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.

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.

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.

Clinical Significance of Serum Adiponectin and Resistin Levels in Liver Cirrhosis.

INTRODUCTION: Adiponectin and resistin levels are increased in patients with cirrhosis, but it prognostic significance is unknown. We sought to investigate the factors associated with adiponectin and resistin levels and its clinical significance in patients with cirrhosis. MATERIALS AND METHODS: This was a prospective cohort study that included 122 subjects with cirrhosis who attended an outpatient clinic and were initially evaluated in 2012. Serum adiponectin and resistin levels were measured in samples collected in 2012 (adiponectin and resistin) and 2014 (adiponectin). Thirty healthy subjects served as a control group. RESULTS: Higher adiponectin (21.59 µ g/mL vs. 12.52 µg/mL, P < 0.001) and resistin levels (3.83 ng/mL vs. 2.66 ng/mL, P < 0.001) were observed among patients with cirrhosis compared to controls. Patients classified as Child-Pugh B/C had higher adiponectin levels in relation to Child-Pugh A patients. At second measurement, adiponectin levels increased significantly in non-transplant patients and decreased in liver transplant recipients. Univariate Cox analysis showed that among patients with alcoholic liver disease, adiponectin levels were associated with lower transplant-free survival (HR = 1.034, 95% CI 1.006 - 1.062, P = 0.016). The transplant-free survival was significantly lower among patients with alcoholic liver disease and adiponectin ≥ 17 µg/mL (26.55 months, 95% CI 21.40-31.70) as compared to those with levels < 17 µg/mL (33.76 months, 95% CI 30.70-36.82) (P = 0.045). No relationship was found between the levels of resistin and survival. CONCLUSION: Adiponectin but not resistin levels were associated with intensity of liver dysfunction and worse prognosis in patients with alcoholic liver disease, suggesting a potential as a prognostic biomarker.

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.

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.

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.

Cholestasis as the initial presentation of relapsing polychondritis.

Relapsing polychondritis is an immune-mediated disease associated with inflammation in cartilaginous structures and other tissues throughout the body, particularly the ears, nose, eyes, joints, and respiratory tract. Although association with other conditions is seen in about one-third of the cases, liver involvement is not usually observed in those patients. We described a case of liver involvement in relapsing polychondritis, 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. We discuss the spectrum of the liver involvement in relapsing and review the literature.

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.

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.

Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C.

BACKGROUND: Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV-DNA detection. AIMS: We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection. METHODS: This cross-sectional study included hepatitis B surface antigen- and human immunodeficiency virus-negative subjects with positive HCV-RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV-DNA using a commercial assay. The METAVIR system was used for histological analysis. RESULTS: One-hundred and eleven patients were evaluated. Thirty-one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti-HBc). HBV-DNA was not detected in any sample. Anti-HBc-positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti-HBc-positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532; P=0.032] and significant hepatic fibrosis (OR=3.364; P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti-HBc-negative subjects who acquired HCV before the age of 30 and in 57% of those anti-HBc-positive patients who were infected by HCV after 30 years of age (P<0.001). CONCLUSION: Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.

Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co-infection.

AIM: To assess the diagnostic value of modified cutoffs for aspartate aminotransferase to platelet ratio index (APRI) to predict significant liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) patients. PATIENTS AND METHODS: This retrospective cross-sectional study included consecutive patients with HIV/HCV co-infection who underwent percutaneous liver biopsy. The accuracy of APRI for the diagnosis of significant fibrosis (F2/F3/F4 METAVIR) was evaluated by estimating the positive and negative predictive values (PPV and NPV respectively) and by measuring the area under the receiver operating characteristics curve (AUROC). RESULTS: One hundred and eleven patients were included (73% men, mean age 40.2+/-7.8 years). Significant fibrosis was observed in 45 patients (41%). To discriminate these subjects, the AUROC of APRI was 0.774+/-0.045. An APRI > or = 1.8 showed a PPV of 75% for the presence of significant fibrosis, and an index < 0.6 excluded significant fibrosis with an NPV of 87%. If biopsy indication was based only on APRI and restricted to scores in the intermediate range (> or = 0.6 and < 1.8), 46% of liver biopsies could have been avoided as compared with 40% using the classical cutoffs. CONCLUSION: APRI with adjusted cutoffs can predict significant liver fibrosis in patients with HIV/HCV co-infection and might obviate the need to perform a biopsy in a considerable percentage of those subjects.

Breast reconstruction after mastectomy for breast cancer: comparative analysis of early and delayed reconstruction.

BACKGROUND: Early reconstruction after mastectomy for breast cancer with definitive implants has been widely used, especially with the evolution of conservative surgical breast cancer treatments. We aimed to identify different characteristics associated with plastic surgery, based on immediate or delayed reconstruction time and evaluate quality of life in patients undergoing mastectomy for cancer. METHODS: This is a cross-sectional analytical study that evaluated adult patients undergoing mastectomy for breast cancer and breast reconstruction in Plastic Surgery Service at a tertiary hospital. RESULTS: Between March 2011 and November 2015, 58 patients who underwent mastectomy were included, with a mean age of 51.6±10.6 years and 98.3% of them being women. Eighty percent of the patients underwent a radical mastectomy and 20% underwent segmentectomies. Immediate and delayed surgical reconstructions occurred in 22.4% and 77.6% of the cases, respectively, including immediate reconstruction with the local flap trade (15.5%), immediate reconstruction with prosthesis (6.9%), transverse rectus abdominis myocutaneous (TRAM) flap (6.9%), delayed reconstruction with local flap (8.6%), expander and prosthesis (35.7%), and reconstruction with latissimus dorsi flap and prosthesis (22.4%). When comparing subjects undergoing reconstructive surgery based on timing of reconstruction, it was observed that patients undergoing delayed breast reconstruction surgery presented a higher proportion of radical mastectomy (90.7% vs. 41.7%; P=0.001) and the need for two or more surgical interventions (64.1% vs. 20.0%; P=0.029). There was no difference in the quality of life according to reconstruction time. CONCLUSIONS: The characteristics associated with postmastectomy reconstruction timing are related to preoperative factors such as the procedure employed and the number of interventions performed and have no influence on complications or the quality of life.

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.

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.