Therapeutic plasma-exchange improves systemic inflammation and survival in acute-on-chronic liver failure: A propensity-score matched study from AARC.

BACKGROUND AND AIM: Plasma-exchange (PE) has improved survival in acute liver failure by ameliorating systemic inflammatory response syndrome (SIRS). We evaluated PE and compared it to Fractional Plasma Separation and Adsorption (FPSA) and standard medical treatment (SMT) in a large multinational cohort of ACLF patients. METHODS: Data were prospectively collected from the AARC database and analysed. Matching by propensity risk score (PRS) was performed. Competing risk survival analysis was done to identify deaths because of multiorgan failure (MOF). In a subset of 10 patients, we also evaluated the mechanistic basis of response to PE. RESULTS: ACLF patients (n = 1866, mean age 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either artificial liver support (ALS) (n = 162); [PE (n = 131), FPSA (n = 31)] or were continued on standard medical therapy (SMT) (n = 1704). In the PRS-matched cohort (n = 208, [ALS-119; PE-94, FPSA-25)], SMT-89). ALS therapies were associated with a significantly higher resolution of SIRS (Odd's ratio 9.23,3.42-24.8), lower and delayed development of MOF (Hazard ratio 7.1, 4.5-11.1), and lower liver-failure-related deaths as compared to FPSA and SMT (P < .05). PE cleared inflammatory cytokines, damage-associated molecular patterns, and endotoxin in all patients. Responders improved monocyte phagocytic function and mitochondrial respiration and increased the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA) compared to non-responders. PE was associated with lesser adverse effects as compared to FPSA. CONCLUSIONS: PE improves systemic inflammation and lowers the development of MOF in patients with ACLF. Plasma-exchange provides significant survival benefit over FPSA and could be a preferred modality of liver support for ACLF patients.

Effect of Pretransplant Infections on Clinical Outcomes in Live-Donor Liver Transplant Recipients.

Owing to impaired immune function, surgical procedures, and multiple hospitalizations, patients with end-stage liver disease are at risk for numerous infectious complications while waiting for transplantation. Infection in transplant recipients remains the main cause of mortality and morbidity, despite advances in surgical techniques and the development of new repressive agents. The purpose of this study is to examine the infections that develop during the pretransplantion period in live donor liver transplant recipients and their effect on post-transplant clinical outcomes. The retrospective analysis of adult live donor liver transplant recipients in the last 4 years was conducted at Ankara University Hospital, a 1900-bed tertiary-care university hospital, in Ankara, Turkey. Demographic characteristics, preoperative infections, and clinical outcomes were analyzed. Patients were divided into 2 groups according to whether they had developed an infection before transplantation. The diagnoses were based on clinical, laboratory, and microbiological findings. Statistical analyses were performed using Stata version 9.0 (StataCorp, College Station, Tex., United States), and P < .05 were considered statistically significant. In univariate analyses, having diabetes mellitus or a pretransplant infection, the number of pretransplant infection attacks, the need for a reoperation, and developing a post-transplant infection were the statistically significant factors associated with 1-year mortality (P < .001, χ2 test). In multivariate analyses, diabetes mellitus (Odds ratio [OR] = 7.44, 95% confidence interval [CI], .03-45.79; P = .013), reoperation (OR = .33, 95% CI, .25-2.20; P < .001), having a pretransplantation infection (OR = 12.47, 95% CI, .011-87.67; P = .013), and the number of pretransplantation infection attacks (OR = .028, 95% CI, .013-.47; P < .001) were found to be statistically significant risk factors for 1-year mortality. Our study showed the effect of pretransplantation infections on post-transplant morbidity but not on rejection or mortality. According to the situation of patients, manageable pretransplantation infection is not an absolute contraindication for liver transplantation. Awareness of the increased risk for post-transplant infections and fast-acting antimicrobial coverage are the most important facts for patient survival.

Carbapenemase-Producing Bacterial Infections in Patients With Liver Transplant.

Carbapenemase-producing Enterobacteriacea (CPE) cause serious and life-threatening infections. They are resistant to carbapenems and many other classes of commonly used antimicrobial agents; therefore, managing infections caused by them poses a substantial challenge in clinical practice. They can also cause morbidity and mortality in patients with liver transplant. A retrospective analysis of CPE culture-positive patients with a history of liver transplant can help to examine the epidemiology and microbiology of these bacteria, as well as gain information on the possible infection sources, susceptibility patterns, and expected mortality in infected populations. In addition, study of these bacteria could help formulate a consensus on the appropriate use of empirical and directed antibiotic therapy, which can effectively reduce infections in these patients. We reviewed the medical records of 142 subjects who underwent liver transplantation at Ankara University Hospital, a 1900-bed tertiary care university hospital, in Ankara, Turkey, between January 2014 and August 2018. Patients showing signs of infection with culture positivity for CPE-producing organisms were included from the study. Statistical analysis was performed and a value of P < .05 is considered statistically significant. In most cases, the source of infection was the abdomen. Klebsiella species was also predominant in these cases. Model for End-Stage Liver Disease scores and length of hospital stay were higher and statistically significant when compared to patients who were CPE negative. Mortality was highest in the CPE-positive group. Infection is the most important cause of mortality and morbidity after liver transplantation and increases the cost of treatment. Regarding the culture sensitivity patterns and resistance mode, empirical therapy with carbapenems does not produce a solid result. The high mortality observed with these infections reflects very limited therapeutic options.

Impact of Periampullary Diverticula on Bile Duct Stones and Ampullary Carcinoma.

INTRODUCTION: Periampullary diverticula (PD) is caused by extraluminal pouching of duodenal mucosa. Using a very common endoscopic procedure to diagnose or treat gastrointestinal disorders, we encountered duodenal diverticulum. MATERIALS AND METHODS: This is a retrospective, single-center study. Three thousand and sixteen patients on whom endoscopic retrograde cholangiopancreatography (ERCP) was performed at Ankara University Medical School, Department of Gastroenterology, from June 2009 to June 2014 were included to the study. RESULTS: Hundred and thirty patients (males 65, females 65) among the 3,016 had PD. Two hundred and sixty patients without diverticulum were randomly chosen from the 3,016 patients, as a control group [121 (47%) females, 139 (53%) males]. There was no statistical difference between the two groups. The mean age of the patients with PD was 69.9 years, while the mean age was 62.3 years for patients without PD (p < 0.001). Incidence for PD was 4.6%. The papilla of Vater was located in the inter-diverticular area (Type 1) in 9 patients (8.3%), at the edge of the diverticulum (Type 2) in 31 patients (28.4%), and at a distance of 2 to 3 cm from the papilla (Type 3) in 69 patients (63.3%). DISCUSSION: Although numerically more common bile duct stones occurred in patients with PD compared to those without PD, there was no statistical difference between the two groups. The rate of pancreato-biliary carcinomas was higher in patients without diverticulum. Cannulation was successful in both groups at the rate of 97.6 and 92% respectively, but cannulation failed more often in patients without PD. Duodenal perforation occurred in one patient with PD. Bleeding after sphincterotomy occurred in two patients without PD. HOW TO CITE THIS ARTICLE: Örmeci N, Deda X, Kalkan Ç, Tüzün AE, Karakaya F, Dökmeci A, Bahar DK, Özkan H, Idilman R, Çinar K. Impact of Periampullary Diverticula on Bile Duct Stones and Ampullary Carcinoma. Euroasian J Hepato-Gastroenterol 2016;6(1):31-34.

Tenofovir-best hope for treatment of chronic hepatitis B infection?

BACKGROUND/AIMS: To evaluate the effectiveness of tenofovir in patients with chronic hepatitis B infection in a real life setting. MATERIALS AND METHODS: We performed a retrospective analysis of data from 164 patients with chronic hepatitis B who were treated with Tenofovir. Eighty-six patients (52.4%) were naïve. Seventy-seven (46.9%) patients were previously treated with anti-viral drugs, including standard interferon (n=4), pegylated (PEG) interferon (n=14), standard interferon together with lamivudine (n=13), lamivudine alone (n=41), adefovir (n=2), lamivudine together with adefovir (n=1), and entecavir (n=2). Six patients (3.7%) had liver cirrhosis before treatment of tenofovir. RESULTS: The patients who have hepatitis B viral DNA>104 copy/mL with chronic hepatitis B infection were included in the treatment of Tenofovir. Average follow up time was 30.31±14.33 months. HBV DNA negativity and alanine aminotransferase (ALT) normalization were 86.5% and 71.3%, respectively, at the last visit. Hepatitis B e-Antigen (HBeAg) seroconversion occurred in 11 (19.6%) out of 164 patients. During the follow-up period, 4 (2.4%) patients developed liver cirrhosis and in 5 (3%) patients hepatocellular carcinoma (HCC) occurred out of 164 patients. HBsAg seroconversion occurred in one patient (0.6%). CONCLUSION: Tenofovir can be used safely and successfully in those patients that were naive, experienced with immune modulators and/or antivirals, HBeAg-positive, and HBeAg-negative patients.

The association between insulin resistance and hepatic fibrosis in patients with chronic hepatitis C: an observational, multicenter study in Turkey.

BACKGROUND/AIMS: To evaluate the association between insulin resistance and hepatic fibrosis in patients with chronic hepatitis C. MATERIALS AND METHODS: A total of 104 chronic hepatitis C patients were included in this non-interventional, open-label, observational, multicenter, cross-sectional study conducted at 20 gastroenterology clinics in Turkey. The primary end point was the correlation between stage of hepatic fibrosis and insulin resistance evaluated via the homeostasis model of assessment-insulin resistance index. Confounders of hepatic fibrosis and insulin resistance were the secondary end points. RESULTS: The mean age of patients was 52.8 years; 65.4% were female. Type 2 diabetes was present in 6.8% and insulin resistance noted in 38.0% of patients. Further, 45.7% of the patients had mild (A0/A1) and the remaining had moderate/severe (A2/A3) hepatic necroinflammatory activity. Patient distribution according to Metavir fibrosis stage was as follows: F0/F1 (57.0%); F2 (6.5%); F3 (23.7%); and F4 (12.9%). A univariate analysis revealed significant positive correlations between Metavir fibrosis stage and insulin resistance (r=0.297; p=0.007). Logistic regression analysis showed that significant predictors of insulin resistance were high alanine transaminase levels (odds ratio, 0.97; 95% confidence interval, 0.944-0.997) and liver fibrosis stage (odds ratio, 0.114; 95% confidence interval, 0.021-0.607). CONCLUSION: Our findings revealed significant associations between insulin resistance and hepatic fibrosis.

Amantadine in non-responder patients with chronic hepatitis C: a randomized prospective study.

BACKGROUND/AIMS: The management of non-responders (NR) represents the most challenging of all aspects in the care of patients with chronic hepatitis C (CHC). The purpose of the study was to evaluate the efficacy of amantadine. METHODOLOGY: Fourty- three patients with CHC who did not respond to prior combination therapy [IFNα-2a plus ribavirin for 48 weeks] were enrolled into the study. The first group (n=21) was administered pegylated IFN-α2a (180 mcg/week) plus ribavirin (1000-1200 mg/day) and amantadine (200mg/day) for 48 weeks. After discontinuation of therapy, patients were followed-up for an additional 24 weeks. The second group (n=22) received only amantadine (200mg/day) daily for at least 24 weeks (mean 96 weeks) and starting from the 24th week, HCV-RNA was assessed every 12 weeks without discontinuation of therapy. RESULTS: Mean ALT levels before treatment were 115.30 units in the first and 107.73 units in the second group whereas they were 48.38 and 54.76 units, respectively, after the treatment (p<0.001 for both). Sustained viral response rate for the first group at the 72nd week was 52.3% (11/21) (p<0.025). Among patients receiving amantadine, 1 patient became HCV-RNA negative at the 24th and 3 patients at the 48th week (response rate at week 48 was 18.2%), 1 patient at the second year and 1 patient at the fourth year of the treatment (p=0.031). CONCLUSIONS: Amantadine has a potential anti-inflammatory activity that can be a safe alternative for NR-CHC subjects to combination therapy.

The characteristics and clinical outcome of drug-induced liver injury: a single-center experience.

BACKGROUND AND GOALS: The aim of this cohort study was to determine the characteristics and clinical outcome of 170 patients with drug-induced liver injury (DILI) in a single center. STUDY: Between January 2001 and June 2007, a total of 170 individuals who were diagnosed with DILI were retrospectively analyzed. The median follow-up period was 110.0 days. RESULTS: During the study period, a total of 5471 new patients were assessed for liver test abnormalities. Of those, 170 patients (3.1%) fulfilled the criteria of DILI. A total of 83 different drugs were considered to be related to the hepatotoxicity; a single drug was suspected in 57.6% of individuals. The median interval between the suspicious drug intake and DILI recognition was 15.0 days. Hepatocellular pattern was observed in 50.0% of patients with a mean alanine aminotransferase level of 952.2+/-907.0 U/L. The main causative group of drugs was antibiotics. Sixty-two patients required hospitalization; acute liver failure developed in 14 (8.2%), chronicity was observed in 19 (11.2%), and 7 died (4.1%). Overall, complete recovery occurred in 82% of patients. The presence of jaundice on admission and shorter interval period between drug intake and DILI recognition were identified as risk factors for the development of acute liver failure. CONCLUSIONS: DILI is an important cause of liver test abnormalities in outpatient clinics, and antibiotics represent the most common drug group. Overall, complete recovery after the withdrawal of the suspicious drug occurred in the majority of patients, but DILI may progress to acute liver failure, chronicity, and death.

Endoscopic management of biliary parasitic diseases.

UNLABELLED: AIM/MATERIALS AND METHODS: Between January 2000 and June 2007, 3,548 endoscopic retrograde cholangiopancreatography (ERCP) were performed for extrahepatic cholestasis, cholangitis, and choledocholithiasis. The results of ERCPs were evaluated retrospectively and examined carefully to investigate the management and endoscopic therapy of biliary parasites. RESULTS: Of the 3,548 patients who underwent ERCP, 24 (0.66%) were found to have biliary parasitosis. The mean age of the biliary parasitosis patients (16 women) was 48.6 (15-77) years. Of these 24 cases, 16 patients had hydatid cystic disease (eight with partial obstruction of the biliary tract, and eight with ruptured cysts), four patients had Fasciola hepatica, and four patients had Ascaris lumbricoides infestation. Endoscopic sphincterotomy was performed, after which the choledochus was examined carefully by balloon catheter and basket procedure. CONCLUSION: The ERCP procedure is very useful in the therapy of biliary parasitic infestations.

The usefulness of endoscopic retrograde cholangiopancreatography and (99m)Tc-labeled albumin macroaggregates in diagnosing hydatid disease fistulae.

Hydatid disease is an important health problem in areas where it is endemic. There are several therapeutic modalities, the most important being surgery, antibiotherapy, and percutaneous treatment. In recent years percutaneous treatment has become popular, and for this method or surgery it is sometimes lifesaving to know the relation between the biliary ducts and the cyst cavity. The aim of this study was to examine the usefulness of endoscopic retrograde cholangiopancreatography and (99m)Tc-labeled albumin macroaggregates in diagnosing hydatid disease fistulae before percutaneous or surgical treatment. A total of 72 patients diagnosed with hepatic hydatid disease via ultrasound and serologic tests were enrolled in the study. Endoscopic retrograde cholangiopancreatography was successfully performed in all patients. (99m)Tc-labeled albumin macroaggregates also were injected into cysts at a dose of 1.5-2 mCi just before the treatment. All but three patients were treated percutaneously. Scintigraphy of abdominal and thoracic areas was performed with a GE Starcam 3200 XC/T gamma camera at 30 and 120 min after Tc-labeled albumin macroaggregate injections. Endoscopic retrograde cholangiopancreatography revealed communications between biliary ducts and cyst cavities in nine patients (12.5%). However, (99m)Tc-labeled albumin macroaggregates showed not only leakage into the systemic circulation in nine patients but also into the biliary ducts in two (15.4%). In one patient, mild acute pancreatitis occurred as a complication of endoscopic retrograde cholangiopancreatography. No complications of (99m)Tc-labeled albumin macroaggregates injection were seen. Three patients were surgically treated because of clinically manifested cystobiliary fistulae. We conclude that endoscopic retrograde cholangiopancreatography is a gold standard technique for the diagnosis of communication between the biliary duct and the cyst cavity, and (99m)Tc-labeled albumin macroaggregate injection is useful for revealing leakage into the systemic circulation. The diagnosis of biliary fistulae before percutaneous treatment of hydatid disease may enable planning of the optimal therapy.

Atypical presentation of hepatocellular carcinoma: a mass on the left thoracic wall.

BACKGROUND: Hepatocellular carcinoma is a common malignancy for which chronic hepatitis B infection has been defined as the most common etiologic factor. The most frequent metastatic sites are the lung, bone, lymphatics, and brain, respectively. Metastases to the chest wall have been reported only rarely. CASE PRESENTATION: We report a patient with hepatocellular carcinoma who presented with an isolated metastatic mass on the left anterolateral chest wall in the axillary region. CONCLUSIONS: Metastasis of HCC should be included in the differential diagnosis of rapidly growing lesions in unusual localizations, particularly in patients with chronic liver disease even if a primary tumor can not be radiologically identified.

Clinical outcome of Crohn's disease treated with infliximab.

BACKGROUND/AIMS: Controlled studies in humans have shown the role of antibodies to tumor necrosis factor-alpha in the treatment of both fistulizing and inflammatory Crohn's disease. The aim of this study is to report the results of a multicenter clinical trial to evaluate efficacy of infliximab in Crohn's disease patients who are refractory to conservative drugs or fistulizing Crohn's disease. METHODOLOGY: This trial was carried out at 5 university and community hospitals, in Turkey. A total of 25 patients with Crohn's disease that were unresponsive to conventional medical therapy, participated; 17 of the 25 were in the fistulizing disease group and 8 were in the inflammatory disease group. Clinical response was classified according to fistula drainage, diarrhea as positive response or no response. RESULTS: Overall response rate was 92% (23/25), regardless of the disease group, after first infusion of infliximab. Sixteen out of 17 patients in the fistulizing disease group had a positive response. Fourteen of the 16 positive responders later relapsed. Median duration of response was 8 weeks (range, 2-35 wk). Active inflammatory disease patients had a positive response rate of 75% (6/8) and two of the patients were nonresponders. A further two patients relapsed at week 14. Two patients in both arms of the study were still in remission at the end of the study. Major adverse events were: pneumonia in one patient, skin infections in two patients, pulmonary thromboembolism and death in one patient. CONCLUSIONS: Infliximab treatment seems to be more effective in Crohn's disease patients especially in those with fistulizing disease than those with non-fistulizing, inflammatory disease. It is evident that maintenance of remission might be achieved with ongoing maintenance therapy. We suggest maintenance of infliximab therapy.

Bronchoalveolar lavage fluid analysis in individuals with chronic hepatitis C.

A number of disorders for which an association with hepatitis C virus infection exist. These disorders include essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and idiopathic pulmonary fibrosis. This study was initiated to investigate the cellular content and lymphocyte subpopulations of bronchoalveolar lavage fluid obtained from individuals with chronic hepatitis C and to compare the results to those of controls. Eighteen patients with chronic hepatitis C (male/female, 6/12) and 14 healthy volunteers (male/female, 6/8), were studied. Bronchoalveolar lavage fluid was obtained from each; and the lymphocyte subtypes and the presence of HCV-RNA in the bronchoalveolar lavage fluid were determined. All anti-HCV positive subjects were HCV-RNA positive in serum. One (5.6%) had a HCV-RNA positive bronchoalveolar lavage. The total cell and neutrophil counts of the bronchoalveolar lavage fluid were significantly greater in patients with chronic hepatitis C as compared to controls (5,799.6 +/- 957.4 x 10(3)/ml vs. 1,835.7 +/- 447.8 x 10(3)/ml, P = 0.001; 1,175.8 +/- 634.7 x 10(3)/ml vs. 53.1 +/- 28.1 x 10(3)/ml, P = 0.029). In contrast, the lymphocyte, macrophage and eosinophil counts did not differ. No difference in the percentage, median or range of individual T cell subsets or B cell numbers in the bronchoalveolar lavage fluid existed between the groups. It is concluded that hepatitis C virus infection may be associated with an occult pulmonary inflammatory reaction manifested by an increased number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid. This finding may contribute to the process that leads to idiopathic pulmonary fibrosis seen in a minority of cases of chronic hepatitis C.