Therapeutic success in primary biliary cholangitis and gut microbiota: a safe highway?

Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune disease, characterized by destruction of bile ducts. PBC predominantly affects women between 40 and 60 years of age. The presence of antimitochondrial antibodies (AMA) is a serological feature of PBC. These highly specific antibodies are found in about 95% of patients with the disease. The family of enzymes located in the inner membrane of the mitochondria, called the 2-oxo-acid dehydrogenase complex represents the target of the AMA. Ursodeoxycholic acid (UDCA) is a synthetic bile acid capable of protecting cholangiocytes from cholestatic damage caused by the accumulation of bile acids with a mechanism of action not yet well clarified. UDCA represents the gold standard therapy for PBC patients with recommended dose of 13-15 mg/kg/day. However, not every patient responds to therapy. On the other hand, the gut microbiota plays a key role in the onset of PBC through still unclear biochemical pathways. Less is known about its role as a potential biomarker after drug treatment. Actually, few studies analyzed the changes in gut microbiota composition before and after UDCA treatment. For this reason, this review represents an examination of the studies carried out on changes in gut microbiota composition in patients affected by PBC before and after treatment.

Triglyceride-Glucose Index and Hepatic Steatosis Index for the assessment of liver steatosis in HCV patients.

BACKGROUND: Liver steatosis in patients with chronic infection of hepatitis C virus (HCV) is important from multiple standpoints: faster disease progression, more frequent hepatocellular carcinoma and cirrhosis development or worse therapy response. Liver biopsy as diagnostic method, is in recent years more and more challenged due to its well-known flaws. Hepatic steatosis index (HSI) and triglyceride-glucose (TyG) Index, are surrogate scores developed in the first place for noninvasive assessment of steatosis in patients with nonalcoholic fatty liver disease (NAFLD). However, their use in the context of chronic hepatitis C (CHC) virus infection is still unclear. Aim of our study was to assess the accuracy of both HSI and TyG index in patients with CHC. METHODS: The cohort included 814 patients with CHC infection in whom liver biopsy was performed. After implementing strict criteria for sample adequacy and necessary data, 424 patients were finally enrolled in our study. Histological findings were used as a reference point, and surrogate scores HSI and TyG index were expressed through receiver operating characteristic (ROC) curves in order to assess their ability in determining patients without (<5%) or with steatosis (>5%), but also to address their ability in assessing between different degrees of steatosis. RESULTS: The average age of study population was 37.09 years and the majority of patients were men (67%). Liver steatosis was detected in approximately half of the liver biopsy samples (50.4%). About 5% of them had severe steatosis. The area under the ROC curve values for HSI and TyG index when detecting liver steatosis were 0.76 and 0.629, respectively. Similar values were obtained comparing between absence of steatosis and mild steatosis (5-30%). CONCLUSIONS: Non-invasive surrogate scores HSI and TyG index in CHC patients, have good performance to detect the presence of steatosis. In this context, these tools are cheap, widely available and could be valuable asset in liver steatosis assessment outside liver biopsy.

Liver injury associated with high value of D-dimer plasmatic level in COVID-19 patients.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causal agent of the coronavirus disease (COVID-19), has infected millions of people worldwide. Currently, the scientific community debates on the direct viral responsibility of liver damage or whether the observed changes are secondary manifestations of systemic inflammation triggered by COVID-19. The hepatic involvement is associated with worse clinical outcomes and higher risk of COVID-19 related morbidity and mortality. Furthermore, SARS-CoV-2 infection may predispose patients to thrombotic disease due to excessive inflammation, platelet activation, and endothelial dysfunction. METHODS: In this paper, we reported a cross-sectional analysis of five patients affected by a severe form of COVID-19, who died between April 11 and May 1, 2020. Each patient has been subjected to a medico-legal autopsy in which both gross and histological liver changes were evaluated, as well as the correlation with the related coagulation profile. RESULTS: In three cases of our cohort, the thromboembolism was recognized as cause of death. Furthermore, a significant statistical difference between D-dimer values at hospital admission and death among enrolled patients (P=0.033), was evaluated. No patient has recorded a pre-existing liver disease. CONCLUSIONS: Our results support the evidence that hepatic damage in subjects with severe form of COVID-19 is related to the changes in coagulative and fibrinolytic pathways. Hence, the evaluation of D-dimer blood levels may be useful in clinical practice to predict the involvement of the liver and the prognosis of these patients. This data highlights the fundamental role of coagulation balance in subjects with advanced form of COVID-19.

Noninvasive biochemical markers and surrogate scores in evaluating nonalcoholic steatohepatitis.

The histological features of nonalcoholic steatohepatitis (NASH) are the presence of hepatic steatosis with concomitant inflammation, ballooned hepatocytes, and potential fibrosis, which can lead to liver cirrhosis. To reduce the need for liver biopsy, that is still the gold standard for diagnosing NASH, various noninvasive biomarkers have been investigated. This narrative review summarizes the current knowledge about noninvasive diagnostic biomarkers and scores proposed for patients with NASH. A search was performed in the main medical literature databases. The following search terms were used: NASH, noninvasive biomarkers or NASH scores and panels. We focused only on studies assessing NASH diagnosis or predictive values for biomarkers, panels and scores. Data on their accuracy in predicting NASH were collected. Several panels such as NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4), and FibroMeter presented good predictive values of NASH, with novel proteomics panels such as the NAFLD Fibrosis Protein Panel (NFPP) using mainly the adisintegrin and metalloproteinase with thrombospondin motifs like 2 (ADAMTSL2) that showed an advantage in predicting NASH compared to NFS and FIB-4. Another novel panel, Index of NASH (ION) performed better than cytokeratin 18 (CK-18) in excluding severe fibrosis, but the overall accuracy of ION and CK-18 was modest compared to NFS and FIB-4 as it did not provide any significant advantage. Noninvasive biomarkers are currently unable to replace liver biopsy and histological assessment. However, they may play a key and vital role in triaging patients for liver biopsy, lowering the related financial burden. Future studies are needed to verify the predictive values of the newly emerging tests and panels as well as to find more affordable and reliable noninvasive early diagnostic tools.

Evaluation of serum calprotectin as novel biomarker in psoriatic patients: a prospective pilot study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease characterized by erythematous plaques that can extend along the entire skin surface. In the latest years, it has been shown that serum calprotectin correlated strongly with several inflammatory biomarkers. Since high levels of calprotectin have been found in psoriatic lesions, it is of paramount importance to investigate the role of serum calprotectin as a possible novel diagnostic marker of psoriasis. Aim of our prospective pilot study was to assess the level of serum calprotectin in psoriatic patients. METHODS: Between January 2018 and July 2019, 45 subjects were enrolled at the Dermatology Unit of Magna Graecia University of Catanzaro, Italy. Thirty-two of them were psoriatic patients and 13 healthy controls. Psoriasis severity was assessed by the Psoriasis Area Severity Index. RESULTS: A statistically significant difference between the two groups (P=0.01) was found in terms of body mass index, higher among patients than in controls. By performing the Student's t-test for unpaired data, serum calprotectin resulted significantly higher (P=0.033) among psoriatic patients than in controls. Furthermore, performing the receiver operator characteristic curve analysis, serum calprotectin showed a significant area under the curve, implying its possible role in finding psoriatic patients. Our study aimed to evaluate the serum levels of calprotectin in a group of psoriatic patients and in a control group. The results showed that serum calprotectin levels were significantly higher in the patient group than in the control group. This result confirms the observations present in the literature. CONCLUSIONS: In this pilot study psoriatic patients had a significant high level of serum calprotectin than healthy subjects, and this biomarker had high accuracy in identifying patients. Further studies, with larger sample size will need to confirm our data.

Gut microbiota and non-alcoholic fatty liver disease.

The gastrointestinal tract of the adult human represents the habitat of the ecological community of commensal, symbiotic and pathogenic microorganisms, defined as the gut microbiota, which has more than 100 trillion microorganisms representing one of the most complex ecosystems. Colonization of the gastrointestinal tract by microorganisms begins at the time of birth. Contrary to what was previously hypothesized, a large number of fundamental functions for the host are attributed to the gut microbiota to date. Therefore, the gut microbiota does not represent a passive set of microbes hosted inside the human organism but plays a crucial role in the balance of the organism itself. An alteration of the microbiota is a phenomenon known as dysbiosis. The latter can be implicated in the development of complex liver diseases like non-alcoholic fatty liver disease. The aim of this review was to describe the most interesting data linking the development of non-alcoholic fatty liver disease with the gut microbiota and, therefore, to underline the importance of the microbiota itself, as a potential therapeutic target in the treatment of non-alcoholic fatty liver disease.

Ancient wheats: beneficial effects on insulin resistance.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus are two conditions that commonly co-exist in the context of metabolic syndrome. Several scientific advances in understanding this association have identified insulin resistance as the key point in the pathogenesis of both diseases. The first line treatment suggested in the management of these diseases is represented by lifestyle changes, and in particular, the modification of alimentary regimen, with the transition to a healthy diet. In this context, several studies have focused their attention on the identification of food products with beneficial actions, like ancient wheat (AW). AW is defined as the early cereals that were domesticated in their places of origin in the "Fertile Crescent" of the Middle East, and played a central role as a main source of food for the early civilizations in that region. The present narrative review aims at providing a systematic overview of the state of the art on the effects of AW on insulin resistance.

Light Alcohol Drinking and the Risk of Cancer Development: A Controversial Relationship.

BACKGROUND: In accordance with the scientific literature heavy alcohol consumption (>50g per day) represents a risk factor for several diseases development, including cancer. However, the oncogenic role of light alcohol drinking (<12.5g per day) is still unknown. OBJECTIVE: To assess the scientific knowledge about light alcohol consumption and the risk of malignancy onset. METHODS: To collect the scientific evidences regarding this topic the keywords "light alcohol drinking", "light alcohol consumption" and "cancer", were used. Papers published during the last 15 years were analyzed, in order to select the most recent evidence. Meta-analyses with well-defined levels of alcohol intake were included in the present review. Other studies that focused on biochemical, molecular and genetic aspects, as well as duplicate articles, were excluded. RESULTS: Twenty-nine large, meta-analyses were included in this review. Light alcohol drinking was not associated with an increased risk of cancer occurrence, with the exception of breast and prostate cancer and melanoma. Furthermore, a possible protective role of light alcohol consumption on the development of bladder, kidney and ovarian cancer and Non Hodgkin Lymphoma was observed. CONCLUSION: Light alcohol drinking was not associated with the development of several malignancies, except for a light increase of melanoma, breast cancer in women and prostate cancer in men.