A prospective, multicenter, three-cohort study evaluating contrast-induced acute kidney injury (CI-AKI) in patients with cirrhosis.

BACKGROUND & AIMS: Nephrotoxicity of intravenous iodinated contrast media (ICM) in cirrhosis is still a debated issue, due to scarce, low-quality and conflicting evidence. This study aims to evaluate the incidence and predisposing factors of acute kidney injury (AKI) in patients with cirrhosis undergoing contrast-enhanced computed tomography (CECT). METHODS: We performed a prospective, multicenter, cohort study including 444 inpatients, 148 with cirrhosis (cohort 1) and 163 without cirrhosis (cohort 3) undergoing CECT and 133 with cirrhosis (cohort 2) unexposed to ICM. Kidney function parameters were assessed at T0, 48-72 h (T1), 5 and 7 days after CECT/enrollment. Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) was measured in 50 consecutive patients from cohort 1 and 50 from cohort 2 as an early biomarker of tubular damage. RESULTS: AKI incidence was not significantly increased in patients with cirrhosis undergoing CECT (4.8%, 1.5%, 2.5% in cohorts 1, 2, 3 respectively, p = n.s.). Most AKI cases were mild and transient. The presence of concomitant infections was the only independent predictive factor of contrast-induced AKI (odds ratio 22.18; 95% CI 2.87-171.22; p = 0.003). No significant modifications of U-NGAL between T0 and T1 were detected, neither in cohort 1 nor in cohort 2 (median ΔU-NGAL: +0.2 [-7.6 to +5.5] ng/ml, +0.0 [-6.8 to +9.5] ng/ml, respectively [p = 0.682]). CONCLUSIONS: AKI risk after CECT in cirrhosis is low and not significantly different from that of the general population or of the cirrhotic population unexposed to ICM. It mostly consists of mild and rapidly resolving episodes of renal dysfunction and it is not associated with tubular kidney injury. Patients with ongoing infections appear to be the only ones at higher risk of AKI. IMPACT AND IMPLICATIONS: Nephrotoxicity due to intravenous iodinated contrast media (ICM) in patients with cirrhosis is still a debated issue, as the available evidence is limited and based on very heterogeneous studies, often conducted on small and retrospective cohorts. In this prospective three-cohort study we found that intravenous administration of ICM was associated with a low risk of AKI, similar to that of the general population and to that of patients with cirrhosis unexposed to ICM. Patients with ongoing infections were the only ones to have a significantly increased risk of contrast-induced AKI. Therefore, the actual recommendations of performing contrast imaging studies cautiously in cirrhosis do not seem to be reasonable anymore, with the exception of infected patients, who have a significantly higher risk of contrast-induced AKI.

Non-pharmacological strategies to treat irritable bowel syndrome: 2022 update.

Irritable bowel syndrome (IBS) is a chronic functional disorder characterized by abdominal pain associated with changes in stool frequency or form, in absence of organic disease. The treatment of IBS is often challenging and should be individually adjusted according to the prevalent symptomatology. Pharmacological treatment for IBS with diarrhea includes peripheral opioid agonists, bile acid sequestrants and antibiotics, while IBS with constipation can be treated with soluble fibers, osmotic agents or prokinetics. In case of abdominal pain, the available pharmacological options are antispasmodics, peripheral opioid agonists or antidepressants. Along with pharmacotherapy, non-pharmacological interventions should be considered as they can play an important role in symptom control. The first-line approach includes lifestyle modifications and dietary advice. Microbiota manipulation through probiotics, prebiotics and symbiotics is a widely used strategy, although the evidence upon the most effective among these in specific IBS subtypes is still unclear. Fecal microbiota transplantation is still in experimental phase for IBS, but it is giving promising results. Psychological therapies may be effective in patients with IBS, despite their application can be limited by long duration, high costs and poor patient's acceptance. Alternative medicine approaches, such as acupuncture, body relaxation techniques, dietary supplements or Chinese herbs, have been proposed; however, the evidence upon their efficacy and safety is still controversial.

Assessment of glomerular filtration rate in patients with cirrhosis: Available tools and perspectives.

Renal dysfunction often complicates the course of liver disease, resulting in higher morbidity and mortality. The accurate assessment of kidney function in these patients is essential to early identify, stage and treat renal impairment as well as to better predict the prognosis, prioritize the patients for liver transplantation and decide whether to opt for simultaneous liver-kidney transplants. This review analyses the available tools for direct or indirect assessment of glomerular filtration rate, focusing on the flaws and strengths of each method in the specific setting of cirrhosis. The aim is to deliver a clear-cut view on this complex issue, trying to point out which strategies to prefer in this context, especially in the peculiar setting of liver transplantation. Moreover, a glance is given at future promising tools for glomerular filtration rate assessment, including new biomarkers and new equations specifically modelled for the cirrhotic population.

Transjugular intrahepatic porto-systemic shunt in cirrhotic patients with hepatorenal syndrome - chronic kidney disease: Impact on renal function.

BACKGROUND AND AIMS: Transjugular intrahepatic porto-systemic shunt (TIPS) ameliorates renal function in type-2 hepatorenal syndrome (HRS). Available evidence is based on 'old' HRS diagnostic criteria, and not on the current definition of HRS - chronic kidney disease (HRS-CKD). Among patients who underwent TIPS for refractory ascites over the last 12 years, we investigated clinical and renal function evolution of those with HRS-CKD. METHODS: among 212 patients, 41 with HRS-CKD were included. Renal function was evaluated for 12 months after TIPS, along with management of ascites and transplant-free survival (TFS). RESULTS: renal function significantly improved already one week after TIPS [serum creatinine (sCr): 1.37 ± 0.23 vs 1.94 ± 0.54 mg/dl, p< 0.001]; the amelioration was maintained during the whole follow-up and was observed in every CKD stage, defined according to baseline estimated Glomerular Filtration Rate (eGFR). sCr and eGFR became comparable between different CKD stages after only one week, whilst significantly different at baseline. TIPS led to a remarkable improvement in the control of ascites in all CKD stages and no significant differences in TFS were recorded. CONCLUSIONS: TIPS led to an early, substantial and persistent improvement in renal function in patients with HRS-CKD, irrespective of their baseline CKD stage.

Recent advances in the treatment of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder which presents with abdominal pain and altered bowel habits. It affects about 20% of the general population, mainly women, and has a considerable impact on the quality of life and health care costs. Four different entities of IBS have been identified: IBS with constipation (IBS­ C), IBS with diarrhea (IBS D), IBS with a mixed pattern of constipation and diarrhea, and unclassified IBS. Although the precise pathogenesis of IBS remains unclear, its multifactorial nature is evident and includes environmental and host factors. Management of patients with this disease is challenging and a personalized approach is required. A strong, reassuring physician­ patient relationship is crucial, followed by patient education, dietary advice, and stress reduction. For nonresponding patients, the therapeutic approach may include nonpharmacological therapies and / or pharmacotherapy. The choice of pharmacological treatment is based on the predominant symptom and a prespecified time point should be planned for effectiveness evaluation and dose adjustment. In patients with IBS­ D, the therapeutic options include mainly antibiotics, such as rifaximin, peripheral opioid agonists, mixed opioid agonists / antagonists, bile acid sequestrants, and antagonists of serotonin 5­ hydroxytryptamine type 3 receptors. Bulking agents and osmotic laxatives represent the first line therapy for IBS­ C, while lubiprostone and linaclotide should be reserved for difficult to treat patients. The involvement of gastrointestinal microbiota constitutes a fascinating field of exploration as it offers the potential to be modulated by the use of probiotics, prebiotics, synbiotics as well as fecal microbiota transplantation. This review offers an updated overview on the recent advances in the treatment of IBS.

Liver involvement in adult-onset Still's disease: our experience in a third level liver unit and review of the literature.

BACKGROUND: Adult-onset Still's Disease (AOSD) is a systemic inflammatory condition, mainly characterized by high spiking fevers, leukocytosis, skin rash, arthralgia and myalgia. Liver involvement is a frequent feature, usually presenting with hepatomegaly and mild liver enzymes abnormalities, which usually normalize after treatment with anti-inflammatory or immunomodulatory drugs given for AOSD. Although uncommon, the onset of severe acute hepatitis and even of life-threatening liver failure is possible and requires a prompt diagnosis and an aggressive therapy and, in some cases, an emergency liver transplantation. The differential diagnosis of the cause of the liver injury can be very challenging in these patients. METHODS: We reviewed the charts of all consecutive patients admitted for acute hepatitis, between January 2019 and December 2019, to the unit of Gastroenterology and Hepatology, Molinette Hospital, Turin, Northern Italy, searching for episodes AOSD-related. RESULTS: In this period, 21 cases of acute hepatitis were recorded with one among them diagnosed as due to AOSD. The incidence was 5% (1/21). This patient was a woman with a recent diagnosis of AOSD who developed a severe acute seronegative biopsy-proven autoimmune hepatitis. She was successfully treated with high-dose methylprednisolone, with a full and stable recovery from the liver injury. CONCLUSIONS: We discuss the incidence, etiology, pathophysiology, diagnosis, and standard of treatment in the clinical management of AOSD with a special attention and a systematic review on the available therapies for severe liver involvement associated with AOSD.

Management of Dyspepsia and Gastroparesis in Patients with Diabetes. A Clinical Point of View in the Year 2021.

Diabetes mellitus is a widespread disease, and represents an important public health burden worldwide. Together with cardiovascular, renal and neurological complications, many patients with diabetes present with gastrointestinal symptoms, which configure the so-called diabetic enteropathy. In this review, we will focus on upper gastrointestinal symptoms in patients with diabetes, with particular attention to dyspepsia and diabetic gastroparesis (DG). These two clinical entities share similar pathogenetic mechanisms, which include autonomic neuropathy, alterations in enteric nervous system and histological abnormalities, such as interstitial cells of Cajal depletion. Moreover, the differential diagnosis may be challenging because of overlapping clinical features. Delayed gastric emptying should be documented to differentiate between DG and dyspepsia and it can be assessed through radioactive or non-radioactive methods. The clinical management of dyspepsia includes a wide range of different approaches, above all Helicobacter pylori test and treat. As regards DG treatment, a central role is played by dietary modification and glucose control and the first-line pharmacological therapy is represented by the use of prokinetics. A minority of patients with DG refractory to medical treatment may require more invasive therapeutic approaches, including supplemental nutrition, gastric electric stimulation, pyloromyotomy and gastrectomy.

Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives.

Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.

Noninvasive diagnosis of fibrosis in non-alcoholic fatty liver disease: diagnostic accuracy of different scores.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of pathologies characterized by liver damage without history of excessive alcohol intake. Advanced fibrosis, generally detected by transient elastography (TE), is the most significant predictor of poor prognosis and mortality among these patients. This study aimed at assessing the accuracy of five noninvasive methods, compared to TE, for the evaluation of severity of liver fibrosis in patients with NAFLD. METHODS: The cohort included 41 patients, in whom the result of TE was compared to AST/ALT ratio, BARD Score (Body Mass Index, AST/ALT ratio, diabetes), AST To Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4 Index) and NAFLD Fibrosis Score (NFS). RESULTS: The severity of fibrosis, assessed by TE, was the following: F0 (absence of fibrosis): 17%, F1 (mild): 39%, F2 (moderate): 17%, F3 (advanced): 10%, F4 (cirrhosis): 17%. Performances of the diagnostic scores were: 49% for AST/ALT ratio, 68% for BARD Score, 73% for APRI, 59% and 71% for the lower and upper cut-off of FIB-4 Index, 61% and 76% for the lower and upper cut-off of NFS. CONCLUSIONS: Considering the scores compared to TE, AST/ALT ratio was not enough sensitive, while BARD Score had better diagnostic performance and APRI had a superior accuracy than the formers. However, FIB-4 and NFS were the most useful tests and their performance could be improved through the use of a single cut-off. These findings demonstrated that the most accurate scores, compared to TE, were NFS and FIB-4.

Management of functional dyspepsia in 2020: a clinical point of view.

Dyspepsia is a disorder that refers mainly to central upper abdominal pain or discomfort. When a cause of this symptom is not identified the condition is termed functional dyspepsia (FD), that affects a large part of the general population. The relevance of FD is due to its high prevalence, but also to its chronic or intermittent course. This induces a significant burden for each national healthcare system. The pathogenesis of FD is complex and multifactorial, depending on cultural, environmental, and biological factors. Although considered of main importance in the pathophysiology of several gastroduodenal diseases, in the context of FD Helicobacter pylori (H. pylori) infection plays a limited role. The diagnosis of FD requires the exclusion of organic gastroduodenal diseases as well as H. pylori infection. Thus, the diagnostic workup includes a complete anamnesis, biochemical tests, and endoscopy with biopsy (when requested), and the satisfaction of clinic criteria recommended by the Rome IV consensus. The treatment of FD is also challenging, in fact more and more studies focused on a wide range of different therapies, with a multitude of results. The aim of this literature review is to provide an update of the new evidences useful for diagnosis and management of FD.

Liver diseases in the elderly.

Due to the progressive increase in life expectancy, the number of elderly people in the world is growing rapidly. Although there are no liver diseases specific of older age, the ageing liver shows some anatomical and physiological changes that can affect the frequency and the clinical behavior of most hepatopathies. In particular, these changes tend to cause an increased vulnerability to acute liver injury and an increased susceptibility to liver fibrosis, accounting for the predisposition to a generally more severe course of liver diseases compared to younger patients. Furthermore, advanced age is also associated with immune system alterations, influencing the manifestation of those hepatopathies that are mediated by host immune response, like viral hepatitis, autoimmune hepatitis but also hepatocellular carcinoma. Despite these changes, total liver function and laboratory values tend to be well maintained in healthy elderly, so that every enzymatic alteration in a geriatric patient should be investigated with the same attention as in a younger one. A proper and early diagnosis is of great importance both considering the age-related more aggressive course of hepatopathies and that age itself does not seem to be a limit for most treatment options, even if specific data are often lacking. This paper focuses on the peculiarities of main liver diseases in geriatrics, with respect to epidemiology, clinical presentation, diagnosis and management, which can be more challenging in advanced age because of the frequent comorbidities and polytherapies.

Management of primary biliary cholangitis prior to obeticholic acid availability.

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease with unknown etiology. The prognosis of patients affected by PBC is heterogeneous, with a relevant improvement achieved after the introduction of ursodeoxycolic acid (UDCA). Since in the last years obeticholic acid (OCA) has been approved for the combined treatment of PBC, in patient non-responders to UDCA or as monotherapy in those intolerant to UDCA, we evaluated the response to UDCA in a cohort of patients with PBC managed in a specialistic setting. METHODS: We included 38 UCDA-treated non-cirrhotic, early-PBC patients. Data were retrieved from documents compiled during the annual follow-up. The response to therapy was assessed comparing the parameters of our cohort with the inclusion criteria of the POISE Trial and the Paris I and Paris II criteria. RESULTS: The cohort included 34/38 female patients and the average age was 65.34±10.69 years. Over 50% of the patients were affected by at least one disease associated to PBC. Using the POISE criteria and the Paris I and Paris II criteria, we identified 5, 2 and 5 non-responders, respectively. All patients with severe fibrosis had a biochemical response to UDCA according to the three different criteria applied. No side effect was reported. CONCLUSIONS: We confirm that UDCA is a safe and effective treatment in patients with PBC. Non-responder patients represent 13% of our population, with high risk of disease progression and complications. In this context, further therapy using OCA should be considered.