RESIST-HCV Criteria to Monitor Progression of Low-Risk Esophageal Varices in Patients With Compensated Cirrhosis After HCV Eradication: The SIMPLE Study: SIMPLE: Scoring Index to Monitor Progression of Low-risk Esophageal varices.

INTRODUCTION: Noninvasive criteria to predict the progression of low-risk esophageal varices (EV) in patients with compensated hepatitis C virus (HCV) cirrhosis after sustained virological response (SVR) by direct-acting antivirals (DAAs) are lacking. Our aim was to assess the diagnostic performance of Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) criteria for EV progression compared with elastography-based criteria (Baveno VI, Expanded Baveno VI, and Baveno VII-HCV criteria). METHODS: All consecutive patients observed at 3 referral centers with compensated HCV cirrhosis with or without F1 EV who achieved sustained virological response by DAAs were classified at last esophagogastroduodenoscopy (EGDS) as RESIST-HCV low risk (i.e., low probability of high-risk varices [HRV]) if platelets were >120 × 10 9 /L and serum albumin >3.6 g/dL or RESIST-HCV high risk (i.e., high probability of HRV) if platelets were <120 × 10 9 /L or serum albumin <3.6 g/dL. The primary outcome was the progression to HRV. The area under the receiver operating characteristic curve and decision curve analysis of noninvasive criteria were calculated. RESULTS: The cohort consisted of 353 patients in Child-Pugh class A (mean age 67.2 years, 53.8% males). During a mean follow-up of 44.2 months, 34 patients (9.6%, 95% CI 6.7%-13.5%) developed HRV. At the last EGDS, 178 patients (50.4%) were RESIST-low risk, and 175 (49.6%) were RESIST-high risk. RESIST-HCV criteria showed the highest area under the receiver operating characteristic curve (0.70, 95% confidence interval 0.65-0.75), correctly sparing the highest number of EGDS (54.3%), with the lowest false-positive rate (45.7%), compared with elastography-based criteria. Decision curve analysis showed that RESIST-HCV had higher clinical utility than elastography-based criteria. DISCUSSION: Biochemical-based RESIST-HCV criteria are useful to easily predict HRV development after HCV eradication by DAAs in patients with compensated cirrhosis and low-risk EV.

PNPLA3 rs738409 C>G Variant Predicts Fibrosis Progression by Noninvasive Tools in Nonalcoholic Fatty Liver Disease.

Liver fibrosis is the main predictor of events in patients with nonalcoholic fatty liver disease (NAFLD),1 and its evolution is characterized by a nonlinear trend2,3 mostly affected by metabolic risk factors, severity of liver inflammation and steatosis, and weight loss.3 The rs738409 C>G common variant in PNPLA3 gene has been associated with severity of fibrosis and risk of liver-related events in NAFLD.4,5 Noninvasive tests as Fibrosis-4 (FIB-4) and liver stiffness measurement (LSM) are useful to rule-out advanced fibrosis and they could be reliable to predict fibrosis progression.2,6 We aimed to evaluate in patients with NAFLD whether PNPLA3 rs738409 C>G variant impacts on fibrosis progression, noninvasively assessed by FIB-4 and LSM.

Child-Pugh Class and Not Thrombocytopenia Impacts the Risk of Complications of Endoscopic Band Ligation in Patients with Cirrhosis and High Risk Varices.

Background and Aims: Endoscopic band legation (EBL) is an effective method for the prophylaxis of acute variceal bleeding (AVB). This procedure may be associated with several complications, particularly bleeding. Our analysis aimed to evaluate the risk of complications due to EBL in a cohort of patients who underwent EBL for the prophylaxis of variceal bleeding and the eventual presence of risk predictors. Patients and Methods: We retrospectively analysed data from consecutive patients who underwent EBL in a primary prophylaxis regimen. For all patients, simultaneously with EBL, we recorded the Child-Pugh and MELD score, platelet count and US features of portal hypertension. Results: We collected data from 431 patients who performed a total of 1028 EBLs. We recorded 86 events (8.4% of all procedures). Bleeding after EBL occurred 64 times (6.2% of all procedures), with the following distribution: intraprocedural bleeding in 4%; hematocystis formation in 17 cases (1.7%); 6 events (0.6%) of AVB due to post-EBL ulcers. None of these events presented a correlation with platelet count (84,235 ± 54,175 × 103/mL vs. 77,804 ± 75,949 × 103/mL; p = 0.70) or with the condition of severe thrombocitopenia established at PLT < 50,000/mmc (22.7% with PLT ≤ 50,000/mmc vs. 15.9% with PLT ≥ 50,000/mmc; p = 0.39). Our results showed a relationship between cumulative complications of EBL and Child-Pugh score (6.9 ± 1.6 vs. 6.5 ± 1.3; p = 0.043). Conclusions: EBL in cirrhotic patients is a safe procedure. The risk of adverse events depends on the severity of liver disease, without a relationship with platelet count.

A Genetic and Metabolic Staging System for Predicting the Outcome of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is an emerging cause of liver-related events (LREs). Here, we have assessed the ability of a composite score based on clinical features, metabolic comorbidities, and genetic variants to predict LREs. A total of 546 consecutive patients with NAFLD were recruited and stratified according to the fibrosis-4 (FIB-4) index. LREs were defined as occurrence of hepatocellular carcinoma or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LREs. The UK Biobank was used as the validation cohort, and severe liver disease (incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma, and/or liver transplantation) was used as the outcome. LREs were experienced by 58 patients, only one of whom was in the cohort of patients with a FIB-4 score < 1.3. Multivariate Cox regression analysis of 229 patients with a FIB-4 score ≥ 1.3 highlighted clinical variables independently associated with the development of LREs, including older age, low platelet count, low albumin, low high-density lipoprotein cholesterol, certain genetic factors, and interactions between genetic factors and sex or diabetes. The area under the curve (AUC) for the model was 0.87 at 1, 3, and 5 years. Our novel Genetic and Metabolic Staging (GEMS) scoring system was derived from the Cox model linear predictor, ranked from 0 to 10, and categorized into five classes (0-5, 5-6, 6-7, 7-8, and 8-10). The risk of LREs increased from 4% in patients in the best class (GEMS score 0-5) to 91% in the worst (GEMS score 8-10). GEMS score was associated with incident severe liver disease in the study population (hazard ratio, 1.56; 95% confidence interval, 1.48-1.65; P < 0.001) as well as in the UK Biobank cohort where AUCs for prediction of severe liver disease at 1, 3, and 5 years were 0.70, 0.69, and 0.67, respectively. Conclusion: The novel GEMS scoring system has an adequate ability to predict the outcome of patients with NAFLD.

Impact of direct-acting antivirals (DAAs) on cardiovascular diseases in patients with chronic hepatitis C.

INTRODUCTION: In the last years the Hepatitis C virus (HCV) infection was a relevant public health problem due to the large number of affected people worldwide and the impact on hepatic and extrahepatic complications. The availability of direct-acting antivirals (DAAs) and the very high rate of sustained virological response (SVR) after treatment has radically changed the course of HCV chronic infection. EVIDENCE ACQUISITION: We searched PubMed for articles published between January 1, 1995, through December 31, 2020, in English language. EVIDENCE SYNTHESIS: Robust evidence showed a close link between HCV infection and development of cardiovascular disease (CVD), as result of the atherogenic effect of the virus. CONCLUSIONS: This review aimed to explore the evidence linking HCV infection with cardiovascular disease and to evaluate the impact of SVR after DAAs on cardiovascular complications.

Effect of Sunlight Exposure on Anthocyanin and Non-Anthocyanin Phenolic Levels in Pomegranate Juices by High Resolution Mass Spectrometry Approach.

Quali-quantitative analyses of anthocyanins and non-anthocyanin phenolic compounds performed with the use of liquid chromatography coupled with high resolution mass spectrometry, were evaluated in juice of pomegranate fruits ('Dente di Cavallo'), in relation to different light exposures (North, South, West and East). A total of 16 compounds were identified, including phenolic acids, flavonoids, hydrolysable tannins, and anthocyanins, known for their health-promoting effects. Striking differences were observed about the total phenolic content, which was high in juices from fruits with east- and north-facing position, while it was lower in juices facing south. The greatest contents of total flavonoids and anthocyanins were recorded in fruit juices with southern exposure; however, there are no great differences in the content in phenolic acids. Tannins were mainly synthesized in fruit juices with West exposure. The results showed that the position within the tree had no significant effects on color juice, however, it significantly (p < 0.05) affected data on fruit weight, soluble sugars and juice yield. Remarkable synergies existed among polyphenols and phytochemicals in pomegranate juice, but collecting fruits with different solar exposure could enhance different health benefits, i.e., the juices with higher polyphenols content could have more anticancer effect or those with higher tannins content could have more antimicrobial effect.

Trace element compartmentation in the seagrass Posidonia oceanica and biomonitoring applications.

This study investigated the trace element bioaccumulation capacity of the Mediterranean seagrass Posidonia oceanica, and its suitability as a bioindicator of contamination in water and sediments. Results showed that P. oceanica leaves accumulate higher concentrations of Ni and Zn. Since P. oceanica regenerates its leaves periodically, the higher concentrations in aerial organs may suggest a "removal" strategy according to which P. oceanica accumulates greater concentrations of trace elements in its temporary organs. In turn, P. oceanica seems to adopt an exclusion strategy for toxic non-essential elements (As, Cr, Pb). Results showed also that P. oceanica organs are correlated with As, Cd, Cu, Ni, and Zn concentrations in sediments. No significant relationship was found between P. oceanica and water. This study showed that P. oceanica may adopt different tolerance strategies compared to mainland-rooted macrophytes, and its possible use as a bioindicator of trace elements in sediments should be considered.

Levels of heavy metals in wetland and marine vascular plants and their biomonitoring potential: A comparative assessment.

The present study investigated the levels of As, Cd, Cr, Cu, Hg, Mn, Ni, Pb and Zn in the seagrasses Posidonia oceanica and Cymodocea nodosa, and in the wetland macrophytes Phragmites australis, Arundo donax, Typha domingensis, Apium nodiflorum, and Nasturtium officinale. Results showed that the bioaccumulation capacity from sediments, translocation, total levels in plant tissues, and bioindication of metals in sediments, are generally species-specific. In particular, the patterns of metals in the aquatic plants studied were overall independent of ecology (coasts vs wetlands), biomass, anatomy (rhizomatous vs non rhizomatous plants), and life form (hemicrytophytes vs hydrophytes). However, marine phanerogams and wetland macrophytes shared some characteristics such as high levels of heavy metals in their below-ground organs, similar capacity of element translocation in the rhizosphere, compartmentalization of metals in the different plant organs, and potential as bioindicators of Cu, Mn and Zn levels in the substratum. In particular, the present findings indicate that, despite ecological and morphological similarities, different plant species tend to respond differently to exposure to heavy metals. Furthermore, this seems to result from the species individual ability to accumulate and detoxify the various metals rather than being attributed to differences in their ecological and morpho-anatomical characteristics.

Occurrence of mucous aggregates and their impact on Posidonia oceanica beds.

Mucous macro-aggregates of both pelagic and benthic origin are recurrently observed in the meadows formed by the seagrass Posidonia oceanica around the island of Ischia (Gulf of Naples, Italy). In the past two decades, major events occurred in 1991, 1993 and 2000, when a thick layer of mucilage covered vast areas of the meadows. To investigate the environmental triggers for mucilage formation and the effects of macro-aggregates on the functional and structural status of P. oceanica, a number of abiotic and biotic parameters were monitored over three years within the frame of a research project on Adriatic and Tyrrhenian mucilages (MAT). Basic environmental parameters (salinity, temperature, irradiance, dissolved oxygen concentration) in the water column and inorganic nutrient concentrations above and within P. oceanica meadows were measured. As descriptors of the status of the seagrass, shoot density and the nitrogen content of the leaves were monitored. Moreover, a reconstructive technique (lepidochronology) was employed to track back annual plant production. During the three-year study, mucous aggregates produced by benthic algae were observed in spring-summer and a major event of macro-aggregates of pelagic origin affecting P. oceanica canopy was observed in autumn 2000. Each of these episodes was observed for a few weeks to one month. We hypothesize nutrient limitation to explain the short duration of the benthic algal blooms that were responsible of macroaggregate formation; a highly dynamic circulation resulted in the dispersion of the pelagic aggregates deposited on the meadows. None of the descriptors of the structure of the meadow and of plant performance showed any obvious alterations in relation to the occurrence of mucilage coverage. Presumably, the short duration of the mucilage episodes recorded were not enough to induce such alterations, at least at the temporal and spatial scales considered.

H, C, and O Stable Isotope Ratios of Passito Wine.

In this study we investigated the effect of the grape withering process occurring during the production of Italian passito wines on the variability of the (D/H)I, (D/H)II, δ(13)C, and δ(18)O of wine ethanol and the δ(18)O of wine water. The production of PDO Erbaluce di Caluso Passito in five different cellars in Piedmont (Italy) was considered in two successive years. Moreover, samples of 17 different traditional Italian passito wines taken at different stages of maturation were taken into account. We found that the δ(18)O of must and wine water and the δ(18)O of ethanol decrease in the case of passito wines produced in northern and central Italy using postharvest drying of the grapes in dedicated ventilated or unventilated fruit drying rooms (fruttaio), during autumn-winter. For passito wines produced in southern Italy, where the main technique involves withering on the plant (en plein air), δ(18)O tends to increase. The (DH)I of wine ethanol did not change during withering, whereas the (DH)II and δ(13)C values changed slightly, but without any clear trend. Particular attention must be therefore paid in the evaluation of the δ(18)O data of passito wines for fraud detection.

Pneumatic dilation and botulinum toxin: when and why?

Pneumatic dilation and botulinum toxin:when and why? The endoscopic treatment options of achalasia include botulinum toxin (BT) injection and pneumatic dilation (PD) of the lower esophageal sphincter (LES). BT can reduce the LES pressure by blocking the release of acetylcoline from presynaptic cholinergic nerve terminals in the myenteric plexus. Although the procedure is safe and good initial response is reported, there is a wide variability in the duration of the response and the effect tends to decrease over time. BT is usually recommended for elderly patients or patients with comorbid illnesses, who are poor candidates for more invasive procedures. PD aims at tearing the muscle fibers of the LES and is considered the most effective nonsurgical treatment for achalasia. Technical details of the procedure vary in different institutions and in many clinical settings the choice between PD or minimally invasive surgical myotomy depends upon local expertise in the procedures. Further endoscopic treatment options such as submucosal esophageal myotomy or self-expanding metallic stents are being studied.