瓣膜性房颤定义及抗凝治疗研究进展

现阶段对于"瓣膜病变型"房颤(AF)与"非瓣膜病变型"AF的定义尚未达成共识,不仅如此,各指南在表述这些概念时也存在差异。临床试验对于"瓣膜病变型"AF与"非瓣膜病变型"AF定义的阐述不甚理想。两类AF血栓栓塞风险差异较大,抗凝治疗策略也有所不同。本文将对瓣膜性AF定义及抗凝治疗的研究进展予以综述。     

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.     

Recent standardization of treatment strategy for pancreatic neuroendocrine tumors

Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors(PNET).For patients with sporadic functioning PNET,curative resection surgery has been established by localization with the SASI test using secretin or calcium.For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1(MEN 1) which are usually multiple and sometimes numerous,resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test.As resection surgery of PNET has increased,several important pathological features of PNET have been revealed.For example,in patients with Zollinger-Ellison syndrome(ZES),duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma,and in patients with MEN 1 and ZES,gastrinomas have been located mostly in the duodenum,and pancreatic gastrinoma has been found to co-exist in 13% of patients.Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation.The most important prognos-tic factor in patients with PNET is the development of hepatic metastases.The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit.The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.     

Polysomnographic sleep aspects in liver cirrhosis: A case control study

AIM: To study sleep aspects and parameters in cirrhotic patients and assess the role of liver dysfunction severity in polysomnographic results. METHODS: This was a case-control study. Patients with a diagnosis of liver cirrhosis were consecutively enrolled in the study. Clinical examinations and laboratory liver tests were performed in all patients, and disease severity was assessed using the Child-Pugh score. The control group consisted of ageand gender-matched healthy volunteers. All individuals answered a questionnaire about habits, behaviors, and complaints related to sleep and were submitted to polysomnography. Sleep parameters were compared between the two groups, and separate analyses were performed among classesof Child-Pugh classification in the cirrhotic group. RESULTS: Forty-two cirrhotic patients and forty-two controls were enrolled. Compared to the control group, the cirrhotic group exhibited lower sleep efficiency (mean ± SD: 73.89% ± 14.99% vs 84.43% ± 8.55%, P < 0.01), increased latency (151.27 ± 93.24 min vs 90.62 ± 54.74 min, P < 0.01) and a lower percentage of rapid eye movement (REM) sleep (14.04% ± 5.64% vs 20.71% ± 6.77%, P < 0.05) as well as a higher frequency of periodic limb movements (10.56 ± 2.85/h vs 2.79 ± 0.61/h, P < 0.01). The comparison of sleep parameters among Child A, B and C cirrhotic patients revealed a significant reduction of REM sleep stage occurrence in individuals with severe liver disease (Child C patients) compared to Child A/B patients (polysomnography percentage of REM sleep stage of patients Child A: 16.1% ± 1.2%; Child B: 14.9% ± 1.2%; Child C: 8.6% ± 1.6%, P < 0.05). CONCLUSION: Cirrhosis was associated with shorter sleep time, reduced sleep efficiency, increased sleep latency, increased REM latency and reduced REM sleep. Additionally, disease severity influences sleep parameters.     

High-risk symptoms and quantitative faecal immunochemical test accuracy: Systematic review and meta-analysis

BACKGROUND The quantitative faecal immunochemical test for haemoglobin(FIT) has been revealed to be highly accurate for colorectal cancer(CRC) detection not only in a screening setting, but also in the assessment of patients presenting lower bowel symptoms. Therefore, the National Institute for Health and Care Excellence has recommended the adoption of FIT in primary care to guide referral for suspected CRC in low-risk symptomatic patients using a 10 μg Hb/g faeces threshold.Nevertheless, it is unknown whether FIT′s accuracy remains stable throughout the broad spectrum of possible symptoms.AIM To perform a systematic review and meta-analysis to assess FIT accuracy for CRC detection in different clinical settings.METHODS A systematic literature search was performed using MEDLINE and EMBASE databases from inception to May 2018 to conduct a meta-analysis of prospective studies including symptomatic patients that evaluated the diagnostic accuracy of quantitative FIT for CRC detection. Studies were classified on the basis of brand,threshold of faecal haemoglobin concentration for a positive test result,percentage of reported symptoms(solely symptomatic, mixed cohorts) and CRC prevalence(< 2.5%, ≥ 2.5%) to limit heterogeneity and perform subgroup analysis to assess the influence of clinical spectrum on FIT′s accuracy to detect CRC.RESULTS Fifteen cohorts including 13073 patients(CRC prevalence 0.4% to 16.8%) were identified. Pooled estimates of sensitivity for studies using OC-Sensor at 10 μg Hb/g faeces threshold(n = 10400) was 89.6% [95% confidence interval(CI): 82.7%to 94.0%). However, pooled estimates of sensitivity for studies formed solely by symptomatic patients(n = 4035) and mixed cohorts(n = 6365) were 94.1%(95%CI: 90.0% to 96.6%) and 85.5%(95%CI: 76.5% to 91.4%) respectively(P <0.01), while there were no statistically significant differences between pooled sensitivity of studies with CRC prevalence < 2.5%(84.9%, 95%CI: 73.4% to 92.0%)and ≥ 2.5%(91.7%, 95%CI: 83.3% to 96.1%)(P = 0.25). At the same threshold, OCSensor? sensitivity to rule out any significant colonic lesion was 78.6%(95%CI:75.6% to 81.4%). We found substantial heterogeneity especially when assessing specificity.CONCLUSION The results of this meta-analysis confirm that, regardless of CRC prevalence,quantitative FIT is highly sensitive for CRC detection. However, FIT ability to rule out CRC is higher in studies solely including symptomatic patients.     

Laparoscopic cholecystectomy for a left-sided gallbladder

Cholecystectomy is a common procedure.Abnormalities in the anatomy of the biliary system are common but an abnormal location of the gallbladder is much rarer.Despite frequent pre-operative imaging,the aberrant location of the gallbladder is commonly discovered at surgery.This article presents a case of a patient with the gallbladder located to the left of the falciform ligament in the absence of situs inversus totalis that presented with right upper quadrant pain.A laparoscopic cholecystectomy was performed and it was noted that the cystic duct originated from the right side.The presence of a left sided gall bladder is often associated with various biliary,portal venous and other anomalies that might lead to intra-operative injuries.The spectrum of unusual positions and anatomical gallbladder abnormalities is reviewed in order to facilitate elective and emergent cholecystectomy as well as other hepatobiliary procedures.With proper identification of the anatomy,minimally invasive approaches are still considered safe.     

Hepatitis C virus control among persons who inject drugs requires overcoming barriers to care

Despite a high prevalence of hepatitis C virus(HCV)infection,the vast majority of persons who inject drugs(PWID)have not engaged in HCV care due to a large number of obstacles.Education about the infection among both PWID and providers remains an important challenge as does discrimination faced by PWID in conventional health care settings.Many providers also remain hesitant to prescribe antiviral therapy due to concerns about adherence and relapse to drug use resulting in reinfection.Presently,however,as a result of improvements in treatment efficacy combined with professional society and government endorsement of HCV treatment for PWID,a pressing need exists to develop strategies to engage these individuals into HCV care.In this article,we propose several strategies that can be pursued in an attempt to engage PWID into HCV management.We advocate that multidisciplinary approaches that utilize health care practitioners from a wide range of specialties,as well as co-localization of medical services,are strategies likely to result in increased numbers of PWID entering into HCV management.Pursuit of HCV therapy after stabilization through drug treatment is an additional strategy likely to increase PWID engagement into HCV care.The full impact of direct acting antivirals for HCV will only be realized if innovative approaches are pursued to engage all HCV infected individuals into treatment.     

Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection

Hepatitis delta virus(HDV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two viruses.AIM To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected patients.METHODS Twenty-four untreated patients were included: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA levels.The HBX 5' region [nucleotides(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 1 and 2), and functional indices(mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies complexity.RESULTS CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHD(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed statistically significant differences(CHB2.81, IQR 1.11-4.57 vs CHD 8.87, 6.56-11.18, P = 0.038). There were no significant differences in the functional indices, but CI and CHD patients also showed a trend towards greater complexity than CHB. No differences were found for any HBV quasispecies complexity indices between CHD and CI patients. G-to-A and C-to-T nucleotide changes, characteristic of APOBEC3 G, were higher in CHD and CI than in CHB in genotype A haplotypes, but not in genotype D. The proportion of nt G-to-A vs A-to-G changes and C-to-T vs T-to-C changes in genotype A and D haplotypes in CHD patients showed no significant differences. In CHB and CI the results of these comparisons were dependent on HBV genotype.CONCLUSION The lower-replication CHD and CI groups show a trend to higher quasispecies complexity than the higher-replication CHB group. The mechanisms associated with this greater complexity require elucidation.     

Individualized hepatocellular carcinoma risk: The challenges for designing successful chemoprevention strategies

Hepatocellular carcinoma (HCC) develops in the context of environmental risk factors like chronic viral hepatitis, diabetes and alcohol exposure, often associated to an increased risk of cirrhosis. Antiviral treatments that are effective to counteract hepatitis B and C may also attenuate the risk of tumor development. However, since hepatitis B-related carcinogenesis is promoted independently of the onset of cirrhosis, such antiviral treatments as nucleo(t)side analogs can promote regression of cirrhosis, prevent clinical decompensation and variceal bleeding but not HCC. This means that in successfully treated patients with cirrhosis, HCC is often the consequence of their extended survival. In hepatitis C patients, a sustained virological response to interferon-based therapies can reduce the rate of HCC development, even in patients with cirrhosis who experience histological regression of their liver disease. Future therapies aimed at this endpoint in at risk populations should take into consideration pretreatment patient stratification for host, viral and environmental risk factors. In this context the recent discovery of single nucleotide polymorphisms involved in the immune system function and tumorigenesis, might permit enrollment of populations of patients enriched with HCC risk factors for targeted chemopreventive therapies. This could finally pave the way to personalized algorithms, as already seen in the diagnosis and treatment schemes for chemoprevention.     

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.