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This paper reviews a meeting at which basic pathophysiology of infections, mechanisms of action of hyperimmune products and pharmacokinetic and pharmacodynamic parameters, as well as currently available hyperimmunes and their potential new targets and uses, were discussed. A hyperimmune product was defined as either a monoclonal antibody or a polyclonal preparation enriched with antibody directed against one or more particular targets. A number of issues were emphasised, including: resistant bacterial pathogens, such as Staphylococcus aureus and Streptococcus pyogenes; the role of hyperimmune intravenous globulins in the prevention of sepsis in low birthweight infants; hepatitis B virus infection associated with liver transplantation; combination therapy; the potential role of hyperimmunes in the prevention and treatment of hepatitis C virus; and the use of immunoglobulins for the prophylaxis of Epstein-Barr virus-related lymphoproliferative disease. Routes of administration were also discussed. It was concluded that the development of hyperimmunes faces numerous obstacles. It was agreed that the use of hyperimmunes in clinical trials must be standardised; clinical trials must be large enough to have sufficient power to demonstrate efficacy with clear-cut end-points, and means need to be developed, in conjunction with regulatory agencies, for the feasible evaluation of combination products. However, progress in all these aspects will provide a wide range of hyperimmunes for future use.
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PMID:Hyperimmune products in the prevention and therapy of infectious disease: a report of a hyperimmune products expert advisory panel. 1803 67

Overwhelming postsplenectomy infection (OPSI) syndrome is a rare condition, but is associated with high mortality. However, recognition and clinical management of OPSI is not well established. The prevalence of splenectomy increased recently because it was a clinically effective treatment for hepatitis C virus-associated thrombocytopenia before the introduction of the interferon/ribavirin combination therapy. We reviewed the literature characterizing the clinicopathological features of OPSI and assessed the most effective and feasible administration of the condition. A Medline search was performed using the keywords 'overwhelming', 'postsplenectomy infection', 'postsplenectomy sepsis', 'chronic liver disease', and/or 'splenectomy'. Additional articles were obtained from references within the papers identified by the Medline search. Durations between splenectomy and onset of OPSI ranged from less than 1 wk to more than 20 years. Autopsy showed that many patients with OPSI also had Waterhouse-Friderichsen syndrome. Although the mortality rate from OPSI has been reduced by appropriate vaccination and education, the precise pathogenesis and a suitable therapeutic strategy remain to be elucidated. Protein energy malnutrition (PEM) is commonly observed in cirrhotic patients. Since the immune response in patients with PEM is compromised, a more careful management for OPSI should therefore be applied for cirrhotic patients after splenectomy. In addition, strict long-term follow up of OPSI patients including informed consent will lead to a better prognosis.
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PMID:Overwhelming postsplenectomy infection syndrome in adults - a clinically preventable disease. 1818 51

Piercing is defined as puncturing an organ in order to place a jewel in the perforated site. There is hardly any external organ in the human body that has escaped piercing. The origin of piercing traces back to the dawn of human history. Piercing is performed for decorative or symbolic purposes. Many different medical specialists are confronted with the increasingly popular practice of body piercing in their daily practice. Until recently body piercing was mainly confined to the ears and/or nose. In the last few years there has been a significant increase in the prevalence of body piercing. There are a lot of side effects, among them especially infections. The most important bacteria cultivated from such patients are Staphylococcus aureus and group A streptococci and Pseudomonas aeruginosa. Viruses which can be transmitted by piercing are especially hepatitis B virus and hepatitis C virus. Besides local complications also systemic infections (sepsis, endocarditis) occur. The main aspects of diagnostics, therapy and prevention are discussed.
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PMID:[Piercing--medical problems from otorhinolaryngological point of view]. 1819 46

Pulmonary manifestations of interferon (IFN) use are a rare but well known complication seen with both standard and pegylated interferon alpha-2b (pegIFNalpha-2b) forms of the agent. These are generally of modest intensity and reversible. We report the first case of fulminant adult respiratory distress syndrome (ARDS) associated with pegylated interferon alpha-2a (pegIFNalpha-2a) and ribavirin use for hepatitis C, complicated by subsequent and ultimately fatal sepsis and multiorgan failure. Practicing gastroenterologists and intensivists alike need to be aware of the potential for serious pulmonary sequelae with the use of combination therapy for chronic hepatitis C viral (CHCV) infections.
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PMID:Adult respiratory distress syndrome after treatment with pegylated interferon alpha-2a and ribavirin. 1837 8

Systemic vasculitis is a rare but devastating problem in patients with human immunodeficiency virus (HIV). The coinfection with hepatitis C virus (HCV) further complicates the clinical management. We report a 46-year-old woman coinfected with HCV and HIV with a CD4 count of 950/mm who presented with a life-threatening vasculitis of the lungs, kidneys, and skin and who initially responded after use of corticosteroids and then 2 monthly pulses of i.v. cyclophosphamide. Her condition deteriorated when she was switched to azathioprine. Ultimately, the patient died of neutropenic sepsis. On the basis of our experience and an analysis of the literature, we suggest that monthly pulsed i.v. cyclophosphamide and steroids might be used as an induction therapy, followed by antiviral treatment for patients with HIV, HCV, and a life-threatening ischemic vasculitis if the CD4 count is >400/mm. For patients in this complex condition who are receiving immunosuppressants close surveillance for signs of secondary infection, and prophylactic trimethoprim/sulfamethoxazole, are advised. The use of interferon alpha, ribavirin, i.v. immunoglobulin, and plasmapheresis are alternatives for patients with milder vasculitis.
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PMID:Systemic Necrotizing Vasculitis in a Patient Co-infected with Human Immunodeficiency Virus and Hepatitis C. 1907 77

Hepatitis C virus (HCV) is a leading cause of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. HCV nearly always recurs in liver-transplanted patients, and 10 to 25% of them develop cirrhosis within 5 to 10 years. One of the strategies suggested to limit virological HCV recurrence is pretransplant antiviral treatment, but studies are warranted on the pharmacokinetics of antiviral drugs in cirrhotic patients, the benefits of fixed or escalating antiviral drug dosage schedules, the duration of the treatment, and the indications for using growth factors. Several risk factors are associated with a more aggressive recurrent HCV and early allograft failure, such as an older donor age. The relationship between immunosuppression and fibrosis progression in HCV recurrence remains uncertain. Concerning the antiviral treatment, treating established recurrent disease with a combination of interferon and ribavirin has been the mainstay of management to date, but when it is best to start and how to manage the side effects are still controversial issues. Antiviral treatment should be started once the disease has been confirmed by a biopsy when the fibrosis develops, providing that ongoing acute or chronic rejection, biliary obstruction, vascular damage, autoimmune diseases and sepsis, and any other standard contraindications for antiviral therapy, have been excluded. HCV recurrence after liver transplantation may well lead to graft failure and become an indication for retransplantation, but this is done in a relatively small number of cases, accounting for only 3 to 5% of retransplanted patients, since retransplantation is associated with much worse results than primary liver transplant procedures. We must be prepared for the fact that increasing numbers of HCV-positive recipients with allografts failing due to recurrent HCV will be asking to be retransplanted-and we do not know yet how to respond to this request.
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PMID:Hepatitis C. 1923 59

Nonalcoholic steatohepatitis (NASH) associated cirrhosis is an increasing indication for liver transplant (LT). The aim of this study was to determine outcome and poor predictive factors after LT for NASH cirrhosis. We analyzed patients undergoing LT from 1997 to 2008 at a single center. NASH was diagnosed on histopathology. LT recipients with hepatitis C, alcoholic or cholestatic liver disease and cryptogenic cirrhosis acted as matched controls. Ninety-eight LT recipients were identified with NASH cirrhosis. Compared to controls, NASH patients had a higher BMI (mean 32.3 kg/m2), and were more likely to be diabetic and hypertensive. Mortality after transplant was similar between NASH patients and controls but there was a tendency for higher earlier mortality in NASH patients (30-day mortality 6.1%, 1-year mortality 21.4%). Sepsis accounted for half of all deaths in NASH patients, significantly higher than controls. NASH patients > or =60 years, BMI > or =30 kg/m2 with diabetes and hypertension (HTN) had a 50% 1-year mortality. In conclusion, patients undergoing LT for NASH cirrhosis have a similar outcome to patients undergoing LT for other indications. The combination of older age, higher BMI, diabetes and HTN are associated with poor outcome after LT. Careful consideration is warranted before offering LT to these high-risk patients.
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PMID:Outcome after liver transplantation for NASH cirrhosis. 1934 67

Thousands of patients are awaiting liver transplantation, mainly owing to the lack of donors. The aim of this study was to analyze the characteristics of discarded livers from donors seeking to understand how to increase the number of grafts. A retrospective analysis of 1432 discarded donor livers was performed in the period between 1994 and 2007. Data were stored in a standardized database in accordance with expanded donor criteria. The average donor age was 35.2 years with; 67.7% male subjects and 20.9% over age 50 years. The main cause of donor discard was family refusal (46.6%), followed by cardiorespiratory arrest (CRA) in 28.3%, and surgeon discard (16.9%), principally owing to sepsis (24.5%). Vasopressor drugs were used in 97.2%. Alcoholism was detected in 44.56% and drug addiction in 12.4%. There was infections documented in 23.9% of records, mainly of the respiratory type (75%). Intensive care time was over 120 hours in 11.0%. Hepatitis B infection was detected in 22.5%, (n = 338), and hepatitis C in 3.5% (n = 593). Finally, there were losses due to hypotension in 45.7% (516/1130) and also loss due to CRA. As family refusal was the principal cause for discarding a donor, it is necessary to investigate the role of information about organ transplantation to increase acceptance.
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PMID:Reviewing the causes for 1432 discharged liver donors: can donations be increased? 1937 55

A 46-year-old man with cirrhosis secondary to hepatitis C virus infection and alcohol underwent orthotopic liver transplantation, which required urgent re-grafting because of biliary sepsis from necrosis of the left liver lobe. Recovery was complicated by renal failure and nephrogenic systemic fibrosis (probably related to intravenous gadolinium exposure). He subsequently developed a malignant fibrous histiocytoma. We present this case highlighting the occurrence of two rare conditions in the same patient following liver transplantation. We believe this is the first case of its kind to be reported.
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PMID:Malignant fibrous histiocytoma complicating nephrogenic systemic fibrosis post liver transplantation. 1976 82

We report about a 39-year-old female patient with severe essential mixed cryoglobulinemia of type III with leukocytoclastic vasculitis. The patient was admitted into our hospital with mesenteric lymphangiitis, which caused enteral perforation, sepsis, and pneumonia. Cryoglobulins, cryocrit, Ig-titers, and biopsy were positive for mixed cryoglobulinemia type III. We detected no signs of hepatitis C, B, or any other infectious disease. At first, disease activity could be kept under control with high doses of glucocorticoids and multiple cyclophosphamide pulses. However, after therapy with three pulses of rituximab, steroids were stopped, and the patient has not presented any symptoms for 2 years. Therefore, we suggest that rituximab affected her disease rapidly and effectively. In conclusion, rituximab is an alternative therapy for mixed cryoglobulinemia of type III with leukocytoclastic vasculitis.
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PMID:Essential mixed cryoglobulinemia type III with leukocytoclastic vasculitis: remission by rituximab. 2021 27


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