Functional renal failure and haemorrhagic gastritis associated with endotoxaemia in cirrhosis

Forty-three patients with cirrhosis and ascites, 21 with normal renal function, 10 with a progressive functional renal failure (FRF), and 12 with a steady FRF, were investigated for the presence of endotoxaemia by the Limulus lysate test. Endotoxaemia was found in nine patients with FRF and in none of the 21 with normal renal function (P less than 0-01). A positive Limulus test was almost exclusively associated with a progressive FRF (eight of 10 patients) and all but one of them died. Renal function improved as endotoxaemia disappeared in the survivor. Endotoxaemia was also associated with haemorrhage due to acute erosions of the gastric mucosa, being present in six of the seven patients who had this complication. Intravascular coagulation was not found in any patient. The Limulus test was positive in the ascitic fluid in 18 of 21 patients tested, although only two of them had peritonitis. These results suggest that endotoxaemia may play a critical role in the development of progressive renal failure and haemorrhagic gastritis in cirrhosis, and emphasise the potential risk of procedures involving reinfusion of ascitic fluid.

Prognostic Importance of the Cuse of Renal Failure in Patients With Cirrhosis

BACKGROUND & AIMS: The prognostic value of the different causes of renal failure in cirrhosis is not well established. This study investigated the predictive value of the cause of renal failure in cirrhosis. METHODS: Five hundred sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine 1.5 mg/dL on 2 successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into 4 groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end point was survival at 3 months. RESULTS: Four hundred sixty-three patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to cause of renal failure, 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (P .0005). In a multivariate analysis adjusted for potentially confounding variables, cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at time of diagnosis of renal failure. CONCLUSIONS: A simple classification of patients with cirrhosis according to cause of renal failure is useful in assessment of prognosis and may help in decision making in liver transplantation.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS: In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS: Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS: Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Is magnetic resonance imaging of hepatic hemangioma any different in liver fibrosis and cirrhosis compared to normal liver?

PURPOSE: To compare qualitative and quantitative magnetic resonance (MR) imaging characteristics of hepatic hemangiomas in patients with normal, fibrotic and cirrhotic livers. MATERIALS AND METHODS: Retrospective, institutional review board approved study (waiver of informed consent). Eighty-nine consecutive patients with 231 hepatic hemangiomas who underwent liver MR imaging for lesion characterization were included. Lesions were classified into three groups according to the patients' liver condition: no underlying liver disease (group 1), fibrosis (group 2) and cirrhosis (group 3). Qualitative and quantitative characteristics (number, size, signal intensities on T1-, T2-, and DW MR images, T2 shine-through effect, enhancement patterns (classical, rapidly filling, delayed filling), and ADC values) were compared. RESULTS: There were 160 (69%), 45 (20%), and 26 (11%) hemangiomas in groups 1, 2 and 3, respectively. Lesions were larger in patients with normal liver (group 1 vs. groups 2 and 3; P=.009). No difference was found between the groups on T2-weighted images (fat-suppressed fast spin-echo (P=.82) and single-shot (P=.25)) and in enhancement patterns (P=.56). Mean ADC values of hemangiomas were similar between groups 1, 2 and 3 (2.11±.52×10(-3)mm(2)/s, 2.1±.53×10(-3)mm(2)/s and 2.14±.44×10(-3)mm(2)/s, P=87, respectively). T2 shine-through effect was less frequently observed in cirrhosis (P=.02). CONCLUSION: MR imaging characteristics of hepatic hemangioma were similar in patients with normal compared to fibrotic and cirrhotic livers. Smaller lesion size was observed with liver disease and less T2 shine-through effect was seen in hemangiomas developed on cirrhosis, the latter being an important finding to highlight in these patients at risk of developing hepatocellular carcinoma.

Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis.

with specific ANA, in particular of the IgG3 isotype, had significantly more severe biochemical and histological disease compared with those who were seronegative. None of the controls was positive.Conclusions: Disease specific ANA are present in the majority of patients with PBC when investigated at the level of immunoglobulin isotype. PBC specific ANA, in particular of the IgG3 isotype, are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.

Incidence, prevalence and clinical significance of abnormal hematological indices in compensated cirrhosis.

Background & Aims: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prog-nostic significance. Methods: We analyzed a database of 213 subjects with compensated cirrhosis without esopha-geal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglo-bin,<13.5 g/dL for men and 11.5 g/dL for women), leuko-penia (white blood cell counts,<4000/mm 3 ), or thrombo-cytopenia (platelet counts, < 150,000/mm 3 ). The primary end points were death or transplant surgery. Results: Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P .0191) and leukope-nia (P.0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years,a significant difference in death or transplant, mortality,and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at base- line compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r 0.35, P < .0001; white blood cell count, r 0.31, P < .0001). Conclusions: Thrombocy-topenia is the most common and first abnormal HI to occurin patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baselin predicted increased morbidity and mortality.

Management of varices and variceal hemorrhage in cirrhosis.

Variceal hemorrhage is a lethal complication of cirrhosis, particularly in patients in whom clinical decompensation (i.e., ascites, encephalopathy, a previous episode of hemorrhage, or jaundice) has already developed. Practice guidelines for the management of varices and variceal hemorrhage1 in cirrhosis are mostly based on evidence in the literature that has been summarized and prioritized at consensus conferences...

Non-invasive diagnostic and prognostic evaluation of liver cirrhosis and portal hypertension.

Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non-invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information.

Systematic review with meta-analysis: self-expanding metal stents in patients with cirrhosis and severe or refractory oesophageal variceal bleeding.

BACKGROUND: The prognosis of patients with cirrhosis and acute variceal bleeding is very poor when the standard-of-care fails to control bleeding. New treatment modalities are needed in these patients. AIM: To synthesise the available evidence on the efficacy of self-expanding metal stents (SEMS) in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. METHODS: Meta-analysis of trials evaluating SEMS in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. RESULTS: Thirteen studies were included. The pooled estimate rates were 0.40 (95% confidence interval, CI = 0.31-0.49) for death, 0.41 (95% CI = 0.29-0.53) for liver-related death and 0.36 (95% CI = 0.26-0.47) for death at day 30, with low heterogeneity between studies. The pooled estimate rates were 0.12 (95% CI = 0.07-0.21) for mortality related to variceal bleeding, and 0.18 (95% CI = 0.11-0.29) for failure to control bleeding with SEMS, with no or low heterogeneity between studies. The pooled estimate rate were 0.16 (95% CI = 0.04-0.48) for rebleeding after stent removal and 0.28 (95% CI = 0.17-0.43) for stent migration, with high heterogeneity. A significant proportion of patients had access to liver transplantation or to TIPSS [pooled estimate rate 0.10 (95% CI = 0.04-0.21) and 0.26 (95% CI = 0.18-0.36), respectively]. CONCLUSIONS: Fewer than 40% of patients treated with SEMS were dead at 1 month. SEMS can be used as a bridge to TIPSS or to liver transplantation in a significant proportion of patients. Additional studies are required to identify potential risk factors leading to a poor prognosis in patients with acute variceal bleeding in whom the use of SEMS could be considered.

A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis.

Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 (P = 1.03 × 10(-9)) and TM6SF2 (P = 7.89 × 10(-10)) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 × 10(-48)) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis.

Prognostic Importance of the Cuse of Renal Failure in Patients With Cirrhosis

BACKGROUND & AIMS: The prognostic value of the different causes of renal failure in cirrhosis is not well established. This study investigated the predictive value of the cause of renal failure in cirrhosis. METHODS: Five hundred sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine 1.5 mg/dL on 2 successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into 4 groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end point was survival at 3 months. RESULTS: Four hundred sixty-three patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to cause of renal failure, 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (P .0005). In a multivariate analysis adjusted for potentially confounding variables, cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at time of diagnosis of renal failure. CONCLUSIONS: A simple classification of patients with cirrhosis according to cause of renal failure is useful in assessment of prognosis and may help in decision making in liver transplantation.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS: In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS: Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS: Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.