Hepatic stellate cell (HSC), initially analyzed by von Kupffer, in 1876, revealed to be an extraordinary mesenchymal cell, essential for both hepatocellular function and lesions, being the hallmark of hepatic fibrogenesis and carcinogenesis. Apart from their implications in hepatic injury, HSCs play a vital role in liver development and regeneration, xenobiotic response, intermediate metabolism, and regulation of immune response. In this review, we discuss the current state of knowledge regarding HSCs morphology, human HSCs markers and human HSC cell lines. We also summarize the latest findings concerning their roles in normal and liver pathology, focusing on their impact in fibrogenesis, chronic viral hepatitis and liver tumors.

Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (n = 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation.

In the last years, animal testing in medical research has been a controversial topic because of various reasons, such as ethical considerations and species differences. Therefore, more attention has been given to develop new technologies that can replace animal experiments and create in vitro models. Organ-on-a-chip (OOC) technology is a new and advanced technology based on microfluidic devices that can mimic the structure and function of entire organs and tissues as in vitro models. OOC models are miniature tissues and organs that assign characteristics for three-dimensional (3D) cell culture representation that resemble the original organs, together with their specific microenvironment microfluidic systems and specific biophysical processes, in order to mimic the normal physiological conditions and functionalities of the organs. Existing OOC models, such as liver, pancreas, heart, skin, brain, kidney, vessels, have been developed and designed for a specific function study. This review focuses on the main knowledge concerning OOC research and especially vascular endothelium-on-a-chip (EOC) model, developed in order to offer specific tools for studying vascular functions in physiological and pathological conditions. The field of OOC devices is still at the beginning, but in the future, this technology may have important roles in developing novel therapeutic approaches, offering new therapeutic molecules and providing the first step towards personalized medicine.

Background and Aims: The aim of this study is to determine whether activated hepatic stellate cells (HSCs) may represent a prognostic marker of progressive liver fibrosis in chronic viral hepatitis C (VHC) before antiviral therapy. The possible correlation between HSCs immunohistochemical features, histopathological aspects and clinical data before therapy were also studied. Methods: This retrospective pilot study was conducted on 27 liver biopsies from VHC patients before antiviral therapy. HSCs’s immunohistochemical analysis used the antibodies alpha-smooth muscle actin (α-SMA), glial fibrillary acidic protein (GFAP) and vinculin. We correlated immunopositive HSCs with HCV load, liver stiffness (LS), fibrosis stage and necro-inflammatory degree before treatment. Also, we assessed the association between liver fibrosis after therapy, the sustained virological response at 12 weeks after therapy (SVR 12) and the type of therapy. Results: HSCs were increased in VHC patients compared to controls, mainly in the intermediate and periportal lobular regions. α-SMA and vinculin HSCs correlated positively with fibrosis stage (p=0.044), (p=0.028). Furthermore, α-SMA and vinculin HSCs were associated with LS (p=0.027), (p=0.002) and viral load (p=0.021), (p=0.006), but not with necro-inflammation degree. GFAP HSCs inversely correlated with fibrosis stage (r= -0.475), LS (r= -0.422) and HCV load (r= -0.517), but positively with necro-inflammation degree (p=0.038). Liver fibrosis post therapy correlated positively with SVR12 (p<0.001) and the type of therapy (p=0.006) and SVR12 correlated positively with treatment’s type (p=0.002). Conclusions: Activated HSCs may represent a marker of increased liver fibrosis in VHC. Different immunohistochemical markers can detect various HSCs subpopulations involved in the evolution of VHC and liver fibrosis.

Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most widely used drugs due to their anti-inflammatory, analgesic and antipyretic pharmacological effects. Gastrointestinal side effects are some of the most severe and frequent side effects of NSAIDs. These depend on the balance of the gut microbiome, the abundance of Gram-negative bacteria, and the amount of lipopolysaccharide released. Therefore, restoring or improving gut bacteria balance with probiotic supplements could prove to be an adjuvant therapy against mild NSAID-induced enteropathy. Twenty-five Wistar albino male rats were divided into five groups. The negative control group was administered carboxymethylcellulose and the positive control group diclofenac (DIC), 8 mg/kg for 7 days, which represented the enteropathy model. Treatment groups consisted of a combination of pro-biotic spores (MSB), amino acids and immunoglobulins supplement (MM), which were also administered for 7 days. We analyzed hepatic injury markers (AST, ALT) and creatinine, and inflammatory markers, IL-6, TNF-α, PGE2, iNOS, as well as total antioxidant capacity. The results obtained in the present study suggest that the modulation of the intestinal microbiota by administration of probiotics (Bacillus spores), alone or in combination with immunoglobulins and amino acids, represents an attractive therapy for the prevention of NSAID-induced enteropathy.