Clinical course of infection with hepatitis C.
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Biomedical subjects
Publications and source records attributed to Francesca Cainelli.
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Infections are major complications and constitute the second most common cause of mortality and a main cause of morbidity in patients with thalassaemia, a group of genetic disorders of haemoglobin synthesis characterised by a disturbance of globin chain production. Thalassaemias are among the most common genetic disorders in the world. Predisposing factors for infections in thalassaemic patients include severe anaemia, iron overload, splenectomy, and a range of immune abnormalities. Major causative organisms of bacterial infections in thalassaemic patients are Klebsiella spp in Asia and Yersinia enterocolitica in western countries. Transfusion-associated viral infections (especially hepatitis C) can lead to liver cirrhosis and hepatocellular carcinoma. A unique and challenging infection detected in Asian patients is pythiosis, caused by a fungus-like organism, the mortality rate of which is very high. Because the prognosis for thalassaemia has much improved, with many patients surviving to the fifth decade of life in developed countries, it is mandatory to reduce mortality by recognising and presumptively treating infections in these patients as quickly as possible.
Despite dramatic declines in HIV-associated morbidity and mortality as a result of highly active antiretroviral therapy, management of heavily treatment-experienced patients remains complex and challenging. Treatment response rates with subsequent antiretroviral regimens are lower than with initial antiretroviral therapy. Additionally, increased mortality has been associated with multidrug-resistant HIV. We review data relevant to management of such patients and offer a systematic approach to constructing a salvage antiretroviral regimen.
Peripheral neuropathy has emerged as the most common neurologic complication of human immunodeficiency virus (HIV) infection. It will continue to play an Important role in HIV Infection given the fact that HIV-infected Individuals are living longer, are at risk of long-term metabolic complications, and face an Increasing exposure to potentially neurotoxic antiretroviral drugs. We review the various types of peripheral neuropathy that have been associated with HIV infection, including distal symmetrical polyneuropathy, toxic neuropathy from antiretroviral drugs, diffuse infiltrative lymphocytosis syndrome, inflammatory demyelinating polyneuropathies, multifocal mononeuropathies, and progressive polyradiculopathy.
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Tipranavir is a newly approved protease inhibitor that belongs to the class of 4-hydroxy-5,6-dyhydro-2-pyrones. It exhibits potent in vitro activity against both human immunodeficiency virus (HIV)-1 and HIV-2, including clinical isolates with multiple protease inhibitor-resistant mutations. Tipranavir requires coadministration with ritonavir to achieve clinically meaningful serum concentration. In randomized, phase III, open-label trials, it was found to be superior to the currently available boosted protease inhibitors in highly treatment-experienced patients with multiple protease inhibitor mutations. Thus, it provides a welcome new option for salvage antiretroviral therapy. The most common adverse effects associated with tipranavir are diarrhea, nausea and vomiting. Common laboratory abnormalities include elevations of total cholesterol, triglycerides and liver enzymes.
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A role for viruses in autoimmune hepatitis (AH) has been repeatedly proposed but convincing evidence links only two viruses, hepatitis A and Epstein-Barr virus, to the type 1 form of the disease, and only in those rare cases where a genetic predisposition exists and the viral infection occurs at the right time, i.e. when other unknown factors are cooperating. In spite of an impressive amount of information conclusively showing molecular mimicry between cytochrome P450IID6 (the target autoantigen of autoantibodies characteristic of AH type 2) sequences and viral (hepatitis C virus, herpes simplex virus 1, cytomegalovirus, human T lymphotropic viruses 1 and 2) or bacterial (Salmonella typhimurium) antigens, no infectious agent is clearly able to induce this second form of the disease. In conclusion, the molecular mimicry theory has so far found little clinical evidence in its support and many more clinical observations are needed in order to unreveal possible links between viruses and AH.
Currently, there are 20 individual antiretroviral drugs and two co-formulation products that are approved by the FDA for the treatment of HIV-infected individuals. It is widely accepted that the selection of an appropriate first-line regimen is critical in assuring durable treatment response. This article reviews the factors that should be considered in the selection of an initial antiretroviral regimen and present the currently available evidence regarding the status of individual antiretroviral agents and treatment strategies relative to these factors.
Patients with cancer who are undergoing chemotherapy are highly susceptible, especially if neutropenic, to almost any type of bacterial or fungal infection. These infections cause substantial morbidity and mortality. Prophylactic use of antibiotics should be avoided, however, since this practice is associated with a risk of emergence of resistant bacteria and it does not lower the risk of death. However, chemoprophylaxis has a role for candidal fungal infections. Because infection in a neutropenic host can be rapidly fatal if not treated, the empirical administration of broad-spectrum intravenous antibiotics is generally indicated for these patients, and the local frequencies, susceptibility, and resistance patterns of various pathogens must be taken into account. Once therapy has been initiated, changes in antibiotic regimens during the first 5 days are useless unless the patient's clinical condition deteriorates substantially. The treatment of invasive fungal infections is particularly difficult. Many unsolved questions remain, and studies are proposed here that may shed light on these issues.
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The liver is susceptible to the toxic effects of many cytotoxic or immunosuppressive treatments. However, in carriers of hepatitis B virus (HBV) and, less frequently, of hepatitis C virus, liver damage due to reactivation of viral replication can occur after withdrawal of immunosuppressive drugs. These reactivations, which are associated with fulminant forms of hepatitis in up to 25% of cases, are observed both in symptom-free chronic carriers of hepatitis B surface antigen and in patients who have chronic hepatitis B or C and concurrent haematological tumours or solid neoplasms or who have received transplants. HBV-related complications may cause delays or modifications of therapy, and the chance of cure is reduced. In this review, we analyse clinical, biochemical, and serological issues in reactivation of viral replication and examine the role of immune reactions in the pathogenesis and the possible toxicity of immunosuppressive drugs. We emphasise the importance of identifying predictive markers of a clinically relevant reactivation, review difficulties in drug prevention and treatment, indicate studies that are needed to address the key clinical issues, and give practical recommendations to practising physicians and oncologists.
Hepatitis C virus (HCV) infects about 170 million people worldwide, and has been portrayed in the media as a silent killer, incorrectly implying that cirrhosis and hepatocellular carcinoma are the certain final outcomes of infection. Results of numerous population-based surveys indicate that chronic HCV infection is highly prevalent in elderly people who, in most instances, do not develop end-stage liver disease. In individuals who do progress to cirrhosis and hepatocellular carcinoma alcohol plays a fundamental part, via mechanisms that result in increased viral replication, enhanced HCV quasispecies complexity, increased liver-cell death, suppression of immune responses, and iron overload. Although overlaps are present in the histological appearance of the liver in patients with hepatitis C who do and do not drink alcohol, histology could be of some help in revealing the role of alcohol in HCV disease progression even in people who deny drinking. Interventions and high-impact, continuous public-health campaigns are needed to persuade doctors and patients infected with HCV of the importance of abstaining from alcohol if risk of progression towards cirrhosis and hepatocellular carcinoma is to be reduced.