Determinants of clinical response to empirical antibiotic treatment in patients with cirrhosis and bacterial and fungal infections-Results from the ICA "Global Study" (EABCIR-Global Study).

BACKGROUND: The administration of an appropriate empirical antibiotic treatment is essential in cirrhosis and severe bacterial infections. We aimed to investigate the predictors of clinical response of empirical antibiotic treatment in a prospective cohort of patients with cirrhosis and bacterial and fungal infections included in the International Club of Ascites "Global Study." METHODS: Patients hospitalized with cirrhosis and bacterial/fungal infection were prospectively enrolled at 46 centers. Clinical response to antibiotic treatment was defined according to changes in markers of infection/inflammation, vital signs, improvement of organ failure, and results of cultures. RESULTS: From October 2015 to September 2016, 1302 patients were included at 46 centers. A clinical response was achieved in only 61% of cases. Independent predictors of lack of clinical response to empirical treatment were C-reactive protein (OR = 1.16; 95% CI = 1.02-1.31), blood leukocyte count (OR = 1.39;95% CI = 1.09-1.77), serum albumin (OR = 0.70; 95% CI = 0.55-0.88), nosocomial infections (OR = 1.96; 95% CI = 1.20-2.38), pneumonia (OR = 1.75; 95% CI = 1.22-2.53), and ineffective treatment according to antibiotic susceptibility test (OR = 5.32; 95% CI = 3.47-8.57). Patients with a lack of clinical response to first-line antibiotic treatment had a significantly lower resolution rate of infections (55% vs. 96%; p < 0.001), a higher incidence of second infections (29% vs. 15%; p < 0.001), shock (35% vs. 7%; p < 0.001) and new organ failures (52% vs. 19 %; p < 0.001) than responders. Clinical response to empirical treatment was an independent predictor of 28-day survival ( subdistribution = 0.20; 95% CI = 0.14-0.27). CONCLUSIONS: Four out of 10 patients with cirrhosis do not respond to the first-line antibiotic therapy, leading to lower resolution of infections and higher mortality. Broader-spectrum antibiotics and strategies targeting systemic inflammation may improve prognosis in patients with a high degree of inflammation, low serum albumin levels, and severe liver impairment.

Development and external validation of a model to predict multidrug-resistant bacterial infections in patients with cirrhosis.

With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. METHODS: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture-positive and culture-negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism-adjusted model using calibration and discrimination statistics and evaluated its clinical utility. RESULTS: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD-Na, use of vasopressors, acute-on-chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI .48-1.05), and the area under the ROC curve was .68 (95% CI .61-.73). The application of the model significantly changed the post-test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community-acquired infections at significant risk (36%). CONCLUSION: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies.

Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure.

BACKGROUND & AIMS: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital. METHODS: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death. RESULTS: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p <0.001). Spontaneous bacterial peritonitis, pneumonia or infections caused by extensively drug resistant (XDR) bacteria were more frequently associated with ACLF development. More patients with ACLF had a positive quick sequential organ failure assessment score and septic shock, resulting in a lower infection resolution rate (all p <0.001). CONCLUSIONS: Bacterial infections, especially with XDR organisms, are associated with the highest risk of ACLF development, accounting for almost half of cases globally. Geographic differences result in variable epidemiology and clinical outcomes. LAY SUMMARY: Bacterial infections can trigger a sudden deterioration in an otherwise stable cirrhotic patient, a condition known as acute-on-chronic liver failure or ACLF. This study has found that the development of ACLF following bacterial infection occurs most commonly in the Indian subcontinent and less so in Southern Europe. The common infections that can trigger ACLF include infection of the abdominal fluid, known as spontaneous bacterial peritonitis, pneumonia and by bacteria that are resistant to multiple antibiotics. Patients who develop ACLF following a bacterial infection have high death rates and are frequently unable to clear the infection.

Epidemiology and Effects of Bacterial Infections in Patients With Cirrhosis Worldwide.

BACKGROUND & AIMS: Bacterial infections are common and life-threatening in patients with cirrhosis. Little is known about the epidemiology of bacterial infections in different regions. We performed a multicenter prospective intercontinental study to assess the prevalence and outcomes of bacterial and fungal infections in patients with cirrhosis. METHODS: We collected data from 1302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and 5 in North America) from October 2015 through September 2016. We obtained demographic, clinical, microbiology, and treatment data at time of diagnosis of infection and during hospitalization. Patients were followed until death, liver transplantation, or discharge. RESULTS: The global prevalence of multidrug-resistant (MDR) bacteria was 34% (95% confidence interval 31%-37%). The prevalence of MDR bacteria differed significantly among geographic areas, with the greatest prevalence in Asia. Independent risk factors for infection with MDR bacteria were infection in Asia (particularly in India), use of antibiotics in the 3 months before hospitalization, prior health care exposure, and site of infection. Infections caused by MDR bacteria were associated with a lower rate of resolution of infection, a higher incidence of shock and new organ failures, and higher in-hospital mortality than those caused by non-MDR bacteria. Administration of adequate empirical antibiotic treatment was independently associated with improved in-hospital and 28-day survival. CONCLUSIONS: In a worldwide study of hospitalized patients, we found a high prevalence of infection with MDR bacteria in patients with cirrhosis. Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different continents and countries. While we await new antibiotics, effort should be made to decrease the spread of MDR bacteria in patients with cirrhosis.

Investigation of autonomic function and orocecal transit time in patients with nonalcoholic cirrhosis and the potential influence of these factors on disease outcome.

BACKGROUND: The presence of autonomic dysfunction in nonalcoholic cirrhosis and its influence on intestinal transit and disease outcome still need clarification. GOALS: To investigate the function of the autonomic nervous system in patients with nonalcoholic cirrhosis and the possible associations among autonomic dysfunction, severity of liver disease, disturbed intestinal transit, and the development of complications during follow-up. STUDY: Measurements of heart rate variability obtained by analysis of 24-hour ambulatory electrocardiographic recordings to assess autonomic function and lactulose breath hydrogen test to determine orocecal transit time were performed in 32 patients with nonalcoholic cirrhosis divided into Child A and B. RESULTS: Child B patients showed significantly lower values (P<0.05) of those parameters reflecting parasympathetic (high frequency, log-transformed high frequency, pNN50) and sympathetic function (low frequency, log-transformed low frequency) in comparison with controls and Child A patients. Orocecal transit time values were significantly (P=0.02) higher in Child B patients than in controls, but no relationship was found between delayed orocecal transit time and autonomic dysfunction. During follow-up, 42% of Child B patients developed encephalopathy. This complication was significantly associated with autonomic dysfunction. In addition, in the 4 patients who died the parameters reflecting parasympathetic function were significantly reduced in comparison with those of survivors. CONCLUSIONS: Autonomic dysfunction and delayed intestinal transit are related to the severity of disease in nonalcoholic cirrhosis. Autonomic dysfunction seems to predispose cirrhotic patients to the development of encephalopathy and may be associated with a poor prognosis of these patients.

Serum sodium, model for end-stage liver disease, and a recent invasive procedure are risk factors for severe acute-on-chronic liver failure and death in cirrhotic patients hospitalized with bacterial infection.

INTRODUCTION: Bacterial infection is present in up to 30% of hospitalized cirrhotic patients. It can lead, even after its resolution, to organ dysfunction and even acute-on-chronic liver failure (ACLF). It is the precipitating factor of ACLF in one third of the cases and is the main cause of mortality in patients with liver cirrhosis. OBJECTIVES: The aim of this study was to evaluate the prevalence and identify early risk factors for severe ACLF and death in hospitalized patients with liver cirrhosis with bacterial infection. PATIENTS AND METHODS: This was a prospective observational study. Hospitalized patients with liver cirrhosis and bacterial infection were included. Clinical and laboratory data and their evolution to organ dysfunction and death were assessed. A statistical analysis were carried out to identify predictors of severe ACLF and in-hospital mortality. RESULTS: This study included 88 patients. ACLF was observed in 62 (70%) patients, with 48 (55%) grade 2 or higher. Of the 27 deaths (31% of all patients), 26 had severe ACLF (54% mortality) (P<0.0001). The independent risk factors for ACLF of at least 2 and death were baseline serum sodium [odds ratio (OR): 0.874; P=0.01, and OR: 0.9, P=0.04], initial MELD (OR: 1.255, P=0.0001, and OR: 1.162, P=0.005), and a recent invasive procedure (OR: 3.169, P=0.01, and OR: 6.648, P=0.003). CONCLUSION: Lower serum sodium values, higher MELD scores at diagnosis of infection, and a recent history of invasive procedures were independent risk factors for severe ACLF and death in patients with cirrhosis and bacterial infection.

Decrease of type IV collagen and TIMP-1 serum levels after splenectomy in patients with schistosomiasis mansoni.

The role of the spleen in the process of liver fibrosis in schistosomiasis still needs clarification. The aim of this study was to assess the effect of splenectomy on serum levels of two markers of fibrosis, type IV collagen and TIMP-1, in patients with schistosomiasis mansoni. Twenty-four patients with hepatosplenic schistosomiasis mansoni participated in the study. Type IV collagen and TIMP-1 serum levels were measured preoperatively, and after 2 (POD-1) and 60 days (POD-2) of spleen removal. Before splenectomy, both type IV collagen and TIMP-1 serum levels were elevated in the majority of patients. After splenectomy, the levels of type IV collagen showed a significant decrease in relation to the preoperative values both in POD-1 (median pre-splenectomy: 143.7 ng/ml versus 77.01 ng/ml; p=0.04) and POD-2 (103.3 ng/ml; p=0.015). Serum levels of TIMP-1 also showed a significant decrease in relation to the preoperative values both in POD-1 (pre-splenectomy: 585.9 ng/ml versus 196.4 ng/ml; p=0.008) and POD-2 (97.4 ng/ml; p<0.001). There was no difference between POD-1 and POD-2 values for each serum marker. In conclusion, splenectomy in schistosomotic patients was associated with a decrease in serum markers of fibrosis levels, which persisted for at least 60 days. These results suggest that the spleen may play a role in the extra cellular matrix production, and therefore may contribute to liver fibrosis in schistosomiasis mansoni.

Grading and staging chronic hepatitis C and its relation to genotypes and epidemiological factors in Brazilian blood donors.

Progression of chronic hepatitis C is known to be associated with some factors, but influence of HCV genotypes is still controversial. Association between HCV genotypes and other risk factors was examined to determine which factors are associated with progression of infection. One hundred consecutive anti-HCV positive volunteer blood donors were evaluated for several risk factors, examined for HCV genotypes, and submitted to hepatic biopsy and biochemical exams.HCV genotyping were carried out in 89 patients and hepatic biopsy in 78. Transmission routes were found to be illicit intravenous drug use (26%), Gluconergan use in a non-safe manner (48%) and blood transfusion (15%). HCV genotype was 1 in 45%, 3 in 40%, and it was not associated with the stage of fibrosis or with inflammatory activity. There was no significant association of factors related to infection, chronic alcohol use, or duration of illness, with progression of the lesion. There was a significant association of aminotransferase levels and the fibrosis stage. Univariate analysis showed that the age at contamination, patient's age, GT-gamma, and aminotransferase levels over three times the upper normal limits, were associated with fibrosis stages 2 to 4. Multivariate analysis detected age (odds ratio=1.19), and GT-gamma (odds ratio=2.02) as independent factors.

High serum laminin and type IV collagen levels in schistosomiasis mansoni.

BACKGROUND: Fibrosis is the process of excessive deposition of collagen and other extra cellular matrix components and large amounts of these components have been shown in periovular schistosomal granulomas, especially in the liver. Laminin and type IV collagen have been investigated in various hepatic disorders but their accuracy in fibrosis detection and in the evaluation of its progression in schistosomiasis have not been fully explained. AIM: To measure the serum levels of two markers of fibrosis, laminin and type IV collagen in schistosomiasis. PATIENTS AND METHODS: Sixty-four patients with different clinical forms of schistosomiasis mansoni: intestinal (group I), hepatointestinal (group II), compensated (group III) and decompensated hepatosplenic (group IV) and 18 healthy volunteers were included. RESULTS: Serum type IV collagen and laminin levels were significantly increased in patients compared to controls. At about clinical forms, serum type IV collagen was increased in groups II and IV, compared to controls and was significantly higher in group IV than in group I. Serum laminin was significantly increased in groups II, III and IV and was significantly higher in group IV than in group II. Serum type IV collagen was closely correlated with serum laminin in groups II and IV. CONCLUSIONS: Connective tissue marker levels did not correlate with periportal thickness. In schistosomiasis mansoni there is an increase of type IV collagen and laminin levels at the initial stage of the disease, as well as in advanced forms. We also suggest that these markers may be a useful predictor of disease progression.

Five days of ceftriaxone to treat spontaneous bacterial peritonitis in cirrhotic patients.

BACKGROUND: The aim of this study was to determine whether a short course of ceftriaxone was sufficient to cure spontaneous bacterial peritonitis (SBP) in cirrhotic patients. METHODS: We studied 33 cirrhotic patients with SBP. All of them were treated with ceftriaxone, 1.0 g IV, every 12 h for 5 days. Twenty-one variables were recorded to evaluate their relationship to the resolution of SBP. RESULTS: The mean age of the patients was 45 years. Twenty-three were males and 10 females. The etiology of cirrhosis was alcoholic in 42% of the patients, and 82% of the patients belonged to Child-Pugh Class C. Hepatic encephalopathy was present in 39% of the patients. The most frequent organism causing SBP was Escherichia coli (60%). Resolution of SBP on day 5 of treatment was achieved in 73% of the patients. Total resolution of SBP after prolonged therapy with ceftriaxone or another agent. selected according to antibiotic susceptibility, was achieved in 94% of the patients. Hospital mortality was 12%. Multivariate analysis showed no factor that was significantly related to the resolution of SBP, but univariate analysis showed that renal impairment and positive culture tended to be related. CONCLUSIONS: A short course (5 days) of ceftriaxone is useful therapy for SBP. If the polymorphonuclear differential count in ascitic fluid is less than 250 cells/mm3 on day 5 of treatment, the antibiotic can be discontinued.

Nutritional risk factors for postoperative complications in Brazilian elderly patients undergoing major elective surgery.

OBJECTIVE: In this prospective study, we assessed nutritional and immunologic risk factors for infectious complications and deaths related to infection in elderly patients undergoing major elective surgery. METHODS: Seventy patients 60 y or older were enrolled in this study. The preoperative variables analyzed were body mass index, body mass index knee height, triceps skinfold, subscapular skinfold, mid-arm muscle circumference, mid-arm muscle area, albumin, transferrin, prealbumin, and retinol-binding protein levels, immunoglobulins G, A, and M, C3, and C4 levels, total lymphocyte counts, and the occurrence of delayed hypersensitivity reactions (multitest). RESULTS: Abnormally low levels of prealbumin (P = 0.004), retinol-binding protein (P = 0.05), and transferrin (P = 0.04) were related to infectious complications. Prealbumin levels (P = 0.02) and lymphocyte counts below 1500 cells/mm(3) (P = 0.04) were associated with mortality secondary to infection. Univariate regression analysis showed that levels of prealbumin (P = 0.02, odds ratio = 13.3, 95% confidence limits = 1.6, 110.9), retinol-binding protein (P = 0.03, odds ratio = 4.8, 95% confidence limits = 1.2, 19.3), and transferrin (P = 0.03; odds ratio = 4.2, 95% confidence limit = 1.2, 15.6) were associated with infectious complications. Multivariate analysis associated only prealbumin levels with infectious complications (P = 0.02, odds ratio = 13.3, 95% confidence limit = 1.6, 110.9). Regression analysis provided no conclusion regarding mortality because of the small number of deaths recorded. CONCLUSIONS: In patients with a good cardiac index (Goldman I and II) who underwent major elective surgery, prealbumin protein, retinol-binding protein, and transferrin levels below normal values represented a significant risk for postoperative infectious complications. Lymphocyte counts lower than 1500/m(3) and abnormal prealbumin values were associated with postoperative mortality secondary to infection. The anthropometric variables evaluated did not predict postoperative infectious complications and mortality.

Fine needle aspiration biopsy for improving the diagnostic accuracy of cut needle biopsy of focal liver lesions.

OBJECTIVE: To determine the value of fine needle aspiration biopsy (FNAB) in comparison to cut needle biopsy (CNB) for the diagnosis of malignancy of focal liver lesions. STUDY DESIGN: A retrospective analysis was conducted on 68 FNAB and 49 CNB procedures performed on 62 patients with focal liver lesions. RESULTS: Cytology permitted a diagnosis of the lesion in 78% of cases. When punctures with insufficient material were excluded (11), the diagnostic accuracy of FNAB was 93%. For the 49 patients who underwent both procedures, FNAB and CNB had the same diagnostic accuracy, 78%, when considered separately and of 88% when considered in combination. Sensitivity, specificity and positive predictive value were similar for the 2 techniques. The negative predictive value was 64% for FNAB and CNB used separately and reached 78% when the 2 techniques were combined. There were no complications during the execution of FNAB and CNB. CONCLUSION: FNAB is an effective and safe method for the diagnosis of focal hepatic lesions, with diagnostic accuracy similar to that of CNB. When the 2 techniques are combined, the accuracy of the diagnosis of malignancy of focal liver lesions increases.

Progression of liver fibrosis in blood donors infected with hepatitis C virus.

BACKGROUND/AIMS: Chronic hepatitis by HCV is progressive towards cirrhosis, with variable rate. We evaluated the rate of fibrosis progression (RFP), risk factors associated with advanced fibrosis (F3 and F4), and estimated the evolution time to cirrhosis. METHODS: We transversely selected 142 blood donors infected only with HCV, with a known route of infection, submitted to liver biopsy at admission. RFP= ratio between stage of fibrosis (METAVIR)/estimated duration of infection in years. Non-parametric tests and logistic regression analysis, with significance level of 5% were used. RESULTS: Median RFP was 0.086 U/year (0.05-0.142). Ten patients had F4 and 25 had F3. Median RFP values were significantly different (p=0.001) from one age group at contamination to the others and ALT and AST levels. There were no differences in the expected evolution to cirrhosis between intermediate fibrosers (F2) and the rapid fibrosers (F3 and F4). The independent variables associated with advanced fibrosis were ALT (OR 7.2) and GGT (OR 6.4) and age at inclusion (OR 1.12). CONCLUSION: This study suggests that RFP is extremely variable, it is exponential with age, and mainly influenced by host characteristics, especially age at contamination and possibly ethnical group. These asymptomatic patients had high percentage of fibrosis F2, F3 and F4.

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study.

BACKGROUND: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. METHODS: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. RESULTS: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5-9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p=0.24). SVR rates according to Child-Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. CONCLUSION: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.

Weight loss and resting energy expenditure in patients with chronic hepatitis C before and during standard treatment.

OBJECTIVE: Infection with hepatitis C virus (HCV) is a serious public health problem worldwide. In clinical studies, weight loss has been reported in 11% to 29% of patients treated with pegylated interferon-α-2a/2b. Few reports have tried to explain such a weight loss. The aim of this study was to evaluate nutritional status, body composition, and resting energy expenditure (REE) in patients with chronic hepatitis C before and during treatment with pegylated interferon and ribavirin. METHODS: This was a prospective study with the evaluation of patients with hepatitis C virus before and after 12 wk of treatment with pegylated interferon and ribavirin. The evaluation consisted of anthropometry (weight, height, body mass index, and waist circumference), and body composition was determined by bioelectrical impedance analysis. The REE of each individual was obtained by indirect calorimetry. To compare the two phases of treatment, the Wilcoxon test was used. The significance level was 5%. RESULTS: Subjects had significant weight loss during treatment with a consequent decrease in body mass index. This weight decrease was accompanied by a significant decrease in body fat and no decrease in fat-free mass. There was a significant decrease in energy intake as assessed by 24-h recall. However, there was no change in REE and in REE corrected for fat-free mass. CONCLUSION: Our study of patients with hepatitis C treatment showed that these patients had significant weight loss and this was not associated with changes in energy expenditure. However, we observed a significant decrease in energy intake, pointing to a possible need for intervention measures to decrease the damage.

Acute hepatotoxicity caused by enalapril: a case report.

A case of enalapril-induced acute hepatotoxicity with an unusual morphology is described. This morphology was characterized by macro- and microvesicular steatosis associated with neutrophil infiltration and Mallory bodies, occasionally with satellitosis. These alterations were most abundant in zone 1 of the periportal region, less common in zone 2 and rare in zone 3. There was also confluent periportal necrosis with sinusoidal fibrin deposits associated with intense ductal metaplasia and an infiltrate of inflammatory cells that included plasmocytes and a few eosinophils, as well as focal biliary damage. This morphology, that may be referred as "predominantly periportal steatohepatitis", was distinct from that associated with non-alcohol and alcohol-induced steatohepatitis, both initiated in acinar zone 3 and subsequently extended to other zones.

Microwave coagulation versus sclerotherapy after band ligation to prevent recurrence of high risk of bleeding esophageal varices in Child-Pugh's A and B patients.

BACKGROUND: The combination of endoscopic band ligation (EBL) with either endoscopic injection sclerotherapy (EIS) or thermal therapy has been shown to reduce recurrence of esophageal varices compared to EBL alone. The aim of this prospective trial was twofold: 1) to evaluate the safety and efficacy of EBL used in association with microwave coagulation (MC), a thermal endoscopic therapy method, for treating esophageal varices and preventing recurrence; and 2) to compare these results to the joint application of EBL and EIS. METHODS: Seventy cirrhotic patients with bleeding esophageal varices were treated with EBL until only thin vessels remained. Thirty-six randomly selected patients received EIS (group A) and 34 received MC (group B) until complete eradication had been achieved. Endoscopic follow-up was performed to detect recurrence. The effectiveness of the treatment was measured using variceal recurrence, rebleeding, intervention complications, and recurrence factors. RESULTS: During follow-up evaluations averaging 34.9 +/- 11.4 months, no significant differences were found between groups A and B in variceal recurrence (27.7 vs. 17.6%, P = 0.31) or rebleeding (8.3 vs. 0%, P = 0.23). Complications were rare, with no difference detected between groups. The presence of gastric varices influenced recurrence with an odds ratio of 3.9 (95% CI 1.14-13.1, P = 0.029). CONCLUSIONS: Application of MC to esophageal varices after band ligation is safe. The post-MC recurrence rate may be comparable to that observed following the combined treatment of EBL and EIS. The presence of gastric varices increases the risk of esophageal variceal recurrence.

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment. .

Hepatocellular carcinoma developing at the puncture site after percutaneous ethanol injection.

Percutaneous ethanol injection (PEI) is an option for hepatocellular carcinoma (HCC) treatment that is most effective for solitary lesions

Osteodistrofia hepática / Hepatic osteodystrophy

Osteodistrofia hepática é distúrbio de mineralização óssea associada à doença hepática crônica, sendo a osteoporose, e mais raramente a osteomalácia, sua forma de apresentação clínica. Apesar de pouco diagnosticada e com prevalência de grande variação na literatura, na maioria das vezes, apresenta-se de forma assintomática e, quando não identificada, aumenta consideravelmente o risco de fratura e sequelas permanentes. Seu diagnóstico, portanto, requer alta suspeição e faz-se, na prática clínica, por meio da avaliação da densitometria óssea. De fisiopatogenia multifatorial, envolve fatores genético, ambiental e do próprio estado clínico-nutricional do paciente. Uma atenção maior deve ser despendida a hepatopatas desnutridos, com cirrose hepática avançada, doença colestática crônica e transplantados pelo maior risco de desmineralização óssea. Nesta revisão, será discorrido sobre o metabolismo fisiológico da síntese óssea e a fisiopatologia do distúrbio de mineralização óssea, desde mecanismos fisiopatogênicos na doença hepática crônica, seu diagnóstico e revisão da terapêutica atual empregada.

Hepatic osteodystrophy is a disorder of bone mineralization associated to liver disease, clinically manifested by osteoporosis and more rarely osteomalacia. Although seldomly diagnosed and varying greatly in literature, most of the time, it presents asymptomatically and, when it is not recognized, it enhances considerably the risk of fracture and permanent sequelae. Indeed it requires a high grade of suspicion and it is confirmed by means of bone densitometry evaluation in clinical practice. Presenting with a multifactorial physiopathology, it involves factors, such as genetical, environmental, and patient clinical-nutritional status. A greater attention must be spent on patients with liver disease, especially those malnourished, with advanced cirrhosis, chronic cholestatic disease, and transplanted, because of a higher risk of bone demineralization. In this data, it will be reviewed the bone synthesis metabolism and the physiopathology of bone mineralization disorder ? since fisiopatogenic mechanisms in chronic liver disease, diagnosis and recent therapeutic review employed.