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Liver damage can progress through different stages, resulting in cirrhosis or hepatocellular carcinoma (HCC), conditions that are often associated with viral infections. Globally, 42% and 21% of cirrhosis cases correlate with HBV and HCV, respectively. In the Americas, the prevalence ranges from 1% to 44%. The WHO has the goal to eliminate viral hepatitis, but it is important to consider occult HBV infection (OBI), a clinical condition characterized by the presence of HBV genomes despite negative surface antigen tests. This review aims to provide an overview of recent data on OBI, focusing on its role in the development of hepatic diseases and its significance in the WHO Viral Hepatitis Elimination Plan. Specific HBV gene mutations have been linked to HCC and other liver diseases. Factors related to the interactions between OBI and mutated viral proteins, which induce endoplasmic reticulum stress and oxidative DNA damage, and the potential role of HBV integration sites (such as the TERT promoter) have been identified in HCC/OBI patients. Health initiatives for OBI research in Latin American countries are crucial to achieving the WHO's goal of eradicating viral hepatitis by 2030, given the difficulty in diagnosing OBI and its unclear association with hepatic diseases.

The growth differentiation factor 11 (GDF11), a member of the superfamily of the transforming growth factor β, has gained relevance in the last few years due to its remarkable effects in cellular biology, particularly in the nervous system, skeletal muscle, the heart, and many epithelial tissues. Some controversies have been raised about this growth factor. Many of them have been related to technical factors but also the nature of the cellular target. In liver biology and pathobiology, the GDF11 has shown to be related in many molecular aspects, with a significant impact on the physiology and the initiation and progression of the natural history of liver diseases. GDF11 has been involved as a critical regulator in lipid homeostasis, which, as it is well known, is the first step in the progression of liver disease. However, also it has been reported that the GDF11 is involved in fibrosis, senescence, and cancer. Although there are some controversies, much of the literature indicates that GDF11 displays effects tending to solve or mitigate pathological states of the liver, with reasonable evidence of correlation with other organs or systems. To a large extent, the controversy, as mentioned, is due to technical problems, such as the specificity of GDF11 antibodies, confusion with its closer family member, myostatin, and the state of differentiation in the tissues. In the present work, we reviewed the specific effects of GDF11 in the biology and pathobiology of the liver as a potential and promising factor for therapeutic intervention shortly., Competing Interests: Declaration of competing interest The authors indicate no conflict of interest., (Copyright © 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Alcohol-induced pancreas damage remains as one of the main risk factors for pancreatitis development. This disorder is poorly understood, particularly the effect of acetaldehyde, the primary alcohol metabolite, in the endocrine pancreas. Hepatocyte growth factor (HGF) is a protective protein in many tissues, displaying antioxidant, antiapoptotic, and proliferative responses. In the present work, we were focused on characterizing the response induced by HGF and its protective mechanism in the RINm5F pancreatic cell line treated with ethanol and acetaldehyde. RINm5F cells were treated with ethanol or acetaldehyde for 12 h in the presence or not of HGF (50 ng/ml). Cells under HGF treatment decreased the content of reactive oxygen species and lipid peroxidation induced by both toxics, improving cell viability. This effect was correlated to an improvement in insulin expression impaired by ethanol and acetaldehyde. Using a specific inhibitor of Erk1/2 abrogated the effects elicited by the growth factor. In conclusion, the work provides mechanistic evidence of the HGF-induced-protective response to the alcohol-induced damage in the main cellular component of the endocrine pancreas., (© 2023 Wiley Periodicals LLC.)

Cadmium is a toxic element to which man can be exposed at work or in the environment. Cd's most salient toxicological property is its exceptionally long half-life in the human body. Once absorbed, Cd accumulates in the human body, particularly in the liver. The cellular actions of Cd are extensively documented, but the molecular mechanisms underlying these actions are still not resolved. The liver manages the cadmium to eliminate it by a diverse mechanism of action. Still, many cellular and physiological responses are executed in the task, leading to worse liver damage, ranging from steatosis, steatohepatitis, and eventually hepatocellular carcinoma. The progression of cadmium-induced liver damage is complex, and it is well-known the cellular response that depends on the time in which the metal is present, ranging from oxidative stress, apoptosis, adipogenesis, and failures in autophagy. In the present work, we aim to present a review of the current knowledge of cadmium toxicity and the cellular response in the liver., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hepatocyte growth factor (HGF) has been proved to protect the liver against α-naphthylisothiocyanate (ANIT)-induced cholestasis by acting as an antioxidant agent and redirecting toxic biliary solutes towards blood for urinary excretion. However, this may represent an additional potential risk for kidney integrity, which is already compromised by the cholestatic process itself (cholemic nephropathy). Therefore, in the present work, we studied the renal damage caused by ANIT-induced cholestasis and whether it is aggravated or, on the contrary, counteracted by HGF; if the latter holds, the involvement of its antioxidant properties will be ascertained. ANIT-induced cholestatic deleterious renal effects were corroborated by the presence of urine bile salts, impairment of renal function, and the alterations of renal damage markers, such as HSP72, creatinine clearance, and albuminuria. HGF fully reverted all these, and the cast formation in the tubules was significantly decreased. These findings were associated with the control of renal oxidative stress. In summary, despite HGF enhancing the overload of potentially harmful biliary constituents that the kidney should remove from the bloodstream as an alternative depuration organ in cholestasis, it simultaneously protects the kidney from this damage by counteracting the prooxidant effects resulting from this harmful exposure., (Copyright © 2022. Published by Elsevier Inc.)

Cancer cells are characterized by accelerated proliferation and an outstanding adaptation of their metabolic pathways to meet energy demands. The folate cycle, also known as folate metabolism or one-carbon metabolism, through enzymatic interconversions, provides metabolites necessary for nucleotide synthesis, methylation, and reduction power, helping to maintain the high rate of proliferation; therefore, the study of this metabolic pathway is of great importance in the study of cancer. Moreover, multiple enzymes involved in this cycle have been implicated in different types of cancer, corroborating the cell's adaptations under this pathology. During the last decade, nonalcoholic fatty liver disease has emerged as the leading etiology related to the rise in the incidence and deaths of hepatocellular carcinoma. Specifically, cholesterol accumulation has been a determinant promoter of tumor formation, with solid evidence that an enriched-cholesterol diet plays a crucial role in accelerating the development of an aggressive subtype of hepatocellular carcinoma compared to other models. In this review, we will discuss the most recent findings to understand the contribution of folate metabolism to cancer cells and tumor microenvironment while creating a link between the dynamics given by cholesterol and methylenetetrahydrofolate dehydrogenase 1-like, a key enzyme of the cycle located in the mitochondrial compartment.

Introduction and Aim: Occult hepatitis B virus infection (OBI) is characterized by the presence of replication-competent hepatitis B virus (HBV) DNA in the liver and/or serum of patients with undetectable levels of the HBV surface antigen (HBsAg). Due to the shared infection routes HIV positive patients are at higher risk of developing OBI, thus, the aim of this study was to determine the frequency of OBI in Mexican HIV-infected patients and to identify mutations in the HBV S gene that could be associated to the development of OBI., Materials and Methods: Plasma samples from 50 HIV-infected patients with undetectable levels of the HBsAg were obtained and analyzed. The Core, PreS and S genes were amplified by nested PCR and sequenced by the Sanger method. To analyze HBV diversity in the OBI-positive patients, ten sequences of 762bp from the HBV S gene were selected, cloned, and subsequently sequenced for mutational analyses., Results: OBI infection was found with a frequency of 36% (18/50). All the HBV sequences corresponded to the H genotype. The most common mutations were: C19Y, Q129H, E164D, and I195M, with a frequency of 44%, 36%, 39% and 48% respectively., Conclusions: In this study, we report the presence of OBI in a cohort of Mexican HIV-infected patients with an overall prevalence of 36%. Mutational analyses revealed that four non-silent mutations were frequent in different regions of the HBsAg gene, suggesting that they might be associated to the development of OBI in this population, nevertheless, further studies are required to determine their role in the pathogenesis of OBI., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Cholestasis is a clinical syndrome common to a large number of hepatopathies, in which either bile production or its transit through the biliary tract is impaired due to functional or obstructive causes; the consequent intracellular retention of toxic biliary constituents generates parenchyma damage, largely via oxidative stress-mediated mechanisms. Hepatocyte growth factor (HGF) and its receptor c-Met represent one of the main systems for liver repair damage and defense against hepatotoxic factors, leading to an antioxidant and repair response. In this study, we evaluated the capability of HGF to counteract the damage caused by the model cholestatic agent, α-naphthyl isothiocyanate (ANIT). HGF had clear anti-cholestatic effects, as apparent from the improvement in both bile flow and liver function test. Histology examination revealed a significant reduction of injured areas. HGF also preserved the tight-junctional structure. These anticholestatic effects were associated with the induction of basolateral efflux ABC transporters, which facilitates extrusion of toxic biliary compounds and its further alternative depuration via urine. The biliary epithelium seems to have been also preserved, as suggested by normalization in serum GGT levels, CFTR expression and cholangyocyte primary cilium structure our results clearly show for the first time that HGF protects the liver from a cholestatic injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)