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SUMMARY Background and AimThe potential prognostic value for survival of nutritional status in cirrhotics after adjusting Child-Pugh classification and Model for EndStage Liver Disease has not been evaluated.

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The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.

We hypothesized that current trough concentrations of tacrolimus after liver transplantation are set too high, considering that clinical consequences of rejection are not severe while side effects are increased. We systematically reviewed 64 studies (32 randomized controlled trials and 32 observational studies) to determine how lower tacrolimus trough concentrations than currently recommended affect acute rejection rates and renal impairment. Among randomized trials the mean of tacrolimus trough concentration during the first month was positively correlated with renal impairment within 1 year (r = 0.73; p = 0.003), but not with acute rejection, either defined using protocol biopsies (r =−0.37; p = 0.32) or not (r = 0.11; p = 0.49). A meta‐analysis of randomized trials directly comparing tacrolimus trough concentrations (five trials for acute rejection [n = 957] and two trials for renal impairment [n = 712]) showed that “reduced tacrolimus” trough concentrations (<10 ng/mL) within the first month after liver transplantation were associated with less renal impairment at 1 year (RR = 0.51 [0.38–0.69]), with no significant influence on acute rejection (RR = 0.92 [0.65–1.31]) compared to “conventional tacrolimus” trough levels (>10 ng/mL). Lower trough concentrations of tacrolimus (6–10 ng/mL during the first month) would be more appropriate after liver transplantation. Regulatory authorities and the pharmaceutical industry should allow changes of regulatory drug information.

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Hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) was undertaken in 85 patients with histologically proven cirrhosis of varying etiologies and functional severity. Reference data were acquired from 16 healthy volunteers who had no history or evidence of liver disease or alcohol abuse. In vivo hepatic 31P MR spectra were acquired with pulse angle 45 degrees and repetition times (TR) of 5 and 0.5 seconds. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) relative to beta ATP, and of PME relative to PDE were calculated from spectra acquired at TR 5 seconds. Estimates of saturation effects for individual resonances were obtained by dividing the peak height at TR 5 seconds by that at TR 0.5 seconds to yield a T1-related signal height ratio (SHR). When compared with reference values, the patients with liver disease showed a significantly higher PME/ATP (P < .0001), PME/PDE (P < .0001), PME SHR (P < .001), and Pi SHR (P < .02), and a lower PDE/ATP (P < .001) and PDE SHR (P < .001). The magnitude of these changes increased significantly and progressively with increasing functional impairment. In patients with compensated cirrhosis spectral appearances varied with etiology; thus, patients with postviral cirrhosis showed a significantly higher Pi/ATP; those with alcoholic cirrhosis, a significantly lower PDE/ATP; and those with cirrhosis secondary to primary sclerosing cholangitis, a significantly lower Pi/ATP than the healthy volunteers or other etiological groups. However, spectral appearances did not vary with etiology in patients with decompensated disease. In vitro 31P MRS of perchloric extracts of samples of liver tissue obtained from 10 patients with cirrhosis at transplant hepatectomy showed increases in levels of the soluble PME metabolites, phosphorylcholine and phosphorylethanolamine, and reductions in the levels of the soluble PDE metabolites, glycerophosphorylcholine and glycerophosphorylethanolamine. These changes suggest regenerative activity in cirrhotic livers. The increases in soluble phosphomonoesters in the aqueous extracts accounted for the increased PME/ATP ratio seen in the in vivo spectra, and might account for the increase in PME SHR. The reduction in soluble phosphodiesters in the aqueous extracts did not entirely account for the reduction PDE/ATP ratio seen in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)