Vitamin D deficiency in chronic liver disease

Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.

Plasma betatrophin levels in patients with liver cirrhosis

AIM: To investigate the plasma levels of betatrophin in patients with cirrhosis.METHODS: Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic,or histological criteria were included.The severity of cirrhosis was classified according to Pugh's modification of Child's classification and MELD score. Insulin resistance(IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched subjects.Fasting blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay(DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were < 4% and < 10%,respectively. The normal values were between 2 and17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA(Aviscera Bioscience). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility were< 6% and < 10%, respectively.RESULTS: Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with those in healthy subjects(P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B(P< 0.0005) and in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation(P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification(r = 0.53; P < 0.01) or MELD score(r = 0.45; P <0.01). In the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin(r= 0.39; P < 0.01) has been observed, as well as an inverse correlation between betatrophin and albumin(r =-0.41; P < 0.01) or prothrombin time(r =-0.44;P <0.01). Moreover, insulin resistance was observed in82.5% of the cirrhotic patients. In this group of patients,betatrophin levels were significantly higher than those in the group of patients without IR(P < 0.05).CONCLUSION: Plasma betatrophin is increased in patients with cirrhosis. This increase is related to the severity of cirrhosis, as well as with the emergence of insulin resistance.

Impact of an acute hemodynamic response-guided protocol for primary prophylaxis of variceal bleeding

AIM To evaluate the long-term outcome of an acute hemodynamic response-guided protocol in which acute responders to intravenous propranolol received traditional nonselective beta-blockers(NSBBs) and acute nonresponders received carvedilol.METHODS Retrospective review of a protocol for primary prophylaxis of variceal bleeding guided by the acute hemodynamic response to intravenous propranolol. Fifty-two acute responders treated with traditional NSBB(i.e. propranolol or nadolol) were compared with 24 acute nonresponders receiving carvedilol. A second hemodynamic study was performed in 27 and 13 patients, respectively. The primary endpoint was development of first or further decompensation. Secondary endpoints included death from any cause, association between acute and chronic hemodynamic response, and baseline clinical and laboratory variables related to the acute hemodynamic response.RESULTS Acute responders and acute nonresponders presented similar 1, 2, and 3-year probabilities of first decompensation(NSBB: 0%, 13.7%, 26.1% vs carvedilol: 0%, 20%, 20%, P = 0.968) or further decompensation(21.2%, 26.1%, 40.9% vs 21.2%, 50.0%, 50.0%, P = 0.525). A previous episode of hepatic encephalopathy was the only independent predictor of decompensation [hazard ratio(95% confidence interval): 8.03(2.76-23.37)]. Mortality rates were similar in acute responders and acute nonresponders with compensated(P = 0.428) or decompensated cirrhosis(P = 0.429). No clinical, laboratory, endoscopic or hemodynamic parameter predicted the acute hemodynamic response. In patients receiving traditional NSBB, the acute and chronic changes of hepatic venous pressure gradient were correlated(r = 0.59, P = 0.001). Up to 69.2% of acute nonresponders gained chronic response with carvedilol.CONCLUSION Early identification and treatment with carvedilol of acute nonresponders to intravenous propranolol improves the clinical outcome of this high-risk group of patients, probably due to its greater effects for reducing portal pressure.

Clinical significance of donor-specific human leukocyte antigen antibodies in liver transplantation

Antibody-mediated rejection(AMR) caused by donorspecific anti-human leukocyte antigen antibodies(DSA) is widely accepted to be a risk factor for decreased graft survival after kidney transplantation. This entity also plays a pathogenic role in other solid organ transplants as it appears to be an increasingly common cause of heart graft dysfunction and an emerging issue in lung transplantation. In contrast, the liver appears relatively resistant to DSA-mediated injury. This "immune-tolerance" liver property has been sustained by a low rate of liver graft loss in patients with preformed DSA and by the intrinsic liver characteristics that favor the absorption and elimination of DSA; however, alloantibody-mediated adverse consequences are increasingly being recognized, and several cases of acute AMR after ABO-compatible liver transplant(LT) have been reported. Furthermore, the availability of new solid-phase assays, allowing the detection of low titers of DSA and the refinement of objective diagnostic criteria for AMR in solid organ transplants and particularly in LT, have improved the recognition and management of this entity. A cost-effective strategy of DSA monitoring, avoidance of class Ⅱ human leukocyte antigen mismatching, judicious immunosuppression attached to a higher level of clinical suspicion of AMR, particularly in cases unresponsive to conventional antirejection therapy, can allow a rational approach to this threat.

Long-term survival after liver transplantation for alcoholic liver disease

Currently,alcoholic cirrhosis is the second leading indication for liver transplantation in the United States and Europe.The quality of life and survival after a liver transplantation(LT)in patients with alcoholic liver disease(ALD)are similar to those in patients with other cirrhosis etiologies.The alcoholic relapse rate after a LT varies from 10%-50%,and these relapse patients are the ones who present a reduced long-term survival,mainly due to cardiovascular diseases and the onset of de novo neoplasms,including lung and upper aerodigestive tract.Nearly 40%of ALD recipients resume smoking and resume it early post-LT.Therefore,our pre-and post-LT follow-up efforts regarding ALD should be focused not only on alcoholic relapse but also on treating and avoiding other modifiable risk factors such as tobacco.The psychiatric and psychosocial pre-LT evaluation and the post-LT follow-up with physicians,psychiatrists and addiction specialists are important for reversing these problems because these professionals help to identify patients at risk for relapse as well as those patients who have relapsed,thus enabling responsive actions.

Binge drinking: Burden of liver disease and beyond

The consumption of alcoholic beverages is harmful to human health. In recent years, consumption patterns of alcoholic beverages have changed in our society, and binge drinking has generalized. It is considered to be a socio-sanitary problem with few known consequences in terms of individual and third-party social impacts(in the form of violence or traffic accidents) and its organic impact(affects the liver and other organs and systems, such as the nervous and cardiovascular systems) and represents an important financial burden due to its increasing economic impact. This review provides a global approach to binge drinking and emphasizes its epidemiological character, the effect of this type of consumption and the possible management of a problem with an increasing tendency in our society.

Periprocedural management of hemostatic alterations in patients with cirrhosis and vascular liver disorders: a step forward of the American Association for the Study of Liver Diseases

“Time flies over us,but leaves its shadow behind”(Nathaniel Hawthorne,1860,The Marble Faun).The shadow that separates the latest guidance on vascular liver disorders of the American Association for the Study of Liver Diseases(AASLD)from its former counterpart is 12 years long(1,2).Along the course,several guidelines from different societies have been published on this topic(3-7).As acknowledged in the preamble,the lack of high-quality evidence in the field led the AASLD to commission a guidance from an expert panel based on formal review and analysis of the literature.It thus differs from other guidelines that perform systematic reviews with explicit methods of searching,selection,and rating the quality of evidence and,if appropriate,meta-analysis on certain clinical questions(2).

Paediatric non-alcoholic fatty liver disease: a more complex disease than in the adulthood?

While the association between obesity,type 2 diabetes(T2D)and the presence of steatosis has been established since the beginning of the last century(1),it was not until 1980 that the first references were made about a form of histologic liver lesion designated as non-alcoholic steatohepatitis(NASH).NASH is characterised by the presence of a variable degree of steatosis accompanied by lobular inflammatory infiltrate and hepatocellular damage with or without fibrosis.Subsequently,the broader term of non-alcoholic fatty liver disease(NAFLD)was accepted,which more accurately encompass the entire spectrum of lesions that appear in these patients(2).Ever since then,NAFLD has become progressively the primary cause of chronic liver disease in developed countries(3).