Liver biopsy in type 2 diabetes mellitus: steatohepatitis represents the sole feature of liver damage

Recent studies report a prevalence of non-alcoholic fatty liver disease (NAFLD) of between 70% and 80% in patients with metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Nevertheless, it is not possible to differentiate between simple steatosis and nonalcoholic steatohepatitis (NASH) with non-invasive tests. The aim of this study was to differentiate between simple steatosis and NASH by liver biopsy in patients with hypertransaminasemia and MS or T2DM. Two hundred and fifteen patients with increased ALT levels and MS, and 136 patients at their first diagnosis of T2DM regardless of ALT values were consecutively admitted to a tertiary hepatology center between January 2004 and November 2014. Exclusion criteria were other causes of liver disease/ALT increase. Each patient underwent a clinical, laboratory and ultrasound evaluation, and a liver biopsy. Gender distribution, age, and body mass index were similar in the two groups of patients, whereas cholesterol levels, glycemia and blood pressure were significantly different between the two groups. The prevalence of NAFLD was 94.82% in MS patients and 100% in T2DM patients. NASH was present in 58.52% of MS patients and 96.82% of T2DM. Consequently, this study reveals that, by using liver biopsy, almost all patients with T2DM or MS have NAFLD, which in patients with T2DM means NASH. Importantly, it suggests that NASH may be one of the early complications of T2DM due to its pathophysiological correlation with insulin resistance

Platelets and hepatocellular cancer: Bridging the bench to the clinics

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells\u2019 extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet\u2013tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted

Platelets and hepatocellular cancer: Bridging the bench to the clinics

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells' extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet-tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC

Viral hepatitis: Milestones, unresolved issues, and future goals

In this review the current overall knowledge on hepatitis A, B, C, D, and E will be discussed. These diseases are all characterized by liver inflammation but have significant differences in distribution, transmission routes, and outcomes. Hepatitis B virus and hepatitis C virus are transmitted by exposure to infected blood, and in addition to acute infection, they can cause chronic hepatitis, which in turn can evolve into cirrhosis. It is estimated that more than 300 million people suffer from chronic hepatitis B or C worldwide. Hepatitis D virus, which is also transmitted by blood, only affects hepatitis B virus infected people, and this dual infection results in worse liver-related outcomes. Hepatitis A and E spread via the fecal-oral route, which corresponds mainly to the ingestion of food or water contaminated with infected stools. However, in developed countries hepatitis E is predominantly a zoonosis. Although hepatitis A virus and hepatitis E virus are usually responsible for a self-limiting hepatitis, a serious, rarely fatal illness is also possible, and in immunosuppressed patients, such as organ transplant recipients, hepatitis E virus infection can become chronic. The description of goals achieved, unresolved issues, and the latest research on this topic may make it possible to speculate on future scenarios in the world of viral hepatitis

NAFLD and extra-hepatic comorbidities: Current evidence on a multi-organ metabolic syndrome

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its incidence is definitely increasing. NAFLD is a metabolic disease with extensive multi-organ involvement, whose extra-hepatic manifestations include type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, chronic kidney disease, osteoporosis, and polycystic ovarian syndrome. Recently, further evidence has given attention to pathological correlations not strictly related to metabolic disease, also incorporating in this broad spectrum of systemic involvement hypothyroidism, psoriasis, male sexual dysfunction, periodontitis, and urolithiasis. The most common cause of mortality in NAFLD is represented by cardiovascular disease, followed by liver-related complications. Therefore, clinicians should learn to screen and initiate treatment for these extra-hepatic manifestations, in order to provide appropriate multidisciplinary assessments and rigorous surveillance. This review evaluates the current evidence regarding extra-hepatic associations of NAFLD, focusing on the pathogenic hypothesis and the clinical implications

Real‐Life Efficacy and Safety of Glecaprevir/Pibrentasvir in HCV Infected Patients with Chronic Kidney Disease

Background: Clinical trials have shown that Glecaprevir/Pibrentasvir (G/P) therapy is effective and safe for HCV‐infected patients with chronic kidney disease (CKD), but data in a real‐life setting are scarce. Aim: To evaluate the efficacy and safety of G/P in HCV‐infected patients with reduced renal function. Patients and Methods: All consecutive HCV‐infected patients with chronic kidney disease (eGFR<60 ml/min/1.73m2) treated with G/P were enrolled. An adverse event (AE) was defined as any untoward medical occurrence or any unfavorable sign or symptom, during drug administration that was not necessarily causally treatment‐related. An AE causing death, hospitalization or therapy discontinuation was considered a serious AE (SAE).Results: One‐hundred‐twenty‐one patients were enrolled. Thirty‐six patients had end‐stage renal disease (ESRD), 57 were male, overall median age was 69±13 years, and 20 had cirrhosis. Genotype 2 was the most frequent (53.7%). Treatment lasted 8 weeks in 93 patients, 21 of whom had ESRD, and 12 weeks in 28 patients. At modified ITT analysis, 119/120 patients achieved a sustained virologic response (SVR) without differences between cirrhotics and non‐cirrhotics, whereas at PP analysis all patients achieved a SVR. Notably, SVR did not differ between patients with and without ESRD (35/35 vs 84/85 p=0.427). There were no virologic failures. Thirteen patients reported an AE (mostly pruritus), three had a SAE (death in a car accident and two jaundice), and one spontaneously stopped treatment. Conclusion: This real‐life study confirms the high efficacy and safety of G/P, also administered for 8 weeks, in HCV‐infected patients with CKD or with ESRD

Hepatitis C virus infection in jail: Difficult-to-reach, not to-treat. Results of a point-of-care screening and treatment program

Background: An unmet objective in the pursuit of HCV elimination is the creation of a simple and fast operating model to identify difficult-to-treat populations, like prisoners. Of many obstacles, the first is represented by the poor knowledge of inmates HCV-Ab prevalence. Moreover, due to the peculiar status of conviction, often their access to antiviral therapy is neglected. Aims: To evaluate the prevalence of HCV infection in a penitentiary Institution of Southern Italy through a point-of-care screening and treatment program. Methods: We conducted a prospective observational study in two phases: first, we reviewed all the prisoners’ clinical records, to verify HCV-Ab execution. Subsequently, we performed a universal point-of-care screening and treatment program. Results: We enrolled 670 patients. Overall, 310(46.27%) were already HCV-Ab tested. At the screening initiation, 23.28% patients were discharged, whereas 8.35% refused. Of the remaining 458 subjects, 58(12.67%) were HCV-Ab positive and 46 HCVRNA positive. All these underwent DAA, obtaining 100% SVR. At the end of the program, a total of 491(73.28%) subjects had HCV-Ab available. Sixty-nine (14.05%) were positive. A total of 214(31.94%) subjects were lost to follow-up. Conclusions: We revealed a prevalence of 14.05% of HCV-Ab in conviction. Antiviral treatment was safe and efficacious. More efforts are advisable to provide screening for HCV-Ab in conviction