Digestive and Liver Disease

Editorial Board

2010-04-01

Introduction to Mini-Symposium on Cholangiocyte Pathophysiology—Part I

Gianfranco Alpini — 2010-02-22

It is my great pleasure to present in this issue of Digestive and Liver Disease, Part I of the 2010 Mini-Symposium on Cholangiocyte Pathophysiology, for which I have gladly accepted the role of Guest Editor. For this collection of articles, the Editorial Board has invited an impressive line-up of renowned international experts to write comprehensive and up-to-date reviews on a wide range of topics centered on cholangiocyte proliferation, differentiation, and mechanisms of disease. To all the dedicated Authors whose efforts made this series possible I would like to extend the gratitude of the Editorial Board, and congratulate them for the outstanding quality of their manuscripts. I am confident that these articles will benefit both researchers and clinicians alike, and I look forward to enriching the series in upcoming issues of the Journal throughout the year.

Clinical implications of novel aspects of biliary pathophysiology

2010-02-18

Abstract: Cholangiocytes are the epithelial cells that line the biliary tree; they are the target of chronic diseases termed cholangiopathies, which represent a daily challenge for clinicians, since definitive medical treatments are not available yet.It is generally accepted that the progression of injury in the course of cholangiopathies, and promotion and progression of cholangiocarcinoma are at least in part due to the failure of the cholangiocytes’ mechanisms of adaptation to injury.Recently, several studies on the pathophysiology of the biliary epithelium have shed some light on the mechanisms that govern cholangiocyte response to injury. These studies provide novel information to help interpret some of the clinical aspects of cholangiopathies and cholangiocarcinoma; the purpose of this review is thus to describe some of these novel findings, focusing on their significance from a clinical perspective.

Recent advances in the regulation of cholangiocyte proliferation and function during extrahepatic cholestasis

2010-02-15

Abstract: Bile duct epithelial cells (i.e., cholangiocytes), which line the intrahepatic biliary epithelium, are the target cells in a number of human cholestatic liver diseases (termed cholangiopathies). Cholangiocyte proliferation and death is present in virtually all human cholangiopathies. A number of recent studies have provided insights into the key mechanisms that regulate the proliferation and function of cholangiocytes during the pathogenesis of cholestatic liver diseases. In our review, we have summarised the most important of these recent studies over the past 3 years with a focus on those performed in the animal model of extrahepatic bile duct ligation. In the first part of the review, we provide relevant background on the biliary ductal system. We then proceed with a general discussion of the factors regulating biliary proliferation performed in the cholestatic animal model of bile duct ligation. Further characterisation of the factors that regulate cholangiocyte proliferation and function will help in elucidating the mechanisms regulating the pathogenesis of biliary tract diseases in humans and in devising new treatment approaches for these devastating diseases.

Cholangiocarcinoma: Update and future perspectives

2010-01-25

Abstract: Cholangiocarcinoma is commonly considered a rare cancer. However, if we consider the hepato-biliary system a single entity, cancers of the gallbladder, intra-hepatic and extra-hepatic biliary tree altogether represent approximately 30% of the total with incidence rates close to that of hepatocellular carcinoma, which is the third most common cause of cancer-related death worldwide. In addition, cholangiocarcinoma is characterized by a very poor prognosis and virtually no response to chemotherapeutics; radical surgery, the only effective treatment, is not frequently applicable because late diagnosis. Biomarkers for screening programs and for follow-up of categories at risk are under investigation, however, currently none of the proposed markers has reached clinical application. For all these considerations, cancers of the biliary tree system should merit much more scientific attention also because a progressive increase in incidence and mortality for these cancers has been reported worldwide. This manuscript deals with the most recent advances in the epidemiology, biology and clinical presentation of cholangiocarcinoma.

Polycystic liver diseases

2010-02-08

Abstract: Polycystic liver diseases (PCLDs) are genetic disorders with heterogeneous etiologies and a range of phenotypic presentations. PCLD exhibits both autosomal or recessive dominant pattern of inheritance and is characterized by the progressive development of multiple cysts, isolated or associated with polycystic kidney disease, that appear more extensive in women. Cholangiocytes have primary cilia, functionally important organelles (act as mechanosensors) that are involved in both normal developmental and pathological processes. The absence of polycystin-1, 2, and fibrocystin/polyductin, normally localized to primary cilia, represent a potential mechanism leading to cyst formation, associated with increased cell proliferation and apoptosis, enhanced fluid secretion, abnormal cell–matrix interactions, and alterations in cell polarity. Proliferative and secretive activities of cystic epithelium can be regulated by estrogens either directly or by synergizing growth factors including nerve growth factor, IGF1, FSH and VEGF.The abnormalities of primary cilia and the sensitivity to proliferative effects of estrogens and different growth factors in PCLD cystic epithelium provide the morpho-functional basis for future treatment targets, based on the possible modulation of the formation and progression of hepatic cysts.

Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease: A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee

2010-02-22

Abstract: We report the evidence-based Italian Association for the Study of Liver guidelines for the appropriate diagnosis and management of patients with nonalcoholic fatty liver disease in clinical practice and its related research agenda.The prevalence of nonalcoholic fatty liver disease varies according to age, gender and ethnicity. In the general population, the prevalence of nonalcoholic fatty liver disease is about 25% and the incidence is of two new cases/100 people/year. 2–3% of individuals in the general population will suffer from nonalcoholic steatohepatitis. Uncomplicated steatosis will usually follow a benign course. Individuals with nonalcoholic steatohepatitis, however, have a reduced life expectancy, mainly owing to vascular diseases and liver-related causes. Moreover, steatosis has deleterious effects on the natural history of HCV infection.Nonalcoholic fatty liver disease is usually diagnosed in asymptomatic patients prompted by the occasional discovery of increased liver enzymes and/or of ultrasonographic steatosis. Medical history, complete physical examination, etiologic screening of liver injury, liver biochemistry tests, serum lipids and insulin sensitivity tests should be performed in every patient. Occult alcohol abuse should be ruled out.Ultrasonography is the first-line imaging technique. Liver biopsy, the gold standard in diagnosis and prognosis of nonalcoholic fatty liver disease, is an invasive procedure and its results will not influence treatment in most cases but will provide prognostic information. Assessment of fibrosis by composite scores, specific laboratory parameters and transient elastography might reduce the number of nonalcoholic fatty liver disease patients requiring liver biopsy.Dieting and physical training reinforced by behavioural therapy are associated with improved nonalcoholic fatty liver disease.Diabetes and the metabolic syndrome should be ruled out at timed intervals in nonalcoholic fatty liver disease. Nonalcoholic steatohepatitis patients should undergo periodic evaluation of cardiovascular risk and of advancement of their liver disease; those with nonalcoholic steatohepatitis-cirrhosis should be evaluated for early diagnosis of hepatocellular carcinoma.

Maintenance ribavirin monotherapy: The case for post-transplantation recurrent hepatitis C

Christian Trepo, Francois Bailly — 2010-03-02

Hepatitis C is a world pandemic with more than 175 million people affected world wide. As a leading cause of cirrhosis and hepatocellular carcinoma it is a major health problem.

A new way for improving the quality of colonoscopy?

Giorgio Minoli, Franco Radaelli — 2010-02-08

Colonoscopy is currently regarded as the “gold standard” for diagnosing diseases of colon and rectum; it also plays a key role in colorectal cancer screening, as either a primary approach in average-risk subjects or a second level test in asymptomatic individuals with positive faecal occult test or abnormal findings at CT colonography.

Helicobacter pylori first-line treatment and rescue option containing levofloxacin in patients allergic to penicillin

2009-07-27

Abstract: Aim: To assess the efficacy and tolerability of Helicobacter pylori first-line treatment (omeprazole–clarithromycin–metronidazole) and second-line rescue option (omeprazole–clarithromycin–levofloxacin) in patients allergic to penicillin.Methods: Patients: Prospective multicenter study including consecutive patients allergic to penicillin. Therapy regimens: First-line treatment (50 patients): Omeprazole (20mg b.i.d.), clarithromycin (500mg b.i.d.) and metronidazole (500mg b.i.d.) for 7 days. Second-line treatment (15 therapy failures out of the aforementioned 50 patients): Omeprazole (20mg b.i.d.), clarithromycin (500mg b.i.d.) and levofloxacin (500mg b.i.d.) for 10 days. Outcome variable: Negative 13C-urea breath test 8 weeks after completion of treatment.Results: (1) First-line treatment (omeprazole–clarithromycin–metronidazole): Per-protocol and intention-to-treat eradication rates were 55% (27/49; 95%CI=40–70%) and 54% (27/50; 95%CI=39–69%). Compliance with treatment and follow-up was complete in 98% of cases (one patient was not compliant due to nausea). Adverse events were reported in 5 patients (10%): 4 nausea, 1 diarrhoea. (2) Second-line treatment (omeprazole–clarithromycin–levofloxacin): Per-protocol and intention-to-treat eradication rates were both 73% (11/15; 95%CI=45–92%). Compliance with treatment and follow-up was complete in all the cases. Adverse events were reported in 4 patients (20%), which did not prevent the completion of treatment: Mild nausea (2 patients), and vomiting and myalgias/arthralgias (1 patient).Conclusion: In H. pylori infected patients allergic to penicillin, the generally recommended first-line treatment with omeprazole, clarithromycin and metronidazole has low efficacy for curing the infection. On the other hand, a levofloxacin-containing regimen (together with omeprazole and clarithromycin) represents an encouraging second-line alternative in the presence of penicillin allergy.

Colon anatomy based on CT colonography and fluoroscopy: Impact on looping, straightening and ancillary manoeuvres in colonoscopy

Axel Eickhoff, Perry J. Pickhardt, Dirk Hartmann, Jürgen F. Riemann — 2009-06-08

Abstract: Background: Unsedated colonoscopy is an uncomfortable procedure for most patients. Discomfort during colonoscopy is largely related to looping of the colonoscope which displaces the colon from its native configuration. Therefore, complete intubation of the colon is considerably difficult in up to 10–20% of procedures. Aims of this study were to determine the “normal” colon anatomy in CT-colonoscopy with special focus on length, number of flexures and tortuosity and to assess frequency and type of looping as well as straightening manoeuvres based on fluoroscopic findings.Methods: 100 consecutive screening patients underwent CT colonography and another 100 cases traditional colonoscopy with fluoroscopic aid. Interactive 3D colon maps and 2D MPR images from virtual procedures were reviewed by two experienced GI-radiologists and GI-endoscopists. Colonoscopy was performed by three board-certified gastroenterologists. Fluoroscopic films of each case were recorded and retrospectively analysed.Results: There was a considerable difference in overall colonic length between CT colonography and conventional colonoscopy (167cm vs. 93.5cm). Number of acute angle flexures and degree of tortuosity was higher in CT colonography than previously assumed. The caecum was reached in 98/100 cases with conventional colonoscopy. Procedures were incomplete due to an obstructing sigmoid cancer and a floppy redundant colon. Looping occurred in 73/100 cases and straightening manoeuvres with fluoroscopy were highly effective in 95%. Looping was more common in older and smaller women.Conclusions: Predictive anatomical factors for potentially difficult endoscopic colonoscopy can be defined by CT colonography. Looping occurs frequently during routine colonoscopy but hindered caecal intubation in only one case. Short-term fluoroscopy is extremely helpful to guide straightening and ancillary manoeuvres and should be used selectively in patients with looping during conventional colonoscopy.

Maintenance ribavirin monotherapy delays fibrosis progression in liver transplant recipients with recurrent hepatitis C at high risk of progression

2009-10-09

Abstract: Background: Fibrosis in liver transplant recipients with recurrent HCV is fast, yet, different patterns of progression are recognized.Aims: To investigate histological findings associated with maintenance ribavirin monotherapy in patients with recurrent HCV transplanted ≥4 years earlier.Methods: 14 recipients at high risk of progression (fibrosis progression rate >0.33 units/year and/or persistently elevated ALT) were assigned to receive ribavirin for 3 years. 11 patients at lower risk of progression (FPR ≤0.33 units/year and normal ALT) as controls. Biopsies were obtained yearly since transplant and 7 consecutive biopsies were evaluated.Results: Improved necroinflammation (reduction ≥2 grading) was observed in 7 treated with ribavirin and 3 untreated patients, while 1 and 3 patients worsened respectively. Fibrosis improved (reduction >1 staging) in 2 ribavirin-treated patients, unchanged in 10 and worsened (increase ≥1 staging) in 2. Fibrosis progression decreased from 0.48±0.27 observed during the 3-year pre-treatment period to 0.04±0.31 units/year (p=0.003) during the 3 years of ribavirin. Among untreated fibrosis remained unchanged in 1 and worsened in 10 (p<0.001), yearly fibrosis progression rate increasing from 0.15±0.17 units/year to 0.42±0.39 units/year (p=0.10).Conclusions: Maintenance ribavirin monotherapy delays fibrosis progression in high risk patients, offering an alternative strategy for those failing to respond to conventional treatment.

An unusual skull lesion in a hepatitis B infected patient

Tao Xu, Wei Chen, Juxiang Chen, Chunyan Xia — 2009-02-02

A 47-year-old man, who had a history of chronic hepatitis B infection for 20 years, found a painless mass in the frontal region 6 months prior to admission. On admission, neurological examination showed no abnormalities, and serum AFP concentration was 452.50μg/L. Liver function tests were within normal limits. Cranial CT scan showed a 4.0cm×4.0cm×4.0cm, well-defined, dumb-bell shaped, osteolytic mass expanding to the epidural and subcutaneous spaces. The MRI revealed the tumor was homogeneous, of low-signal intensity on a T1-weighted image, low-signal intensity on a T2-weighted image and had an enhancement effect (Fig. 1). Chest and abdominal CT scans demonstrated the presence of multiple nodules located in the right hepatic lobe, and several pulmonary nodules located in the right lung, consistent with primary hepatocellular carcinoma (HCC) metastasized to the lung and skull; the patient underwent surgery. Intraoperatively, the tumor was totally removed, and the dura mater and the affected skull were reconstructed with artificial tissue. The pathological findings confirmed a diagnosis of metastatic HCC (Fig. 2). Although he received a full course of chemotherapy and symptomatic treatment after surgery, he presented with liver failure 10 months later. The patient died 11 months after resection of his skull metastasis.

Comment to “Treating chronic hepatitis C in recovering opiate addicts: Yes, we can”

Vincenzo Guadagnino — 2009-08-26

Sir, I read with great interest the Commentary by Kreek et al. regarding the treatment of chronic hepatitis C in recovering opiate addicts . In their Commentary, the authors detail the American and Italian perspectives in this field and state that the Belfiori et al. study is the first published Italian experience of treating chronic hepatitis C in the SerT setting. I would like to point out that, as cited by Belfiori et al., in 2007 we reported the efficacy of a multidisciplinary standardised management model for chronic hepatitis C in 53 drug addicts in the SerT setting in Italy . Although Belfiori and co-workers reported a slightly lower sustained virological response (50%) than we obtained (58.6%), their conclusions essentially confirm our data.

Author's reply to Comment on “Treating chronic hepatitis C in recovering opiate addicts: Yes, we can”

Paola Piccolo — 2009-08-25

The authors of the commentary published in the April 2009 issue of Digestive and Liver Disease by no means wish to diminish the relevance of the study by Guadagnino et al., who investigated treatment of chronic hepatitis C in former drug addicts receiving agonist or antagonist therapy in 6 Italian drug treatment centres during 2002–2003 . In their study population 56.6% of patients was infected by HCV genotype 3, and was treated with pegylated interferon alpha plus ribavirin for 24 weeks, while the remainder was infected with genotype 1 or 4, and was treated for 48 weeks, as per current guidelines. The overall rate of sustained virological response was similar to that reported in registration trials (58.6%), even though their genotype distribution was more favourable; however the reported drop-out rate of 35.8% was significantly higher than reported in non-addiction settings . With over one third of participants discontinuing therapy prematurely, the feasibility of antiviral treatment within the adopted multi-disciplinary standardized management model cannot be considered entirely successful. Indeed, the principal aim of similar feasibility studies carried out by other investigators is to demonstrate that former opiate addicts receiving proper treatment of addiction with agonist pharmacotherapy can comply – as well as respond – to their antiviral treatment regimen for hepatitis C .

Breast carcinoma presenting as linitis plastica

G. Brandi, E. Campadelli, E. Nobili, O. Leone — 2009-08-21

Gastrointestinal metastases are rare because the gastrointestinal tract is seldom a metastatic site from other types of cancer. Among these, melanoma and breast cancer are the most common .

Can protocol liver biopsy be avoided to evaluate post-transplant hepatitis C recurrence? Transient elastography makes it possible

M.F. Donato, C. Rigamonti, M. Colombo — 2009-08-26

Non-invasive evaluation of recurrent hepatitis C in liver transplanted patients is an unmet clinical need. While protocol liver biopsy (LB) is still the standard of care, it could be potentially avoided in patients with mild/stable hepatitis, by monitoring routine blood chemistries combined with transient elastography (TE) .

Corrigendum to “Menetrier's disease coexisting with ulcerative colitis and sclerosing cholangitis” [Dig. Liver Dis. 40 (2008) 78–80]

I. Hatemi, E. Caglar, D. Atasoy, S. Goksel, A. Dobrucali — 2009-11-02

The corresponding author regrets that author D. Atasoy's name was incorrectly spelled in the original article. The complete and corrected list of authors are given.