Insulin resistance: a predictor for response to interferon-based therapy in Egyptian patients with chronic HCV genotype 4

Egypt has the highest worldwide hepatitis C virus infection (HCV), it estimated about 13.8 %. Interferon alpha is considered the backbone for any effective treatment. These therapies are not without adverse effects nor are they always cost effective. Accordingly, it is important to identify patients with a considerable chance of response before initiation of therapy. Rapid virological response (RVR) is important for identification of non-responders permitting therapy discontinuation and avoiding adverse effects and costs. Evaluate the reliability of homeostasis model assessment (HOMA) method in prediction of HCV treatment response among Egyptian patients with chronic HCV genotype 4 infections. Our study included 80 participants; 50 non-cirrhotic non-diabetic patients with chronic HCV genotype 4 (group I), and 30 age- and sex-matched patients negative for HCV RNA and consequently they did not receive hepatitis treatment at the time of sampling (group II) were included. According to HOMA score, group I was further divided into group Ia with insulin resistance (IR) >2.5 (36 %) and group Ib with IR <2.5 (64 %). HOMA-IR was significantly associated with high RVR, progressive fibrosis stages, high pretreatment ALT levels, and body mass index. Our data suggests that IR strongly affects VR. HOMA-IR would appear to be useful in predicting RVR and should be evaluated at baseline in all chronic HCV patients before initiating interferon therapy to reduce unnecessary and ineffective treatments and enhance cost effectiveness of treatment.     

Recipient IL28B genotype CT is a predictor of new onset diabetes mellitus in liver transplant patients with chronic hepatitis C

International Journal of Diabetes in Developing Countries - New onset diabetes after liver transplantation (NODAT) is increasingly recognized as a complication that affects the quality of life. In...     

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL)

Liver fibrosis is a common pathway leading to cirrhosis, which is the final result of injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Liver biopsy has been considered to be the “gold standard” to assess fibrosis. However, liver biopsy being invasive and, in many instances, not favored by patients or physicians, alternative approaches to assess liver fibrosis have assumed great importance. Moreover, therapies aimed at reversing the liver fibrosis have also been tried lately with variable results. Till now, there has been no consensus on various clinical, pathological, and radiological aspects of liver fibrosis. The Asian Pacific Association for the Study of the Liver set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The process for the development of these consensus guidelines involved the following: review of all available published literature by a core group of experts; proposal of consensus statements by the experts; discussion of the contentious issues; and unanimous approval of the consensus statements after discussion. The Oxford System of evidence-based approach was adopted for developing the consensus statements using the level of evidence from 1 (highest) to 5 (lowest) and grade of recommendation from A (strongest) to D (weakest). The consensus statements are presented in this review. The members of Jury of the APASL Consensus Development Meeting are given in Appendix 1.     

In vitro mesenchymal stem cells differentiation into hepatocyte-like cells in the presence and absence of 3D microenvironment

Our study was aimed to select the best growth factor cocktail for differentiation of mesenchymal stem cells (MSCs) into hepatocytes-like cells (HLCs) in absence and presence of three dimensional (3D) microenvironment. Ninety milliliters of bone marrow was aspirated from the iliac bone for separation of MSCs. This study was conducted on 20 patients with advanced liver cirrhosis. They were divided into two groups. Group I; MSCs were plated onto 96-well plates without microenvironment (control group). Group II; MSCs were plated onto 96-well plates with 3D microenvironment. Surface expression of CD271, CD29, and CD34 were analyzed using flow cytometry. MSCs were differentiated in vitro into HLCs by adding four growth factor cocktails in presence and absence of 3D microenvironment. Hepatogenesis was assessed by immunohistochemical analysis of OV6, α-fetoprotein, albumin, and cytokeratin 18 expressions. There was statistically significant increase in the expression of CD271 and CD29 after MSCs culture (P?<?0.001). Heterogeneous cell population composed of MSCs and differentiated HLCs were encountered (40 % hepatocytes and 60 % MSCs). Furthermore, our results showed that growth factor cocktails 1 and 2 gave the best result for differentiation of MSCs into HLCs. MSCs could be feasible, readily available, and novel source for differentiation of MSCs into HLCs for future therapeutic implication.     

Alpha-Fetoprotein as a Modifier of Anatomic Criteria for Transplantation of HCC Patients

BackgroundThe current listing criteria (Milan, University of California San Francisco [UCSF]) for orthotropic liver transplants (OLT) in hepatocellular carcinoma (HCC) patients emphasize the anatomic features of the tumor such as size, burden, and multiplicity. Recent reports showed that patients with large tumors may have equivalent survival to Milan criteria patients. This suggests that differences in biologic behavior of tumors may contribute to the outcome.AimThe aim of this article is to understand the impact of biologic modifiers such as alpha-fetoprotein (AFP) on survival in both Milan and UCSF HCC patients.MethodsWe reviewed all liver transplants reported to the United Network for Organ Sharing between 2002 and 2013. We analyzed the survival of patients transplanted for HCC who fit the Milan criteria and those transplanted with tumors beyond Milan and within UCSF criteria. We tested various AFP level cutoffs in both groups in relationship to the 1-, 3-, and 5-year survival rates below and above the proposed cutoffs.ResultsSurvival difference was significant between Milan patients with AFP ≤ 2500 ng/mL and those with AFP > 2500 ng/mL (59.1% vs 37.4%; P < .001). The mean 5-year survival was 55% for beyond Milan within UCSF patients with AFP ≤ 150 ng/mL and 35.7% for those with AFP > 150 ng/mL (P = .003).ConclusionAFP level should be incorporated in the selection criteria for HCC patients considered for OLT. Milan patients with an AFP level exceeding 2500 ng/mL have reduced survival. Patients with tumors beyond Milan and within UCSF criteria whose AFP ≤ 150 ng/mL achieve acceptable 5-year survival and are good candidates for OLT.     

Immunotherapy by autologous dendritic cell vaccine in patients with advanced HCC

Background

Dendritic cells (DCs) could be used as potential cellular adjuvant for the production of specific tumor vaccines.

Objectives

Our study was aimed to evaluate the safety and efficacy of autologous pulsed DC vaccine in advanced hepatocellular carcinoma (HCC) patients in comparison with supportive treatment.

Methods

Thirty patients with advanced HCC not suitable for radical or loco-regional therapies were enrolled. Patients were divided into 2 groups, group I consisted of 15 patients received I.D vaccination with mature autologous DCs pulsed ex vivo with a liver tumor cell line lysate. Group II (control group, no. 15) received supportive treatment. One hundred and 4 ml of venous blood were obtained from each patient to generate DCs. DCs were identified by CD80, CD83, CD86 and HLA-DR expressions using flow cytometry. Follow up at 3, and 6 months post injection by clinical, radiological and laboratory assessment was done.

Results

Improvement in overall survival was observed. Partial radiological response was obtained in 2 patients (13.3 %), stable course in 9 patients (60 %) and 4 patients (26.7 %) showed progressive disease (died at 4 months post-injection). Both CD8⁺ T cells and serum interferon gamma were elevated after DCs injection.

Conclusion

Autologous DC vaccination in advanced HCC patients is safe and well tolerate.