AIM: To evaluate single balloon enteroscopy in diagnostic and therapeutic endoscopic retrograde cholangiography (ERC) in patients with Roux-en-Y hepaticojejunoanastomosis (HJA).
METHODS: The study took place from January 2009 to December 2011 and we retrospectively assessed 15 patients with Roux-en-Y HJA who had signs of biliary obstruction. In total, 23 ERC procedures were performed in these patients and a single balloon videoenteroscope (Olympus SIF Q 180) was used in all of the cases. A transparent overtube was drawn over the videoenteroscope and it freely moved on the working part of the enteroscope. Its distal end was equipped with a silicone balloon that was inflated by air from an external pump at a pressure of ≤ 5.4 kPa. The technical limitations or rather the parameters of the single balloon enteroscope (working length - 200 cm, diameter of the working channel - 2.8 mm, absence of Albarran bridge) showed the need for special endoscopic instrumentation.
RESULTS: Cannulation success was reached in diagnostic ERC in 12 of 15 patients. ERC findings were normal in 1 of 12 patients. ERC in the remaining 11 patients showed some pathological changes. One of these (cystic bile duct dilation) was subsequently resolved surgically. Endoscopic treatment was initialized in the remaining 10 patients (5 with HJA stenosis, 2 with choledocholithiasis, and 3 with both). This treatment was successful in 9 of 10 patients. The endoscopic therapeutic procedures included: balloon dilatation of HJA stenosis - 11 times (7 patients); choledocholitiasis extraction - five times (5 patients); biliary plastic stent placement - six times (4 patients); and removal of biliary stents placed by us - six times (4 patients). The mean time of performing a single ERC was 72 min. The longest procedure took 110 min and the shortest took 34 min. This shows that it is necessary to allow for more time in individual procedures. Furthermore, these procedures require the presence of an anesthesiologist. We did not observe any complications in these 15 patients.
CONCLUSION: This method is more demanding than standard endoscopic retrograde cholangiopancreatography due to altered postsurgical anatomy. However, it is effective, safe, and widens the possibilities of resolving biliary pathology.
Single balloon enteroscopy; Endoscopic retrograde cholangiography; Roux-Y hepaticojejunoanastomosis; Endoscopic diagnosis; Endoscopic treatment
Acute alcoholic hepatitis (AAH) is characterised by deep jaundice in patients with a history of heavy alcohol use, which can progress to liver failure. A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure. Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered. Liver biopsy remains the only reliable method to make an accurate diagnosis. However, there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy. We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH. In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor. Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions, we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology. It also adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology. Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH.
Alcoholic hepatitis; Liver biopsy; Diagnosis; Prognosis; Transjugular liver biopsy
AIM: To understand the changes and development of World Journal of Gastroenterology (WJG) in recent years.
METHODS: The Journal Citation Report (JCR) and SCI-E database of the ISI Web of Knowledge were used to search the articles and data of related indices in WJG during 2008-2012. Bibliometric methods were used for statistical analysis of the author’s degree of collaboration, collaboration rate, the first author’s publications, high-productivity authors, the authors’ origins in each year; the distribution of the countries and journals of the authors citing WJG papers was also analyzed. In addition, the indices related to this journal in each year were compared with the data from 6 SCI journals in the field of gastroenterology in the 2012 volume.
RESULTS: A total of 4409 papers in WJG were examined in this study. For the period 2008-2012, the self-citation rate was 8.59%, 6.02%, 5.50%, 4.47% and 5.21%. Of a total of 3898 first authors, 3526 published 1 paper, 291 published 2 papers, 59 published 3 papers, and 22 published 4 or more papers. The origin of WJG authors covered the six continents, and the majority came from Asia, Europe and North America. The number of countries of origin of WJG authors was 65, 66, 61, 65 an 60 for the period 2008-2012. Authors from 66 countries cited a total of 3194 of the 4409 papers, and these citations were found in 1140 journals.
CONCLUSION: The results suggest that WJG has stayed on the track of normal international publication and all the indices of this journal are stable and reasonable.
Author analysis; Bibliometrics; World Journal of Gastroenterology; Science Citation Index
Hepatitis C virus (HCV) infection is one of main causes of hepatocellular carcinoma (HCC) and the prevalence of HCV-associated HCC is on the rise worldwide. It is particularly important and helpful to identify potential markers for screening and early diagnosis of HCC among high-risk individuals with chronic hepatitis C, and to identify target molecules for the prevention and treatment of HCV-associated-HCC. Small non-coding RNAs, mainly microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) with size greater than 200 nucleotides, are likely to play important roles in a variety of biological processes, including development and progression of HCC. For the most part their underlying mechanisms of action remain largely unknown. In recent years, with the advance of high-resolution of microarray and application of next generation sequencing techniques, a significant number of non-coding RNAs (ncRNAs) associated with HCC, particularly caused by HCV infection, have been found to be differentially expressed and to be involved in pathogenesis of HCV-associated HCC. In this review, we focus on recent studies of ncRNAs, especially miRNAs and lncRNAs related to HCV-induced HCC. We summarize those ncRNAs aberrantly expressed in HCV-associated HCC and highlight the potential uses of ncRNAs in early detection, diagnosis and therapy of HCV-associated HCC. We also discuss the limitations of recent studies, and suggest future directions for research in the field. miRNAs, lncRNAs and their target genes may represent new candidate molecules for the prevention, diagnosis and treatment of HCC in patients with HCV infection. Studies of the potential uses of miRNAs and lncRNAs as diagnostic tools or therapies are still in their infancy.
MicroRNA; Long non-coding RNAs; Non-coding RNAs; Hepatitis C virus; Hepatocellular carcinoma
Despite a high prevalence of hepatitis C virus (HCV) infection, the vast majority of persons who inject drugs (PWID) have not engaged in HCV care due to a large number of obstacles. Education about the infection among both PWID and providers remains an important challenge as does discrimination faced by PWID in conventional health care settings. Many providers also remain hesitant to prescribe antiviral therapy due to concerns about adherence and relapse to drug use resulting in reinfection. Presently, however, as a result of improvements in treatment efficacy combined with professional society and government endorsement of HCV treatment for PWID, a pressing need exists to develop strategies to engage these individuals into HCV care. In this article, we propose several strategies that can be pursued in an attempt to engage PWID into HCV management. We advocate that multidisciplinary approaches that utilize health care practitioners from a wide range of specialties, as well as co-localization of medical services, are strategies likely to result in increased numbers of PWID entering into HCV management. Pursuit of HCV therapy after stabilization through drug treatment is an additional strategy likely to increase PWID engagement into HCV care. The full impact of direct acting antivirals for HCV will only be realized if innovative approaches are pursued to engage all HCV infected individuals into treatment.
Treatment of hepatitis C; Viral infection; Human immunodeficiency virus; Hepatitis C virus coinfection; Persons who inject drugs; Obstacles to treatment
Hepatitis C virus (HCV) frequently elicits only mild immune responses so that it can often establish chronic infection. In this case HCV antigens persist and continue to stimulate the immune system. Antigen persistence then leads to profound changes in the infected host’s immune responsiveness, and eventually contributes to the pathology of chronic hepatitis. This topic highlight summarizes changes associated with chronic hepatitis C concerning innate immunity (interferons, natural killer cells), adaptive immune responses (immunoglobulins, T cells, and mechanisms of immune regulation (regulatory T cells). Our overview clarifies that a strong anti-HCV immune response is frequently associated with acute severe tissue damage. In chronic hepatitis C, however, the effector arms of the immune system either become refractory to activation or take over regulatory functions. Taken together these changes in immunity may lead to persistent liver damage and cirrhosis. Consequently, effector arms of the immune system will not only be considered with respect to antiviral defence but also as pivotal mechanisms of inflammation, necrosis and progression to cirrhosis. Thus, avoiding Scylla - a strong, sustained antiviral immune response with inital tissue damage - takes the infected host to virus-triggered immunopathology, which ultimately leads to cirrhosis and liver cancer - the realm of Charybdis.
Natural killer cells; CD4+ T helper cells; Regulatory T cells; Interferon; Hepatitis C; Hepatic stellate cells; Hepatocytes; Immunoglobulin; Retinoic acid inducible gene-I; Toll like receptors
Tumor necrosis factor-α (TNF-α) inhibitors are known to increase reactivation of concurrent chronic hepatitis B, but their impact on the hepatitis C virus (HCV) is controversial. Some conditions of immunosuppression, such as liver transplantation, typically cause an increase in the rate of HCV evolution. Inhibition of TNF-α, a cytokine involved in the apoptotic signaling pathway of hepatocytes infected by HCV, could potentially increase viral replication. Currently available clinical data appear to contradict this hypothesis. A review of medical literature revealed that a total of 216 patients with HCV were exposed to one or more treatments with TNF-α inhibitors, with a median observation time of 1.2 years and 260 cumulative patient-years of exposure. Only three cases of drug withdrawal due to suspected HCV liver disease recrudescence were reported. Treatment with TNF-α inhibitors in patients with HCV infection appears to be safe in the short term, but there are insufficient data to assess their long-term safety. Universal screening for HCV before beginning treatment with TNF-α inhibitors is currently controversial. The presence of HCV is not a contraindication to therapy with TNF-α inhibitors, with the exception of cirrhotic patients. In cases of cirrhosis, the benefit/risk ratio should be evaluated at the individual level. Prior to treatment with TNF-α inhibitors, patients with HCV should be referred to a hepatologist to determine the necessity of hepatic disease assessment, using liver biopsy or non-invasive methods, and the potential indication for antiviral therapy. In patients with HCV infection who are treated with TNF-α inhibitors, liver function monitoring every three months is advised.
Infliximab; Etanercept; Adalimumab; Hepatitis C virus; Rheumatoid arthritis; Inflammatory bowel disease; Psoriasis
The relationships between lymphomas and their microenvironment appear to follow 3 major patterns: (1) an independent pattern; (2) a dependent pattern on deregulated interactions; and (3) a dependent pattern on regulated coexistence. Typical examples of the third pattern are hepatitis C virus (HCV)-associated marginal zone lymphomas (MZLs) and mucosa-associated lymphoid tissue lymphomas. In these lymphomas, a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs. At least initially, however, tumor development and cell growth largely depend on external signals from the microenvironment, such as viral antigens, cytokines, and cell-cell interactions. The association between HCV infection and B-cell lymphomas is not completely defined, although this association has been demonstrated by epidemiological studies. MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection. Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis; antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas. Recently, antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas. Importantly, clinically responses were linked to the eradication of the HCV-RNA, providing a strong argument in favor of a causative link between HCV and lymphoproliferation.
Hepatitis C virus-infection; B-cell lymphomas; Marginal zone lymphoma; Mucosa-associated lymphoid tissue lymphomas; Diffuse large B-cell lymphomas; Microenvironment
Hepatitis C virus (HCV) is a major health burden infecting 170-210 million people worldwide. Additional 3-4 millions are newly-infected annually. Prevalence of pediatric infection varies from 0.05%-0.36% in the United States and Europe; up to 1.8%-5.8% in some developing countries. The highest prevalence occurs in Egypt, sub-Saharan Africa, Amazon basin and Mongolia. HCV has been present in some populations for several centuries, notably genotypes 1 and 2 in West Africa. Parenteral anti-schistosomal therapy practiced in the 1960s until the early 1980s had spread HCV infection throughout Egypt. Parenteral acquisition of HCV remains a major route for infection among Egyptian children. Insufficient screening of transfusions, unsterilized injection equipment and re-used needles and syringes continue to be major routes of HCV transmission in developing countries, whereas vertical transmission and adolescent high-risk behaviors (e.g., injection drug abuse) are the major routes in developed countries. The risk of vertical transmission from an infected mother to her unborn/newborn infant is approximately 5%. Early stages of HCV infection in children do not lead to marked impairment in the quality of life nor to cognitive, behavioral or emotional dysfunction; however, caregiver stress and family system strain may occur. HCV slowly progresses to serious complications as cirrhosis (1%-2%) and hepatocellular carcinoma (HCC) especially in the presence of risk factors as hemolytic anemias, obesity, treated malignancy, and concomitant human immune deficiency and/or hepatitis B virus co-infection. HCV vaccine remains elusive to date. Understanding the immune mechanisms in patients who successfully cleared the infection is essential for vaccine development. The pediatric standard of care treatment consists of pegylated interferon-α 2a or b plus ribavirin for 24-48 wk. The new oral direct acting antivirals, approved for adults, need further evaluation in children. Sustained virologic response varies depending on the viral load, genotype, duration of infection, degree of aminotransferase elevation, adiposity and single nucleotide polymorphisms of interleukin (IL)-28B locus. The goals of treatment in individual patients are virus eradication, prevention of cirrhosis and HCC, and removing stigmatization; meanwhile the overall goal is decreasing the global burden of HCV. IL-28B polymorphisms have been also associated with spontaneous clearance of vertically acquired HCV infection. The worldwide economic burden of HCV for children, families and countries is estimated to be hundreds of millions of US dollars per year. The United States, alone, is estimated to spend 199-336 million dollars in screening, monitoring and treatment during one decade. The emotional burden of having an HCV infected child in a family is more difficult to estimate.
Hepatitis C virus; Burden; Genotypes; Cost; Pediatrics
It has been reported that the direct binding of hepatitis C virus (HCV) and/or the replication of HCV in the extrahepatic organs and, especially, lymphoid cells, might affect the pathogenesis of extrahepatic diseases with HCV infection. More than one decade ago, several reports described the existence of HCV-RNA in peripheral blood mononuclear cells. Moreover, many reports describing the existence of HCV in B lymphocytes and B cell lymphoma have been published. In addition to B lymphocytes, it was reported that HCV replication could be detected in T lymphocytes and T cell lines. Among the extrahepatic diseases with HCV infection, mixed cryoglobulinemia-related diseases and autoimmune-related diseases are important for understanding the immunopathogensis of HCV persistent infection. Moreover, HCV persistent infection can cause malignant lymphoma. The biological significance of lymphotropic HCV has not yet become clear. However, several candidates have been considered for a long time. One is that lymphotropic HCV is an HCV reservoir that might contribute to the recurrence of HCV infection and difficult-to-treat disease status. The other important issue is the carcinogenesis of the lymphoid cells and disturbances of the immune responses. Therefore, the extrahepatic diseases might be induced by direct interaction between HCV and lymphoid cells. In this article, we summarize various studies showing the direct effect of HCV on lymphoid cells and discuss the biological significance of lymphotropic HCV.
Hepatitis C virus; Lymphotropism; T cell; B cell; Immunology
This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus (HCV) infection over the last few decades. The information based on published literature provides an update on these two aspects of HCV. HCV infection, previously called blood transmitted non-A, non-B infection, is prevalent globally and poses a serious public health problem worldwide. The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction (PCR) technique. Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles. Moreover, multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes. In contrast to previous methods, the newly developed assays are not only fast and economic, but also resolve the problem of the window period as well as differentiate present from past infection. HCV is a non-cytopathic virus, thus, its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress, insulin resistance and hepatic steatosis. Both innate and adaptive immunity play an important role in HCV pathogenesis. Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins, HCV-quasispecies and several metabolic factors regulating liver metabolism. HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.
Hepatitis C virus; Diagnosis; Pathogenesis; Immunity; Steatosis
In the 1970s, scientists learned of a new pathogen causing non-A, non-B hepatitis. Classical approaches were used to isolate and characterize this new pathogen, but it could be transmitted experimentally only to chimpanzees and progress was slow until the pathogen was identified as hepatitis C virus (HCV) in 1989. Since then, research and treatment of HCV have expanded with the development of modern biological medicine: HCV genome organization and polyprotein processing were delineated in 1993; the first three-dimensional structure of HCV nonstructural protein (NS3 serine protease) was revealed in 1996; an infectious clone of HCV complementary DNA was first constructed in 1997; interferon and ribavirin combination therapy was established in 1998 and the therapeutic strategy gradually optimized; the HCV replicon system was produced in 1999; functional HCV pseudotyped viral particles were described in 2003; and recombinant infectious HCV in tissue culture was produced successfully in 2005. Recently, tremendous advances in HCV receptor discovery, understanding the HCV lifecycle, decryption of the HCV genome and proteins, as well as new anti-HCV compounds have been reported. Because HCV is difficult to isolate and culture, researchers have had to avail themselves to the best of modern biomedical technology; some of the major achievements in HCV research have not only advanced the understanding of HCV but also promoted knowledge of virology and cellular physiology. In this review, we summarize the advancements and remaining scotomas in the molecular virology and epidemiology of HCV.
Hepatitis C virus; Hepatitis C virus lifecycle; Molecular virology; Hepatitis C virus models; Epidemiology
Extended hepatectomy, or liver transplantation of reduced-size graft, can lead to a pattern of clinical manifestations, namely “post-hepatectomy liver failure” and “small-for-size syndrome” respectively, that can range from mild cholestasis to irreversible organ non-function and death of the patient. Many mechanisms are involved in their occurrence but in the recent past, high portal blood flow through a relatively small liver vascular bed has taken a central role. Therefore, several techniques of inflow modulation have been attempted in cases of portal hyperperfusion first in liver transplantation, such as portocaval shunt, mesocaval shunt, splenorenal shunt, splenectomy or ligation of the splenic artery. However, high portal flow is not the only factor responsible, and before major liver resections, preoperative assessment of the residual liver function is necessary. Techniques such as portal vein embolization or portal vein ligation can be adopted to increase the future liver volume, preventing post-hepatectomy liver failure. More recently, a new surgical procedure, that combines in situ splitting of the liver and portal vein ligation, has gradually come to light, inducing remarkable hypertrophy of the healthy liver in just a few days. Further studies are needed to confirm this hypothesis and overcome one of the biggest issues in the field of liver surgery.
Small-for-size syndrome; Liver transplantation; Extended hepatectomy; Liver failure; Cirrhosis
This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas (AISP). We covered the main diseases associated with exocrine pancreatic insufficiency (EPI) which are of common interest to internists/gastroenterologists, oncologists and surgeons, fully aware that EPI may also occur together with many other diseases, but less frequently. A preliminary manuscript based on an extended literature search (Medline/PubMed, Cochrane Library and Google Scholar) of published reports was prepared, and key recommendations were proposed. The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012. Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached. The final draft of the manuscript was then sent to the AISP Council for approval and/or modification. All concerned parties approved the final version of the manuscript in June 2013.
Exocrine pancreatic insufficiency; Chronic pancreatitis; Gastric surgery; Pancreatic surgery; Pancreatic neoplasms; Risk factors; Clinical studies
In spite of the introduction in therapy of highly effective biological agents, glucocorticoids (GCs) are still employed to induce remission in moderate to severe inflammatory bowel diseases (IBD), but considerable inter-individual differences in their efficacy and side effects have been reported. The effectiveness of these drugs is indeed very variable and side effects, particularly severe in pediatric patients, are common and often unpredictable: the understanding of the complex gene regulation mediated by GCs could shed light on the causes of this variability. In this context, microRNAs (miRNAs) represent a new and promising field of research. miRNAs are small non-coding RNA molecules that suppress gene expression at post-transcriptional level, and are fine-tuning regulators of diverse biological processes, including the development and function of the immune system, apoptosis, metabolism and inflammation. Emerging data have implicated the deregulated expression of certain miRNA networks in the pathogenesis of autoimmune and inflammatory diseases, such as IBD. There is a great interest in the identification of the role of miRNAs in the modulation of pharmacological response; however, the association between miRNA and GC response in patients with IBD has not yet been evaluated in a prospective clinical study. The identification of miRNAs differently expressed as a consequence of GC treatment in comparison to diagnosis, represents an important innovative approach that could be translated into clinical practice. In this review we highlight the altered regulation of proteins involved in GC molecular mechanism by miRNAs, and their potential role as molecular markers useful for predicting in advance GC response.
Glucocorticoids; Inflammatory bowel diseases; MicroRNA; Molecular markers; Pharmacogenomics
Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the second leading cause of cancer death in both men and women in the United States, with about 142820 new cases and 50830 deaths expected in 2013. Metastatic disease (mCRC) remains a challenge for oncologists worldwide due to its potential comorbidities. Recently, chemotherapy regimens containing 5-fluorouracil, leucovorin, oxaliplatin and irinotecan combinations are a standard of care in the metastatic disease. Currently, biological therapies involving vascular endothelial growth factor and epidermal growth factor receptor pathways, such as bevacizumab and cetuximab, have emerged as good option for improving mCRC patient survival. Now, aflibercept plus standard chemotherapy has also been approved in second line regimen for mCRC patients. Our review will discuss novel biological drugs and their indications for mCRC patients and will bring future perspectives in this regard.
Colorectal cancer; Bevacizumab; Cetuximab; Aflibercept; FOLFOX; FOLFIRI
Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide.
Alcohol; Genes; Alcoholism; Alcohol dependence; Alcohol addiction; Alcohol abuse; Alcoholic liver cirrhosis; Anthropology
Hepatic resection had an impressive growth over time. It has been widely performed for the treatment of various liver diseases, such as malignant tumors, benign tumors, calculi in the intrahepatic ducts, hydatid disease, and abscesses. Management of hepatic resection is challenging. Despite technical advances and high experience of liver resection of specialized centers, it is still burdened by relatively high rates of postoperative morbidity and mortality. Especially, complex resections are being increasingly performed in high risk and older patient population. Operation on the liver is especially challenging because of its unique anatomic architecture and because of its vital functions. Common post-hepatectomy complications include venous catheter-related infection, pleural effusion, incisional infection, pulmonary atelectasis or infection, ascites, subphrenic infection, urinary tract infection, intraperitoneal hemorrhage, gastrointestinal tract bleeding, biliary tract hemorrhage, coagulation disorders, bile leakage, and liver failure. These problems are closely related to surgical manipulations, anesthesia, preoperative evaluation and preparation, and postoperative observation and management. The safety profile of hepatectomy probably can be improved if the surgeons and medical staff involved have comprehensive knowledge of the expected complications and expertise in their management. This review article focuses on the major postoperative issues after hepatic resection and presents the current management.
Hepatectomy; Postoperative complication; Management
Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension. This experimental model causes minimal alternations in the liver, thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension. Low-grade splanchnic inflammation after long-term triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy. In fact, we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans. Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension. Among the systemic impairments, aortopathy characterized by oxidative stress, increased levels of proinflammatory cytokines and profibrogenic mediators stand out. In this experimental model of long-term triple portal vein ligated-rats, the abdominal aortic proinflammatory response could be attributed to oxidative stress. Thus, the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation. Also, oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis. The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension.
Portal hypertension; Inflammation; Aortopathy; Hepatic steatosis
AIM: To characterize the nuclear import of hepatitis B virus (HBV) polymerase (P) and its relevance for the viral life cycle.
METHODS: Sequence analysis was performed to predict functional motives within P. Phosphorylation of P was analyzed by in vitro phosphorylation. Phosphorylation site and nuclear localization signal (NLS) were destroyed by site directed mutagenesis. Functionality of the identified NLS was analyzed by confocal fluorescence microscopy and characterizing the karyopherin binding. Relevance of the structural motives for viral life cycle was studied by infection of primary Tupaia hepatocytes with HBV.
RESULTS: We identified by sequence alignment and functional experiments a conserved bipartite NLS containing a casein kinase II (CKII) phosphorylation site located within the terminal protein domain (TP) of the HBV polymerase. Inhibition of CKII impairs the functionality of this NLS and thereby prevents the nuclear import of the polymerase. Binding of the import factor karyopherin-α2 to the polymerase depends on its CKII-mediated phosphorylation of the bipartite NLS. In HBV-infected primary Tupaia hepatocytes CKII inhibition in the early phase (post entry phase) of the infection process prevents the establishment of the infection.
CONCLUSION: Based on these data it is suggested that during HBV infection the final import of the genome complex into the nucleus is mediated by a novel bipartite NLS localized in the TP domain of HBV polymerase.
Hepatitis B virus; Nuclear localization signal; Casein kinase II; Trafficking; Replication
AIM: To assess the acceptance, safety and efficacy of care and treatment for chronic hepatitis C (CHC) in drug addicts.
METHODS: We designed a multidisciplinary, phase IV prospective cohort study. All illicit drug users (IDUs) visited a Territorial Addiction Service (SerT) in the District of Brescia, and hepatitis C antibody (HCVAb) testing positive were offered as part of a standardised hepatologic visit in our Gastroenterology Unit. Patients with confirmed CHC and without medical contraindications were administered peginterferon alfa-2b 1.5 μg/kg per week plus ribavirin (800-1400 mg/d) for 16-48 wk. All IDUs were unselected because of ongoing addiction and read and signed an informed consent form. Virologic responses at weeks 4 and 12 of therapy, at the end of treatment and 24 wk after the end of treatment were the main measures of efficacy. Adherence was estimated according to the 80/80/80 criteria.
RESULTS: From November 2007 to December 2009, 162 HCVAb+ IDUs were identified. Sixty-seven patients (41% of the initial cohort) completed the diagnostic procedure, and CHC was diagnosed in 54 (33% of the total). Forty-nine patients were offered therapy, and 39 agreed (80% of acceptance rate). The prevalent HCV genotype was type 1, and the HCV RNA baseline level was over 5.6 log/mL in 61% of cases. Five patients dropped out, two because of severe adverse events (SAEs) and three without medical need. Twenty-three and 14 patients achieved end of treatment responses (ETRs; 59%) and sustained virologic responses (SVRs; 36%), respectively. Thirty-one patients were fully compliant with the study protocol (80% adherence). The prevalence of host and viral characteristics negatively affecting the treatment response was high: age over 40 years (54%), male gender (85%), overweight body type (36%), previous unsuccessful antiviral therapy (21%), HCV genotype and viral load (60% and 62%, respectively), earlier contact with HBV (40%) and steatosis and fibrosis (44% and 17%, respectively). In a univariate analysis, alcohol intake was associated with a non-response (P = 0.0018, 95%CI: 0.0058-0.4565).
CONCLUSION: Drug addicts with CHC can be successfully treated in a multidisciplinary setting using standard antiviral combination therapy, despite several “difficult to reach, manage and treat” characteristics.
Chronic hepatitis C; Addiction; Antiviral therapy; Interferon; Multidisciplinary
AIM: To investigate the expression of the hepatitis B virus (HBV) 1.3-fold genome plasmid (pHBV1.3) in an immortalized mouse hepatic cell line induced by SV40 T-antigen (SV40T) expression.
METHODS: Mouse hepatic cells were isolated from mouse liver tissue fragments from 3-5 d old Kunming mice by the direct collagenase digestion method and cultured in vitro. The pRSV-T plasmid was transfected into mouse hepatic cells to establish an SV40LT-immortalized mouse hepatic cell line. The SV40LT-immortalized mouse hepatic cells were identified and transfected with the pHBV1.3 plasmid. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the supernatant were determined by an electrochemiluminescence immunoassay at 24, 48, 72 and 96 h after transfection. The expressions of HBsAg and hepatitis B c antigen (HBcAg) in the cells were investigated by indirect immunofluorescence analysis. The presence of HBV DNA replication intermediates in the transfected cells and viral particles in the supernatant of the transfected cell cultures was monitored using the Southern hybridization assay and transmission electronic microscopy, respectively.
RESULTS: The pRSV-T plasmid was used to immortalize mouse hepatocytes and an SV40LT-immortalized mouse hepatic cell line was successfully established. SV40LT-immortalized mouse hepatic cells have the same morphology and growth characteristics as primary mouse hepatic cells can be subcultured and produce albumin and cytokeratin-18 in vitro. Immortalized mouse hepatic cells did not show the characteristics of tumor cells, as alpha-fetoprotein levels were comparable (0.58 ± 0.37 vs 0.61 ± 0.31, P = 0.37). SV40LT-immortalized mouse hepatic cells were then transfected with the pHBV1.3 plasmid, and it was found that the HBV genome replicated in SV40LT-immortalized mouse hepatic cells. The levels of HBsAg and HBeAg continuously increased in the supernatant after the transfection of pHBV1.3, and began to decrease 72 h after transfection. The expressions of HBsAg and HBcAg were observed in the pHBV1.3-transfected cells. HBV DNA replication intermediates were also observed at 72 h after transfection, including relaxed circular DNA, double-stranded DNA and single-stranded DNA. Furthermore, a few 42 nm Dane particles, as well as many 22 nm subviral particles with a spherical or filamentous shape, were detected in the supernatant.
CONCLUSION: SV40T expression can immortalize mouse hepatic cells, and the pHBV1.3-transfected SV40T-immortalized mouse hepatic cell line can be a new in vitro cell model.
SV40 T-antigen; Mouse hepatic cell; Hepatitis B virus 1.3-fold genome plasmids; Immortalized; Liposomes; Transfection
AIM: To evaluate the three-dimensional (3-D) representation performance of 4 publicly available Shape-from-Shading (SfS) algorithms in small-bowel capsule endoscopy (SBCE).
METHODS: SfS techniques recover the shape of objects using the gradual variation of shading. There are 4 publicly available SfS algorithms. To the best of our knowledge, no comparative study with images obtained during clinical SBCE has been performed to date. Three experienced reviewers were asked to evaluate 54 two-dimensional (2-D) images (categories: protrusion/inflammation/vascular) transformed to 3-D by the aforementioned SfS 3-D algorithms. The best algorithm was selected and inter-rater agreement was calculated.
RESULTS: Four publicly available SfS algorithms were compared. Tsai’s SfS algorithm outperformed the rest (selected as best performing in 45/54 SBCE images), followed by Ciuti’s algorithm (best performing in 7/54 images) and Torreão’s (in 1/54 images). In 26/54 images; Tsai’s algorithm was unanimously selected as the best performing 3-D representation SfS software. Tsai’s 3-D algorithm superiority was independent of lesion category (protrusion/inflammatory/vascular; P = 0.678) and/or CE system used to obtain the 2-D images (MiroCam®/PillCam®; P = 0.558). Lastly, the inter-observer agreement was good (kappa = 0.55).
CONCLUSION: 3-D representation software offers a plausible alternative for 3-D representation of conventional capsule endoscopy images (until optics technology matures enough to allow hardware enabled-“real” 3-D reconstruction of the gastrointestinal tract).
Capsule endoscopy; Small-bowel; Three-dimensional; Software; Algorithm; Reconstruction; Technology; Advance
AIM: To describe and analyse factors associated with Clostridium difficile infection (CDI) severity in hospitalised medical intensive care unit patients.
METHODS: We performed a retrospective cohort study of 40 patients with CDI in a medical intensive care unit (MICU) at a French university hospital. We include patients hospitalised between January 1, 2007 and December 31, 2011. Data on demographics characteristics, past medical history, CDI description was collected. Exposure to risk factors associated with CDI within 8 wk before CDI was recorded, including previous hospitalisation, nursing home residency, antibiotics, antisecretory drugs, and surgical procedures.
RESULTS: All included cases had their first episode of CDI. The mean incidence rate was 12.94 cases/1000 admitted patients, and 14.93, 8.52, 13.24, 19.70, and 8.31 respectively per 1000 admitted patients annually from 2007 to 2011. Median age was 62.9 [interquartile range (IQR) 55.4-72.40] years, and 13 (32.5%) were women. Median length of MICU stay was 14.0 d (IQR 5.0-22.8). In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. The duration of diarrhoea was 13.0 (8.0-19.5) d. In addition to diarrhoea, the clinical symptoms of CDI were fever (> 38 °C) in 23 patients, abdominal pain in 15 patients, and ileus in 1 patient. Prior to CDI, 38 patients (95.0%) were exposed to antibiotics, and 12 (30%) received at least 4 antibiotics. Fluoroquinolones, 3rd generation cephalosporins, coamoxiclav and tazocillin were prescribed most frequently (65%, 55%, 40% and 37.5%, respectively). The majority of cases were hospital-acquired (n = 36, 90%), with 5 cases (13.9%) being MICU-acquired. Fifteen patients had severe CDI. The crude mortality rate within 30 d after diagnosis was 40% (n = 16), with 9 deaths (9 over 16; 56.3%) related to CDI. Of our 40 patients, 15 (37.5%) had severe CDI. Multivariate logistic regression showed that male gender [odds ratio (OR): 8.45; 95%CI: 1.06-67.16, P = 0.044], rising serum C-reactive protein levels (OR = 1.11; 95%CI: 1.02-1.21, P = 0.021), and previous exposure to fluoroquinolones (OR = 9.29; 95%CI: 1.16-74.284, P = 0.036) were independently associated with severe CDI.
CONCLUSION: We report predictors of severe CDI not dependent on time of assessment. Such factors could help in the development of a quantitative score in ICU’s patients.
Clostridium difficile; Health-care associated infection; Hospital-acquired infection; Intensive care unit; Nosocomial infection; Severe Clostridium difficile infection
AIM: To study the prognosis (recurrence and mortality) of patients with ischemic colitis (IC).
METHODS: This study was conducted in four Spanish hospitals, participants in the Ischemic Colitis in Spain study We analyzed prospectively 135 consecutive patients who met criteria for definitive or probable IC according to Brandt criteria, and follow up these patients during the next five years, retrospectively. Long-term results (recurrence and mortality) were evaluated retrospectively after a median interval of 62 mo (range 54-75 mo).
RESULTS: Estimated IC recurrence rates were 2.9%, 5.1%, 8.1% and 9.7% at years 1, 2, 3 and 5 years, respectively. Five-year survival was 69% (93 of 135) and 24% (10 of 42 patients) died for causes related to the IC. Among these 10 patients, 8 died in their first episode at hospital (4 had gangrenous colitis and 4 fulminant colitis) and 2 due to recurrence.
CONCLUSION: The five-year recurrence rate of IC was low. On the other hand, mortality during follow-up was high and was not associated with ischemic colitis.
Colonic; Ischemic; Recurrence; Follow-up; Mortality