Hepatitis: Germany

Cornberg M, Protzer U, Dollinger MM, Petersen J, Wedemeyer H, Berg T, Jilg W, Erhardt A, Wirth S, Schirmacher P, Fleig WE, Manns MP, Anonymous00064, Anonymous00065, Anonymous00066, Anonymous00067, Anonymous00068. · Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. · J Viral Hepat. · Pubmed #18713127 No free full text.

This publication has no abstract.

Rockstroh JK, Bhagani S, Benhamou Y, Bruno R, Mauss S, Peters L, Puoti M, Soriano V, Tural C, Anonymous00076. · Department of Medicine I, University of Bonn, Bonn, Germany. · HIV Med. · Pubmed #18257771 No free full text.

Abstract: OBJECTIVES: With the decline in HIV-associated morbidity and mortality following the introduction of highly active antiretroviral therapy (HAART), liver disease has emerged as a major cause of death in HIV/hepatitis B virus (HBV) and HIV/hepatitis C virus (HCV) coinfected persons. Therefore, screening for underlying viral hepatitis coinfection and the provision of management and treatment recommendations for patients with chronic viral hepatitis are of great importance in preventing, as far as possible, the development of liver disease. With the introduction of new agents for the treatment of hepatitis B and increased knowledge of how best to manage hepatitis C, an update of current guidelines for management of HBV and HCV coinfection with HIV is warranted. SUMMARY: Clearly, all HIV-infected patients should be screened for hepatitis A, B and C, taking into account shared pathways of transmission. Patients who are seronegative for hepatitis A and B should be considered for vaccination. In HIV-infected patients with chronic hepatitis B, the first important differentiation is whether HAART is required or not. In the setting of stable HIV infection, with no need for HAART, several treatment options are available, namely treatment with interferon, early initiation of HAART, or selective non-HIV active anti-HBV nucleoside therapy, with the aim of achieving undetectable HBV DNA levels. In most cases, undetectable HBV DNA can only be achieved with combination therapy. With regard to hepatitis C, individualized tailoring of the duration of HCV therapy is advisable, taking into account rapid or delayed virological response. In patients who do not achieve at least a 2 log drop in HCV RNA at week 12, treatment can be terminated because of the low probability of achieving sustained virological response. Overall, with the currently available treatment algorithms, HCV can be eradicated in over 50% of patients. Therefore, HCV therapy should be considered and discussed with the patient if an indication for HCV therapy (elevated liver enzymes, positive HCV RNA and >F1 fibrosis) is present. CONCLUSIONS: Management of underlying hepatitis B and/or C in patients with HIV infection is of great importance in preventing liver disease-associated morbidity and mortality.

Plauth M, Cabré E, Riggio O, Assis-Camilo M, Pirlich M, Kondrup J, Anonymous00255, Ferenci P, Holm E, Vom Dahl S, Müller MJ, Nolte W, Anonymous00256. · Department Internal Medicine, Staedtisches Klinikum, Dessau, Germany. · Clin Nutr. · Pubmed #16707194 No free full text.

Abstract: Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility to increase or to insure nutrient intake in case of insufficient oral food intake. The present guideline is intended to give evidence-based recommendations for the use of ONS and TF in patients with liver disease (LD). It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. EN by means of ONS is recommended for patients with chronic LD in whom undernutrition is very common. ONS improve nutritional status and survival in severely malnourished patients with alcoholic hepatitis. In patients with cirrhosis, TF improves nutritional status and liver function, reduces the rate of complications and prolongs survival. TF commenced early after liver transplantation can reduce complication rate and cost and is preferable to parenteral nutrition. In acute liver failure TF is feasible and used in the majority of patients.

Niederau C. · St. Josef Hospital Oberhausen, Klinik für Innere Medizin, Akademisches Lehrkrankenhaus der Universität Essen, Oberhausen. · Z Gastroenterol. · Pubmed #15314715 No free full text.

This publication has no abstract.

Zepp F, Schmitt HJ, Cleerbout J, Verstraeten T, Schuerman L, Jacquet JM. · University Hospital, Department of Pediatrics, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany. · Expert Rev Vaccines. · Pubmed #19485747 No free full text.

Abstract: Combination vaccines that include multiple antigens within one formulation are now widely accepted as an effective means of eliciting protection against several diseases at the same time. Owing to improvements in quality and convenient modes of administration, they have become part of routine pediatric practice. Hexavalent vaccines, including diphtheria, tetanus, pertussis, hepatitis B, polio and Haemophilus influenzae type b antigens represent the latest advance in the development of combination vaccines. Over 8 years since its first licensure, this review looks at the immunogenicity, efficacy and safety profile of the only hexavalent pediatric vaccine currently in use--Infanrix hexa (diphtheria, tetanus, acellular pertusis-hepatitis B virus-inactivated poliovirus vaccine/Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]; GlaxoSmithKline Biologicals, Rixensart, Belgium)--through published clinical trials and postmarketing surveillance data. These data show DTPa-HBV-IPV/Hib to be highly immunogenic and well tolerated across a range of different primary and booster vaccination schedules, as well as when administered concomitantly with other licensed vaccines (e.g., pneumococcal conjugate vaccine). Additional issues surrounding the use of hexavalent vaccines are also reviewed.

Zeuzem S, Rizzetto M, Ferenci P, Shiffman ML. · JW Goethe University Hospital, Frankfurt, Germany. · Antivir Ther. · Pubmed #19430089 No free full text.

Abstract: Current guidelines recommend a full 24-week regimen for all patients undergoing treatment for genotype 2 or 3 hepatitis C virus (HCV) infection. Recent data from two large randomized studies, one with pegylated interferon-alpha2a plus ribavirin (RBV) and one with pegylated interferon-alpha2b plus RBV assessed treatment duration and on-treatment predictors, such as rapid virological response (RVR; HCV RNA <50 IU/ml at week 4) or sustained virological response rates. Overall, these studies have shown that abbreviated regimens are generally less effective than standard 24-week regimens in genotype 2 or 3 patients because of a higher rate of relapse. However, abbreviated treatment might be offered to selected patients with an RVR provided that they have a low baseline viral load and minimal hepatic fibrosis.

Diepolder HM. · Medical Department II, University of Munich, Germany. · Antiviral Res. · Pubmed #19428600 No free full text.

Abstract: Despite the high propensity of hepatitis C virus to establish chronic viral persistence, immune-mediated viral clearance occurs in some patients, fostering hopes that therapeutic induction of specific antiviral immune responses might be able to contribute to viral clearance in chronically infected patients. Indeed, recent clinical trials of therapeutic vaccination have provided clear proof of concept that specific immunotherapy can reduce the viral load in some patients. Further improvement of these strategies will depend on a detailed analysis of the immunopathogenesis of chronic hepatitis C. Recent advances in our understanding of the mechanisms of down-regulation of virus-specific immune responses during chronic infection, including the role of regulatory T cells and inhibitory molecules such as programmed death receptor 1, may open up new avenues for second-generation immunotherapeutic interventions.

Neeff H, Makowiec F, Harder J, Gumpp V, Klock A, Thimme R, Drognitz O, Hopt UT. · Universität Freiburg, Allgemein- und Viszeralchirurgie, Freiburg, Germany. · Zentralbl Chir. · Pubmed #19382043 No free full text.

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth-leading cause of cancer death world-wide. Although less frequent in Western Europe, its incidence is increasing in this region. Causes involved in the pathogenesis of HCC are, besides viral hepatitis, metabolic and nutritional factors (alcohol, diabetes, obesity). The therapeutic management depends strongly on the initial extent of disease and includes hepatic resection, liver transplantation and local ablation. In this context, we present our results on liver resection for HCC and a discussion of the current literature about (potentially curative) treatment for HCC. PATIENTS: From 1999 until 2008 93 patients [83 % male, median age 64 (range: 39-94) years] underwent hepatic resection for HCC. Postoperative follow-up was available in 85 patients [median follow-up: 1.2 (0.25-8) years]. RESULTS: In contrast to data, especially from Asia, a viral hepatitis as the origin of HCC was found in only 28 % of the patients in our series. Half of the patients had proven liver cirrhosis. The median number of intrahepatic tumours was one (1-11), median size of the largest tumour was 55 mm (5-250 mm). 58 % of the HCC were removed by atypical or segmental resection, 42 % of the patients underwent hemihepatectomy or extended -hemihepatectomy. Tumor-free resection margins were -achieved in 95 %. Total postoperative morbidity was 61 %. A reoperation for complications was -necessary in 10 %. Hospital mortality was 8.6 % in the entire study period but decreased from 14.9 % in 1999-2004 to 2.2 % in 2005 to 2008 (p = 0.03). Actuarial survival was 81 % after 1 year, 58 % after 3 years and 26 % after 5 years. The T-stage could be identified tendentially as a prognostic factor influencing survival. CONCLUSION: With the proper selection of patients, liver resection for HCC may be performed with a curative intention (i. e., free resection margins) in over 90 %. Although it decreased during the study period peri-operative mortality was higher than after resection of other hepatic tumours. Long-term survival in our series was comparable to reports from other European centres.

Pratschke S, Loehe F, Graeb C, Jauch KW, Angele MK. · Klinikum Grosshadern, Department of Surgery, Munich, Germany. · Zentralbl Chir. · Pubmed #19382040 No free full text.

Abstract: The transplantation of marginal organs or those meeting the so-called extended donor criteria (EDC) is today a significant option to alleviate the low availability or organs and to increase the number of transplantation which in turn is -accompanied by a lower mortality among wait-ing-list patients. However such an extension of the spender pool carries the risks of an increased incidence of organ dysfuntions and a higher recipient mortality. This situation presents an ethical problem when marginal organs are accepted for transplantation because the anticipated mortality for the individual recipient cannot be determined. The transplantation of marginal organs from -donors with a high MELD score seems to be linked to a higher mortality. In particular, the combina-tions of high donor age and long ischaemic time or advanced donor age and hepatitis C infection in the recipient are definitively associated with a significantly poorer organ survival rate. In view of the serious lack of organs, efforts should be made, for example, by shortening of the is-chae-mic time and the development of therapeutic strategies, to improve the function and increase the number of usable marginal organs and thus to increase pool of donor organs. The refusal of marginal organs on the basis of individual EDC without consideration of the status of recipient does not seem to be adequate.

Meier V, Ramadori G. · Universitätsmedizin Göttingen, Abteilung für Gastroenterologie und Endokrinologie, Göttingen, Germany. · Expert Rev Anti Infect Ther. · Pubmed #19344246 No free full text.

Abstract: Hepatitis C virus (HCV) infection is the leading cause of chronic liver disease. An estimated 130 million people worldwide are persistently infected with HCV. Almost half of patients who have chronic HCV infection cannot be cured with the standard treatment consisting of pegylated IFN-alpha and ribavirin. For those patients who do not respond to this standard antiviral therapy, there is currently no approved treatment option available. Recent progress in structure determination of HCV proteins and development of a subgenomic replicon system enables the development of a specifically targeted antiviral therapy for hepatitis C. Many HCV-specific compounds are now under investigation in preclinical and clinical trials.

Knuf M, Szenborn L, Moro M, Petit C, Bermal N, Bernard L, Dieussaert I, Schuerman L. · Zentrum für Kinder- und Jugendmedizin, Johannes Gutenberg Universität Mainz, Mainz, Germany. · Pediatr Infect Dis J. · Pubmed #19325452 No free full text.

Abstract: BACKGROUND: The choice of non-typeable Haemophilus influenzae Protein D as main carrier protein in the candidate 10-valent pneumococcal conjugate vaccine (PHiD-CV, GlaxoSmithKline Biologicals), was driven in part to avoid carrier-mediated suppression and possible bystander interference with coadministered vaccines. Immunogenicity data from 3 primary and 2 booster vaccination studies were assessed for possible impacts of PHiD-CV coadministration on immune responses to routinely administered childhood vaccines, in comparison to 7-valent pneumococcal conjugate vaccine (7vCRM) coadministration. METHODS: Randomized, controlled studies in which PHiD-CV or 7vCRM vaccines were coadministered with DTPa-[HBV]-IPV/Hib, DTPa-[HBV]-IPV, DTPw-HBV/Hib, IPV, and OPV, combined Hib-Neisseria meningitidis serogroup C vaccine (Hib-MenC-TT), standalone MenC-TT or MenC-CRM vaccines. RESULTS: One month after primary vaccination, >96% of PHiD-CV recipients had seroprotective antibody concentrations against diphtheria, tetanus, poliovirus types 1 and 3, Hib (>or=0.15 microg/mL), SBA-MenC (>or=1:8), and >94% were seropositive for antibodies against pertussis antigens. Somewhat lower responses against poliovirus type 2 in study A (compared with poliovirus type 1 and 2 responses) and hepatitis B in the 6-, 10-, and 14-week schedule in the Philippines (compared with hepatitis B responses in the other studies) were observed after coadministration of both PHiD-CV and 7vCRM vaccines. Antitetanus and anti-PRP antibody geometric mean concentrations (GMCs) tended to be higher after PHiD-CV coadministration, probably because of the TT carrier protein for serotype 18C in PHiD-CV. Booster vaccination induced substantial increases in antibody GMCs for all coadministered antigens. These responses were generally within the same range in PHiD-CV and 7vCRM groups. Observed anti-PRP responses remained higher in PHiD-CV recipients after the booster dose. CONCLUSIONS: Coadministration of PHiD-CV with commonly used childhood vaccines induced high levels of seroprotection/seropositivity against all targeted diseases. No evidence of negative interference on the immune response to any of the coadministered vaccine antigens was observed when compared with the current routine practice of 7vCRM coadministration.

Lüth S, Weiler-Normann C, Schramm C, Lohse AW. · I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 24046, Hamburg, Deutschland. · Internist (Berl). · Pubmed #19225747 No free full text.

Abstract: Autoimmune hepatitis (AIH) can occur in all age groups. AIH affects women more commonly than men (3:1). Clinical presentation may be an acute hepatitis up to fulminant liver failure, but can also be asymptomatic. AIH is characterized by lymphoplasmacellular infiltrates on liver biopsy, elevated liver enzymes in serum and the absence of active viral markers. Patients characteristically present with hypergammaglobulinemia, elevated serum levels of IgG and autoantibodies. Corticosteroids are the drug of choice for induction of remission, azathioprine the drug of choice for maintenance of remission. Rapid response to immunosuppressive treatment supports the diagnosis and leads to a good long-term prognosis.Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are immune mediated diseases affecting bile ducts. While PBC has a slow progression to cirrhosis and complications mostly will be limited to complications of cirrhosis, PSC additionally carries a high risk of developing cholangiocellular carcinoma. The treatment of choice in PBC and PSC is oral ursodeoxycholic acid which may slow progression of liver disease and may ameliorate lab findings.

Etgen T, Brönner M, Sander D, Bickel H, Sander K, Förstl H. · Neurologische Klinik, Klinikum Traunstein, Cuno-Niggl-Strasse 3, Traunstein. · Fortschr Neurol Psychiatr. · Pubmed #19221969 No free full text.

Abstract: Mild cognitive impairment describes a cognitive decline greater than expected for an individual's age and education level that does not interfere significantly with activities of daily life. In the recent years concepts of "mild cognitive impairment" with divergent definitions have been discussed as potential preclinical forms of dementia. The etiology of cognitive impairment is heterogeneous and it can be promoted or caused by numerous somatic factors. Relevant somatic factors include hypertension, diabetes mellitus, heart failure, chronic obstructive airways disease and bronchial asthma. Cognitive impairment may be facilitated by hypercholesterolemia, chronic renal failure, hypothyroidism, testosterone deficiency, minimal hepatic encephalopathy, HIV- and hepatitis C-infection. Knowledge and diagnosis of these somatic factors is essential in cognitive impairment, as diligent treatment may lead to improve cognitive performance and postpone the manifestation of dementia.

Farnik H, Mihm U, Zeuzem S. · Department of Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany. · Liver Int. · Pubmed #19207963 No free full text.

Abstract: Most infections with hepatitis C virus (HCV) fail to resolve spontaneously and progress to chronic hepatitis C. Genotype 1 HCV accounts for most hepatitis C infections in North America, Western Europe, and Japan. Patients infected with HCV genotype 1 are the most resistant to treatment, which results in poor treatment outcomes. Although sustained virologic response (SVR) rates have significantly improved with introduction of combination therapy with pegylated interferon alfa and ribavirin, the rates are still lower than those in genotype 2 or 3 infections. This review discusses how treatment outcomes in patients with HCV genotype 1 infection can be optimized by using the drugs currently licensed for treatment of hepatitis C: pegylated interferon alfa-2a/b and ribavirin. Dose modifications and variations of treatment duration are the two strategies that have been investigated best, so far. Treatment--naïve patients and non-responders and relapsers to prior antiviral therapy are discussed separately.

Mederacke I, Wedemeyer H, Manns MP. · Department of Gastroenterology, Hepatology and Endocrinology, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. · Curr Opin Investig Drugs. · Pubmed #19197796 No free full text.

Abstract: Boceprevir is an HCV NS3 (non-structural protein 3) serine protease inhibitor being developed by Schering-Plough Corp as a capsule formulation. In pharmacokinetic studies, boceprevir was adequately absorbed, with the most effective mode of administration appearing to be a three-times-daily regimen. In phase I clinical trials, monotherapy with boceprevir led to a distinct viral load reduction. In phase Ib combination trials of boceprevir with PEGylated IFNalpha2b and ribavirin, the reduction in viral replication was further increased. Early data reported from phase II clinical trials have been promising, suggesting a rapid early HCV-RNA reduction. Phase III trials for the drug began in 2008. Results available to date have demonstrated the compound to be well tolerated, with adverse events that were within the range of current standard-of-care therapy. Thus, boceprevir may have the potential to increase sustained virological response rates and possibly also to shorten duration of therapy; data from ongoing clinical trials are awaited.

Kronenberger B, Zeuzem S. · Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. · Best Pract Res Clin Gastroenterol. · Pubmed #19187871 No free full text.

Abstract: Specifically Targeted Antiviral Therapy against hepatitis C virus (STAT-C) stands for a new era in the treatment of patients with chronic hepatitis C. Results from recent trials with protease and polymerase inhibitors indicate that therapy with a single HCV specific compound will not be sufficient to eradicate hepatitis C virus infection and that combination therapy will be necessary to improve sustained virologic response rates. The search for the optimal combination of STAT-C compounds with peginterferon alfa with or without ribavirin is currently under investigation in several clinical trials. Overall the current studies indicate that peginterferon alfa and ribavirin remain the backbone of antiviral therapy of chronic hepatitis C even in the era of STAT-C. Nevertheless, it can be anticipated that combination of STAT-C compounds with non-overlapping resistance profiles could improve response to antiviral therapy. Promising combinations are protease inhibitors plus nucleoside analogue and non-nucleoside analogue polymerase inhibitors.

Wursthorn K, Manns MP, Wedemeyer H. · Clinic for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. · Best Pract Res Clin Gastroenterol. · Pubmed #19187867 No free full text.

Abstract: Chronic hepatitis B and hepatitis C virus infections are the major causes of liver disease, hepatocellular carcinoma (HCC) and liver-related mortality worldwide. Among factors known to influence the natural history of viral hepatitis are age at the time of infection, duration of infection, serum alanine aminotransferase (ALT) levels, male sex, alcohol consumption, and coinfections. In hepatitis B, serum HBV DNA concentration emerges as the key factor for predicting the development of liver disease. Even patients with low viraemia seem at increased risk for liver cirrhosis and HCC. Coinfections with hepatitis C, hepatitis D and/or HIV are common and are associated with a more severe liver disease. The course of chronic hepatitis C is variable, but usually fibrosis advances slowly. In addition to the better-known factors- including coinfections with HBV and HIV- progression of liver disease is adversely affected by smoking, hepatic steatosis and insulin resistance.

von Wagner M, Zeuzem S. · Medizinische Klinik I, Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt a.M, Germany. · Dtsch Med Wochenschr. · Pubmed #19180418 No free full text.

Abstract: Immunosuppression because of local or systemic chemotherapy or immunosuppressive therapy of autoimmune diseases is an increasing risk for reactivation of hepatitis B and may lead to acute hepatitis and rarely to fulminant hepatitis. Intensive immunosuppression, e. g. in advance of bone marrow transplantation, may lead to re-seroconversion with loss of anti-HBs and detection of HBsAg and HBV-DNA and a risk of (fulminant) hepatitis. Distinct chemotherapeutics and immunosuppressive medication promote reactivation or re-seroconversion of HBV infection. Several studies have shown a significant benefit by antiviral therapy with nucleosidanalogue lamivudine to avoid reactivation. For other nucleoside analogues (telbivudine, entecavir) or nucleotide analogues (adefovir dipivoxil, tenofovir) larger experiences are yet missing in this situation. Prophylaxis with antiviral agents may be superior to therapy of reactivation. Prior to onset of immunosuppressive treatment patients must be tested for HBV. Patients without detection of HBsAg and without sufficient anti-HBs-titer should receive active immunisation. In case of chronic HBV infection antiviral therapy should be initiated before intense immunosuppression. In case of HBV infection in medical history (anti-HBc positive, HBsAg negative) HBV serostatus should be tested frequently. In case of reactivation, therapy with nucleos(t)ide analogue should immediately be initiated. In case of bone marrow transplantation prophylaxis with nucleos(t)idanalogue has to be initiated before onset of treatment if anti-HBc is detectable, independent from HBsAg result.

Küpper TE, Schöffl V, Milledge JS. · Institute of Occupational and Social Medicine, Aachen Technical University, Pauwelsstr. 30, D-52074 Aachen, Germany. · Travel Med Infect Dis. · Pubmed #19174294 No free full text.

Abstract: This paper provides the official recommendation of the Union Internationale des Associations d'Alpinisme (UIAA) Medical Commission to manage the problem of safe drinking water. The recommendation was accepted and authorized for publication by the Medical Commission during their annual meeting at Treplice, Tzechia, 2008. Safe water is essential for mountaineers worldwide in order to balance challenges associated with high altitude dehydration. The paper summarizes the advantages and disadvantages of several procedures used to procure safe drinking water in the mountains or at high altitude. Limitations or critical details, which may cause failure of the methods are mentioned systematically. We differentiate between "conventional" methods, which should be preferred because they produce safe water and "improvisation". The latter does not produce safe water but may be used if conventional methods are not available for any reason. They decrease the concentration of pathogenic microorganisms and by this they reduce the risk of enteral infection. Water filtration using a ceramic filter system or chemical disinfection is recommended as a standard method. Boiling water should be avoided because it is too fuel consuming and has the potential to increase deforestation. Generally, with regard to infections by water or food, all mountaineers should be vaccinated against hepatitis A and poliomyelitis in regions where they may be at-risk.

Weissenborn K, Tryc AB, Heeren M, Worthmann H, Pflugrad H, Berding G, Bokemeyer M, Tillmann HL, Goldbecker A. · Department of Neurology, Hannover Medical School, 30623 Hannover, Germany. · Metab Brain Dis. · Pubmed #19130196 No free full text.

Abstract: There is growing evidence that hepatitis C virus (HCV)-infection may affect the brain. About half of the HCV-infected patients complain of chronic fatigue irrespective of their stage of liver disease or virus replication rate. Even after successful antiviral therapy fatigue persists in about one third of the patients. Many patients, in addition, report of deficits in attention, concentration and memory, some also of depression. Psychometric testing revealed deficits in attention and verbal learning ability as characteristic for HCV-afflicted patients with normal liver function. Magnetic resonance spectroscopic studies showed alterations of the cerebral choline, N-acetyl-aspartate, and creatine content in the basal ganglia, white matter and frontal cortex, respectively. Recently, pathologic cerebral serotonin and dopamine transporter binding and regional alterations of the cerebral glucose utilisation compatible with alterations of the dopaminergic attentional system were observed. Several studies detected HCV in brain samples or cerebro-spinal fluid. Interestingly, viral sequences in the brain often differed from those in the liver, but were closely related to those found in lymphoid tissue. Therefore, the Trojan horse hypothesis emerged: HCV-infected mononuclear blood cells enter the brain, enabling the virus to reside within the brain (probably in microglia) and to infect brain cells, especially astrocytes.

Welker MW, Zeuzem S. · Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. · Hepatology. · Pubmed #19105211 No free full text.

This publication has no abstract.

Asli NS, Pitulescu ME, Kessel M. · Research Group Developmental Biology, Department of Molecular Cell Biology, Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany. · Curr Mol Med. · Pubmed #19075669 No free full text.

Abstract: Large numbers and quantities of different, small RNA molecules are present in the cytoplasm of animal and plant cells. One subclass of these molecules is represented by the noncoding microRNAs. Since their discovery in the 1990s a multitude of basic information has accumulated, which has identified their function in post-transcriptional control, either via degradation or translational inhibition of target mRNAs. This function is in most of the cases a finetuning of gene expression, working in parallel with transcriptional regulatory processes. MicroRNA expression profiles are highly dynamic during embryonic development and in adulthood. Misexpression of microRNAs can perturb embryogenesis, organogenesis, tissue homeostasis and the cell cycle. Evidence from gain- and loss-of function studies indicates roles for microRNAs in pathophysiologic states including cardiac hypertrophy, muscle dystrophy, hepatitis infection, diabetes, Parkinson syndrome, hematological malignancies and other types of cancer. In this review, we focus on studies addressing the role of various microRNAs in heart, muscle, liver, pancreas, central nervous system, and hematopoiesis.

Myint AM, Schwarz MJ, Steinbusch HW, Leonard BE. · Laboratory Section for Psychoneuroimmunology and Therapeutic Drug Monitoring, Ludwig-Maximilians University, Nussbaumstrasse 7, 80336 Munich, Germany. · Metab Brain Dis. · Pubmed #19067144 No free full text.

Abstract: Certain cytokines such as interferon-alpha and interleukin-2 are often used in the treatment certain cancers and chronic diseases such as melanoma, hepatitis C infection and multiple sclerosis. Several neuropsychiatric side effects such as depression, anxiety, psychosis, suicidal ideation, hypomanic mood and cognitive impairment were reported in those patients who received those medications. In certain patients with those neuropsychiatric side effects, the symptoms ceased when the medication was stopped. However, in some cases, the cognitive impairment persisted even for years after cessation of the medication. In animal studies, those cytokines could induce sickness behaviour, anxiety behaviour and social anhedonia. The increased in pro-inflammatory cytokines in certain neuropsychiatric disorders was widely reported. In addition, in animal studies, the treatment with interferon-alpha or interleukin-1 could induce depressive like behaviour. Recently, the role of certain pro-inflammatory cytokines that could enhance the activity of the enzyme, indoleamine 2-3, dioxygenase (IDO) which in turn would increase tryptophan degradation into kynurenine and decrease tryptophan availability of tryptophan in the brain to synthesize serotonin, a neurotransmitter which is necessary for the normal mood state became of interest in pathophysiology of psychiatric disorders. Furthermore, the imbalance in the further downward catabolic kynurenine pathway and their interactions with other neurotransmitters has been proposed to play an important role. The presence of such an imbalance in patients being treated with cytokines and in patients with psychiatric disorders and the possible consequence of those changes on the neuroprotective function in the brain are discussed in this review.

Wohlfarth C, Efferth T. · University of Heidelberg, Institute of Pharmacy and Molecular Biotechnology, Heidelberg, Germany. · Acta Pharmacol Sin. · Pubmed #19060918 links to  free full text

Abstract: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infections are a major threat worldwide. Combination therapy of interferon-alpha and ribavirin is currently the treatment of choice for HCV-infected patients. However, this regimen is only effective in approximately 50% of patients and provokes severe side-effects. Numerous natural alternatives for treating HCV have been suggested. Deoxynojirimycin and its derivatives are iminosugars which exert anti-HCV activity by inhibiting alpha-glucosidases. A non-immunosuppressive derivate of cyclosporine A, NIM811, exerts anti-HCV activity by binding to cyclophilin. Other natural products with promising anti-HCV activity are 2-arylbenzofuran derivatives, Mellein, and pseudoguaianolides. For HBV treatment, several drugs are available, specifically targeting the virus polymerase (lamivudine, entecavir, telbivudine, and adefovir dipivoxil). The efficacy of these drugs is hampered by the development of resistance due to point mutations in the HBV polymerase. Due to drug resistance and adverse side-effects, the search for novel drugs is mandatory. Wogonin, ellagic acid, artemisinin and artesunate, chrysophanol 8-O-beta-D-glucoside, saikosaponin C, and protostane triterpenes are active against HBV. Natural products need to be investigated in more detail to explore their potential as novel adjuncts to established HBV or HCV therapy.

Hofmann WP, Herrmann E, Sarrazin C, Zeuzem S. · Department of Internal Medicine 1, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany. · Liver Int. · Pubmed #19055642 No free full text.

Abstract: Ribavirin is an old broad-spectrum antiviral that is highly effective when used in combination with interferon-alpha and also as part of triple therapies containing new inhibitors of the hepatitis C virus (HCV) non-structural (NS)3/4 protease or HCV NS5B polymerase for the treatment of patients with chronic hepatitis C. However, the molecular mechanisms by which ribavirin enhances early and sustained virological response rates during interferon-based antiviral HCV therapy are still unknown. Several mechanisms including (i) immunomodulatory properties, (ii) inhibition of the inosine monophosphate dehydrogenase, (iii) direct inhibition of the HCV-encoded NS5B RNA polymerase, (iv) induction of lethal mutagenesis and (v) modulation of interferon-stimulated gene expression are currently proposed. Here, we discuss recent advances from in vitro data and their importance for the situation in patients with chronic hepatitis C. Furthermore, theoretical aspects from mathematical modelling of ribavirin action in chronic hepatitis C are reviewed.