Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors:A case report and literature analysis

Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.

Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

Serum ferritin and the risk of early-onset colorectal cancer

BACKGROUND The incidence of early-onset colorectal cancer(EO-CRC)is rising in the United States,and is often diagnosed at advanced stages.Low serum ferritin is often incidentally discovered in young adults,however,the indication for endoscopy in EO-CRC is unclear.AIM To compare serum ferritin between patients with EO-CRC and healthy controls(HCs),and examine the association of serum ferritin in EO-CRC with patient-and disease-specific characteristics.METHODS A retrospective study of patients<50 years with newly-diagnosed EO-CRC was conducted from 1/2013-12/2023.Patients were included if serum ferritin was measured within 2 years prior to 1 year following CRC histologic diagnosis.To supplement the analysis,a cohort of HCs meeting similar inclusion and exclusion criteria were identified for comparison.A sensitivity analysis including only patients with serum ferritin obtained at or before diagnosis was separately performed to minimize risk of confounding.RESULTS Among 85 patients identified with EO-CRC(48 females),the median serum ferritin level was 26 ng/mL(range<1-2759 ng/mL).Compared to HCs(n=80211),there were a higher proportion of individuals with EO-CRC with serum ferritin<20 ng/mL(female 65%,male 40%)versus HCs(female 32.1%,male 7.2%)age 29-39 years(P=0.002 and P<0.00001,respectively).Stage IV disease was associated with significantly higher serum ferritin compared to less advanced stages(P<0.001).Serum ferritin obtained before or at the time of diagnosis was lower than levels obtained after diagnosis.Similar findings were confirmed in the sensitivity analysis.CONCLUSION Severe iron deficiency may indicate an increased risk of EO-CRC,particularly at earlier stages.Further studies defining the optimal serum ferritin threshold and routine incorporation of serum ferritin in screening algorithms is essential to develop more effective screening strategies for EO-CRC.

Current guidelines for the management of non-alcoholic fatty liver disease:A systematic review with comparative analysis

The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and dyslipidemia has led to a worldwide diffusion of NAFLD.In parallel to the increased availability of effective anti-viral agents,NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries,and a similar trend is expected in Eastern Countries in the next years.This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis,management,and treatment of NAFLD.Different scientific societies from Europe,America,and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD.These guidelines are consistent with the key elements in the management of NAFLD,but still,show significant difference about some critical points.We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences.We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions.Differences were noted in: the definition of NAFLD,the opportunity of NAFLD screening in high-risk patients,the noninvasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis,in the follow-up protocols and,finally,in the treatment strategy(especially in the proposed pharmacological management).These difference have been discussed in the light of the possible evolution of the scenario ofNAFLD in the next years.

Risk of cardiovascular,cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.

Systematic review of surgical resection vs radiofrequency ablation for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. Surgical resection and local ablative therapies represent the most frequent first lines therapies adopted when liver transplantation can not be offered or is not immediately accessible. Hepatic resection (HR) is currently considered the most curative strategy, but in the last decade local ablative therapies have started to obtain satisfactory results in term of efficacy and, of them, radiofrequency ablation (RFA) is considered the reference standard. An extensive literature review, from the year 2000, was performed, focusing on results coming from studies that directly compared HR and RFA. Qualities of the studies, characteristics of patients included, and patient survival and recurrence rates were analyzed. Except for three randomized controlled trials (RCT), most studies are affected by uncertain methodological approaches since surgical and ablated patients represent different populations as regards clinical and tumor features that are known to affect prognosis. Unfortunately, even the available RCTs report conflicting results. Until further evidences become available, it seems reasonable to offer RFA to very small HCC (< 2 cm) with no technical contraindications, since in this instance complete necrosis is most likely to be achieved. In larger nodules, namely > 2 cm and especially if > 3 cm, and/or in tumor locations in which ablation is not expected to be effective or safe, surgical removal is to be preferred.

Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers

Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.

Clinical features and management of primary biliary cirrhosis

Primary biliary cirrhosis(PBC),which is characterised by progressive destruction of intrahepatic bile ducts,is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies.The prognosis of the disease has improved due to both the recognition of earlier and indolent cases,and to the wide use of ursodeoxycholic acid(UDCA).New indicators of prog-nosis are available that will be useful especially for the growing number of patients with less severe disease.Most patients are asymptomatic at presentation.Pruri-tus may represent the most distressing symptom and,when UDCA is ineffective,cholestyramine represents the mainstay of treatment.Complications of long-standing cholestasis may be clinically relevant only in very ad-vanced stages.Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while,in advanced stages,the only thera-peutic option remains liver transplantation.

Clinical importance of aspirin and clopidogrel resistance

Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked "aspirin and/or clopidogrel resistance", as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel.

Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells

AIM： To investigate the effect of hot water-extracted Lydurn barbarum （LBE） and Rehrnannia glutinosa （RGE） on cell proliferation and apoptosis in rat and/or human hepatocellular carcinoma （HCC） cells. METHODS： Rat （H-4-Ⅱ-E） and human HCC （HA22T/ VGH） cell lines were incubated with various concentrations （0-10 g/L） of hot water-extracted LBE and RGE. After 6-24 h incubation, cell proliferation （n = 6） was measured by a colorimetric method. The apoptotic cells （n = 6） were detected by flow cytometry. The expression of p53 protein （n = 3） was determined by SDS-PAGE and Western blotting. RESULTS： Crude LBE （2-5 g/L） and RGE （2-10 g/L） dose-dependently inhibited proliferation of H-4-Ⅱ-E cells by 11% （P 〈 0.05） to 85% （P 〈 0.01） after 6-24 h treatment. Crude LBE at a dose of 5 g/L suppressed cell proliferation of H-4-Ⅱ-E cells more effectively than crude RGE after 6-24 h incubation （P 〈 0.01）. Crude LBE （2-10 g/L） and RGE （2-5 g/L） also dose-dependently inhibited proliferation of HA22T/VGH cells by 14%-43% （P 〈 0.01） after 24 h. Crude LBE at a dose of 10 g/L inhibited the proliferation of HA22T/VGH cells more effectively than crude RGE （56.8% ＋ 1.6% vs 70.3% ＋ 3.1% of control, P = 0.0003 〈 0.01）. The apoptotic cells significantly increased in H-4-Ⅱ-E cells after 24 h treatment with higher doses of crude LBE （2-5 g/L） and RGE （5-10 g/L） （P 〈 0.01）. The expression of p53 protein in H-4-Ⅱ-E cells was 119% and 143% of the control group compared with the LBE-treated （2, 5 g/L） groups, and 110% and 132% of the control group compared with the RGE -treated （5, 10 g/L） groups after 24 h. CONCLUSION： Hot water-extracted crude LBE （2-5 g/L） and RGE （5-10 g/L） inhibit proliferation and stimulate p53-mediated apoptosis in HCC cells.

Management of inflammatory bowel disease with Clostridium difficile infection

To address the management of Clostridium difficile (C. difficile) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare. METHODSA systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBD-related hospitalizations. RESULTSIn those with IBD, CDI is associated with increased morbidity, including subsequent escalation in IBD medical therapy, urgent colectomy and increased hospitalization, as well as excess mortality. Vancomycin-containing regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid, immunomodulator, or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI, while immunomodulators and biologics are not. CONCLUSIONStrong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However, based on expert opinion and observational data, initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.

Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease

Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients, as induction and maintainance treatment. Infliximab, as well as cyclosporine, is considered a second line therapy in the case of severe ulcerative colitis, or non-responders to intravenous corticosteroids. An adequate dosage and duration of therapy with thiopurines should be reached before evaluating their efficacy. Methotrexate is a valid option in patients with Crohn&#x02019;s disease but its use is confined to patients who are intolerant or non-responders to thiopurines. Evidence for the use of methotrexate in ulcerative colitis is insufficient. The use of thalidomide and mycophenolate mofetil is not recommended in patients with inflammatory bowel disease, these treatments could be considered in case of failure of all other therapeutic options. In patients with moderately active ulcerative colitis, refractory to thiopurines, the use of tacrolimus is considered an alternative to biologics. An increase of the dose or a decrease in the interval of administration of biological treatment could be useful in the presence of an incomplete clinical response. In the case of primary failure of an anti-tumor necrosis factor alpha a switch to another one should be considered. Data on the efficacy of combination therapy are up to now insufficient to consider this strategy in all IBD patients. The final outcome of the treatment should be considered the clinical remission, with mucosa healing, and not the clinical response. The evaluation of serum concentration of thiopurine methyl transferase activity, thiopurine metabolites, biologic serum levels and antibiologic antibodies could be useful for the management of the treatment but it has not been routinely applied in clinical practice. The evidence of high risk development of lymphoma and cutaneous malignancies should be considered in patients treated with immunosuppressants and biologics for a long period.

Diagnostic evaluation of acute pancreatitis in two patients with hypertriglyceridemia

We present two diagnostically challenging cases of acute pancreatitis with hypertriglyceridemia accompanied with chylomicronemia caused with a deficiency of lipoprotein lipase and with the presence of type Ⅴ hyperlipidemia. Both cases suffered from acute abdomen following the ingestion of fatty food and revealed the increase in parameters of inflammation without significant elevation of serum amylase levels.The imaging examination of ultrasonography could not detect significant findings of acute pancreatitis and a computer tomography scan eventually confirmed the findings of acute pancreatitis.Both cases responded to a low fat diet and administration of a cholecystokinin receptor antagonist,exhibiting a relief of abdominal symptoms.As in the present cases with acute abdomen following the ingestion of fatty food,the identification of serum hypertriglyceridemia and an abdominal computer tomography scan might be useful in establishing the diagnosis of acute pancreatitis and in developing the therapeutic regimen,when hypertriglyceridemia interferes with the evaluation of pancreatic enzyme activities and ultrasound examination provides poor pancreatic visualization.

Pathogenesis and significance of hepatitis C virus steatosis:An update on survival strategy of a successful pathogen

Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host&#x02019;s metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ. Steatosis, therefore, is associated with HCV infection by necessity rather than by chance alone. Approximately 6% of HCV patients have steatohepatitis. Interestingly, HCV steatosis occurs in the setting of multiple metabolic abnormalities (hyperuricemia, reversible hypocholesterolemia, insulin resistance, arterial hypertension and expansion of visceral adipose tissue) collectively referred to as &#x0201c;hepatitis C-associated dysmetabolic syndrome&#x0201d; (HCADS). General, nonalcoholic fatty liver disease (NAFLD)-like, mechanisms of steatogenesis (including increased availability of lipogenic substrates and de novo lipogenesis; decreased oxidation of fatty substrates and export of fatty substrates) are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein; peroxisome proliferator-activated receptor alpha; sterol regulatory element-binding proteins and phosphatase and tensin homologue. HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis; for impaired treatment response to interferon and ribavirin; and development of hepatocellular carcinoma. Recent data, moreover, suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms. In conclusion, HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle. A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.

Hepatocellular carcinoma in viral and autoimmune liver diseases:Role of CD4+CD25+Foxp3+regulatory T cells in the immune microenvironment

More than 90%of cases of hepatocellular carcinoma(HCC)occurs in patients with cirrhosis,of which hepatitis B virus and hepatitis C virus are the leading causes,while the tumor less frequently arises in autoimmune liver diseases.Advances in understanding tumor immunity have led to a major shift in the treatment of HCC,with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells.Regulatory T cells(Tregs)are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression,invasiveness,as well as metastasis.Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function.Notably,Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor(ICI)immunotherapy.Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity,it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events(irAEs).Since the use of ICI becomes common in oncology,with an increasing number of new ICI currently under clinical trials for cancer treatment,the occurrence of irAEs is expected to dramatically rise.Herein,we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease,and we discuss their involvement in irAEs due to the new immunotherapies.

Is endoscopic ultrasound examination necessary in the management of esophageal cancer?

Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer(EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970 s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound(EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection(ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography(PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis(over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, crosssectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented.

Role of genetics in the diagnosis and prognosis of Crohn's disease

Considering the epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have so far been related to the diagnosis of Crohn's disease. These genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the strongest and most replicated associations with Crohn's disease have been demonstrated with NOD2 , IL23R and ATG16L1 genes. Many genes have so far been implicated in the prognosis of Crohn's disease and many attempts have been made for classification of genetic profiles in Crohn's disease.CARD15 seems to be not only a susceptibility gene, but also a disease-modifier gene for Crohn's disease. Enriching our understanding of Crohn's disease genetics is of value, but when combining genetic data with functional data the outcome could be of major importance to clinicians.

Systematic review and meta-analysis of colon cleansing preparations in patients with inflammatory bowel disease

AIM To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing colon-cleansing products in patients with inflammatory bowel disease.METHODS Systematic searches were performed( January 1980-September 2016) using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials assessing preparations with or without adjuvants, given in split and non-split dosing, and in high(> 3 L) or low-volume(2 L or less) regimens. Bowel cleansing quality was the primary outcome. Secondary outcomes included patient willingness-torepeat the procedure and side effects/complications.RESULTS Out of 439 citations, 4 trials fulfilled our inclusion criteria(n = 449 patients). One trial assessed the impact of adding simethicone to polyethylene glycol(PEG) 4 L with no effect on bowel cleansing quality, but a better tolerance. Another trial compared senna to castor oil, again without any differences in term of bowel cleansing. Two trials compared the efficacy of PEG high-volume vs PEG low-volume associated to an adjuvant in split-dose regimens: PEG low-dose efficacy was not different to PEG high-dose; OR = 0.84(0.37-1.92). A higher proportion of patients were willing to repeat low-volume preparations vs high-volume; OR = 5.11(1.31-20.0). CONCLUSION In inflammatory bowel disease population, PEG lowvolume regimen seems not inferior to PEG high-volume to clean the colon, and yields improved willingness-torepeat. Further additional research is urgently required to compare contemporary products in this population.

Role of liver biopsy in hepatocellular carcinoma

The role of liver biopsy in the diagnosis of hepatocellular carcinoma(HCC)has been challenged over time by the ability of imaging techniques to characterize liver lesions in patients with known cirrhosis.In fact,in the diagnostic algorithm for this tumor,histology is currently relegated to controversial cases.Furthermore,the risk of complications,such as tumor seeding and bleeding,as well as inadequate sampling have further limited the use of liver biopsy for HCC management.However,there is growing evidence of prognostic and therapeutic information available from microscopic and molecular analysis of HCC and,as the information content of the tissue sample increases,the advantages of liver biopsy might modify the current risk/benefit ratio.We herein review the role and potentiality of liver biopsy in the diagnosis and management of HCC.As the potentiality of precision medicine comes to the management of HCC,it will be crucial to have rapid pathways to define prognosis,and even treatment,by identifying the patients who could most benefit from target-driven therapies.All of the above reasons suggest that the current role of liver biopsy in the management of HCC needs substantial reconsideration.

Therapy of gallstone disease:What it was,what it is,what it will be

Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.