Systemic Inflammatory Response Syndrome in Patients Hospitalized for Acute Decompensation of Cirrhosis.

Background: Although recently challenged, systemic inflammatory response syndrome (SIRS) criteria are still commonly used in daily practice to define sepsis. However, several factors in liver cirrhosis may negatively impact its prognostic ability. Goals. To investigate the factors associated with the presence of SIRS, the characteristics of SIRS related to infection, and its prognostic value among patients hospitalized for acute decompensation of cirrhosis. Study. In this cohort study from two tertiary hospitals, 543 patients were followed up, up to 90 days. Data collection, including the prognostic models, was within 48 hours of admission. Results: SIRS was present in 42.7% of the sample and was independently associated with upper gastrointestinal bleeding (UGB), ACLF, infection, and negatively related to beta-blockers. SIRS was associated with mortality in univariate analysis, but not in multiple Cox regression analysis. The Kaplan-Meier survival probability of patients without SIRS was 73.0% and for those with SIRS was 64.7%. The presence of SIRS was not significantly associated with mortality when considering patients with or without infection, separately. Infection in SIRS patients was independently associated with Child-Pugh C and inversely related to UGB. Among subjects with SIRS, mortality was independently related to the presence of infection, ACLF, and Child-Pugh C. Conclusions: SIRS was common in hospitalized patients with cirrhosis and was of no prognostic value, even in the presence of infection.

Serial assessment of hepatic encephalopathy in patients hospitalised for acute decompensation of cirrhosis.

INTRODUCTION AND AIM: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, but the clinical and prognostic significance of the progression of mental status in hospitalised cirrhotics is unknown. We aimed to investigate the prognostic significance of serial evaluation of HE in patients hospitalised for acute decompensation (AD) of cirrhosis. MATERIALS AND METHODS: Patients (n=293) were evaluated for HE (West-Haven criteria) at admission and at day-3 and classified in two groups: (1) Absent or improved HE: HE absent at admission and at day-3, or any improvement at day-3; (2) Unfavourable progression: Development of HE or HE present at admission and stable/worse at day-3. RESULTS: Unfavourable progression of HE was observed in 31% of patients and it was independently associated with previous HE, Child-Pugh C and acute-on-chronic liver failure (ACLF). MELD score and unfavourable progression of HE were independently associated with 90-day mortality. The 90-day Kaplan-Meier survival probability was 91% in patients with MELD<18 and absent or improved HE and only 31% in subjects with both MELD≥18 and unfavourable progression of HE. Unfavourable progression of HE was also related to lower survival in patients with or without ACLF. Worsening of GCS at day-3 was observed in 11% of the sample and was related with significantly high mortality (69% vs. 27%, P<0.001). CONCLUSION: Among cirrhotics hospitalised for AD, unfavourable progression of HE was associated with high short-term mortality and therefore can be used for prognostication and to individualise clinical care.

Applicability of Sepsis-3 criteria and quick Sequential Organ Failure Assessment in patients with cirrhosis hospitalised for bacterial infections.

BACKGROUND & AIMS: An algorithm including Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) was recently proposed to predict severity of infection in cirrhosis. However, its applicability among patients without a baseline SOFA available for Sepsis-3 definition is unknown. We sought to investigate the applicability and prognostic value of qSOFA and Sepsis-3 criteria in patients with cirrhosis hospitalised for bacterial infections, without pre-hospitalisation SOFA. METHODS: In this cohort study, 164 patients were followed up to 30 days. Data collection, including the prognostic models, was performed at admission and at day-3. RESULTS: All patients fulfilled Sepsis-3 criteria (admission SOFA ≥ 2) and, therefore, admission Sepsis-3 was not included in further analysis. Admission qSOFA was an independent predictor of survival (HR = 2.271, P = 0.015). For patients initially classified as high risk by qSOFA, Chronic Liver Failure - Sequential Organ Failure Assessment (CLIF-SOFA) was the only prognostic predictor. Among patients initially classified as low risk by qSOFA, the following parameters evaluated at day-3 were independent predictors of survival: qSOFA, acute-on-chronic liver failure, and Child-Pugh classification. Although not independently related to survival, Sepsis-3 criteria at day-3 was associated with lower 30-day survival in Kaplan-Meier analysis (66% vs 85%, P = 0.008). However, prognosis was better predicted by day-3 qSOFA, with 30-day Kaplan-Meier survival probability of 88% when qSOFA < 2 and 24% among those with qSOFA ≥ 2. CONCLUSION: Sepsis-3 criteria evaluated at admission are very limited in infected patients with cirrhosis without baseline SOFA. qSOFA was independently related to survival and appears to be a valuable tool for determining severity of infection and to follow patients initially classified as low risk.

Prognostic Significance of The New Criteria for Acute Kidney Injury in Cirrhosis.

BACKGROUND: New criteria for acute kidney injury (AKI) in cirrhosis have been proposed, but its prognostic significance is unclear. This study aims to evaluate the prognostic significance of the AKI criteria in cirrhotic patients hospitalized for acute decompensation. MATERIAL AND METHODS: This is a prospective cohort study. AKI was defined as an increase in creatinine (Cr) levels ≥ 0.3 mg/dL in 48 h or ≥ 50% of the basal value in the last 7d. AKI was divided into stages 1 (elevation: < 2x basal), 2 (2 or 3x), and 3 (> 3x). RESULTS: In this study, 227 patients aged 53.9 ± 11.5 years were included, of whom 37% had AKI (28% AKI1, 5% AKI2, and 4% AKI3). Thirty percent of the patients died or were transplanted within 90 days from causes related to the presence of ascites at hospital admission and higher values of Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) scores, but not to the presence of AKI. In a regression analysis conducted to assess the effect of the final Cr level in patients with AKI, 90-day mortality was associated with ascites, higher CLIF-SOFA score, and AKI with final Cr level ≥ 1.5 mg/dL. The patients with AKI with Cr levels ≥ 1.5 mg/dL showed lower transplant-free survival rates than those without AKI, and those with AKI1 with final Cr level < 1.5 mg/dL. CONCLUSIONS: Early AKI was frequent and associated with 90-day mortality or transplantation only when the final Cr level was ≥ 1.5 mg/dL. Distinct approaches are needed for patients with AKI1 according to final Cr.

Challenges in diagnosing and monitoring diabetes in patients with chronic liver diseases.

The prevalence and mortality of diabetes mellitus and liver disease have risen in recent years. The liver plays an important role in glucose homeostasis, and various chronic liver diseases have a negative effect on glucose metabolism with the consequent emergence of diabetes. Some aspects related to chronic liver disease can affect diagnostic tools and the monitoring of diabetes and other glucose metabolism disorders, and clinicians must be aware of these limitations in their daily practice. In cirrhotic patients, fasting glucose may be normal in up until 23% of diabetes cases, and glycated hemoglobin provides falsely low results, especially in advanced cirrhosis. Similarly, the performance of alternative glucose monitoring tests, such as fructosamine, glycated albumin and 1,5-anhydroglucitol, also appears to be suboptimal in chronic liver disease. This review will examine the association between changes in glucose metabolism and various liver diseases as well as the particularities associated with the diagnosis and monitoring of diabetes in liver disease patients. Alternatives to routinely recommended tests will be discussed.

Recurrent anaemia in a patient with lymphocytic gastritis and vitamin B12 deficiency.

Lymphocytic gastritis is an idiopathic disease, characterized by intraepithelial infiltration of large numbers of T lymphocytes and often described in association with coeliac disease and Helicobacter pylori infection. Although usually associated with iron deficiency anaemia, there is no description on the association between lymphocytic gastritis and secondary vitamin B12 deficiency anaemia. We describe a rare case of recurrent anaemia in a patient with lymphocytic gastritis reversed with vitamin B12 replacement.

Circulating levels of pentraxin-3 (PTX3) in patients with liver cirrhosis.

BACKGROUND: Despite the circulating levels of PTX3 were related to the severity of various diseases, there are no studies investigating its role in patients with liver cirrhosis. We aimed to study PTX3 levels in patients with liver cirrhosis. MATERIAL AND METHODS: A prospective cohort study included 130 patients hospitalized for acute decompensation of liver cirrhosis, 29 stable cirrhotic outpatients and 32 healthy controls evaluated in a tertiary hospital in Southern Brasil. RESULTS: The median PTX3 level was significantly higher in stable cirrhotic patients compared to controls (2.6 vs. 1.1 ng/mL; p < 0.001), hospitalized cirrhotic patients compared to controls (3.8 vs. 1.1 ng/mL; p < 0.001), and hospitalized cirrhotic patients compared to stable cirrhotic patients (3.8 vs. 2.6 ng/mL; p = 0.001). A positive correlation was found between PTX3 and serum creatinine (r = 0.220; p = 0.012), Chronic Liver Failure - Sequential Organ Failure Assessment score (CLIF-SOFA) (r = 0.220; p = 0.010), MELD (r = 0.279; p = 0.001) and Child-Pugh score (r = 0.224; p = 0.010). Significantly higher levels of PTX3 were observed in patients on admission with ACLF (8.9 vs. 3.1 ng/mL; p < 0.001) and MELD score ≥ 20 (6.6 vs. 3.4 ng/mL; p = 0.002). Death within 90 days occurred in 30.8% of patients and was associated with higher levels of PTX3 (5.3 vs. 3.4 ng/mL; p = 0.009). The probability of Kaplan-Meier survival was 77.0% in patients with PTX-3 < 5.3 ng mL (upper tercile) and 53.5% in those with PTX3 ≥ 5.3 ng/mL (p = 0.002). CONCLUSION: These results indicate the potential for use of PTX3 as an inflammatory biomarker for the prognosis of patients with hepatic cirrhosis.

Liver dysfunction and fibrosis as predictors of biochemical response to autoimmune hepatitis treatment.

BACKGROUND: Autoimmune hepatitis (AIH) is a disease that presents itself in various forms, ranging from aminotransferase asymptomatic alteration, acute hepatitis to decompensated cirrhosis. Few studies have evaluated the predictive criteria as a response to treatment. METHODS: A cross-sectional analytical study examined patients with AIH who were visited in the hepatology clinic of a university hospital between January 2013 and July 2015. RESULTS: A total of 36 patients were included (44.7 ± 14.3 years, 22.2% male, and 19.2% of patients presented with liver failure). Patients with significant fibrosis had lower mean aminotransferases and bilirubins and higher mean prothrombin activity (PA) than those with insignificant fibrosis. Most patients (94.5%) underwent treatment with azathioprine and prednisone. In a comparison between individuals who exhibited biochemical response (ALT and AST < 55 U/L in the sixth month of treatment) and those without biochemical response, it was observed that those with biochemical response presented minor proportion of patients with significant fibrosis, and these patients had a higher proportion of liver failure in initial presentation and lower mean PA. Furthermore, it was observed that the lower the PT on admission was, the lower ALT levels (r = 0.682, P = 0.020) and AST (r = 0.431, P = 0.040) in the sixth month of treatment were. CONCLUSIONS: Individuals with liver dysfunction and elevated aminotransferases show insignificant fibrosis histologically. AIH patients who initially present liver failure and insignificant fibrosis are more likely to develop biochemical response to treatment.

Factors associated with steatosis in liver biopsies of individuals with chronic hepatitis C infection in southern Brazil.

BACKGROUND AND STUDY AIMS: Infection by the hepatitis C virus (HCV) is associated with various metabolic disorders that are collectively referred to as dysmetabolic syndrome associated with HCV. Hepatic steatosis is a common finding in chronic HCV infection and has been reported in 30-70% of patients. Here, we determine the prevalence of steatosis in patients with HCV, identify the characteristics associated with the presence of steatosis in liver biopsies and assess the association between steatosis and the severity of liver disease. PATIENTS AND METHODS: This analytic cross-sectional study evaluated HCV carriers (adults) at the Gastroenterology and Hepatology Outpatient Clinic of a public university hospital between July 2013 and June 2014 using retrospective data collection. The patients were divided into two groups according to the presence or absence of steatosis in their liver biopsies. The groups were compared for the presence of risk factors for steatosis and clinical, laboratory, virological and histological characteristics. RESULTS: One hundred and four patients aged 49.5±9.3 years were included in the study; 56.0% of the patients were men. Steatosis was observed in 65.4% of the liver biopsies. When comparing individuals with and without steatosis, patients with steatosis exhibited a higher proportion of non-1 genotype (43.9 vs. 20.7%; p=0.034), higher median triglyceride levels (101.0 vs. 75.0; p=0.034), ferritin levels (333.0 vs. 193.5; p=0.025) and gamma glutamyl transferase levels (2.92 xULN vs. 1.87; p=0.030). Multivariate analysis demonstrated that triglyceride levels were independently associated with the presence of steatosis (OR=1.016; 95% CI 1.002-1.031; p=0.026). CONCLUSIONS: Hepatic steatosis was observed in 65.4% of individuals with HCV. We observed that elevated triglyceride levels were associated independently with the presence of hepatic steatosis; we did not demonstrate an association between hepatic steatosis and histological severity.

Significance of alanine aminotransferase levels in patients admitted for cocaine intoxication.

BACKGROUND: Experimental studies in animal models and case reports in humans have described the hepatotoxic potential of cocaine. However, there are few data regarding the clinical and laboratory characteristics of patients admitted for cocaine intoxication, particularly regarding the status of the liver enzymes. GOAL: To investigate the significance of alanine aminotransferase (ALT) levels in individuals hospitalized for acute cocaine intoxication. METHODS: Retrospective study with standardized chart review that included patients admitted between January 2003 and December 2010. Bivariate analyses were used to investigate factors associated with ALT above the upper tertile according to gender. Cases of marked ALT elevation were described in detail. RESULTS: Ninety-three patients were included (79% men, mean age of 27.73±9.97 y). ALT above the upper tertile was associated with higher aspartate aminotransferase (AST), creatine phosphokinase, creatinine, and international normalized ratio. Higher levels of ALT were also related to acute renal failure and death. Five subjects had severe ALT elevation during follow-up and all had evidence of hepatocellular dysfunction (jaundice, prolonged prothrombin time with or without hepatic encephalopathy), rhabdomyolysis, and acute renal failure. AST/ALT ratio <2 was present in 2 subjects with severe ALT elevation at admission, but AST/ALT ratio >2 was observed in 3 cases with evidence of progression to acute liver injury. CONCLUSIONS: In acute cocaine intoxication, higher ALT levels were associated with evidence of muscle damage, progression to acute renal failure, and death. Severe liver damage was observed in 5% of the sample and was associated with rhabdomyolysis and renal failure in all cases.

Single-centre validation of the EASL-CLIF consortium definition of acute-on-chronic liver failure and CLIF-SOFA for prediction of mortality in cirrhosis.

BACKGROUND & AIMS: The idea of acute-on-chronic liver failure (ACLF) has emerged to identify those subjects with organ failure and high mortality rates. However, the absence of a precise definition has limited the clinical application and research related to the ACLF concept. We sought to validate the ACLF definition and the CLIF-SOFA Score recently proposed by the EASL-CLIF Consortium in a cohort of patients admitted for acute decompensation (AD) of cirrhosis. METHODS: In this prospective cohort study, patients were followed during their hospital stay and thirty and 90-day mortality was evaluated by phone call, in case of hospital discharge. All subjects underwent laboratory evaluation at admission. RESULTS: Between December 2010 and November 2013, 192 cirrhotic patients were included. At enrollment, 46 patients (24%) met the criteria for ACLF (Grades 1, 2 and 3 in 18%, 4% and 2% respectively). The 30-day mortality was 65% in ACLF group and 12% in the remaining subjects (P < 0.001). Logistic regression analysis showed that 30-day mortality was independently associated with ascites and ACLF at admission. The Kaplan-Meier survival probability at 90-day was 92% in patients without ascites or ACLF and only 22% for patients with both ascites and ACLF. The AUROC of CLIF-SOFA in predicting 30-day mortality was 0.847 ± 0.034, with sensitivity of 64%, specificity of 90% and positive likelihood ratio of 6.61 for values ≥9. CONCLUSION: In our single-centre experience the CLIF-SOFA and the EASL-CLIF Consortium definition of ACLF proved to be strong predictors of short-term mortality in cirrhotic patients admitted for AD.

Central nervous system vasculitis and polyneuropathy as first manifestations of hepatitis C.

Sensory or motor peripheral neuropathy may be observed in a significant proportion of hepatitis C virus (HCV)-infected patients. However, central nervous system (CNS) involvement is uncommon, especially in cryoglobulin-negative subjects. We describe a case of peripheral neuropathy combined with an ischemic CNS event as primary manifestations of chronic HCV infection without cryoglobulinemia. Significant improvement was observed after antiviral therapy. We discuss the spectrum of neurological manifestations of HCV infection and review the literature.

Late-onset systemic lupus erythematosus-associated liver disease.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease, which predominantly affects women under 50 years old. Although liver disease is not included in the diagnostic criteria, abnormal liver tests are common among patients with SLE and, in a significant proportion of those patients, no other underlying condition can be identified. We described a case of liver involvement in late-onset SLE presenting with a predominantly cholestatic pattern. Other conditions associated with abnormal liver tests were excluded, and the patient showed a prompt response to steroid therapy. The spectrum of the liver involvement in SLE is discussed, with emphasis on the differential diagnosis with autoimmune hepatitis.

Evidence of a significant role for Fas-mediated apoptosis in HCV clearance during pegylated interferon plus ribavirin combination therapy.

BACKGROUND: The role of apoptosis in treatment-induced HCV clearance is controversial. We sought to assess the kinetics of serum apoptosis-related cytokines during pegylated interferon-α2a or -α2b plus weight-based ribavirin therapy for genotype 1 chronic HCV infection. METHODS: Serum levels of soluble Fas (sFas), soluble Fas ligand (sFasL) and soluble tumour necrosis factor receptor I (sTNF-RI) were measured at baseline, week 12 and 24 weeks after the end of therapy. RESULTS: Sustained virological response (SVR) was achieved in 46% of the 164 included patients, 29% had a non-response (NR) and 25% had relapse (RR). NR patients presented with higher levels of sFasL at baseline and lower levels of sTNF-RI at week 12 as compared to RR and SVR patients. Lower concentrations of sFas were observed in SVR patients 24 weeks after treatment as compared to RR and NR patients. An increase in sFas at week 12 followed by a significant drop 24 weeks after therapy was observed among SVR patients. An increase in sFasL during and after treatment was observed in RR and SVR patients. NR patients exhibited an earlier drop in sTNF-RI levels as compared to RR and SVR patients. CONCLUSIONS: Virological response during HCV therapy was associated with an increase of sFas and sFasL, and maintenance of increased concentrations of sTNF-RI.

YKL-40 and hyaluronic acid (HA) as noninvasive markers of liver fibrosis in kidney transplant patients with HCV chronic infection.

OBJECTIVE: Hepatitis C is highly prevalent among kidney transplant (KT) recipients. In this population, the natural history of hepatitis C virus (HCV) infection and its proper management remains controversial. The invasiveness of the procedure and the interpretation variability of liver biopsy limit its use in these patients. We sought to evaluate the performance of YKL-40 and HA as markers of liver fibrosis in KT patients with HCV infection. MATERIAL AND METHODS: This cross-sectional study included HCV infected KT individuals. Univariate analysis was used to identify variables associated with significant fibrosis (METAVIR >or= F2). The diagnostic values of the YKL-40 and HA were compared using receiver operating characteristic (ROC) curves. RESULTS: Eighty-five patients were included (60% males, mean age 44.9 +/- 9.4 years). Significant fibrosis was observed in 14 patients (17%). When compared to F0/F1 individuals, patients with significant fibrosis were older, showed a higher time since transplantation, and higher prevalence of diabetes. No difference was observed in YKL-40 levels between the groups. Significantly higher levels of HA were noted in METAVIR >or= F2 subjects (108 vs. 37 ng/ml, p = 0.002). The AUROCs of YKL-40 and HA for predicting significant fibrosis were 0.615 and 0.765, respectively (p = 0.144). Levels of YKL-40 or= 418 ng/ml and HA >or= 120 ng/ml exhibited a PPV of 31% and 39%, respectively. CONCLUSIONS: Increased serum levels of HA but not of YKL-40 were associated with more advanced stages of liver fibrosis in KT HCV-infected patients.

Subcutaneous Emphysema, Pneumothorax and Pneumomediastinum Following Endoscopic Sphincterotomy.

Retroperitoneal perforation during therapeutic endoscopic retrograde cholangiopancreatography (ERCP) is uncommon and is usually manifested by abdominal pain, fever and leukocytosis. We report the case of a patient with post-ERCP subcutaneous emphysema, pneumomediastinum and pneumothorax treated conservatively. A 79-year-old woman with a diagnosis of choledocholitiasis was referred to our institution for an elective outpatient therapeutic ERCP. At the end of the procedure, subcutaneous emphysema was observed, and a thoracic computed tomography revealed a right pneumothorax and pneumomediastinum. Supportive care was instituted and she was discharged asymptomatic after 10 days of hospitalization. Subcutaneous emphysema, pneumothorax and pneumomediastinum are potencial complications of ERCP and sphincterotomy. We review the other cases previously reported and discuss the management.