Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver

Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.

HCV-specific cytokine induction in monocytes of patients with different outcomes of hepatitis C

AIM：Cytokine release by macrophages critically determines the type of immune response to an antigen Therefore.we studied hepatitis C virus (HCV0-Specific induction of interleukins-1β,-10,-12(IL-1β,il-10,IL-12),and tumor necrosis factor-α(TNF-α) in monocytes.METHODS:Intracellular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C,14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear cells with recombinant core,NS3,NS4 NS5a and NS5b proteins .RESULTS:Patients with HCV viremia revealed greater spontaneous exprssion of IL-1β,TNF-α,and IL-10,Furthermore,greater than twofold higher IL-10 epression was induced by the HCV antigens in chronic hepatitis C than in the other two groups (P<0.05) In contrast,neither IL-12 noir TNF-α was induced preferentially.CONCLUSION:In chonic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction-not counterbalanced by antiviral type 1 cytokines,This may contribute to persistent viral replication.

Distribution and effects of polymorphic RANTES gene alleles in HIV/HCV coinfection - A prospective cross-sectional study

AIM: Chemokines and their receptors are crucial for immune responses in HCV and HIV infection. RANTES gene polymorphisms lead to altered gene expression and influence the natural course of HIV infection. Therefore,these mutations may also affect the course of HIV/HCV coinfection.METHODS: We determined allele frequencies of RANTES-403 (G→A), RANTES-28 (C→G) and RANTESIN1.1 (T→C) polymorphisms using real-time PCR and hybridization probes in patients with HIV (n = 85), HCV (n= 112), HIV/HCV coinfection (n = 121), and 109 healthy controls. Furthermore, HIV and HCV loads as well as CD4+ and CD8+ cell counts were compared between different RANTES genotypes.RESULTS: Frequencies of RANTES-403 A, RANTES-28 G and RANTES-IN1.1 C alleles were higher in HIV infected patients than in healthy controls (-403: 28.2% vs 15.1%,P = 0.002; -28: 5.4% vs 2.8%, not significant; IN1.1:19.0% vs 11.0%, P = 0.038). In HIV/HCV coinfected patients, these RANTES alleles were less frequent than in patients with HIV infection alone (15.4% P = 0.002;1.7%; P = 0.048; 12.0%; not significant). Frequencies of these alleles were not significantly different between HIV/HCV positive patients, HCV positive patients and healthy controls.CONCLUSION: All three RANTES polymorphisms showed increased frequencies of the variant allele exclusively in patients with HIV monoinfection. The finding that the frequencies of these alleles remained unaltered in HIV/HCV coinfected patients suggests that HCV coinfection interferes with selection processes associated with these alleles in HIV infection.

Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations:A case report and review of the literature

Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.

Between Scylla and Charybdis:The role of the human immune system in the pathogenesis of hepatitis C

Hepatitis C virus(HCV)frequently elicits only mild immune responses so that it can often establish chronic infection.In this case HCV antigens persist and continue to stimulate the immune system.Antigen persistence then leads to profound changes in the infected host’s immune responsiveness,and eventually contributes to the pathology of chronic hepatitis.This topic highlight summarizes changes associated with chronic hepatitis C concerning innate immunity(interferons,natural killer cells),adaptive immune responses(immunoglobulins,T cells,and mechanisms of immune regulation(regulatory T cells).Our overview clarifies that a strong anti-HCV immune response is frequently associated with acute severe tissue damage.In chronic hepatitis C,however,the effector arms of the immune system either become refractory to activation or take over regulatory functions.Taken together these changes in immunity may lead to persistent liver damage and cirrhosis.Consequently,effector arms of the immune system will not only be considered with respect to antiviral defence but also as pivotal mechanisms of inflammation,necrosis and progression to cirrhosis.Thus,avoiding Scylla-a strong,sustained antiviral immune response with inital tissue damage-takes the infected host to virus-triggered immunopathology,which ultimately leads to cirrhosis and liver cancerthe realm of Charybdis.

Ribavirin in Acute Hepatitis E Infection in Patients with Gynecological Cancer:A Case Series

Hepatitis E virus infection is usually a self-limited disease.However,during the last years there has been growing evidence for prolonged and chronic infection occurring in patients with immunosuppression.Also patients with malig-nant and rheumatic diseases have been identified to be at risk for chronic hepatitis E.However,their course and prognosis are not well characterized and there have been no reports of hepatitis E virus infection in patients with gynecological cancer.Here,we report three Caucasian females with breast and ovarian cancers presenting with elevation of amino-transferase levels during anticancer treatment.Although only few or no clinical hints suggested hepatitis E virus infection,the diagnosis of hepatitis E virus infection was confirmed by seroconversion,which might occur with some delay,and/or by polymerase chain reaction.While two patients had a self-limited course,the third patient with a high-risk oncological constellation required ribavirin in order to resume chemo-therapy.These cases highlight the need for hepatitis E virus testing in patients with gynecological cancer and elevated aminotransferase levels.Further,these cases show that in selected high-risk patients,ribavirin treatment may be nec-essary based on the decision of a multidisciplinary team.