Honeybee venom therapy and viral infection: a systematic synthesis of venom antiviral activity

Antiviral biomaterials

Host-targeting agents for prevention and treatment of chronic hepatitis C – Perspectives and challenges

5-Hydroxytryptamine in the venom of the honey bee (Apis mellifera L.): Variation with season and with insect age

Hepatitis C. Development of new drugs and clinical trials: promises and pitfalls. Summary of an AASLD hepatitis single topic conference, Chicago, IL, February 27-March 1, 2003.

The demand for using natural compounds as control methods for honey bee viruses have increased in recent decades. In this study, a chemical profile of honey bee venom (HBV) has been determined by FTIR spectroscopy and Egyptian ethanolic propolis (EP) extract by GC-MS and HPLC. Also, the enzymatic activities of HBV were determined. HBV and EP were tested for antiviral activity. The cytotoxicity and cell viability were evaluated using the MTT assay. The results revealed the first identification of methyl gallate and phthalic acid using GC-MS and HPLC. HBV and EP showed antiviral activity against honey bee cell lines infected with deformed wing virus, black queen cell virus, Varroa destructor virus-1 and Kakugo virus. Also, cell proliferation was determined after incubating with HBV and EP, cells were produced with no evidence of cell death up to 1 g/L for HBV and 5 g/L for EP, despite cytotoxicity that was determined at higher doses of both treatments. The data demonstrated that EP and HBV exhibited a significant reduction of all identified viruses in the cultured cell. These findings suggest that HBV and EP in low concentrations could be used as potential supplements and antiviral drugs in honey bee apiaries.

Since the end of 2019, the emergence of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accelerated the research on host immune responses toward the coronaviruses. When there is no approved drug or vaccine to use against these culprits, host immunity is the major strategy to fight such infections. Type I interferons are an integral part of the host innate immune system and define one of the first lines of innate immune defense against viral infections. The in vitro antiviral role of type I IFNs against Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV (severe acute respiratory syndrome coronavirus) is well established. Moreover, the involvement of type I IFNs in disease pathology has also been reported. In this study, we have reviewed the protective and the immunopathogenic role of type I IFNs in the pathogenesis of MERS-CoV, SARS-CoV, and SARS-CoV-2. This review will also enlighten the potential implications of type I IFNs for the treatment of COVID-19 when used in combination with IFN-γ.

Hepatitis C virus resistance to protease inhibitors

Hepatic Gene Expression Discriminates Responders and Nonresponders in Treatment of Chronic Hepatitis C Viral Infection

Interferon-stimulated genes and their role in controlling hepatitis C virus

Haematological diseases are frequently accompanied by liver dysfunction. Mechanisms include direct liver damage by the haematological disorder, indirect liver damage as a result of therapy for the haematological disease and concomitant liver disease; all of these may co-exist. This review summarizes a clinical approach to liver-related abnormalities in stem cell transplantation recipients. Several factors need evaluation in the clinical assessment: (i) the underlying haematological condition, as this may make some liver problems more probable than others, (ii) the presence of previous liver disease, (iii) liver function and clotting tests, (iv) a viral marker profile, (v) a drug history, (vi) results of imaging procedures, and, finally, (vii) liver biopsy appearance. Liver biopsy remains an important diagnostic tool. If coagulation is seriously impaired, which precludes a percutaneous liver biopsy, it can be performed by the transjugular route, as this is safe, simple and rapid in experienced hands (Papatheodoridis et al, 1999); moreover, multiple passes, hepatic venography, CO2 portography, and wedged hepatic venous and caval pressure measurements increase the diagnostic value and scope of the procedure (Vlachogiannakos et al, 2000). This review is centred on the major clinical presentations of and reasons for referral for hepatic abnormalities during haematopoietic stem cell transplantation: (i) positive hepatic viral markers, (ii) abnormal liver function tests, and (iii) hepatomegaly and liver failure with its complications. The diagnosis of the primary haematological disease is almost always known to the hepatologist. The principal causes of liver injury during haematopoietic stem cell transplantation (SCT) are: (i) high-dose cytoreductive therapy (chemotherapy and/or irradiation) given prior to transplantation which may result in veno-occlusive disease (VOD) or nodular regenerative hyperplasia (NRH), (ii) liver toxicity owing to other drugs used after transplantation, (iii) viral and bacterial infections, and (iv) acute and chronic graft-vs.-host disease (GVHD) in the case of allogeneic transplantation. The differential diagnosis of these complications is guided by knowledge of the timing of their appearance. Veno-occlusive disease of the liver, jaundice owing to sepsis (cholangitis lenta) and drug-induced hepatotoxicity appear in the first few weeks after SCT, acute GVHD usually appears after donor engraftment (approximately d 14–21), viral infection usually appears after d 40, and chronic GVHD and NRH occur after d 100. (Fig 1). Time course of liver complications after bone marrow transplantation. GVHD, graft-vs.-host disease; CMV, cytomegalovirus; HSV, herpes simplex virus; HBV, hepatitis B virus; HCV, hepatitis C virus; EBV-PTLD, Epstein-Barr virus post-transplant lymphoproliferative diseases; VZV, varicella zoster virus. Hepatitis B (HB) virus serology is routinely performed in the pretransplant period for both recipient and donor. Apart from hepatitis B surface antigen (HBsAg) and anti-HBs, anti-HBc (antibody to hepatitis B core) should be assessed, as its positivity will confirm either a previous infection or will reveal a window phase following recent infection when HBsAg has disappeared and anti-HBs has not yet appeared. Anti-HBs may not be measurable in some patients with anti-HBc who have recovered from infection. Quantification of IgM anti-HBc gives valuable additional information. Thus, in an HBsAg-positive patient, IgM anti-HBc of > 600 units suggests acute infection. Titres between 30 and 600 U/l suggest either chronic infection, very early phase of acute infection, very late acute phase or an immunodeficient patient. Titres of less than 30 U/l usually signify chronic disease, a healthy carrier state or immune deficiency. HBeAg and anti-HBe markers will help to distinguish asymptomatic HBsAg carriers with high and low viraemia, but hepatitis B virus (HBV) DNA detection using polymerase chain reaction (PCR) in the serum confirms continuous viral replication, which implies a potential for progressive disease and high infectivity. HBV DNA must always be measured, even if HBeAg (HBe antigen) is absent in the serum, as precore genetic HBV mutants may exist that prevent formation of HBeAg (Laras et al, 1998). Liver biopsy should be performed in HBsAg(+) recipients pretransplant in order to determine the existence of cirrhosis and/or fibrosis. When HBV DNA is positive, appropriate assessment for anti-viral therapy must be made before transplantation. Several agents (interferon-alpha, lamivudine, famciclovir or ganciclovir) are effective in reducing HBV replication (Main et al, 1996; Carreno et al, 1999; Dienstag et al, 1999; Hadziyannis et al, 1999; Janssen et al, 1999). Lamivudine 100 mg/d suppresses HBV replication in as many as 97% of patients within 2 weeks of initiation of therapy (Hagmeyer & Pan, 1999), although therapy needs to be continued in the post-transplant phase. It has fewer side-effects than interferon which has the potential for myelotoxicity. Combination therapy with more than one nucleoside analogue may be evaluated in the future (Lau, G.K., et al, 1999). If recipient HBV DNA is negative before transplantation, systematic monitoring should begin from the second week post-transplant onwards at regular intervals. If seroconversion occurs, assessment for anti-viral therapy should be undertaken. Although there is a low risk of HBV transmission from HBV-infected donors to HBV-unaffected recipients, it has been proposed that HBV DNA testing in donors should be undertaken routinely (Locasciulli et al, 1995). If the donor is HBV DNA-positive, the diagnostic interpretation will be the same as that of an HBV-infected recipient. An excellent approach to the interpretation of the serum hepatitis markers in both patients and donors before haematopoietic cell transplantation has recently been reported (Strasser & McDonald, 1999). For hepatitis C infection, antibodies against HCV (hepatitis C virus) (anti-HCV) and molecular assessment of HCV RNA, using branch DNA assay and PCR techniques in cases of seronegativity, are used to diagnose chronic HCV infection. If the recipient is anti-HCV-positive and HCV RNA-negative by PCR, it is always worthwhile repeating the PCR before categorizing the patient as a rare example of recovery from acute hepatitis C infection. If HCV RNA is positive, a liver biopsy should be considered to stage and grade the hepatitis before SCT. If there is an anti-HCV-positive donor and HCV RNA is negative after confirmation, SCT can be safely performed. If HCV RNA is positive, a search should commence for an alternative donor. If this is not possible, it is recommended that the donor is treated, as HCV transmission can potentially occur via infected stem cells (Shuhart et al, 1994). Pretreatment of the hepatitis C viraemic donor with interferon-alpha may prevent HCV transmission to an HCV-seronegative recipient, and current therapy of combination interferon and ribavirin is more effective (Vance et al, 1996; European Association for the Study of the Liver (EASL) International Consensus Conference on Hepatitis C, 1999). Interferon should be discontinued at least 1 week before harvest (Vance et al, 1996). We are not aware of any literature on the relationship between hepatitis D virus and bone marrow transplantation patients. Hepatitis D infection (HDV) only occurs together with HBV infection, either as a co-infection or as a superinfection, and can be treated in the same way as HBV infection. Although there is currently no satisfactory therapy, recently it has been reported that prolonged high doses of interferon-alpha led to resolution of chronic delta hepatitis and HBV viral markers disappearance, and lamivudine should prove effective (Lau, D.T., et al, 1999). Sudden, progressive elevations of serum aminotransferases and cholestatic enzymes are a major problem in SCT recipients and can be as a result of reactivation of de novo viral illnesses or owing to non-viral illnesses. Viral illnesses Mild to severe flares of hepatitis can be observed in pre-existing HBV-infected recipients owing to HBV reactivation in the post-transplant period, especially at the time of immunosuppression tapering and immune reconstitution, even in long-term HBsAg-positive survivors (Martin et al, 1995). Moreover, studies have shown that HBV carriers who receive a marrow graft from an HBsAg(+) donor have a significantly increased risk of severe liver impairment, which may lead to fulminant hepatitis (Chen et al, 1999). SCT patients (particularly allogeneic) are more susceptible to HBV reactivation because of impairment of both T- and B-cell function (caused by poor immune reconstitution or drugs) that modulate HBV hepatitis. Moreover, corticosteroid treatment stimulates HBV replication directly (Tur-Kaspa et al, 1988). Acute HBV infection usually occurs 60 d post transplant. Liver biopsy must always be considered when elevations of liver enzymes appear in an HBV-infected recipient in order to differentiate and exclude a viral reactivation, GVHD, a drug-induced hepatotoxicity or other cause. In cases of increasing titres of HBV DNA post transplant (de novo viral infection or reactivation during cytotoxic chemotherapy), the use of lamivudine or famciclovir may reduce transaminase levels and suppress HBV replication (Lau, G.K., et al, 1998; Picardi et al, 1998). This is particularly necessary in cases of HBV reactivation in order to prevent severe hepatic decompensation (Yeo et al, 1999). Although no guidelines exist as to the duration of treatment or the particular drug regimen (monotherapy or combination) and dosage that should be used, experience in liver transplantation suggests that long-term therapy should be applied. Adefovir may be a useful additional drug if there is no response or in patients who are ‘treatment naive’ (Pessoa & Wright, 1999). Mild to moderate elevations of serum aminotransferases are commonly seen in HCV-infected SCT recipients, but typically do not exceed 300 U/l (Zuckerman et al, 1998). These flares frequently appear when immunosuppression is tapered (Ljungman et al, 1995). Acute HCV infection usually occurs after d 60 post transplant. Measurement of anti-HCV is not sufficient for diagnosis, as antibody formation is affected by immunosuppression. Consequently, HCV RNA estimation is required (Fujii et al, 1994; Strasser et al, 1999a). There is no correlation between HCV genotype and severity of post-transplant liver disease (Locasciulli et al, 1997). Interferon therapy can be used and, although there is potential for dose-dependent myelotoxicity, it does not adversely affect marrow engraftment (Giardini et al, 1997). Nevertheless, it has been suggested that the use of interferon is associated with a significant risk of GVHD in SCT recipients (Samson et al, 1996). The role of chelation treatment or phlebotomy prior to interferon therapy when iron overload co-exists is not clear and current guidelines do not recommend its use (Bonkovsky et al, 1997). Ribavirin therapy can be given safely to HCV-infected patients undergoing bone marrow transplantation (BMT) and long-term treatment may result in normal liver function and clearance of HCV RNA (Ljungman et al, 1996). Although previous studies suggested a minor risk of liver failure and cirrhosis secondary to HCV, recent data show that this is an important risk in long-term SCT survivors (Ljungman et al, 1996; Strasser et al, 1999b). No role for hepatitis G virus (HGV)/GB virus C (GBV-C) infection has been established in relation to liver dysfunction as the virus is not pathogenic in normal individuals. However, there is a high prevalence of HGV infection (20–60%) in BMT recipients (Skidmore et al, 1997; Yamada-Osaki et al, 1999). Identification of HGV RNA in serum using PCR can confirm the presence of the virus, but current knowledge suggests that it has no pathological role even in SCT recipients. Cytomegalovirus (CMV) infection is a common complication in SCT recipients. It usually occurs between d 40–100 in non-T cell-depleted allografts but has a much wider range in T cell-depleted allografts. Since primary prophylaxis or early pre-emptive therapy with nucleoside analogues was introduced, disseminated CMV infection has decreased markedly. Jaundice with elevation of serum transaminases and alkaline phosphatase levels are the main clinical and laboratory signs of hepatic infection which, in the SCT setting, is usually accompanied by disseminated disease (Rees et al, 1990). Severe liver impairment is rare with CMV infection. Diffuse intra- and extrahepatic duct strictures, as well as ampulla of Vater obstruction, can also occur but these are rarely seen now (Murakami et al, 1997). When CMV infection needs to be excluded or confirmed, in situ PCR techniques show the highest sensitivity for CMV detection in liver specimens with a high negative predictive value (Einsele et al, 1994). Immunohistochemical methods are also very sensitive. An increased expression of human leucocyte antigen (HLA) class II and intercellular adhesion molecule-1 (ICAM-1) have been demonstrated on hepatocytes with local viral presence, and this may be the mechanism whereby CMV viraemia significantly increases the risk of acute (grade III–IV) and chronic GVHD (Matthes-Martin et al, 1998). In protocols of pre-emptive therapy, patients are screened serially using PCR for CMV reactivation in blood. Ganciclovir is most effective in the prevention of CMV infection following reactivation after SCT (Noble & Faulds, 1998). Adenovirus infection has been reported to occur in approximately 6% of paediatric SCT patients, similar to the percentage reported in the adult population (Shields et al, 1985; Hale et al, 1999). It usually occurs after d 30 in paediatric recipients and after d 90 in adult recipients. Hepatic manifestations of this infection are hepatomegaly, coagulopathy, severe hepatitis and, rarely fulminant hepatic failure (Somervaille et al, 1999). PCR techniques are useful to detect adenovirus DNA in blood, sputum, urine, broncoalveolar lavage samples and liver tissue, either pre- or post mortem (Echavarria et al, 1999). If performed, liver biopsy shows widespread necrosis with intranuclear, irregular, dark, viral inclusions in the surviving hepatocytes. On electron microscopy, paracrystalline arrays of adenovirus virions may be seen. No established form of treatment exists to date, although cidovidir and ribavarin have been used with some success. Herpes simplex virus (HSV) infection usually occurs after d 45, affecting multiple organs including the liver. Hepatitis is a rare but severe infection in patients with impaired immunity, presenting with markedly raised aminotransferases (often in the many 1000s U/l), progressive jaundice and coagulopathy (Hayashi et al, 1991). Nevertheless, the early prophylactic use of acyclovir post transplant has virtually eliminated HSV hepatic damage of this kind (Hayashi et al, 1991). Histological findings are hepatocytes containing intranuclear basophilic inclusion bodies and focal necrosis. The virus can be demonstrated immunohistochemically using specific anti-HSV type 1 or type 2 antibodies or using in situ hybridization methods (Nikkels et al, 1996). Fulminant hepatic failure owing to HSV type 2 has been reported during acyclovir prophylactic treatment in the early phase of SCT (Gruson et al, 1998). Foscarnet treatment may be a valuable alternative in the presence of acyclovir-resistant HSV-infected SCT patients (Reusser, 1996). The varicella zoster virus (VZV) infection rate is 30% by 1 year post transplant (Locksley et al, 1985). The mean time interval from BMT to symptomatic VZV infection ranges from 60 d to 280 d et al, 1998). Hepatic complications include serum transaminase elevation fulminant hepatic failure et al, 1995). similar to that seen in HSV infection and similar intranuclear inclusions can be seen at the of the using specific or and in situ using can an diagnosis on tissue, even in the of or (Nikkels et al, 1996). PCR, both from and liver, can detect the virus and diagnose the infection. prophylaxis has virtually eliminated this infection, but acyclovir-resistant VZV has been from SCT recipients et al, et al, 1996). It has been suggested that should be early in patients with of acyclovir-resistant VZV infection. This treatment can be continued for at least d or are et al, 1994). infection following SCT is usually associated with graft GVHD, and but hepatitis is a rare complication et al, 1997; et al, 1998). can be on either DNA detection using PCR in or from multiple liver, antigen detection or increases in antibodies using assay or 1998; et al, 2000). and have been used for this viral infection with Epstein-Barr virus infection usually as but it is also associated with lymphoproliferative disease especially after transplantation et al, 1988). Liver usually appears with liver function or diagnosis of post-transplant lymphoproliferative diseases is of as a in immunosuppression and donor et al, may result in the of et al, of in serum with a using either a or a PCR appears to be a and specific marker for the early detection of after SCT et al, 1999; et al, 1999). Apart from PCR, in situ hybridization and can be used to specific RNA or DNA 1994). with are B is seen. virus) infection has been in of SCT recipients and it may hepatitis with abnormal liver et al, 1999). It may occur after but it is known that the virus can in patients for to et al, can be made using and PCR techniques to DNA et al, 1997). Liver biopsy shows hepatocytes with inclusions and with high-dose has been if there is liver GVHD, corticosteroid treatment may be useful et al, 1999). However, there is no established treatment for infection. virus infection has been reported to occur at a high prevalence in SCT recipients et al, 1999). Although not always hepatitis with transaminase levels has been DNA detection is either from the serum or from the using PCR et al, 1998). is not to interferon-alpha 2 shows a proposed clinical for use when a viral infection is proposed when viral infection is HBV, hepatitis B virus; HCV, hepatitis C virus; hepatitis G virus; CMV, cytomegalovirus; HSV, herpes simplex virus; VZV, varicella zoster virus; hepatitis B surface hepatitis B antibody to hepatitis B antibody to hepatitis B hepatitis of viral hepatitis has been a and severe of hepatitis may be owing to or blood, or or may be to the for the of donors for hepatitis B and C has the and, the risk of infection. The risk of HBV infection at this time is in the order of units of blood, for HCV infection it is in the order of units 1998). These are that it can be that hepatitis has been virtually when patients hepatitis following other of transmission should be that have been in as and to be These not to be methods and treatment in case of viral infection have been Veno-occlusive disease (VOD) The diagnosis of of the liver is usually on clinical a of hepatomegaly, more than and It is an early complication usually in the first 2 weeks after SCT. of may to abnormal liver function necrosis. transaminase are associated with a poor et al, usually appears before d et al, Hepatic include widespread damage to in of the liver including and of and necrosis of hepatocytes. The diagnosis of in most has on that et al, suggest that there is no diagnostic although the severity of clinical appears to be to the of in of the liver et al, et al, 1994). particularly is the diagnosis of when it co-exists with GVHD or of hepatic pressure using the transjugular also transjugular liver biopsy to be is et al, 1995). The hepatic venous pressure is significantly in than in liver in one of patients with a pressure than but no patient with GVHD a this value et al, In a of more than was significantly with a diagnosis of with a and positive predictive value et al, 1995). may suggest the diagnosis on decreased or venous et al, 1990). Moreover, significant elevation of the hepatic in may be a of liver damage to et al, However, any of liver damage may hepatic venous and and, in other studies have not demonstrated any between and some findings et al, markers have been suggested for serum than of the of type for by to very high d after the diagnosis of the liver disease, or et al, & 1997; et al, 1997). However, these have not been and are not If of the liver is or treatment should be proposed as therapy for established include and but one of patients owing to the complications of progressive liver failure et al, et al, 1997). results the role of in the treatment of of the liver et al, 1999). suggests that prophylaxis to the of hepatic after allogeneic SCT in patients who a regimen with et al, 1998). The prophylactic of on after SCT was recently in a et al, 2000). have been used for treatment of following SCT. et that was significantly in all their patients pressure decreased to post with before Although there is is an effective procedure for and is associated with clinical of jaundice and in a of patients et al, 1996). However, the on as well as data on and needs to be evaluated Acute GVHD In acute GVHD, transaminases are usually to normal in chronic GVHD these enzymes are usually only approximately the normal However, a high elevation of the aminotransferases may occur because chronic GVHD may as acute hepatitis in patients tapering immunosuppression or no immunosuppression (Strasser et al, 1997). in acute GVHD of the liver ranges from a form to to elevations in alkaline phosphatase are and et al, Liver biopsy is not necessary for the diagnostic of acute GVHD when the liver abnormalities are associated with and of the Nevertheless, it may be when the clinical be by liver diseases as early viral or or for of a diagnosis of hepatic The time course of may help in the differential However, it should be that findings may appear only after 2 weeks of of acute These and the at the of the the disease in both the and the is seen. to of the The of acute GVHD is the damage to with necrosis and of hepatic and are other associated et al, that is the or the of and is a specific of is a form of chronic sepsis associated with It typically occurs in the early phase post SCT. with jaundice may and directly the cholestatic of the infection et al, 1994; et al, et al, 1996). and alkaline phosphatase elevation are the most manifestations that occur in the of or acute hepatic GVHD are important differential The diagnosis of is usually one of and resolution following Mild elevations in alkaline and transaminases are commonly seen in post-transplant patients treated with and of jaundice owing to therapy may in patients with sepsis or multiple and Although is an of the formation and have been associated with et al, Liver biopsy can show and, in cases of long-term and abnormalities which are for the diagnosis of hepatotoxicity & The diagnosis is made by of other causes of liver damage in this clinical In cases of or of initiation of and of timing or all have a role & & 1995). liver dysfunction is common after may which is most frequently seen as alkaline phosphatase and The cholestatic is as a result of a of and & 1997). levels should be in order to as damage is is used in the treatment of chronic GVHD and can asymptomatic elevation of liver tests, hepatic and or hepatic and of these can also be observed in chronic GVHD et al, 1991). of other of a injury and, most clinical after drug can be in order to diagnose high-dose and drugs can also hepatotoxicity with a infection infection usually occurs in the first weeks post transplant or in patients treated for GVHD with or who have graft raised serum alkaline phosphatase is liver imaging studies show low sensitivity for the detection of liver et al, 1995). imaging to be to other techniques in hepatic et al, 1996). Liver biopsy, of biopsy guided or may be useful for the diagnosis et al, and human of and may be for liver infection. prophylaxis results in a significant in infection et al, 1998). is an important infection in BMT patients. Liver infection is but has been in the literature (de et al, 1999); this infection is rarely seen in stem cell transplant recipients, in is its after to be than that in the population et al, 2000). in the liver may be observed in patients with either or infection. Liver imaging techniques liver biopsy, and PCR of biopsy specimens can be useful for the therapy, either in the pre- or post-transplant period, will resolution of the infection et al, should be considered in recipients with a of treated known recent or patients from of high GVHD Although chronic GVHD usually occurs after d the differential diagnosis chronic viral hepatitis. In chronic GVHD, and elevations of alkaline phosphatase are the normal The main is a and in and the duct et al, 1996). are severe of duct and necrosis. et that the diagnosis of GVHD a positive predictive value of a sensitivity of and a of liver biopsy an important diagnostic for GVHD is a therapy for the treatment of both acute and chronic GVHD that are to therapy including or et that of patients with liver after However, these results need to be may be or Liver transplantation can be considered for liver disease et al, 1990). iron overload overload is one of the late complications of therapy seen in survivors of SCT. transplant recipients have a high liver iron at d post transplant with the hepatic iron in the range (Strasser et al, 1998). Liver biopsy with iron and is the for the assessment of iron for patients with iron overload et al, 2000). This should be performed in all patients prior to SCT. of of SCT for treatment of include hepatomegaly, hepatic and a poor of chelation with iron overload et al, 2000). of marrow iron is a of hepatic iron in stem cell transplant recipients (Strasser et al, 1998). measurements as and imaging are used in order to iron but are 1997; et al, 1997). It is important for these patients to receive iron chelation as as is a safe, and form of et al, 1997). iron chelation is a and effective alternative therapy in the of iron (Giardini et al, 1995). therapy during SCT does not to affect the engraftment the of or GVHD et al, 1995). This therapy should be by iron either by or by in order to the clearance of iron et al, 2000). of the hepatic iron can a of the long-term iron et al, 2000). Moreover, it is to for the before any kind of therapy, in order to diagnostic for abnormal liver function is proposed in in cases of abnormal liver function after bone marrow transplantation. of type SCT, stem cell veno-occlusive disease; GVHD, graft-vs.-host disease; hepatic venous In of the liver, in and in of patients et al, regenerative hyperplasia of the liver is a rare by of the hepatic with of regenerative with of between the It can with similar signs as although it is associated with and after d 100 post BMT 1990). for the diagnosis of NRH do not exist and is although liver biopsy or guided may be necessary et al, et al, and imaging may be useful to diagnose the but these are not specific et al, 1999). Although no specific treatment or of potentially drugs is performed.

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Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

Pathogenesis and Treatment of Hepatitis E Virus Infection

Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses. In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and post-herpetic pain were not significantly affected. Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections. Despite some aspects of the drug's use which require further clarification, acyclovir will make a major impact on the treatment of herpesviral infections. Barring unexpected findings with wider clinical use, it will become the agent of choice in several conditions.

Hepatitis C Virus Triggers Apoptosis of a Newly Developed Hepatoma Cell Line Through Antiviral Defense System