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Background Bacterial and fungal infections (BFIs) are frequent in patients with cirrhosis and often trigger acute-on-chronic liver failure (ACLF). This prospective observational study aims to describe the interactions between BFI and ACLF in terms of mortality and related risk factors. Methods We performed a 2-center prospective observational study enrolling hospitalized patients with cirrhosis admitted for acute decompensation. Data were recorded at admission and during hospitalization. Survival was recorded up to 1 year. Results Among the 516 patients enrolled, 108 (21%) were infected at admission, while an additional 61 patients (12%) developed an infection during hospital stay. In the absence of ACLF, the 1-year mortality rate of patients with BFI did not differ from that of patients without BFI (33% vs 31%; P = .553). In contrast, those with ACLF triggered or complicated by BFI had a significantly higher mortality rate than those who remained free from BFI (75% vs 54%; P = .011). Competing risk analysis showed that the negative impact of ACLF-related BFI on long-term prognosis was independent from Model for End-stage Liver Disease (MELD) incorporating serum sodium concentration score, comorbidity, and basal C-reactive protein level. Finally, multivariable logistic regression showed that higher MELD score (P, The adverse prognosis of bacterial or fungal infections in patients with decompensated cirrhosis is linked to the development of acute-on-chronic liver failure. Severity, type and microbiological features of infections are main predictors of the development of acute-on-chronic liver failure.

The aim of this study was to evaluate the morphologic appearance, the clinical scenario, and the outcomes of patients with portal hypertensive biliopathy (PHB), particularly in the symptomatic subgroup treated with interventional radiology (IR) procedures. The outcome of 20 patients with PHB were retrospectively reviewed over a 5-year period. In all cases, the extrahepatic portal vein occlusion (EHPVO) and the compensatory cavernomatosis was the cause of PHB. Eight out of 20 patients had severe symptoms (jaundice and bleeding). Five out of these eight patients were successfully treated with IR procedures. PHB is a rare but serious complication of PH from EHPVO. IR treatments are highly effective in controlling symptoms. Moreover, IR procedures, as drainage and transjugular intrahepatic portosystemic shunt placement, are the first-line treatment in cases of life-threatening bleeding from ruptures of the varices.

Background & Aims Nosocomial acute-on-chronic liver failure (nACLF) develops in at least 10% of patients with cirrhosis hospitalized for acute decompensation (AD), greatly worsening their prognosis. In this prospective observational study, we aimed to identify rapidly obtainable predictors at admission, which allow for the early recognition and stratification of patients at risk of nACLF. Methods A total of 516 consecutive patients hospitalized for AD of cirrhosis were screened: those who did not present ACLF at admission (410) were enrolled and surveilled for the development of nACLF. Results Fifty-nine (14%) patients developed nALCF after a median of 7 (IQR 4–18) days. At admission, they presented a more severe disease and higher degrees of systemic inflammation and anemia than those (351; 86%) who remained free from nACLF. Competing risk multivariable regression analysis showed that baseline MELD score (sub-distribution hazard ratio [sHR] 1.15; 95% CI 1.10–1.21; p ≪0.001), hemoglobin level (sHR 0.81; 95% CI 0.68–0.96; p = 0.018), and leukocyte count (sHR 1.11; 95% CI 1.06–1.16; p ≪0.001) independently predicted nACLF. Their optimal cut-off points, determined by receiver-operating characteristic curve analysis, were: 13 points for MELD score, 9.8 g/dl for hemoglobin, and 5.6x109/L for leukocyte count. These thresholds were used to stratify patients according to the cumulative incidence of nACLF, being 0, 6, 21 and 59% in the presence of 0, 1, 2 or 3 risk factors (p ≪0.001). Nosocomial bacterial infections only increased the probability of developing nACLF in patients with at least 1 risk factor, rising from 3% to 29%, 16% to 50% and 52% to 83% in patients with 1, 2 or 3 risk factors, respectively. Conclusions Easily available laboratory parameters, related to disease severity, systemic inflammation, and anemia, can be used to identify, at admission, hospitalized patients with AD at increased risk of developing nACLF. Lay summary More than 10% of patients with cirrhosis hospitalized because of an acute decompensation develop acute-on-chronic liver failure, which is associated with high short-term mortality, during their hospital stay. We found that the combination of 3 easily obtainable variables (model for end-stage liver disease score, leukocyte count and hemoglobin level) help to identify and stratify patients according to their risk of developing nosocomial acute-on-chronic liver failure, from nil to 59%. Moreover, if a nosocomial bacterial infection occurs, such an incidence proportionally increases from nil to 83%. This simple approach helps to identify patients at risk of developing nosocomial acute-on-chronic liver failure at admission to hospital, enabling clinicians to put in place preventive measures., Graphical Abstract Unlabelled Image, Highlights • ACLF complicates more than 10% of hospitalizations for acute decompensation of cirrhosis. • Easily available predictors of nosocomial ACLF are fundamental to implement appropriate preventive strategies. • MELD score, leucocyte count and hemoglobin can stratify patients according to their risk of developing nosocomial ACLF. • Further studies are required to validate these results and provide additional insights.

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P

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Liver involvement in patients with sickle cell anemia/trait includes a wide range of alterations, from mild liver function test abnormalities to cirrhosis and acute liver failure. Approximately 15-30% of patients with sickle cell anemia present cirrhosis at autopsy. The pathogenesis of cirrhosis is usually related to chronic hepatitis B or C infection or to iron overload resulting from the many transfusions received by these patients in their lifetime. Thus, cirrhosis has been described almost exclusively in patients with sickle cell anemia, while only mild liver abnormalities have been associated with the sickle cell trait. In the present case study, we describe a young Mediterranean man carrying a sickle cell trait (Hb Sβ(+) thalassemia) who developed liver cirrhosis being negative for hepatitis C and B viruses or for other causes of cirrhosis and not receiving chronic blood transfusions.

The mode of transmission of Helicobacter pylori is largely unknown and is a matter of circumstantial evidence and speculation rather than fact. However, the principle evidence is of two sorts: the epidemiological data, providing evidence of possible risk factors associated with transmission, and the identification of potential sources from which H. pylori could be acquired. Evidence exists for several potential sources of infection and several possible modes of transmission, and it is feasible that the transmission of H. pylori varies according to the cultural and demographic circumstances. However, the most likely recognized source for H. pylori is the human stomach, although it is not known by what route the organism is transmitted to the stomach. Evidence suggests close personal contact is important and that acquisition occurs mainly in childhood. This article reviews the evidence for the source of infection and the route of transmission of H. pylori.

Helicobacter pylori is a human pathogen that causes chronic gastritis, has a role in gastric and duodenal ulcer, is involved in gastric carcinogenesis (so that the bacterium has been classified as a class I definite gastric carcinogen to humans), 7 and is regarded as a possible important factor in at least a subset of patients with functional dyspepsia. In addition to its definite role as a gastroduodenal pathogen, H. pylori now is being investigated actively for possible involvement in various nongastroenterologic conditions, such as impaired growth, coronary heart disease, headache, Raynaud's phenomenon, diabetes, and gallstone disease. 4 H. pylori causes a chronic gastric infection that usually is lifelong, and many epidemiologic studies have shown that this is probably one of the most common bacterial infections throughout the world, involving 40% to 50% of the population in developed countries and 80% to 90% of the population in developing regions. 21 The diagnosis of H. pylori infection represents at least a key step in the management of many patients referred to the gastroenterologist. Because of the wide range and relevance of pathologies possibly related to infection (including malignancies), H. pylori harbors the potential to become a major health problem. H. pylori infection can be diagnosed by invasive (i.e., requiring endoscopy) and noninvasive techniques (i.e., techniques that do not require endoscopy with biopsy sampling). 11 Each of the available diagnostic techniques (which are discussed in detail in other articles) has advantages and disadvantages. The discussion of the different diagnostic methods cannot be oversimplified by thinking only in terms of which is the best diagnostic tool. The problem should be addressed by asking which is the best diagnostic tool in each definite clinical situation. The choice of diagnostic tool has to take into account different factors, as follows: Is the clinician dealing with normal subjects screened for epidemiologic purposes or with patients referred to the gastroenterologist? Has the patient already had failed eradication attempts? Is the clinician looking for susceptibility to antibodies? Is the clinician interested in diagnosing the infection in a clinical setting or in other possibly relevant factors (i.e., putative markers of increased virulence or pathogenicity of the strain, such as cagA or vacA ) in a research setting? Eventually the clinician also should ask the cost of the diagnostic technique used, taking into account all the factors involved, such as the need for endoscopy, a technician or nurse to assist the patient, and dedicated laboratory instrumentation and materials (i.e., to evaluate breath sample) as well as available facilities (in the case of serologic tests, facilities usually are available even in small hospitals or developing countries). Bearing in mind these and other similar questions, the possibility of testing stool samples to diagnose H. pylori infection noninvasively is discussed. Previously, there were only two widely available noninvasive methods: (1) 13 C-labeled or 14 C-labeled urea breath test, which is based on the detection of 13 C-labeled or 14 C-labeled carbon dioxide expired air as result of H. pylori urease activity, 9,11 and (2) serologic testing, which is based on the detection of a specific anti– H. pylori immune response, mostly by IgG antibodies, in the patient's serum. 11,22 Being noninvasive, these tests (mostly serologic testing because of its simplicity and lower cost) have been used widely in epidemiologic studies to assess the prevalence of H. pylori infection in different populations. Apart from epidemiologic research, noninvasive H. pylori testing can be used successfully in two other main settings: (1) pre-endoscopic screening of patients to refer to a gastroenterology service for investigation of dyspepsia and (2) therapeutic monitoring after eradication therapy to confirm cure of infection. Because of the widespread availability of endoscopy, this technique has become the mainstay for investigation of dyspepsia, and this has led to increased waiting lists and medical costs. In an attempt to obviate the need for endoscopy, without affecting the safety of the patients, several pre-endoscopic screening procedures have been proposed, and it has been shown that young H. pylori –negative patients (as determined by noninvasive tests) without alarming symptoms or nonsteroidal anti-inflammatory drug intake could avoid endoscopy safely and be treated with a trial of medical therapy. Endoscopy could be reserved for patients whose symptoms do not improve or relapse shortly after discontinuation of therapy. 18 Apart from patients with gastric ulcer, who probably are managed best with control endoscopy because of the possibility of underlying gastric malignancy, two approaches have been advocated for patients treated with H. pylori –eradicating regimens. The first approach is to wait and see (i.e., not testing to confirm eradication, suggesting that if patients experience prolonged symptom relief, this could be taken as an indirect sign of successful eradication). This approach may not be accepted by some patients, for whom fear of consequences of H. pylori infection dictates a positive confirmation of eradication. Such a strategy is based on the unproven assumption of a clear relationship between H. pylori and symptoms. The second approach is to test and confirm eradication, and this probably is best accomplished by noninvasive testing. Urea breath test can be used 4 weeks after treatment, whereas serologic testing requires waiting a longer time to allow the antibody titer to fall.

Department of Digestive Disease and Internal Medicine (S Berardi MD, A Cappelli MD, M Mastroroberto MD, C Serra MD, C Sama MD), Department of Hematology, Oncology and Laboratory Medicine (A D’Errico MD), and Cardio-Thoracic-Vascular Department (V Russo MD), St Orsola-Malpighi University Hospital, Bologna, Italy; Hepatic Hemodynamic Laboratory, Liver Unit, Institut d’Investigacions Biomediques August Pi i Sunyer and Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas, Barcelona, Spain (A Berzigotti MD); and Abdominal Imaging Section, Centre Diagnostic per la Imatge, Hospital Clinic i Provincial, Barcelona, Spain (A Berzigotti, A Garcia-Criado MD)

Background: Interferon may trigger autoimmune disorders, including autoimmune hepatitis, in immunocompetent patients. To date, no such disorders have been described in liver transplanted patients. Methods: 9 of 44 liver transplanted patients who had been receiving pegylated-interferon alpha-2b and ribavirin for at least 6 months for hepatitis C virus (HCV) recurrence, developed graft dysfunction despite on-treatment HCV-RNA clearance in all but one case. Laboratory, microbiological, imaging and histological evaluations were performed to identify the origin of graft dysfunction. The International Autoimmune Hepatitis scoring system was also applied. Results: In all cases infections, anastomoses complications and rejection were excluded, whereas the autoimmune hepatitis score suggested a “probable autoimmune hepatitis” (score from 10 to 14). Three patients developed other definite autoimmune disorders (overlap anti-mitochondrial antibodies (AMA)-positive cholangitis, autoimmune thyroiditis and systemic lupus erythematosus, respectively). In all cases, pre-existing autoimmune hepatitis was excluded. Anti-lymphocyte antibodies in immunosuppressive induction treatment correlated with the development of the disorder, whereas the use of granulocyte colony-stimulating factor to treat interferon-induced neutropenia showed a protective role. Withdrawal of antiviral treatment and treatment with prednisone resulted in different outcomes (five remissions and four graft failures with two deaths). Conclusions: De novo autoimmune hepatitis should be considered in differential diagnosis along with rejection in liver transplanted patients developing graft dysfunction while on treatment with interferon.

Background: Hepatic encephalopathy (HE) is a metabolic-neurophysiologicsyndrome that occurs in patients with advanced hepatic disease. One of the main pathogenic mechanisms is represented by circulating toxins produced by the intestinal metabolism of nitrogenous compounds. The therapeutic approach to HE is mainly based on drugs that eliminate ammonia-producing bacteria. Objectives: The aim of this study was to evaluate the effects of the nonabsorbable antibiotic rifaximin in patients with HE who were intolerant or nonresponsive to treatment with an oral, nonabsorbable disaccharide (lactulose). Methods: This uncontrolled, open-label, pilot study was conducted at the University of Bologna, Bologna, Italy. Patients aged ≥ 18 years with histologically proven liver cirrhosis and HE were studied. All patients were intolerant or nonresponsive to previous treatment with lactulose. Rifaximin tablets were administered to patients at a dosage of 400 mg TID for 10 days. The portal systemic encephalopathy (PSE) index was evaluated at enrollment and at the end of the treatment period. Tolerability was assessed using hematology, biochemistry, and urinalysis and by recording adverse effects (AEs). Results: Twenty-six patients (18 men, 8 women; mean [SD] age, 55.8 [8.0] years) were enrolled (intolerants, n = 17; nonresponders, n = 9). All patients completed the study. Significant improvement was shown in most of the 5 components of the PSE index after rifaximin administration in both intolerants and nonresponders. At the end of the 10-day treatment period, the PSE index was significantly reduced in both intolerants and nonresponders. Rifaximin was well tolerated; no clinically relevant AEs were observed during the treatment period. Conclusions: This pilot study of patients with liver cirrhosis and HE who were intolerant or nonresponsive to previous treatment with an oral, nonabsorbable disaccharide suggests that treatment with rifaximin may be considered as an adjuvant or an alternative treatment in reducing HE.

There are several types of immunological tests available for the diagnosis and management of Helicobacter pylori infection. Most commercially available serological kits use the enzyme linked immunosorbent assay (ELISA) test format. Originally the kits used crude antigen preparations although many of the newer kits use a more purified antigen preparation, with often increased specificity but lower sensitivity. Near patient test kits are based either on latex agglutination or immunochromatography. Generally they have low sensitivities compared with laboratory tests. Western blotting, ELISA, and recombinant immunoblot assays (RIBA) have also been developed into commercially available kits and can be used to indicate the presence of specific virulence markers. An antigen detection kit has been developed for the detection of Helicobacter pylori in faeces. Immunological reagents have also been combined with other diagnostic modalities to develop immunohistochemical stains and DNA immunoassays. Helicobacter pylori is now recognised as the cause of gastritis and most cases of peptic ulcer disease (PUD); its long term carriage increases the risk of gastric adenocarcinoma sixfold and it is designated as a class I carcinogen. H pylori has also been implicated as a cause of gastric mucosa associated lymphoid tissue lymphomas. Its relation to non-ulcer dyspepsia remains controversial. Additionally, long term carriage of the organism may be associated with short stature in young girls and, in the general population, as a possible risk factor for the development of vasospastic disorders and possibly skin immunopathology such as urticaria. With the recognition of H pylori as an important human pathogen, it has become one of the growing number of organisms to have its complete genome sequence mapped. Serology is an important method of determining colonisation status and can be used for diagnosis, as a screening procedure, or to follow the efficacy of eradication regimens. Most serological assays are in the ELISA format although some are based on the latex agglutination reaction. These latter are used principally as near patient assays. Most assays detect IgG in serum although some detect serum IgA. More recently developed assays detect IgA in saliva and the production of affinity purified antibodies has led to the development of an antigen detection assay for faecal specimens. Serological reagents have also been used in immunocytochemistry and to speed up the detection of amplified products of the polymerase chain reaction (PCR)-DNA immunoassays.