Natural history of NASH and HCC Negro, Francesco
Liver international,
February 2020, 2020-Feb, 2020-02-00, 20200201, Letnik:
40, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
Widespread unhealthy dietary habits associated with a sedentary lifestyle have made NAFLD the most frequent chronic liver disease worldwide, with a global prevalence of ~25%. Although NAFLD is mainly ...considered to be a benign disease, it can progress to severe liver fibrosis and hepatocellular carcinoma (HCC), with the latter found in non‐cirrhotic livers in about 40% of cases. Factors favouring the progression of liver disease in NAFLD are only partially understood. Male sex, older age and Caucasian ethnicity have frequently been identified as factors accelerating the progression of fibrosis in NAFLD, although data are not consistent. Host genetic variants appear to be very important, especially in the gene coding for the patatin‐like phospholipase domain‐containing 3 (PNPLA3), and they may also play a role in the development of HCC, independent of activity and the extent of liver damage. However, the most important factors affecting disease progression are found in the metabolic syndrome, that is, obesity, type 2 diabetes and arterial hypertension. This mini‐review will discuss the contribution of these factors to NAFLD‐associated morbidity, emphasizing the importance of preventive measures such as physical activity and weight control in view of the current pandemic of the metabolic syndrome.
Summary The hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma worldwide. A significant portion of the morbidity and mortality associated with HCV ...is a consequence of numerous HCV-associated comorbidities. Type 2 diabetes and atherosclerosis, two known complications of the metabolic syndrome, are noteworthy, because HCV has been suggested to play a role in their pathogenesis. In addition, HCV also causes steatosis, which may increase the risk of cardiovascular events. This review summarizes the evidence supporting the association between HCV and steatosis, insulin resistance/type 2 diabetes and cardiovascular morbidity and mortality. Their diagnostic, prognostic and management aspects are discussed.
Summary Hepatitis delta virus (HDV) is a defective virus and a satellite of the hepatitis B virus (HBV). Its RNA genome is unique among animal viruses, but it shares common features with some plant ...viroids, including a replication mechanism that uses a host RNA polymerase. In infected cells, HDV genome replication and formation of a nucleocapsid-like ribonucleoprotein (RNP) are independent of HBV. But the RNP cannot exit, and therefore propagate, in the absence of HBV, as the latter supplies the propagation mechanism, from coating the HDV RNP with the HBV envelope proteins for cell egress to delivery of the HDV virions to the human hepatocyte target. HDV is therefore an obligate satellite of HBV; it infects humans either concomitantly with HBV or after HBV infection. HDV affects an estimated 15 to 20 million individuals worldwide, and the clinical significance of HDV infection is more severe forms of viral hepatitis – acute or chronic –, and a higher risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV monoinfection. This review covers molecular aspects of HDV replication cycle, including its interaction with the helper HBV and the pathogenesis of infection in humans.
In considering the role of common synaptic input to motor neurons in force control, we hypothesize that the effective neural drive to muscle replicates the common input and is, thus, the main ...determinant of force production. Such a perspective argues against a significant role for motor unit synchronization in force control.
The pathogenesis of liver damage associated with chronic hepatitis C virus （HCV） infection is thought to be largely immunomediated. However, some frequent histoo pathological features, such as ...steatosis, suggest a direct cytopathic effect of HCV. The direct responsibility of HCV in the pathogenesis of steatosis is shown by： （1） the association with HCV genotype 3 infection, suggesting that some viral sequences are involved in the intracellular aco cumulation of lipids; （2） the correlation between severity of steatosis and HCV replication levels; （3） association between response to treatment and disappearance of steatosis. Experimental studies have shown that the nuo cleocapsid protein of HCV （core protein） is capable and sufficient to induce lipid accumulation in hepatocytes. Moreover, the observation that chronic hepatitis C pao tients have reduced serum levels of ApoB suggests an interference with the very-low density lipoprotein （VLDL） assembly, although other mechanisms are possible. In patients with sustained virological response induced by antiviral therapy, such levels are normalized. Other obo servations suggest that the pathogenesis of steatosis in chronic hepatitis C is not solely due to HCV. The origin of the mild steatosis observed in most patients may be metabolic, since its severity correlates with body mass index and insulin resistance. Most studies have shown a correlation between presence and/or severity of steatosis and fibrosis stage, but it is unclear whether this effect is direct or mediated by the associated insulin resistance, increased susceptibility to apoptosis, or by inflammao tory cytokines. Finally, steatosis negatively influences the rate of response to antiviral treatment, as confirmed by large clinical trials. Management of steatosis in chronic hepatitis C requires knowledge of its pathogenesis and may involve both life-style changes and pharmacological interventions, although the latter remain largely experio mental.
We investigate the behavior of the pseudocritical temperature of Nf=2+1 QCD as a function of a static magnetic background field for different values of the pion mass, going up to mπ≃660 MeV. The ...study is performed by lattice QCD simulations, adopting a stout staggered discretization of the theory on lattices with Nt=6 slices in the Euclidean temporal direction; for each value of the pion mass the temperature is changed moving along a line of constant physics. We find that the decrease of Tc as a function of B, which is observed for physical quark masses, persists in the whole explored mass range, even if the relative variation of Tc appears to be a decreasing function of mπ, approaching zero in the quenched limit. The location of Tc is based on the renormalized quark condensate and its susceptibility; determinations based on the Polyakov loop lead to compatible results. On the contrary, inverse magnetic catalysis, i.e., the decrease of the quark condensate as a function of B in some temperature range around Tc, is not observed when the pion mass is high enough. That supports the idea that inverse magnetic catalysis might be a secondary phenomenon, while the modifications induced by the magnetic background on the gauge field distribution and on the confining properties of the medium could play a primary role in the whole range of pion masses.
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Clinical care for patients with HCV-related ...liver disease has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease, as well as developments in diagnostic procedures and improvements in therapy and prevention. These therapies make it possible to eliminate hepatitis C as a major public health threat, as per the World Health Organization target, although the timeline and feasibility vary from region to region. These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.
Genotype 3 of the hepatitis C virus (HCV) has been long considered an easy‐to‐treat infection, with higher cure rates (∼70%) than other viral genotypes with the standard combination of pegylated ...interferon‐α and ribavirin. However, the relative insensitivity of this genotype to most protease inhibitors and the recent unexpected data on decreased effectiveness of sofosbuvir have raised questions on how to achieve universal cure, a goal that seems reasonable for other genotypes. In addition, increasing clinical and experimental data show that HCV genotype 3 may be associated not only with severe steatosis, but also with accelerated fibrosis progression rate and increased oncogenesis. Conclusion: Currently available data suggest that we should increase our efforts to understand the virology and pathogenesis of HCV genotype 3, aiming at better and more potent, genotype‐targeted treatments. (Hepatology 2014;59:2403–2412)
The surface interference EMG signal provides some information on the neural drive to muscles. However, the association between neural drive to muscle and muscle activation has long been debated with ...controversial indications due to the unavailability of motor unit population data. In this study, we clarify the potential and limitations of interference EMG analysis to infer motor unit recruitment strategies with an experimental investigation of several concurrently active motor units and of the associated features of the surface EMG. For this purpose, we recorded high-density surface EMG signals during linearly increasing force contractions of the tibialis anterior muscle, up to 70% of maximal force. The recruitment threshold (RT), conduction velocity (MUCV), median frequency (MDF
), and amplitude (RMS
) of action potentials of 587 motor units from 13 individuals were assessed and associated with features of the interference EMG. MUCV was positively associated with RT (
= 0.64 ± 0.14), whereas MDF
and RMS
showed a weaker relation with RT (
= 0.11 ± 0.11 and 0.39 ± 0.24, respectively). Moreover, the changes in average conduction velocity estimated from the interference EMG predicted well the changes in MUCV (
= 0.71), with a strong association to ankle dorsiflexion force (
= 0.81 ± 0.12). Conversely, both the average EMG MDF and RMS were poorly associated with motor unit recruitment. These results clarify the limitations of EMG spectral and amplitude analysis in inferring the neural strategies of muscle control and indicate that, conversely, the average conduction velocity could provide relevant information on these strategies.
The surface EMG provides information on the neural drive to muscles. However, the associations between EMG features and neural drive have been long debated due to unavailability of motor unit population data. Here, by using novel highly accurate decomposition of the EMG, we related motor unit population behavior to a wide range of voluntary forces. The results fully clarify the potential and limitation of the surface EMG to provide estimates of the neural drive to muscles.
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