HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6:a systematic review and meta-analysis

OBJECTIVE: The objective of this study was to assess the possibility of HBV reactivation (HBVr) in patients with RA under anti-IL-6 treatment.METHODS: Using PubMed, Scopus and EMBASE, we performed a systematic literature search for articles related to HBVr in RA patients under anti-IL-6 treatment. The search was performed with no date limits and was last updated 28 January 2023. The results from all the databases were combined and duplicates were excluded, as were non-English articles, case reports, position articles, comments, and paediatric studies.RESULTS: Our initial search led to 427 articles; 28 were duplicates, 46 non-English, 169 reviews, 31 books/letters, 25 case reports, and 88 irrelevant to the meta-analysis aim; 21 were excluded due to inadequate information, leaving 19 articles, with a sum of 372 RA patients with chronic HBV (CHB) or resolved HBV infection, for further analysis. The overall risk for HBVr in RA patients with CHB was 6.7%, increasing to 37% when only RA patients with CHB and no antiviral prophylaxis were included. On the contrary, HBVr was close to 0% in RA patients with resolved HBV infection, irrespective of antiviral prophylaxis. All RA patients experiencing HBVr in these studies were successfully managed with antiviral treatment and/or drug withdrawal.CONCLUSION: Overall, anti-IL-6 treatment comes with a significant risk of HBVr in RA patients with CHB; risk is diminished when antiviral prophylaxis is used. In contrast, in RA patients with resolved HBV infection, the risk of HBVr seems to be extremely low. Large, well-designed studies (either controlled trials or multicentre/international observational studies) are warranted to further validate these results.</p

Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD

SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection?

Non-alcoholic fatty liver disease (NAFLD) is an ‘umbrella’ term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment

Endothelial cell dysfunction and nonalcoholic fatty liver disease (NAFLD) : a concise review

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. It is strongly associated with obesity, type 2 diabetes (T2DM), and other metabolic syndrome features. Reflecting the underlying pathogenesis and the cardiometabolic disorders associated with NAFLD, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has recently been proposed. Indeed, over the past few years, growing evidence supports a strong correlation between NAFLD and increased cardiovascular disease (CVD) risk, independent of the presence of diabetes, hypertension, and obesity. This implies that NAFLD may also be directly involved in the pathogenesis of CVD. Notably, liver sinusoidal endothelial cell (LSEC) dysfunction appears to be implicated in the progression of NAFLD via numerous mechanisms, including the regulation of the inflammatory process, hepatic stellate activation, augmented vascular resistance, and the distortion of microcirculation, resulting in the progression of NAFLD. Vice versa, the liver secretes inflammatory molecules that are considered pro-atherogenic and may contribute to vascular endothelial dysfunction, resulting in atherosclerosis and CVD. In this review, we provide current evidence supporting the role of endothelial cell dysfunction in the pathogenesis of NAFLD and NAFLD-associated atherosclerosis. Endothelial cells could thus represent a “golden target” for the development of new treatment strategies for NAFLD and its comorbid CVD

Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease:friend or foe

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD

HIV and the liver

The introduction of antiretroviral treatment (ART) for HIV-infected patients has led to a change of these patients' life expectancy, making HIV infection a chronic rather than a fatal disease. This prolongation of patients' survival has resulted in a change of the diseases most commonly seen during HIV infection's natural course, with cardiovascular and liver disease presenting more often than opportunistic infections. As far as liver is concerned, diseases like chronic HBV and HCV infections lead to liver cirrhosis faster in patients with HIV infection, while the prevalence of alcoholic and non-alcoholic disease is steadily rising in these patients. The best method for assesing liver fibrosis is liver biopsy; however it is an invasive procedure that requires hospitalization and is prone to complications. For that reason, non invasive methods for assesing liver fibrosis have been developed; among them transient elastography, measuring liver stifness, seems to provide the most reliable results with high creditability. Transient elastography, however, has also limitations, like high cost, low availability, especially in low income countries, and dependence on operator experience. For that reason various scores have been developed that take into account commonly used laboratory results for determining liver fibrosis. The use of these, so called non-invasive biomarkers of liver disease, in specific groups of patients like those suffering for hepatitis C virus are trustworthy and can replace transient elastography in everyday practice. Even though the application of these non-invasive biomarkers in the general population and patients with HIV/HCV infection is widespread, few studies exist in patients with HIV infection. The aim of the present study was to search for possible risk factors for significant liver fibrosis in a cohort of HIV-infected patients, as well as which non-invasive biomarkers can better determine liver fibrosis in HIV-monoinfected patients. Furthermore we tried to evaluate the efficacy of the new, all oral, treatment against HCV infection in patients with HIV/HCV coinfection. Our study included patients followed by the outpatient liver and the outpatient infectious diseases clinics of the Pathophysiology Department of 'Laiko' General Hospital. As gold standard method for determining liver fibrosis, transient elastography was used.Η διάδοση, τα τελευταία χρόνια, της αντιρετροϊκής αγωγής για τη θεραπεία ασθενών με HIV λοίμωξη, συνετέλεσε ώστε οι ασθενείς αυτοί να έχουν προσδόκιμο επιβίωσης ανάλογο του γενικού πληθυσμού και μετέτρεψε τη λοίμωξη αυτή από θανατηφόρο σε χρόνια νόσο. Η παράταση της επιβίωσης των οροθετικών ασθενών έχει ως συνέπεια την διαφοροποίηση των νοσημάτων που αυτοί εμφανίζουν, με συνέπεια να καταλήγουν συχνότερα λόγω επιπλοκών από το καρδιαγγειακό σύστημα ή το ήπαρ παρά λόγω ευκαιριακών λοιμώξεων. Ιδιαίτερα όσον αφορά το ήπαρ, νοσήματα όπως οι χρόνιες ηπατίτιδες B και C, οδηγούν ταχύτερα σε ηπατική κίρρωση σε σχέση με το γενικό πληθυσμό, ενώ αυξάνει σταθερά ο επιπολασμός της μη αλκοολικής και αλκοολικής λιπώδους νόσου του ήπατος. Η καλύτερη μέθοδος για την εκτίμηση της ηπατικής βλάβης είναι η βιοψία ήπατος, η οποία όμως είναι μια επεμβατική διαδικασία, χρήζει νοσηλείας και μπορεί να συνοδεύεται από επιπλοκές. Για το λόγο αυτό έχουν αναπτυχθεί μη επεμβατικές τεχνικές εκτίμησης της ηπατικής βλάβης, με τη σημαντικότερη από αυτές να είναι η ελαστογραφία ήπατος (TE), η οποία εκτιμά έμμεσα την ηπατική ίνωση, μετρώντας τη σκληρότητα του ήπατος, εμφανίζει ικανοποιητική συσχέτιση με τη βιοψία ήπατος και θεωρείται αξιόπιστη εναλλακτική της. Σχετικά προβλήματα όμως έχει και η ΤΕ όπως είναι το υψηλό κόστος, η απουσία ευρείας διαθεσιμότητά της και η εξάρτησή της από την ικανότητα και την εμπειρία του χειριστή του μηχανήματος. Έτσι, γίνεται προσπάθεια ανάπτυξης διάφορων βιοδεικτών (scores), τα οποία χρησιμοποιούν εργαστηριακές παραμέτρους για την εκτίμηση της ηπατικής ίνωσης. Η εφαρμογή των παραπάνω βιοδεικτών σε ειδικές ομάδες ασθενών, όπως οι ασθενείς με χρονία λοίμωξη από τον ιό της ηπατίτιδας C (HCV), είναι αξιόπιστη και συχνά αντικαθιστά την TE στην καθημέρα πράξη. Αν και η εφαρμογή των παραπάνω δεικτών στο γενικό πληθυσμό και σε ασθενείς με HIV/HCV συλλοίμωξη είναι ευρεία, ελάχιστες μελέτες έχουν γίνει σε ασθενείς με HIV μονολοίμωξη. Στόχος της παρούσης μελέτης ήταν η αναζήτηση των παραγόντων κινδύνου για σημαντική ηπατική ίνωση σε μια κοορτή ασθενών με HIV λοίμωξη, καθώς και των μη επεμβατικών βιοδεικτών, οι οποίοι εκτιμούν καλύτερα την ηπατική ίνωση σε ασθενείς με HIV μονολοίμωξη. Επιπλέον ήταν η εκτίμηση της αποτελεσματικότητας των νέων από του στόματος φαρμάκων έναντι της HCV λοίμωξης σε ασθενείς με HIV/HCV συλλοίμωξη. Στη μελέτη συμπεριλήφθηκαν ασθενείς που παρακολουθούνται στο εξωτερικό ηπατολογικό ιατρείο και στο ιατρείο λοιμώξεων της Κλινικής της Παθολογικής Φυσιολογίας του ΓΝΑ «Λαϊκό». Ως ιδανική (gold standard) μέθοδος εκτίμησης της ηπατικής ίνωσης χρησιμοποιήθηκε η ΤΕ

HIV και ήπαρ

Η διάδοση, τα τελευταία χρόνια, της αντιρετροϊκής αγωγής για τη θεραπεία ασθενών με HIV λοίμωξη, συνετέλεσε ώστε οι ασθενείς αυτοί να έχουν προσδόκιμο επιβίωσης ανάλογο του γενικού πληθυσμού και μετέτρεψε τη λοίμωξη αυτή από θανατηφόρο σε χρόνια νόσο. Η παράταση της επιβίωσης των οροθετικών ασθενών έχει ως συνέπεια την διαφοροποίηση των νοσημάτων που αυτοί εμφανίζουν, με συνέπεια να καταλήγουν συχνότερα λόγω επιπλοκών από το καρδιαγγειακό σύστημα ή το ήπαρ παρά λόγω ευκαιριακών λοιμώξεων. Ιδιαίτερα όσον αφορά το ήπαρ, νοσήματα όπως οι χρόνιες ηπατίτιδες B και C, οδηγούν ταχύτερα σε ηπατική κίρρωση σε σχέση με το γενικό πληθυσμό, ενώ αυξάνει σταθερά ο επιπολασμός της μη αλκοολικής και αλκοολικής λιπώδους νόσου του ήπατος. Η καλύτερη μέθοδος για την εκτίμηση της ηπατικής βλάβης είναι η βιοψία ήπατος, η οποία όμως είναι μια επεμβατική διαδικασία, χρήζει νοσηλείας και μπορεί να συνοδεύεται από επιπλοκές. Για το λόγο αυτό έχουν αναπτυχθεί μη επεμβατικές τεχνικές εκτίμησης της ηπατικής βλάβης, με τη σημαντικότερη από αυτές να είναι η ελαστογραφία ήπατος (TE), η οποία εκτιμά έμμεσα την ηπατική ίνωση, μετρώντας τη σκληρότητα του ήπατος, εμφανίζει ικανοποιητική συσχέτιση με τη βιοψία ήπατος και θεωρείται αξιόπιστη εναλλακτική της. Σχετικά προβλήματα όμως έχει και η ΤΕ όπως είναι το υψηλό κόστος, η απουσία ευρείας διαθεσιμότητά της και η εξάρτησή της από την ικανότητα και την εμπειρία του χειριστή του μηχανήματος. Έτσι, γίνεται προσπάθεια ανάπτυξης διάφορων βιοδεικτών (scores), τα οποία χρησιμοποιούν εργαστηριακές παραμέτρους για την εκτίμηση της ηπατικής ίνωσης. Η εφαρμογή των παραπάνω βιοδεικτών σε ειδικές ομάδες ασθενών, όπως οι ασθενείς με χρονία λοίμωξη από τον ιό της ηπατίτιδας C (HCV), είναι αξιόπιστη και συχνά αντικαθιστά την TE στην καθημέρα πράξη. Αν και η εφαρμογή των παραπάνω δεικτών στο γενικό πληθυσμό και σε ασθενείς με HIV/HCV συλλοίμωξη είναι ευρεία, ελάχιστες μελέτες έχουν γίνει σε ασθενείς με HIV μονολοίμωξη. Στόχος της παρούσης μελέτης ήταν η αναζήτηση των παραγόντων κινδύνου για σημαντική ηπατική ίνωση σε μια κοορτή ασθενών με HIV λοίμωξη, καθώς και των μη επεμβατικών βιοδεικτών, οι οποίοι εκτιμούν καλύτερα την ηπατική ίνωση σε ασθενείς με HIV μονολοίμωξη. Επιπλέον ήταν η εκτίμηση της αποτελεσματικότητας των νέων από του στόματος φαρμάκων έναντι της HCV λοίμωξης σε ασθενείς με HIV/HCV συλλοίμωξη. Στη μελέτη συμπεριλήφθηκαν ασθενείς που παρακολουθούνται στο εξωτερικό ηπατολογικό ιατρείο και στο ιατρείο λοιμώξεων της Κλινικής της Παθολογικής Φυσιολογίας του ΓΝΑ «Λαϊκό». Ως ιδανική (gold standard) μέθοδος εκτίμησης της ηπατικής ίνωσης χρησιμοποιήθηκε η ΤΕ.The introduction of antiretroviral treatment (ART) for HIV-infected patients has led to a change of these patients&apos; life expectancy, making HIV infection a chronic rather than a fatal disease. This prolongation of patients&apos; survival has resulted in a change of the diseases most commonly seen during HIV infection&apos;s natural course, with cardiovascular and liver disease presenting more often than opportunistic infections. As far as liver is concerned, diseases like chronic HBV and HCV infections lead to liver cirrhosis faster in patients with HIV infection, while the prevalence of alcoholic and non-alcoholic disease is steadily rising in these patients. The best method for assesing liver fibrosis is liver biopsy; however it is an invasive procedure that requires hospitalization and is prone to complications. For that reason, non invasive methods for assesing liver fibrosis have been developed; among them transient elastography, measuring liver stifness, seems to provide the most reliable results with high creditability. Transient elastography, however, has also limitations, like high cost, low availability, especially in low income countries, and dependence on operator experience. For that reason various scores have been developed that take into account commonly used laboratory results for determining liver fibrosis. The use of these, so called non-invasive biomarkers of liver disease, in specific groups of patients like those suffering for hepatitis C virus are trustworthy and can replace transient elastography in everyday practice. Even though the application of these non-invasive biomarkers in the general population and patients with HIV/HCV infection is widespread, few studies exist in patients with HIV infection. The aim of the present study was to search for possible risk factors for significant liver fibrosis in a cohort of HIV-infected patients, as well as which non-invasive biomarkers can better determine liver fibrosis in HIV-monoinfected patients. Furthermore we tried to evaluate the efficacy of the new, all oral, treatment against HCV infection in patients with HIV/HCV coinfection. Our study included patients followed by the outpatient liver and the outpatient infectious diseases clinics of the Pathophysiology Department of &apos;Laiko&apos; General Hospital. As gold standard method for determining liver fibrosis, transient elastography was used

Liver Fibrosis during Antiretroviral Treatment in HIV-Infected Individuals. Truth or Tale?

After the introduction of antiretroviral treatment (ART) back in 1996, the lifespan of people living with HIV (PLWH) has been substantially increased, while the major causes of morbidity and mortality have switched from opportunistic infections and AIDS-related neoplasms to cardiovascular and liver diseases. HIV itself may lead to liver damage and subsequent liver fibrosis (LF) through multiple pathways. Apart from HIV, viral hepatitis, alcoholic and especially non-alcoholic liver diseases have been implicated in liver involvement among PLWH. Another well known cause of hepatotoxicity is ART, raising clinically significant concerns about LF in long-term treatment. In this review we present the existing data and analyze the association of LF with all ART drug classes. Published data derived from many studies are to some extent controversial and therefore remain inconclusive. Among all the antiretroviral drugs, nucleoside reverse transcriptase inhibitors, especially didanosine and zidovudine, seem to carry the greatest risk for LF, with integrase strand transfer inhibitors and entry inhibitors having minimal risk. Surprisingly, even though protease inhibitors often lead to insulin resistance, they do not seem to be associated with a significant risk of LF. In conclusion, most ART drugs are safe in long-term treatment and seldom lead to severe LF when no liver-related co-morbidities exist

Efficacy, Safety and Immunogenicity of Anti-SARS-CoV-2 Vaccines in Patients with Cirrhosis: A Narrative Review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), has led to a pandemic with more than 6.5 million deaths worldwide. Patients with liver cirrhosis (PWLC) are regarded as prone to severe COVID-19. Vaccination against SARS-CoV-2 has been proven to be the most effective measure against COVID-19 and a variety of different vaccines have been approved for use; namely mRNA and vector-based, inactivated, whole virion, and protein subunit vaccines. Unfortunately, only a small number of PWLC were included in phase I–III vaccine trials, raising concerns regarding their efficacy and safety in this population. The authors, in this review, present available data regarding safety and efficacy of anti-SARS-CoV-2 vaccination in PWLC and discuss post-vaccination antibody responses. Overall, all vaccines seem to be extremely safe, with only a few and insignificant adverse events, and efficient, leading to lower rates of hospitalization and COVID-19-related mortality. T- and B-cell responses, on the other hand, remain an enigma, especially in patients with decompensated disease, since these patients show lower titers of anti-SARS-CoV-2 antibodies in some studies, with a more rapid waning. However, this finding is not consistent, and its clinical impact is still undetermined