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Whether tubular injury develops in patients with acute kidney injury owing to hepatorenal syndrome (AKI-HRS) is controversial. We performed repeated measurements of biomarkers of tubular injury during a 14-day period in 60 patients with cirrhosis and AKI (34 with AKI-HRS meeting the classical definition of type 1 HRS and 26 with AKI owing to acute tubular necrosis, AKI-ATN). Nineteen of 34 patients had resolution of AKI-HRS, while the remainder had persistent AKI-HRS. The persistence of AKI-HRS was associated with remarkably high short-term mortality. There were no significant differences in urinary NGAL or IL-18 between patients with resolution vs those with persistent AKI-HRS throughout the 14-day period. By contrast, biomarker levels were significantly lower in AKI-HRS, even if persistent, compared to AKI-ATN. These findings are highly suggestive of lack of significant tubular injury in AKI-HRS and could be of value in the clinical decision between combined liver-kidney or liver transplantation alone in patients with cirrhosis and AKI candidates to transplantation.

BACKGROUND AND AIMS Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort. METHODS The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n = 1222) or high-risk drinkers (n = 275) (>21 units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n = 263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE). RESULTS Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS ≥ 8 kPa and 3.9 and 9.2 kPa for LS ≥ 9.1 kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers. CONCLUSION MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.

Clinical course and risk factors of death in non-SBP infections are poorly known. We assessed the prevalence of AKI and type-1 HRS, hospital, 30-d and 90-d mortality and risk factors of death in 441 decompensated patients. Methods: Analysis of 615 non-SBP infections (161 urinary infections, 95 cellulitis, 92 suspected infections, 92 bacteremias, 84 pneumonias, 21 bronchitis, 18 cholangitis, 15 spontaneous empyema, 13 secondary peritonitis, 24 other). Results: 96% of infections solved. AKI and type-1 HRS developed in 37% and 9% of infections, respectively. Overall hospital, 30-d and 90-d mortality rates were 11%, 12% and 18%, respectively. Clinical course and mortality differed markedly across infections. Endocarditis, osteoarticular infections, pneumonia, spontaneous bacteremia, cholangitis, secondary peritonitis and UTI showed higher rates of AKI. Prevalence of type-1 HRS was not significantly different among infections. Endocarditis, secondary peritonitis, pneumonia and bacteremia showed lower rates of renal impairment resolution and higher hospital mortality associated to AKI (42% vs. 12%, p

Ascites is the most frequent complication of patients with cirrhosis. Ascites is related to increased renal sodium retention as a result of increased activity of the renin-angiotensin-aldosterone system in response to marked vasodilation of the splanchnic circulation. Management of uncomplicated ascites is based on a low-sodium diet and diuretics. However, approximately 10% of patients develop refractory ascites during follow-up, which is associated with a poor prognosis. The treatment of choice in patients with refractory ascites is large-volume paracentesis associated with intravenous albumin. Moreover, patients who develop refractory ascites should be considered as candidates for liver transplantation. Patients with ascites are all at risk of developing spontaneous bacterial peritonitis (SBP). SBP is a common infection in patients with cirrhosis with a risk of mortality of 20%. Empirical antibiotics are the treatment of choice in patients with SBP but differ depending on the acquisition site of infection, because nosocomial infections have a higher risk of being caused by multiresistant bacteria. In addition to antibiotic treatment, all patients with SBP should also receive intravenous albumin. This review summarizes the management of uninfected ascites and SBP in cirrhosis.

Summary Background We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding. Aim To characterise phenotype presentation, outcome and severity of AAS DILI. Methods Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin-American (5) DILI Registries were collated and compared with previously published cases. Results AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001–2009 to 8% in 2010–2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS-induced acute kidney impairment (AKI) [OR 1.26 (95% CI: 1.035–1.526); P = 0.021], with 21.5 ×ULN being the best bilirubin cut-off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred. Conclusions Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.

Hyponatraemia is common in patients with advanced cirrhosis and is associated with remarkable changes in brain cells, particularly a reduction in myoinositol and other intracellular organic osmolytes related to the hypo-osmolality of the extracellular fluid. It has been recently suggested that hyponatraemia may be an important factor associated with the development of overt hepatic encephalopathy (HE). To test this hypothesis, we retrospectively analysed the incidence and predictive factors of overt HE using a database of 70 patients with cirrhosis included in a prospective study comparing transjugular intrahepatic portosystemic shunts (TIPS) vs large-volume paracentesis in the management of refractory of ascites. Variables used in the analysis included age, sex, previous history of HE, treatment assignment (TIPS vs large volume paracentesis plus albumin), treatment with diuretics, serum bilirubin, serum creatinine and serum sodium concentration. Laboratory parameters were measured at entry, at 1 month and every 3 months during follow-up and at the time of development of HE in patients who developed this complication. During a mean follow-up of 10 months, 50 patients (71%) developed 117 episodes of HE. In the whole population of patients, the occurrence of HE was independently associated with serum hyponatraemia, serum bilirubin and serum creatinine. In conclusion, in patients with refractory ascites, the occurrence of HE is related to the impairment of liver and renal function and presence of hyponatraemia.

Background Activated hepatic stellate cells (HSC) and other fibrogenic cell types are frequently found around hepatocellular carcinoma. It is unknown whether hepatocarcinoma cells regulate the biological functions of HSC. Aims This study aimed to investigate the paracrine effects of hepatocarcinoma cells on human HSC using a co-culture system. Methods Huh7 or HepG2 cells, human hepatocarcinoma cell lines, were co-cultured with primary human HSC. Intracellular calcium mobilization, proliferation, migration, expression of pro-angiogenic and fibrogenic genes, smooth muscle alpha-actin (alpha-SMA) protein expression, inflammatory properties (nuclear factor kappa B activation and interleukin 8 secretion) and intracellular signalling pathways (AKT and ERK) were analysed in HSC. Results Culture of HSC with Huh7 cells for 24 h stimulated HSC proliferation, migration and expression of pro-angiogenic genes. The migration effect was corroborated with HepG2 cells. The effects of Huh7 cells on cell proliferation and migration were mediated mainly by PI3K/AKT activation. Moreover, Huh7 cells reduced the expression of genes involved in fibrogenesis, while they did not modify the inflammatory properties of HSC. The expression of alpha-SMA was induced by Huh7 cells. Because hepatitis C virus (HCV) infection is a major cause of hepatocarcinoma, we next investigated whether these effects are regulated by the expression of HCV in hepatocarcinoma cells. Expression of a subgenomic replicon expressing HCV nonstructural proteins (NS3-NS5) in Huh7 cells did not affect paracrine actions in HSC (cell proliferation and migration). Conclusions These results suggested that there is a cross-talk between hepatocarcinoma cells and HSC. Activated HSC may be stimulated by cancer cells to accumulate and express angiogenic genes.

SUMMARY Hepatorenal syndrome (HRS) is a common complication of advanced cirrhosis characterized not only by renal failure but also by marked alterations in systemic haemodynamics and activity of endogenous vasoactive systems. Renal failure is due to a severe vasoconstriction of the renal circulation. The pathogenesis of HRS is not completely understood but it is probably the result of extreme underfilling of the arterial circulation secondary to arterial vasodilation located in the splanchnic circulation. As well as the renal circulation, all other extrasplanchnic vascular beds appear to be vasoconstricted. The diagnosis of HRS is currently based on the exclusion of nonfunctional causes of renal failure; prognosis of patients with HRS is very poor. Liver transplantation is the best option in selected patients, but it is not always applicable as survival expectancy is short. Vasoconstrictor drugs with preferential effect on the splanchnic circulation (vasopressin analogues with a predominant V1 receptor effect, such as terlipressin ‐ Glypressin) are very effective in improving renal function, with reversal of HRS being achieved in approximately two-thirds of patients. There is no agreement as to the terlipressin treatment regimen that is associated with a greater efficacy and lower incidence of side-effects. It appears that the administration of albumin together with terlipressin improves the therapeutic response rate. The impact of treatment on the natural course of HRS remains to be assessed in prospective investigations, but it seems that the reversal of HRS is associated with improved survival. Finally, treatment of patients with HRS with terlipressin before transplantation seems to improve post-transplantation outcome.

Renal function abnormalities and ascites in cirrhosis are the final consequence of a circulatory dysfunction characterized by marked splanchnic arterial vasodilation. This causes a reduction in effective arterial blood volume and the homoeostatic activation of vasoconstrictor and sodium-retaining systems. Albumin is very effective in preventing renal failure associated with large-volume paracentesis and spontaneous bacterial peritonitis, conditions that are known to cause an impairment of circulatory function in patients with cirrhosis and ascites. Moreover, albumin administration improves survival in patients with spontaneous bacterial peritonitis. In patients with hepatorenal syndrome the administration of vasoconstrictor drugs in combination with albumin improves circulatory and renal function markedly and survival slightly. By contrast, the administration of albumin without vasoconstrictors has marginal or no effects on renal function in this setting.

Ascites is one of the earliest and most common complications of patients with cirrhosis. A typical circulatory dysfunction characterized by arterial vasodilation, high cardiac output and stimulation of vasoactive systems is commonly present in these patients and is associated with a poor prognosis. The treatment of ascites has been based on the combination of a low-sodium diet and the administration of diuretics. The reintroduction of paracentesis and the recent introduction of the transjugular intrahepatic portosystemic shunt (TIPS) are the most relevant innovations in the treatment of ascites during the past two decades, although controlled trials in large series of patients are needed to delineate whether TIPS is a safe and useful treatment for these patients.