killer cells (CIK) therapy and assess its associated toxicity, survival benefit, and changes in the quality of life (QOL) of advanced colorectal cancer (CRC) patients. Methods. We recruited 100 patients with unresectable CRC orrelapsed CRC after surgery who received DC vaccine and CIK cells (group immunotherapy, group I), and, as a control, 251 patients who had similar characteristics and underwent similar treatments, except for this immunotherapy (group nonimmunotherapy, group NI). After a follow-up period of 489.2 ± 160.4 days, overall survival (OS) of the two groups was compared using the Kaplan-Meier method. Results. In group I, 62% of patients developed a positive delayed type hypersensitivity response, and most patients showed an improvement in physical strength (75.2%), appetite (74.2%), sleeping (72.1%), and body weight (70.1%). Adverse events were fever (29.5%), insomnia (19.2%), anorexia (9.1%), sore joints (5.4%), and skin rash (1.0%). No toxicity was observed in patients treated with DC vaccine and CIK therapy. OS was significantly longer in group I than in group NI (P = 0.043). Conclusion. DC vaccine and CIK therapy were safe and could induce an immune response against CRC, thereby improving QOL and prolonging OS.

Summary Background Directly acting antiviral agents (DAA) have been associated with hepatic decompensation, especially in patients with pre‐treatment cirrhosis, but this risk is not well defined. Aim To determine the incidence of hepatic decompensation, liver transplantation, death and worsening renal function in patients treated with a Paritaprevir/ritonavir, Ombitasvir, Dasabuvir (PrOD), sofosbuvir/simeprevir or sofosbuvir/ledipasvir regimen. Methods We followed ERCHIVES participants treated with the above regimens for up to 12 weeks post‐treatment. We excluded those with HIV, HBsAg+ and pre‐existing diagnosis of hepatic decompensation and hepatocellular carcinoma. Results Of 3728 persons on PrOD, 1578 on sofosbuvir/simeprevir and 10 440 on sofosbuvir/ledipasvir, incidence rates (95% CI) of hepatic decompensation/1000 patient‐years were 10.6 (5.89–17.36) for the PrOD, 32.4 (20.74–48.16) for the sofosbuvir/simeprevir and 13.0 (9.74–17.10) for the sofosbuvir/ledipasvir. Among those with baseline cirrhosis, these rates were 36.9 (19.1–64.5), 61.8 (38.2–94.5) and 41.1 (29.9–55.2) respectively, while among those without cirrhosis at baseline, these rates were 2.7 (0.6–8.0), 7.5 (1.5–21.8) and 2.7 (1.2–5.4). Advanced fibrosis was associated with increased risk of hepatic decompensation in all groups [HR (95% CI) per 0.5 unit increase in FIB‐4 score: PrOD 1.11 (1.07–1.16); sofosbuvir/simeprevir 1.03 (1.01–1.05); sofosbuvir/ledipasvir 1.02 (1.01–1.03)]. There were no deaths. Proportion of persons with eGFR decrease >30 ml/min/1.73 m2 was higher among the PrOD group, but presence of cirrhosis did not appear to affect this. Conclusions The incidence of hepatic decompensation in persons treated with PrOD, up to 12 weeks after completion of treatment, was comparable to those treated with sofosbuvir/ledipasvir regimen, and was lower than among those treated with a sofosbuvir/simeprevir regimen. Such risk was predominantly observed in those with pre‐treatment cirrhosis.

BackgroundAs an acute-phase protein, serum amyloid A (SAA) is expressed primarily in the liver. However, its expression in extrahepatic tissues, especially in tumor tissues, was also demonstrated recently. In our study, we investigated the expression of SAA in uterine cervical carcinomas, and our results suggested its potential as a serum biomarker.MethodsQuantitative real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the SAA gene and protein expression levels in the tissues and sera of patients with non-neoplastic lesions (NNLs), cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CC).ResultsCompared with NNLs, the SAA gene (SAA1 and SAA4) expression levels were significantly higher in uterine CC (mean copy numbers: 138.7 vs. 5.01, P < 0.000; and 1.8 vs. 0.079, P = 0.001, respectively) by real-time PCR. IHC revealed cytoplasmic SAA protein staining in tissues from adenocarcinoma and squamous cell carcinoma of the cervix. The median serum concentrations (μg/ml) of SAA were 6.02 in patients with NNLs and 10.98 in patients with CIN (P = 0.31). In contrast, the median serum SAA concentration was 23.7 μg/ml in uterine CC patients, which was significantly higher than the SAA concentrations of the NNL group (P = 0.002) and the CIN group (P = 0.024).ConclusionsOur data suggested that SAA might be a uterine CC cell product. High SAA concentrations in the serum of CC patients may have a role in monitoring disease occurrence and could have therapeutic applications.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1433263219102962.

FIB-4 score is a better predictor of HD and HCC in HCV-positive persons. A score of <3 is associated with a low risk of HD and HCC 1 and 3 years after HCV diagnosis.

Purpose. This retrospective study determined the delayed-type hypersensitivity (DTH) skin test and safety of dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell immunotherapy and the survival compared to chemotherapy in 239 colorectal cancer (CRC) patients. Methods. DTH and safety of the immunotherapy were recorded. The overall survival (OS) and disease free survival curves were compared according to the immunotherapy and/or chemotherapy received with Kaplan-Meier estimates. Results. Of the 70 patients who received immunotherapy, 62.86% had a positive DTH skin test, 38.57% developed fever, 47.14% developed insomnia, 38.57% developed anorexia, 4.29% developed joint soreness, and 11.43% developed skin rash. For 204 resectable CRC patients, median survival time (MST) (198.00 days) was significantly longer in patients with immunotherapy plus chemotherapy than with chemotherapy alone (106.00 days) (P = 0.02). For 35 patients with unresectable or postsurgery relapsed CRC and who were confirmed to be dead, no statistical difference was observed in the MST between the patients treated with immunotherapy and with chemotherapy (P = 0.41). MST in the patients treated with chemotherapy plus immunotherapy was 154 days longer than that of patients treated with chemotherapy alone (P = 0.41). Conclusions. DC vaccination and CIK immunotherapy did not cause severe adverse effects, induce immune response against CRC, and prolong OS.

Recent preclinical studies have suggested an antifibrotic role for tricyclic antidepressants (TCA). Using the Electronically Retrieved Cohort of hepatitis C virus (HCV) Infected Veterans, we aimed to evaluate the impact of TCA use on fibrosis progression and development of hepatocellular carcinoma (HCC) among HCV-infected persons. Subjects were categorized according to use of TCAs, selective serotonin reuptake inhibitors (SSRI) or no antidepressants. TCAs or selective serotonin uptake inhibitors use was defined according to cumulative defined daily dose (cDDD), and categories were mutually exclusive. Subjects with HIV coinfection, hepatitis B surface antigen (HbsAg) positivity, cirrhosis or HCC at baseline were excluded. Outcomes were liver fibrosis progression measured by APRI scores and incident HCC. We utilized Cox proportional hazards regression to determine predictors of cirrhosis, defined as APRI > 2, and incident hepatocellular carcinoma (iHCC). Among 128 201 eligible HCV+ persons, 4% received TCAs, 43% received selective serotonin uptake inhibitors, and 53% received no antidepressants. Fewer TCAs users had drug abuse (34% and 43%) and alcohol abuse (32% vs 42%) compared to selective serotonin uptake inhibitor users. After adjusting for age, baseline APRI score, diabetes, hypertension, alcohol use, drug abuse and HCV RNA levels, TCAs use was associated with decreased risk of cirrhosis (hazard ratio [HR] = 0.77, 95% CI = 0.60, 0.99) and delayed time to development of cirrhosis, but not with decreased iHCC. In conclusion among a large cohort of HCV-positive Veterans, TCAs use was associated with decreased fibrosis progression and lower risk of developing cirrhosis. These data provide supportive evidence for the beneficial effects of TCAs on progression of liver fibrosis in patients with chronic HCV infection.

Abstract. The aim of this study was to determine the therapeutic effects of adoptive immunotherapy following dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell therapy and evaluate its cytotoxicity, survival benefits and quality of life (QOL) changes in patients with hepatobiliary and pancreatic cancer (HPC). We performed a retrospective analysis of 407 clinical cases, including 77 patients with HPC who received immunotherapy with DC vaccine and CIK cells (I group) and 330 patients with similar characteristics who underwent baseline treatment but did not receive immunotherapy [non-immunotherapy (NI) group)] as the control group. After a follow-up period of 294±207.5 days, the median survival time (MST) of the two groups was compared using the Kaplan-Meier method. In the I group, 61% of the patients developed a positive, delayed-type hypersensitivity response and 65% of the patients exhibited an improvement in QOL. The most notable adverse events included fever (28%), insomnia (25%), anorexia (17%), skin rash (12%) and arthralgia (31%). No severe toxicities were observed in patients in the I group; in addition, the MST was significantly longer in the I group compared with that in the NI group (P=0.014). Thus, the DC vaccine and CIK cell therapy was associated with mild adverse effects, but was able to induce an immune response and effectively eliminate tumor cells, thereby improving the QOL and prolonging the MST of the patients. IntroductionHepatobiliary and pancreatic cancer (HPC) is a major threat to human health, with an increasing incidence over the last few years. Surgery, chemotherapy and radiotherapy are currently the mainstay of treatment for HPC. Although surgery is the first treatment of choice, early-stage cancer is diagnosed in a limited number of patients (1,2). Furthermore, the hepatobiliary and pancreatic systems exhibit a complex anatomical structure and serve important physiological functions. Consequently, HPC symptoms lack specificity and have typically reached an advanced stage at diagnosis. Radical resection of HPC is not typically performed, and the majority of HPCs are associated with a poor prognosis (3,4). Chemotherapy and radiotherapy are the primary treatments for advanced-stage disease; however, these treatments may result in major health issues and are associated with severe treatment-related toxicity. Furthermore, the overall health status of HPC patients is generally poor, which may prevent them from being eligible for these standard therapies (2,5).In addition to the common factors affecting the prognosis of cancer patients (disease stage, tumor size, lymph node metastasis and radical surgery), individual differences in the immune factors among patients also affect prognosis. As all cancer patients exhibit varying degrees of low immunity and a significant proportion are in an immunosuppressed state, recovering anticancer immunity is a possible approach to cancer treatment. Autologous immune cell therapy has been the fourth most commonly used treatment method for ca...