It is generally accepted that eradication of Helicobacter pylori (H. pylori) infection may reduce the risk of the development of gastric cancer. Recommendations for global generalized tests and treat all individuals detected positive for H. pylori infection are currently proposed. However, the bacterium is commensal and harmless for the vast majority of the infected population. Moreover, eradication may have detrimental consequences in several groups of patients. In the present review, the current epidemiological data and recommendations for eradication in connection with the possible beneficial effects of the colonization with H. pylori in diseases such as asthma and allergies or chronic gastro-intestinal disorders such as inflammatory bowel disease and Barrett’ esophagus are presented the problems with increasing antibiotic resistance were also examined. Specific groups of patients where eradication of H. pylori may be necessary and endoscopic surveillance is advised were identified. Finally, based on the paradox of high H. pylori prevalence and low gastric risk as reported for areas of Africa, Asia, South America, and Greece, alternatives that may replace the widespread eradication of H. pylori with equal if not better results and more prudent use of the available financial resources are proposed. Mediterranean diets and alcohol and smoking reduction are among the well documented alternatives.

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology that can lead to end stage liver disease if left without treatment. Corticosteroids with or without azathioprine (AZA) are considered the recommended standard first-line treatment option for the induction and maintenance of remission. The aim of treatment is to achieve complete biochemical response (CBR), defined by normal transaminases and immunoglobulin G (IgG) within 6–12 months after treatment initiation. However, response rates to standard treatment vary widely as approximately 10–25% of cases develop intolerance, insufficient response, or rarely non-response to AZA. Mycophenolate mofetil (MMF) is an effective and safe alternative first-line treatment in AIH, based on its high rates of CBR among treatment-naive patients, but can also be considered as second-line drug in patients with poor response or intolerance to AZA. However, even after the administration of second line treatment there is a small proportion of patients with refractory disease that bear the highest probability of developing decompensated cirrhosis and hepatocellular carcinoma. For this difficult to treat subgroup of patients third-line treatments are warranted. Therefore, the aim of this review is to summarize the current evidence on second- and third-line therapies for AIH, as well as, to set the background for future perspectives on safer and more efficient treatment strategies.

This is a case of remarkable alpha-fetoprotein in a female patient with known cryptogenic liver cirrhosis. Both ultrasound and triphasic computed tomography (CT) abdomen cannot diagnose or exclude hepatocellular carcinoma (HCC). It turns out to be a case of portal vein thrombosis and hepatic pseudo-infarction. It is better to postpone the therapeutic intervention, whether surgical or chemotherapeutic, in cases not confirmed to be HCC for at least 3 months to avoid misdiagnosis of hepatic pseudo-infarction.

The liver, characterized by a unique metabolic and immunosuppressive environment, is also the organ to which invasive malignant cells of many different cancer types most frequently metastasize. The reasons for this organ-specific metastatic process have been investigated for decades. This review first provides an overview of recent breakthroughs in this field, introducing intercellular communication between circulating tumor cells and the heterogeneous cell populations of the liver, and modifications to the extracellular matrix (ECM). Subsequently, to improve the understanding of the molecular mechanisms involved in the metastasis of colorectal cancer to the liver, the second leading cause of cancer-related mortality, the recent literature on this question was analyzed. Among the various parameters involved, the mechanisms behind the activation of hepatic stellate cells, proteins inducing ECM remodeling, specific genomic features of liver metastases, metabolic rewiring, and characteristics of stromal-enriched microenvironments were discussed. To provide more insights into the molecular determinants of liver metastatic colonization, important findings reported on a set of mitochondrial proteins were addressed, the relative abundance of which changed in the liver during the progression stage of an aggressive experimental model of peritoneal malignant mesothelioma in immunocompetent rats. Based on previous studies cross-comparing the liver proteomes from curcumin-treated tumor-bearing rats/untreated tumor-bearing rats/normal rats, data from the literature were reviewed for 25 mitochondrial proteins of interest. Their role in lipid metabolism, heme biosynthesis, the electron transport chain, small molecule transport, mitochondrial dynamics, the tricarboxylic acid cycle, and protection against oxidative stress were analyzed in the context of both cancer and non-malignant liver diseases.

Mitochondria are present in all mammalian cells except matured red blood cells. Mitochondria consist of several metabolic pathways for glucose, fatty acids, amino acids, and bioenergetic pathways for ATP synthesis, membrane potential, and reactive oxygen production. In the liver, hepatic mitochondria play a key role in hepatic steatosis because mitochondrial metabolism produces acetyl-CoA which is the building block for synthesis of lipids and cholesterol. Mitochondria inner membrane is impermeable of metabolites, reducing equivalents, and small molecules such as phosphate, and sulfate. Thus, mitochondrial shuttles and carriers function as the routes of influx and efflux of these metabolites and molecules across the inner membrane. The signal regulation of these shuttles and mitochondrial enzymes could play a key role in coordinating the mitochondrial metabolism to adapt the cytosolic part of metabolic pathways in liver metabolic stress. Intriguingly, the interaction of mitochondria protein SH3 domain-binding protein 5 (SAB/SH3BP5) and c-Jun N-terminal kinase (JNK) was found as a pivotal role in sustained activation of JNK and phosphorylated-JNK (P-JNK) mediated activation of lipogenic pathway in nutritional excess. Knockout or knockdown of SAB prevented or reversed the hepatic steatosis, inflammation, and fibrosis, and improved metabolic intolerance and energy expenditure. Moreover, blocking the SAB peptide prevents palmitic acid-induced P-JNK interaction with SAB and inhibition of mitochondrial bioenergetics, implying the P-JNK effect on mitochondrial metabolism. This review focuses on the flow of mitochondrial metabolites in metabolic stress conditions and the contribution of mitochondria and mitochondrial stress signals in hepatic steatosis.

Chronic liver diseases (CLDs), which are typically characterized by fibrogenic progression towards liver cirrhosis and related complications eventually leading to organ failure and can also lead to the development of primary liver cancers, represent a major burden for human health on a worldwide basis. Although the present knowledge on the pathogenesis of CLDs progression and primary liver cancers development has remarkably increased in the last decades, critical molecular mediators remain incompletely understood, and approved antifibrotic therapies to efficiently counteract CLDs progression and liver cancer are lacking. In the present review, this study will specifically analyse the putative contribution of SERPINB3, a member of the superfamily of serine-protease inhibitors (SERPINs), which has been shown to exert significant pro-inflammatory and pro-fibrogenic roles in progressive CLDs as well as to be involved in the development of primary liver cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma, and hepatoblastoma.

Hunting for tumoral material in body fluids, traditionally in blood, the so-called liquid biopsy is set to revolutionize the diagnosis and management of oncological patients. However, other biofluids can also be considered as alternative sources of biomarkers to provide clinically valuable information for multiple diseases. This is the case of bile, a fluid produced in the liver, stored in the gallbladder, and excreted to the duodenum, which complex composition is known to change in different pathological conditions. Remarkably, different works have demonstrated that the identification of mutations in bile cell-free DNA (cfDNA) can outperform blood analysis for the early diagnosis of biliopancreatic tumors causing biliary strictures. Here, the literature in which bile has been tested as a liquid biopsy matrix where lipids, metabolites, proteins, and cfDNA among other analytes were measured is reviewed. Moreover, the clinical situations and procedures where bile can be available, discussing the possible applications and limitations of bile analysis are summarized. The scientific relevance and clinical potential of bile harvesting, biobanking, and analysis are put forward. All this evidence supports the value of bile as a liquid biopsy matrix for the management of patients beyond cancer, and perhaps also beyond “blood, sweat, and tears”.