ABSTRACT Introduction Chronic hepatitis B (CHB) is rarely cured using available treatments. Barriers to cure are: 1) persistence of reservoirs of hepatitis B virus (HBV) replication and antigen production (HBV DNA); 2) high burden of viral antigens that promote T cell exhaustion with T cell dysfunction; 3) CHB-induced impairment of immune responses. Areas Covered We discuss options for new therapies that could address one or more of the barriers to functional cure, with particular emphasis on the potential role of immunotherapy. Expert Opinion/Commentary Ideally, a sterilizing cure for CHB would translate into finite therapies that result in loss of HBV surface antigen and eradication of HBV DNA. Restoration of a functional adaptive immune response, a key facet of successful CHB treatment, remains elusive. Numerous strategies targeting the high viral DNA and antigen burden and aiming to restore the host immune responses will enter clinical development in coming years. Most patients are likely to require combinations of several drugs, personalized according to virologic and disease characteristics, patient preference, accessibility, and affordability. The management of CHB is a global health priority. Expedited drug development requires collaborations between regulatory agencies, scientists, clinicians, and within the industry to facilitate testing of the best drug combinations.

ABSTRACT Introduction Chronic constipation is a frequent symptom encountered in the daily clinical practice. The treatment of this condition mainly relies on the use of laxatives. However, patients’ satisfaction with this approach is limited, and alternative measures are often added to the treatment. Among these, particularly frequent worldwide is the use of enemas, even though literature data on its scientific validity are scarce. Areas covered In this article, by an extensive online search of Medline (through PubMed), Scopus, Cochrane CENTRAL, EMBASE, and the Science Citation Index, the available literature data on the use of enemas in adult patients with chronic constipation, also in the perspective of available guidelines on treatment of this pathological condition, were analyzed. Expert opinion Although the use of enemas remains a frequently employed method and it is considered as useful by many physicians as an adjunctive support for the treatment of chronic constipation in adults, this practice is not substantiated by rigorous scientific data, and some studies are available only for specific instances (fecal impaction, transanal irrigation). Thus, waiting for more robust scientific data, enemas treatment should be carried out on an individual patient’s basis, according to the experience of the caring physicians.

ABSTRACT Introduction Opioid-induced constipation remains undertreated despite effective and safe treatment options exists. Previous guidelines have only been partially effective in improving management, possibly due to their complexity, and studies suggest that a simple setup of concise and behaviorally-orientated steps improves usability. Areas covered This article introduces the concept of opioid-induced constipation and provides an overview of existing guidelines in this field. We also propose simplified recommendations for managing opioid-induced constipation, derived from a synthesis of current guidelines and the principles of optimal guideline design theory. Expert opinion Despite standard treatment with laxatives and fluid intake in patients with opioid-induced constipation, escalation of treatment is often needed where μ-opioid receptor antagonists or newer medications such as lubiprostone, linaclotide, or prucalopride are used. Previous guidelines have not been used sufficiently and thus management of the condition is often insufficient. We therefore propose simplified recommendations to management, which we believe can come into broader use. It was validated in primary care for credibility, clarity, relevance, usability, and overall benefit. We believe that this initiative can lead to better management of the substantial proportion of patients suffering from side effects of opioids.

ABSTRACT Background and Aims Tolvaptan has been approved for the management of cirrhosis-related complications according to the Japanese and Chinese practice guidelines, but not the European or American practice guidelines in view of FDA warning about its hepatotoxicity. This study aimed to systematically evaluate its efficacy and safety in cirrhosis. Methods The PubMed, EMBASE, and Cochrane library databases were searched to identify randomized controlled trials (RCTs) evaluating the efficacy and/or safety of tolvaptan in cirrhosis. Risk ratios (RRs) and weight mean differences (WMDs) were calculated. The incidence of common adverse events (AEs) was pooled. Results Eight RCTs were included. Tolvaptan was significantly associated with higher rates of improvement of ascites (RR = 1.49, P < 0.001) and hyponatremia (RR = 1.80, P = 0.005) and incidence of any AEs (RR = 1.18, P = 0.003), but not serious AEs (RR = 0.86, P = 0.410). Tolvaptan was significantly associated with reductions in body weight (WMD = −1.30 kg, P < 0.001) and abdominal circumference (WMD = −1.71 cm, P < 0.001), and increases in daily urine volume (WMD = 1299.84 mL, P < 0.001) and serum sodium concentration (WMD = 2.57 mmol/L, P < 0.001). The pooled incidences of dry mouth, thirst, constipation, and pollakiuria were 16%, 24%, 6%, and 17%, respectively. Conclusion Short-term use of tolvaptan may be considered in cirrhotic patients with ascites who have inadequate response to conventional diuretics and those with hyponatremia.

ABSTRACT Introduction Intestinal diseases, a leading global cause of mortality and morbidity, carry a substantial socioeconomic burden. Small and large intestines play pivotal roles in gastrointestinal physiology and food digestion. Pathological conditions, such as gut dysbiosis, inflammation, cancer, therapy-related complications, ulcers, and ischemia, necessitate the urgent exploration of safe and effective complementary therapeutic strategies for optimal intestinal health. Areas covered This article evaluates the potential therapeutic effects of melatonin, a molecule with a wide range of physiological actions, on intestinal diseases including inflammatory bowel disease, irritable bowel syndrome, colon cancer, gastric/duodenal ulcers and other intestinal disorders. Expert opinion Due to anti-inflammatory and antioxidant properties as well as various biological actions, melatonin could be a therapeutic option for improving digestive disorders. However, more researches are needed to fully understand the potential benefits and risks of using melatonin for digestive disorders.

ABSTRACT Introduction GERD is a common disorder and is characterized by the presence of typical or atypical symptoms. In GERD patients, the presence of mucosal alterations in endoscopy is detected in up to 30% of individuals. The clinical presentation of GERD patients may be complex and their management is challenging, due to the heterogeneous clinical presentation. The present review has been performed searching all relevant articles in this field, over the past years, using PubMed database. Areas covered The diagnosis and management of GERD have been significantly improved in the last years due to the increasing availability of reflux monitoring techniques and the implementation of new procedures in the therapeutic armamentarium. Beside traditional impedance-pH variables, new metrics have been developed, increasing the diagnostic yield of reflux monitoring and better predicting the treatment response. Traditional pharmacological treatments include acid-suppressive-therapy and/or anti-acid. On the other hand, surgical treatment and, more recently, endoscopic procedures represent a promising field in the therapeutic approach. Expert opinion Diagnosis and treatment of GERD still represent a challenging area. However, we believe that an accurate upfront evaluation is, nowadays, necessary in addressing patients with GERD to a more accurate diagnosis as well as to the best treatment options.

ABSTRACT Objectives The incidence of cholelithiasis is higher among individuals who have undergone gastric surgery. The benefits of concomitant gallbladder removal in asymptomatic gallstone patients remain uncertain. The aim was to investigate the necessity and safety of simultaneous cholecystectomy in this particular patient population. Methods We performed a systematic review and meta-analysis to assess the incidence of asymptomatic cholelithiasis converting to symptomatic after gastric surgery and the complication rate associated with simultaneous cholecystectomy. PubMed, Embase, and the Cochrane Library were searched for relevant articles published until 10 March 202210 March 2022. Results Patients with asymptomatic cholelithiasis after gastric surgery were at a higher risk of developing symptomatic cholelithiasis compared to those without cholelithiasis (relative risk [RR] 2.28, 95% confidence interval [CI] 1.23–4.25) and those with unknown gallbladder conditions (RR 2.70, 95% CI 1.54–4.73). Additionally, patients who underwent simultaneous cholecystectomy did not face a higher risk of complications compared to those who only underwent gastric surgery (RR 0.86, 95% CI 0.48–1.53). Conclusions Simultaneous cholecystectomy is both necessary and safe for patients with asymptomatic cholelithiasis undergoing gastric surgery. It is crucial to assess the gallbladder’s condition before gastric surgery, and if the gallbladder status is unknown, simultaneous cholecystectomy should be avoided.

ABSTRACT Introduction Obesity is considered a poor lifestyle choice. ‘Obesity’ is not a sufficient definition for patients, any more than ‘cancer’ or ’arthritis’ would be. A major obstacle is the lack of understanding of pathogenesis. The disease of obesity is considered homogenous, while response to treatment is thought of as heterogeneous. This can change if pathogenesis, risk profiles for complications, and treatment responses are viewed within the context of obesity consisting of several subsets of disease. Areas covered The European Union-funded Innovative Medicine Initiative project Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy is part of a momentum shift. Operational variables are being used to develop tests and therapies which may allow the prediction of risk of obesities and the prediction of response to obesity treatments. However, changing stakeholder perspectives on obesity may require more than high-quality data and analysis. Expert opinion For patients to benefit, clinicians need to integrate evidence-based treatments and payers need to reimburse the management of the disease of obesity. This will generate commercial opportunities for industry. We need to involve stakeholders (patients, clinicians, regulators, payer, patient organisations) to create a shared value for mutual gain.

ABSTRACT Introduction Children and adolescents with Crohn’s disease present unique challenges due to extensive disease at diagnosis and the effect of bowel inflammation on growth. Historical approaches with corticosteroids and immunomodulators are far less effective than early treatment with anti-TNF biologics. Areas covered This review covers recent literature delineating the crucial role of early anti-TNF therapy in the treatment of moderate- to- severe Crohn’s disease in children and adolescents. The potential risks and benefits of concomitant immunomodulators is discussed, along with therapeutic anti-TNF drug monitoring, and reassessment by endoscopy and cross-sectional imaging to evaluate success beyond symptoms control. Expert opinion Standard of care therapy for moderate-to-severe pediatric Crohn’s disease now entails precision dosing of anti-TNF therapy with periodic reassessment of bowel inflammation. The role of dietary modification continues to evolve. Current and future efforts need to be directed to elucidating ways to predict response to anti-TNF therapy and quickly changing to agents with other mechanisms of action when needed. Inordinate regulatory delays in approval of new therapies approved for adults continues to handicap pediatric clinicians and frequently limits their treatment choices, or forces them to give medications ‘off label.’ Only a concerted effort by clinicians, pharma, and regulators will improve this situation.

ABSTRACT Introduction Since the first discovery of microRNAs (miRs) extensive evidence reveals their indispensable role in different patho-physiological processes. They are recognized as critical regulators of hepatic regeneration, as they modulate multiple complex signaling pathways affecting liver regeneration. MiR-related translational suppression and degradation of target mRNAs and proteins are not limited to one specific gene, but act on multiple targets. Areas Covered In this review, we are going to explore the role of miRs in the context of liver regeneration and discuss the regulatory effects attributed to specific miRs. Moreover, specific pathways crucial for liver regeneration will be discussed, with a particular emphasis on the involvement of miRs within the respective signaling cascades. Expert Opinion The considerable amount of studies exploring miR functions in a variety of diseases paved the way for the development of miR-directed therapeutics. Clinical implementation has already shown promising results, but additional research is warranted to assure safe and efficient delivery. Nevertheless, given the broad functional properties of miRs and their critical involvement during hepatic regeneration, they represent an attractive treatment target to promote liver recovery after hepatic resection.