Hepatitis: Netherlands

Takkenberg RB, Zaaijer HL, ten Cate DF, Biemond BJ, Jansen PL, Reesink HW. · Academisch Medisch Centrum/Universiteit van Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #19489299 No free full text.

This publication has no abstract.

Kremer AE, Rust C, Eichhorn P, Beuers U, Holdenrieder S. · AMC Liver Center, S1-164, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. · Expert Rev Mol Diagn. · Pubmed #19298138 No free full text.

Abstract: Primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis are the three major immune-mediated liver diseases. The etiologies of primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis are largely unknown, but seem to be influenced by genetic and environmental factors. Autoantibodies can be found in nearly all patients with primary sclerosing cholangitis and autoimmune hepatitis, and in the vast majority of patients with primary sclerosing cholangitis. In addition, autoimmune hepatitis is associated with high concentrations of serum globulins. Enhanced liver cell death by apoptosis has been described in all of these liver diseases, although the precise mechanisms remain unclear. In general, apoptosis can be initiated via an extrinsic pathway that is triggered by engagement of death receptors on the cell surface, or via an intrinsic pathway that is induced by mitochondrial injury and is influenced by members of the Bcl-2 family. In both pathways, effector caspases are finally activated that cleave and degrade cell structures, resulting in the release of apoptotic products into the circulation. New diagnostic tests can detect these apoptotic markers and programmed cell death ligands such as Fas and Fas-ligands, nucleosomes, caspases, cytokeratin fragments, macrophage migration inhibitory factor, soluble intracellular adhesion molecule, natural killer cells group 2D and programmed death ligands. Several of these markers have been found to be altered in tissue and/or blood of immune-mediated liver diseases, some also in nonimmune-mediated liver diseases. Beyond their potential usefulness as additional diagnostic markers, they may be valuable for the estimation of disease severity and therapy monitoring. This review summarizes current knowledge on apoptotic mechanisms, death receptor ligands and circulating apoptotic markers in immune-mediated liver diseases.

Buster EH, Schalm SW, Janssen HL. · Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. · Best Pract Res Clin Gastroenterol. · Pubmed #19187869 No free full text.

Abstract: The practising clinician is currently faced with a number of effective treatment options for chronic hepatitis B, including two formulations of interferon (standard IFN and pegylated IFN) and five nucleos(t)ide analogues (lamivudine, adefovir, entecavir, telbivudine and tenofovir). Treatment strategies can be divided into those aiming for sustained response after discontinuation of therapy and those that need to be maintained by prolonged antiviral therapy. Sustained response is particularly achieved with interferon-based therapy, while treatment-maintained response can be achieved with long-term nucleos(t)ide analogue therapy in the majority of patients. Of currently available drugs for the treatment of chronic hepatitis B, PEG-IFN seems to result in the highest rate of off-treatment sustained response after a 1-year course of therapy. Sustained transition to the immune-control phase (inactive HBsAg carrier state) can be achieved in 30-35% of HBeAg-positive patients and 20-25% of HBeAg-negative patients. Loss of HBsAg has been observed in 11% of both HBeAg-positive and HBeAg-negative patients after 3-4 years. Since hepatitis B virus (HBV) genotype is an important predictor of response to PEG-IFN, determination of HBV genotype is essential in patients in whom sustained off-treatment response is pursued. Aiming for sustained response is of particular interest because many HBV-infected patients are in need of antiviral therapy at a young age and may otherwise require indefinite antiviral therapy.

Boonstra A, Woltman AM, Janssen HL. · Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. · Best Pract Res Clin Gastroenterol. · Pubmed #19187866 No free full text.

Abstract: Hepatitis B (HBV) and hepatitis C (HCV) viruses are the two major causes of chronic liver inflammation worldwide. Despite distinct virologic features, both viruses are preferentially hepatotropic, not directly cytopathic, and elicit liver diseases that share several aspects of their natural history. HBV and HCV infections also share some important features of the adaptive antiviral immune response. We describe the innate immune response in the early phase following infection, and how these early events may influence the development of the adaptive immune response in these two important viral infections. The mechanisms by which high levels of viral antigens, liver immunological features, the presence of regulatory T cells and impaired dendritic cell functions may maintain the HBV- and HCV-specific immunological failure, characteristic of chronic hepatitis B and C patients, are also evaluated.

Leenders MW, Nijkamp MW, Borel Rinkes IH. · Department of Surgery, University Medical Center Utrecht, PO box 85500, Utrecht GA 3508, The Netherlands. · World J Gastroenterol. · Pubmed #19058325 links to  free full text

Abstract: Primary liver cancer remains one of the most lethal malignancies worldwide. Due to differences in prevalence of etiological factors the incidence of primary liver cancer varies among the world, with a peak in East-Asia. As this disease is still lethal in most of the cases, research has to be done to improve our understanding of the disease, offering insights for possible treatment options. For this purpose, animal models are widely used, especially mouse models. In this review, we describe the different types of mouse models used in liver cancer research, with emphasis on genetically engineered mice used in this field. We focus on hepatocellular carcinoma (HCC), as this is by far the most common type of primary liver cancer, accounting for 70%-85% of cases.

Nijhuis M, van Maarseveen NM, Boucher CA. · Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. · Handb Exp Pharmacol. · Pubmed #19048205 No free full text.

Abstract: Resistance development is a major obstacle to antiviral therapy, and all active antiviral agents have shown to select for resistance mutations. Aspects of antiviral resistance development are discussed for specific compounds or drug classes in the previous chapters, while this chapter provides an overview regarding the evolution of different viruses (HIV, HBV, HCV, and Influenza) under pressure of antiviral therapy. Virus replication is an error prone process resulting in a large number of variants (quasispecies) in patients. Resistance evolution under suboptimal therapy can be schematically distinguished into three phases. (1) preexisting variants less sensitive to the respective drug are selected from the quasispecies population, (2) outgrowing variants acquire additional mutations increasing their resistance, and (3) compensatory mutations accumulate to overcome the generally reduced replicative capacity of resistant variants. Successful therapy should be aimed at suppression of all existing viral variants, thus preventing selection of minority species and their subsequent evolution. This implies that the amount of mutations required for first escape to the viral regimen (genetic barrier) should be larger than the expected number of mutations present in viruses in the quasispecies. Accordingly, combination therapy can achieve complete inhibition of replication for most HIV, HBV, and Influenza infected patients without resistance development. However, resistant viruses can become selected under circumstances of suboptimal antiviral therapy and these resistant viruses can be transmitted. Proper use of drugs and worldwide monitoring for the presence and spread of drug resistant viruses are therefore of utmost importance.

Bergmann JF, De Knegt RJ, Janssen HL. · Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Minerva Med. · Pubmed #19034255 No free full text.

Abstract: Current guidelines for chronic Hepatitis C recommend peginterferon-alpha and ribavirin combination therapy for 24 or 48 weeks, based on viral factors (genotype, viral load), host factors (stage of liver disease) and virological response during treatment. The main goal of treatment is eradication of Hepatitis C virus (HCV) infection which is defined by HCV RNA negativity 24 weeks after end of treatment (i.e. sustained virological response, SVR). SVR can be achieved in up to 80% of patients. Most patients, however, experience adverse events during therapy which significantly affect drug compliance and treatment outcome. Several strategies have been evaluated in order to optimize outcome of current peginterferon-based therapy, including higher dosing of peginterferon and/or ribavirin, and adjusting therapy duration. Although some patients might benefit from these optimized treatment schedules, viral eradication remains unachievable in a substantial part of patients. In this perspective, there is a clear need for effective alternative or additional agents, especially as the burden of disease is expected to increase over the next decade. Potential novel antiviral targets are now being identified due to improved understanding of the HCV life cycle. Specifically targeted antiviral therapy for Hepatitis C (STAT-C) is in clinical development and has already shown to increase SVR rate. At this moment, however, SVR can only be achieved when combining new molecules with peginterferon therapy. The role of ribavirin has been questioned, but available evidence suggests that ribavirin has significant impact on treatment outcome and should therefore remain part of antiviral therapy. More than a decade of interferon-based therapy and potential new agents will be reviewed.

Polak WG, Soyama A, Slooff MJ. · Division of Hepatobiliary Surgery & Liver Transplantation, Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands. · Ann Transplant. · Pubmed #19034217 links to  free full text

Abstract: Liver transplantation has a definitive place in the treatment of patients with hepatocellular carcinoma (HCC) in a cirrhotic liver. Patients with a tumor load within the Milan criteria have excellent survival comparable to survival in patients with benign indications. When tumor load exceeds the Milan criteria survival decreases. Staging of patients with HCC in a cirrhotic liver is deficient due to the restrictions of the current imaging modalities. The exact place of tumor controlling therapies during the waiting time for transplantation is not yet clear. No evidence of sufficient level is available as to the efficacy of pre-, per- or postoperative chemotherapy. Promising new drugs are currently tested. This counts also for the use of new immunosuppressant with concomitant tumor suppressive capabilities.

Liu B, Woltman AM, Janssen HL, Boonstra A. · Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · J Leukoc Biol. · Pubmed #18818373 No free full text.

Abstract: Worldwide, chronic viral infections cause major health problems with severe morbidity and mortality. HIV and hepatitis C virus (HCV) manifest themselves as persistent infections, but they are entirely distinct viruses with distinct replication mechanisms, tropism, and kinetics. Coinfections with HCV among people with HIV are emerging as a growing problem. Cellular immune responses play an important role in viral clearance and disease pathogenesis. However, cellular immunity to HIV and HCV is affected severely in chronic patients. Various hypotheses have been proposed to explain the dysfunctional T cell response, including viral escape mutations, exhaustion of the T cell compartment, and the activity of regulatory T cells. Also, modulation of the function of dendritic cells (DC) has been suggested as one of the mechanisms used by persistent viruses to evade the immune system. In this review, we will focus on DC interactions with one murine persistent virus (lymphocytic choriomeningitis virus clone 13) and two human persistent viruses (HIV-1 and HCV), intending to examine if general strategies are used by persistent viruses to modulate the function of DC to improve our understanding of the mechanisms underlying the development and maintenance of viral persistence.

Ruijs WL, Timen A. · Rijksinstituut voor Volksgezondheid en Milieu, Centrum Infectieziektebestrijding, Interne postbak 13, Bilthoven. · Ned Tijdschr Geneeskd. · Pubmed #18807333 No free full text.

Abstract: Guideline 'Needle stick injuries': risk assessment and post-exposure management in practice The objective of the national guideline 'Needle stick injuries' is to make the assessment of needle stick injuries more structured and uniform. The injury is classified as high risk or low risk according to the volume of blood transmitted. For high-risk injuries measures to prevent hepatitis B, hepatitis C and HIV infection have to be considered, whereas for low-risk injuries only measures to prevent hepatitis B. The need for post-exposure prophylaxis is determined by the victim's immunity to hepatitis B and the presence of hepatitis B virus, hepatitis C virus or HIV in the source person. Post-exposure prophylaxis against hepatitis B consists primarily of hepatitis B vaccination; hepatitis B immunoglobulin is added in the case of a high-risk injury with a hepatitis B positive source or a source belonging to a risk group for hepatitis B. In high-risk injuries the victim is tested for hepatitis C and HIV transmission (except in case of a seronegative source). Antiretroviral postexposure prophylaxis is advised for high-risk injuries with a HIV seropositive source or a source belonging to a risk group for HIV.

Kallenberg CG, Tadema H. · Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, The Netherlands. · Autoimmun Rev. · Pubmed #18703171 No free full text.

Abstract: Infections are associated with secondary forms of vasculitis. However, there is increasing evidence that microbial agents play a role also in primary systemic vasculitides. For a long time it has been noted that Hepatitis B virus (HBV) is involved in polyarteritis nodosa (PAN) although the incidence of HBV-associated PAN seems to decline. Cryoglobulinemic vasculitis has been shown to be strongly associated with Hepatitis C Virus (HCV) infection, but this is most striking in Southern Europe and less in Northern Europe. Different microbial agents have been suggested to influence disease expression in other primary vasculitides but no specific association has been established. In Wegener's Granulomatosis (WG) chronic carriage of Staphylococcus aureus (S. aureus) is associated with a strongly increased risk for relapsing disease. Various pathogenic pathways for this association have been suggested by clinical and experimental observations. Recent studies even suggest that S. aureus derived peptides, amongst others, may induce proteinase 3-ANCA via idiotypic-anti-idiotypic interactions. Treatment with co-trimoxazole in WG localized to the upper airways may result in (temporary) remission of the disease.

de Bruijne J, Buster EH, Gelderblom HC, Brouwer JT, de Knegt RJ, van Erpecum KJ, Schalm SW, Bakker CM, Zaaijer HL, Janssen HL, Reesink HW, Anonymous00041. · Department of Gastroenterology and Hepatology, Academic Medical Centre Amsterdam, the Netherlands. · Neth J Med. · Pubmed #18663263 links to  free full text

Abstract: The development of this guideline was initiated and coordinated by the Netherlands Association of Gastroenterologists and Hepatologists (Nederlandse Vereniging van Maag-Darm-Leverartsen). The aim is the establishment of practical guidelines in the evaluation and antiviral treatment of patients with chronic hepatitis C virus (HCV) infection. This includes recommendations for the initial evaluation of patients, the choice and duration of antiviral therapy and the follow-up after antiviral therapy. Hepatitis C is a slowly progressive disease. The initial evaluation of chronically HCV-infected patients should include liver biochemistry testing, virological testing and abdominal ultrasound imaging. Liver biopsy is no longer a routine procedure. Antiviral treatment should be considered for all HCV-infected patients. Current antiviral treatment is a long-term process and is associated with substantial side effects. When deciding whether to start treatment or not, the chance of successful treatment (80% with hepatitis C genotype 2 and 3 and 50% with hepatitis C genotype 1 and 4), the fibrosis stage, the expected side effects and the compliance of the patient should be taken into consideration. In the absence of significant fibrosis and necroinflammation in liver biopsy, postponing treatment is an option. Current antiviral treatment is contraindicated in patients with Child-Pugh-class B or C cirrhosis. The possibility of a liver transplantation should be investigated in these patients. Significant comorbidity with a limited life expectancy is an absolute contraindication for antiviral treatment Treatment of chronic hepatitis C consists of administration of peginterferon and ribavirin for 24 or 48 weeks. Patients with hepatitis C genotype 1 or 4 are treated for 48 weeks. Patients with hepatitis C genotype 2 or 3 are treated for 24 weeks. In patients with undetectable HCV RNA after four weeks (28 days) of treatment, a shorter treatment is equally effective (12 to 16 weeks for hepatitis C genotype 2 or 3; 24 weeks for hepatitis C genotype 1 or 4). Outpatient clinic visits are recommended at the start and after 2, 4, 8, and 12 weeks of treatment, and thereafter every four to six weeks until the end of treatment. It is recommended to stop treatment if the HCV RNA level has not decreased by at least 2 log10 IU/ml (c/ml) after 12 weeks of treatment or when HCV RNA is still detectable after 24 weeks of treatment. The recommended frequency of outpatient clinic visits for patients who are not being treated is once every six months in patients with cirrhosis, otherwise every 12 months. It is expected that new anti-HCV-medication (STAT-C, specifically targeted antiviral therapy for HCV) will become available in the near future. Therefore treatment of chronic HCV infection will probably be more effective in the future.

Buster EH, van Erpecum KJ, Schalm SW, Zaaijer HL, Brouwer JT, Gelderblom HC, de Knegt RJ, Minke Bakker C, Reesink HW, Janssen HL, Anonymous00062. · Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, the Netherlands. · Neth J Med. · Pubmed #18663260 links to  free full text

Abstract: The development of this guideline was initiated and coordinated by the Netherlands Association of Gastroenterologists and Hepatologists (Nederlandse Vereniging van Maag-Darm-Leverartsen). The aim is the establishment of national standards in the evaluation and antiviral treatment of patients with chronic hepatitis B virus (HBV) infection. This includes recommendations on the initial evaluation of patients, choice and duration of antiviral therapy, follow-up after antiviral therapy and monitoring of patients not currently requiring antiviral therapy. The initial evaluation of chronic HBV-infected patients should include testing of liver biochemistry, virus serology and abdominal imaging. In patients without cirrhosis, antiviral treatment is recommended for those with a serum HBV DNA of at least 1.0 x 105 c/ml (>or=2.0 x 10(4) IU/ml) in combination with: a) elevation of serum alanine aminotransferase (ALAT) level above twice the upper limit of normal during at least three months, and/or b) histological evidence of porto-portal septa or interface hepatitis on liver histology. In patients with cirrhosis, antiviral treatment is recommended if serum HBV DNA is 1.0 x 10(4)c/ml (>or=2.0 x 10(3) IU/ml) or higher, independent of ALAT levels or histological findings. If the patient has decompensated cirrhosis, antiviral treatment is recommended if serum HBV DNA is 1000 c/ml (>or=200 IU/ml) or higher. Patients who do not have an indication for antiviral treatment should be monitored because there is a risk of (re)activation of disease activity. Monitoring every three to six months is recommended for HBeAg-positive and HBeAg-negative patients with high viraemia (HBV DNA >or=1.0 x 10(5) c/ml or >or=2.0 x 10(4) IU/ml) and normal ALAT levels. For patients with serum HBV DNA below 1.0 x 10(5) c/ml (<2.0 x 10(4) IU/ml) the recommended frequency of monitoring is every three to six months for HBeAg-positive patients and every six to 12 months for HBeAg-negative patients. Peginterferon (PEG-IF N) therapy should be considered as initial therapy in both HBeAg-positive and HBeAg-negative patients without contraindications for treatment with this drug because of the higher chance of achieving sustained response compared with nucleos(t)ide analogue therapy. In patients starting nucleos(t)ide analogue therapy, the use of lamivudine is not preferred if long-term antiviral treatment is expected due to the high risk of antiviral resistance against this drug. Of the currently licensed nucleos(t)ide analogues, entecavir has the lowest risk of antiviral resistance (compared with lamivudine, adefovir and telbivudine), while suppression of viral replication seems most profound with either entecavir or telbivudine. The recommended duration of treatment with PEG-IF N is one year for both HBeAg-positive and HBeAg-negative patients. In HBeAg-positive patents, nucleos(t)ide analogue therapy should at least be continued until HBeAg seroconversion and a decline in HBV DNA to below 400 c/ml (80 IU/ml) has been achieved and maintained for six months during therapy. Whether nucleos(t)ide analogue therapy can be safely discontinued in HBeAg-negative patients is unknown; usually prolonged or indefinite antiviral treatment is necessary. Patients receiving PEG-IF N should be monitored once a month, while three monthly monitoring suffices for those receiving nucleos(t)ide analogues. Genotypic analysis of the HBV polymerase is indicated if an increase in serum HBV DNA of at least 1 log(10) c/ml (IU/ml) compared with the nadir value is observed during nucleos(t)ide analogue therapy. Antiviral therapy should be changed as soon as possible in case of confirmed genotypic resistance. Adding a second antiviral agent seems beneficial over switching to another agent. With the availability of multiple new antiviral drugs for the treatment of chronic hepatitis B, effective treatment is now possible for more patients and for longer periods. However, the complexity of HBV therapy has also increased. Nowadays, virtually all chronic HBV-infected patients can be effectively managed, either by inducing sustained off-treatment response or by maintaining an on-treatment response.

Schreuder TC, Hübscher SG, Neuberger J. · Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK. · Transpl Int. · Pubmed #18662365 No free full text.

Abstract: Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) may all recur after liver transplant. Diagnosis of rPBC is defined by histology; rAIH by serology, biochemistry and histology; rPSC by histology and/or imaging of the biliary tree and exclusion of other causes of nonanastomotic biliary strictures. Criteria for recurrent disease (RD) may differ from those used in similar disease in the native liver: frequent use of immunosuppressive therapy changes the pattern and natural history of RD and can co-exist with other transplant-related causes of graft damage. RD may occur in the presence of normal liver tests; the reported incidence will depend on the way in which diagnostic tests (especially protocol biopsies) are applied. The risk of RD increases with time, but does not correlate with the rate of graft loss. Treatment is largely unproven: ursodeoxycholic acid will improve serology and may slow progression of rPSC and rPBC; introduction or increased dose of corticosteroids may reduce progression of rAIH. Risk factors for rPBC include use of tacrolimus compared with cyclosporine; for rPSC include absence of colon peri-transplantation and for rAIH possible associations with some HLA haplotypes have been suggested.

Maas DW, Westendorp RG, van der Mast RC. · Leids Universitair Medisch Centrum, afd. Psychiatrie, B1-P, Postbus 9600, 2300 RC Leiden. · Ned Tijdschr Geneeskd. · Pubmed #18624003 No free full text.

Abstract: Besides the monoamine hypothesis, the stress hypothesis and the vascular hypothesis, the inflammatory hypothesis might be an etiological explanation for late-life depression. There is a growing amount of evidence to support this hypothesis. In animal studies, injection with cytokines was shown to cause behavioural changes ('sickness behaviour') similar to depressive symptoms in humans. Cytokine treatment of certain tumours and chronic hepatitis can also cause depressive symptoms. The prevalence of depression in patients with autoimmune diseases is higher than in the general population. Etanercept had a favourable effect on the depressive symptoms in patients with psoriasis, independent of improvement of physical symptoms. Cytokines affect the hypothalamus-pituitary-adrenal axis and cerebral neurotransmitter systems, both of which are thought to be involved in depression. Immune activation has been associated with depression, and several anti-depressive treatments affect immune parameters, although inconsistently. Since the aging process is associated with a dysregulation of the immune system, the inflammation hypothesis might be particularly true in late-life depression.

Schutten M. · Department of Virology, s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. · Expert Rev Mol Diagn. · Pubmed #18598219 No free full text.

Abstract: The introduction of commercially available quantitative HIV-1 RNA detection methods at the end of the last century has had a significant impact on the management of patients requiring treatment. Similarly for hepatitis C virus (HCV), clinical decision-making with respect to initiation and prolonging therapy is largely based on data from viral load assays. The methods developed in the early 1990s and further improved since then still have significant drawbacks. For example, they are labor intensive, have a small dynamic range and are contamination sensitive. The development of real-time detection techniques for reverse transcription PCR has in part solved these problems. In the present review the advantages and disadvantages of the recently marketed Abbott Realtime HCV and HIV-1 viral load assays relative to their competitors will be discussed.

Fregonese L, Stolk J. · Alpha1 International Registry, c/o Department of Pulmology, Leiden University Medical Center, Leiden, The Netherlands. · Orphanet J Rare Dis. · Pubmed #18565211 links to  free full text

Abstract: Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI) in human serum. The prevalence in Western Europe and in the USA is estimated at approximately 1 in 2,500 and 1 : 5,000 newborns, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may widely vary between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing), early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis. For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids. The end-stage liver and lung disease can be treated by organ transplantation. In AATD patients with cirrhosis, prognosis is generally grave.

Sonder GJ. · National Coordination Center for Travelers Health Advice, Nieuwe Achtergracht 100, 1018 WT Amsterdam, The Netherlands. · Expert Rev Vaccines. · Pubmed #18564021 No free full text.

Abstract: An increasing number of travelers travel to hepatitis B-endemic countries. In travel medicine, vaccinations should be advised according to risks. The actual incidence of hepatitis B infection in short-term tourists is very low and probably not higher than it is for people who do not travel. There is evidence that long-term travelers and immigrants originating from hepatitis B-endemic countries are at higher risk of infection and they should always be offered vaccination. For all other travelers living in countries with universal hepatitis B vaccination, vaccination could be advised as a catch-up strategy.

Rust C, Beuers U. · Department of Gastroenterology and Hepatology, University of Amsterdam, Amsterdam NL-1100 DE, The Netherlands. · World J Gastroenterol. · Pubmed #18528934 links to  free full text

Abstract: The three major immune disorders of the liver are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Variant forms of these diseases are generally called overlap syndromes, although there has been no standardised definition. Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC. The AIH-PBC overlap syndrome is the most common form, affecting almost 10% of adults with AIH or PBC. Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported. The AIH-PSC overlap syndrome is predominantly found in children, adolescents and young adults with AIH or PSC. Interestingly, transitions from one autoimmune to another have also been reported in a minority of patients, especially transitions from PBC to AIH-PBC overlap syndrome. Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment. Therapy for overlap syndromes is empiric, since controlled trials are not available in these rare disorders. Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes. In end-stage disease, liver transplantation is the treatment of choice.

Takkenberg B, de Bruijne J, Weegink C, Jansen P, Reesink H. · Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. · Curr Gastroenterol Rep. · Pubmed #18417047 No free full text.

Abstract: Chronic hepatitis B and C affect approximately 500 million people in the world, with substantial disease burden including liver cirrhosis and hepatocellular carcinoma. For chronic hepatitis B, two treatment strategies are currently available, both with suboptimal response and significant side effects. Promising new drugs are approaching the stage of approval; however, these agents still need further development to control this disease. Based on the understanding of the hepatitis C virus life cycle, new treatment developments for chronic hepatitis C tend to succeed rapidly; therefore, it is only a matter of time before new therapies emerge. This review summarizes the most important new agents available for treatment of chronic hepatitis B and C.

Idris BI, Brosa M, Richardus JH, Esteban R, Schalm SW, Buti M. · Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. · Eur J Gastroenterol Hepatol. · Pubmed #18334876 No free full text.

Abstract: BACKGROUND: Chronic hepatitis B virus (HBV) infection can lead to fatal complications and death. Only a relatively small proportion of patients actually receive medication, and the majority requires long-term antiviral therapy that can result in the emergence of resistant strains of HBV. The study aimed to estimate the future burden of chronic hepatitis B in Spain over the next 20 years, the impact of current lamivudine treatment and the emergence of drug-resistant HBV. METHODS: We constructed a hypothetical cohort of people with active chronic HBV infection in Spain in 2005, and 'followed' the cohort for 20 years. The cohort was stratified with respect to factors that affect prognosis (i.e. hepatitis B e-antigen and histology-defined status). To estimate the burden, Markov mathematical simulation was performed based on three scenarios: natural history, treatment with antiviral drug (lamivudine) and treatment with a hypothetical drug with identical profiles to lamivudine but to which there is no resistance. RESULTS: We estimated that in 2005 there were around 111,000 individuals suffering from active chronic HBV infection. If the cohort is not treated, by the year 2025 there will be about 60,000 events of morbidity and 40,000 cases of liver-related deaths, with 1.84 billion euro expected to be consumed in providing care for the cohort. Treating 35% of the cohort with lamivudine will reduce the morbidity and mortality by 19 and 15%, respectively; whereas the hypothetical drug will reduce the morbidity and mortality by 27 and 24%. The cumulative cost savings resulting from the use of lamivudine and the hypothetical drug, respectively, are 160 and 300 million euro. Antiviral resistance accounts for a reduction of about one-third in the potential benefit of treatment, and almost a half of the potential cost saving. CONCLUSION: Chronic hepatitis B will pose a great burden in the future if the individuals with active disease are left untreated. Effective antiviral therapy and treatment coverage have substantial impact in reducing the future burden; however, antiviral resistance decreases treatment benefit considerably.

de Man RA, van der Eijck A, Veldhuijzen I. · Erasmus MC, University Medical Center Rotterdam, Department of Gastroenterology & Hepatology, The Netherlands. · Adv Exp Med Biol. · Pubmed #18193658 No free full text.

This publication has no abstract.

Bovill JG. · Department of Anaesthesiology, Leiden University Medical Centre, Leiden, The Netherlands. · Handb Exp Pharmacol. · Pubmed #18175089 No free full text.

Abstract: Modern anaesthesia is said to have began with the successful demonstration of ether anaesthesia by William Morton in October 1846, even though anaesthesia with nitrous oxide had been used in dentistry 2 years before. Anaesthesia with ether, nitrous oxide and chloroform (introduced in 1847) rapidly became commonplace for surgery. Of these, only nitrous oxide remains in use today. All modern volatile anaesthetics, with the exception of halothane (a fluorinated alkane), are halogenated methyl ethyl ethers. Methyl ethyl ethers are more potent, stable and better anaesthetics than diethyl ethers. They all cause myocardial depression, most markedly halothane, while isoflurane and sevoflurane cause minimal cardiovascular depression. The halogenated ethers also depress the normal respiratory response to carbon dioxide and to hypoxia. Other adverse effects include hepatic and renal damage. Hepatitis occurs most frequently with halothane, although rare cases have been reported with the other agents. Liver damage is not caused by the anaesthetics themselves, but by reactive metabolites. Type I hepatitis occurs fairly commonly and takes the form of a minor disturbance of liver enzymes, which usually resolves without treatment. Type II, thought to be immune-mediated, is rare, unpredictable and results in a severe fulminant hepatitis with a high mortality. Renal damage is rare, and was most often associated with methoxyflurane because of excessive plasma fluoride concentrations resulting from its metabolism. Methoxyflurane was withdrawn from the market because of the high incidence of nephrotoxicity. Among the contemporary anaesthetics, the highest fluoride concentrations have been reported with sevoflurane, but there are no reports of renal dysfunction associated with its use. Recently there has been a renewed interest in xenon, one of the noble gases. Xenon has many of the properties of an ideal anaesthetic. The major factor limiting its more widespread is the high cost, about 2,000 times the cost of nitrous oxide.

Leemans WF, Ter Borg MJ, de Man RA. · Department of Gastroenterology & Hepatology, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands. · Aliment Pharmacol Ther. · Pubmed #18081660 No free full text.

Abstract: BACKGROUND: Strong suppression of viral replication and normalization of alanine aminotransferase is feasible with nucleos(t)ide analogues. It is estimated viral replication and liver inflammation can be controlled in 90% of patients with chronic hepatitis B with the current available treatments. AIM: To review the studies currently available on the management of chronic hepatitis B with nucleos(t)ide analogues. RESULTS: Although very potent, nucleos(t)ide analogues are not effective in every patient. Some factors are known to influence treatment outcome, but many host and viral factors are still unknown. Stopping rules have to be defined to assess treatment efficacy in an early stage and change the regimen. Discontinuation of nucleos(t)ide analogues is often followed by reactivation of HBV. Data on the risk factors for relapse are necessary in order to decide if treatment can be safely discontinued. Another major drawback of nucleos(t)ide analogues is the emergence of resistance. The efficacy of compounds for the treatment of mutant virus and the impact of cross-resistance is largely unknown. The use of combination therapy to prevent resistance looks promising, but has to be proven. CONCLUSIONS: HBV has become a treatable disease, however much research is needed to optimize treatment for individual patients and treatment failures.

Chamuleau RA. · Afdeling Hepatologie van het Academisch Medisch Centrum, Universiteit van Amsterdam. · Ned Tijdschr Tandheelkd. · Pubmed #17822245 No free full text.

Abstract: Chronic hepatitis B and C are life-threatening diseases, treated with variable success. Peginterferon-alpha is one of the standard therapies for chronic hepatitis B as well as C. To prevent the development of resistant viruses, combination treatment is preferable to monotherapy. Therefore, in chronic hepatitis B virus peginterferon-alpha combined with nucleoside inhibitors is used. The treatment of chronic hepatitis C virus with a combination of peginterferon-alpha and ribavirine can be improved by new protease inhibitors.