acyclovir and Hepatitis

Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M(2) inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.

Topics: Acyclovir; Adenine; Amantadine; Antiviral Agents; Comorbidity; Drug Therapy, Combination; Foscarnet; Ganciclovir; Guanine; Hepatitis; Hepatitis B, Chronic; Hepatitis C; Herpesviridae Infections; HIV Infections; Humans; Influenza, Human; Interferons; Lamivudine; Nucleosides; Oligopeptides; Organophosphonates; Oseltamivir; Proline; Protease Inhibitors; Pyrimidinones; Ribavirin; Telbivudine; Thymidine; Valacyclovir; Valganciclovir; Valine; Virus Replication; Zanamivir

Topics: Abdominal Pain; Acyclovir; Adult; Antiviral Agents; Diagnosis, Differential; Fatal Outcome; Hepatitis; Herpesvirus 3, Human; Humans; Liver; Liver Failure, Acute; Male

Herpes simplex virus (HSV) hepatitis is a rare complication of HSV infection with a high reported mortality rate in untreated patients. The authors present a case of HSV hepatitis in a 26-year-old female with focal proliferative lupus nephropathy who was status post one cycle of pulse high-dose (1 gm/ m2) cyclophosphamide. Treatment with parenteral acyclovir was successful. A meta analysis of well-documented cases of HSV hepatitis treated with acyclovir, excluding those that omit initial serum concentrations of hepatic transaminases, suggests that the early administration of parenteral acyclovir may have been instrumental in the achievement of a successful outcome, and that a patient's serum levels of hepatic transaminases at the time of treatment initiation may predict outcome. This is the first reported case of successful parenteral acyclovir treatment of HSV hepatitis in a patient with lupus nephritis who has recently undergone cyclophosphamide immunosuppression, and includes a meta analysis to examine the hypothesis that initial markers of hepatic injury may predict outcome of acyclovir treatment.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Hepatitis; Herpesvirus 2, Human; Humans; Liver Function Tests; Lupus Erythematosus, Systemic; Treatment Outcome

Topics: Acyclovir; Aged; Antineoplastic Agents; Antiviral Agents; Bridged Bicyclo Compounds, Heterocyclic; Exanthema; Female; Hepatitis; Herpesvirus 3, Human; Humans; Immunocompromised Host; Leukemia, Lymphocytic, Chronic, B-Cell; Opportunistic Infections; Pancreatitis; Recurrence; Sulfonamides; Treatment Outcome; Varicella Zoster Virus Infection

We report a case of fatal disseminated varicella zoster virus (VZV) with delayed-onset rash in a 66-year-old female more than 2 years following uncomplicated deceased donor renal transplantation. Whilst on a stable regimen of maintenance immunosuppression, the patient presented with chest and abdominal pain with concomitant hepatitis and pancreatitis. After pursuing multiple other potential causes of her symptoms, the correct diagnosis of VZV was only suspected after the development of a widespread vesicular rash-11 days after her initial symptoms. Despite antiviral therapy and inotropic support in the intensive care unit, the patient died. Simultaneous VZV hepatitis and pancreatitis in solid organ transplant recipients is uncommon. The new inactivated VZV vaccines have the potential to prevent post-transplant infections, with promising early clinical data on safety and efficacy in renal transplant recipients. VZV is an important preventable infection that should be considered in immunocompromised patients, even in the absence of rash.

Topics: Acyclovir; Aged; Antiviral Agents; Exanthema; Fatal Outcome; Female; Hepatitis; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Kidney Transplantation; Pancreatitis

Prognosis of hepatitis-associated aplastic anaemia (HAAA) was improved with haematopoietic stem cell transplantation (HSCT) and immunosuppression, but the long-term outcome remains undefined. Case 1: a girl aged 3 years with acute liver failure (ALF) submitted to orthotopic liver transplantation (OLT) subsequently developed aplastic anaemia and HSCT from a compatible sibling was performed. Post-HSCT, the patient developed post-transplant lymphoproliferative disorder and rituximab was administered with good response. Fifteen years later, both grafts show good outcome. Case 2: a girl aged 10 years submitted to OLT due to ALF, developed pancytopenia 2 months later. Due to the absence of a human leucocyte antigen compatible donor, she was treated with ciclosporin and antithymocyte globulin with very good long-term outcome. These clinical cases suggest that, for patients with HAAA that underwent OLT, aggressive therapy with HSCT or immunosuppression may provide a benign long-term outcome.

Topics: Acyclovir; Anemia, Aplastic; Antiviral Agents; Child; Child, Preschool; Diagnosis, Differential; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hepatitis; Humans; Liver Failure, Acute; Liver Transplantation; Postoperative Complications

Topics: Acyclovir; Adult; Antiviral Agents; Back Pain; Exanthema; Face; Female; Hepatitis; Herpes Simplex; Herpesvirus 2, Human; Humans; Lumbosacral Region; Magnetic Resonance Imaging; Neck; Serositis

Topics: Abdominal Pain; Acyclovir; Aged; Antiviral Agents; Exanthema; Hepatitis; Herpes Genitalis; Herpesvirus 2, Human; Humans; Male; Pancreatitis; Skin Diseases, Vesiculobullous; Treatment Outcome

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Black or African American; Blood Coagulation Disorders; Diagnosis, Differential; DNA, Viral; Hepatitis; Herpes Simplex; Herpesvirus 2, Human; Humans; Male; Polymerase Chain Reaction; Skin Diseases, Viral; Young Adult

Herpes simplex virus (HSV) hepatitis is an uncommon cause of acute liver failure (ALF), primarily affecting immunocompromised patients. So far, 148 cases have been published, of which 9 underwent liver transplantation (LT). The reported post-transplant survival is poor, with over 60% dying in the first year. Dosing and duration of antiviral therapy after LT are not established. Concerns include both the risk of hepatic recurrence after LT and emergence of viral resistance during prolonged therapy. HSV DNA plasma levels might be helpful to monitor therapeutic response and guide duration of therapy. We present a case of ALF complicating a primary HSV-1 infection in an immunocompetent host, who required emergency LT. We further discuss the value of measuring serial HSV DNA plasma loads to monitor antiviral therapy.

Topics: Acyclovir; Antiviral Agents; DNA, Viral; Hepatitis; Herpes Simplex; Herpesviridae Infections; Herpesvirus 1, Human; Humans; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Simplexvirus; Viral Load

A previously healthy boy aged 9 years and 11 months was admitted due to herpetic gingivostomatitis with poor intake. He also had fever, neutropenia, and elevated serum aminotransferase level (> 1000 IU/mL). Prolonged prothrombin time, mild gastrointestinal hemorrhage and transient decreased conscious level were noted during hospital days 2 and 3. Intravenous acyclovir therapy commenced on hospital day 2 and his serum aminotransferase level peaked (> 4000 IU/mL) on hospital day 3 and then improved gradually. A throat swab was positive for human herpes simplex virus (HSV)-1, serological test was positive for acute primary HSV-1 infection, and a blood specimen was also strongly positive for HSV-1 by polymerase chain reaction. He received a 14-day course of intravenous acyclovir and recovered uneventfully. Herpetic gingivostomatitis, although mostly benign and self-limited, may be complicated with severe hepatitis, even in immunocompetent hosts.

Topics: Acyclovir; Administration, Intravenous; Antiviral Agents; Child; Fever; Hepatitis; Herpesvirus 1, Human; Humans; Male; Neutropenia; Serologic Tests; Specimen Handling; Stomatitis, Herpetic; Transaminases; Treatment Outcome

If not promptly recognized and treated, herpes simplex virus (HSV) hepatitis is associated with a high mortality. A patient transplanted for primary sclerosing cholangitis required, 4 years later, a colectomy for a steroid-resistant flare of ulcerative colitis. He subsequently developed fever, with genital and oral ulcerations. He was hospitalized for diabetic decompensation with massive elevation of serum aminotransferases. Examination revealed vesicles on the hands. Liver biopsy showed Cowdry type B inclusions. Therapy with acyclovir was immediately initiated and the patient recovered. This case illustrates the diagnostic importance of mucocutaneous lesions in the assessment of complications after liver transplantation.

Topics: Acyclovir; Adult; Antiviral Agents; Cholangitis, Sclerosing; Colectomy; Colitis, Ulcerative; Hepatitis; Herpes Simplex; Humans; Liver Transplantation; Male; Postoperative Complications; Reoperation; Simplexvirus

Five cases of fulminant hepatitis due to herpes simplex virus were identified among patients admitted to the Thomas E. Starzl Transplantation Institute between January 1991 and September 1994. The diagnosis was established in three of the five patients on the basis of transjugular liver biopsy specimen results. These three patients were treated with acyclovir; two survived and one required liver transplantation. Early histologic diagnosis, specific antiviral treatment, and liver transplantation in selected patients may improve the clinical outcome of this almost uniformly fatal disease.

Topics: Acyclovir; Adult; Antiviral Agents; Female; Hepatitis; Herpes Simplex; Humans; Liver Transplantation; Male; Middle Aged; Survival Analysis

The aim of this study was to correlate human herpesvirus (HHV)-6 viral load with clinical symptoms in allogeneic stem cell transplant (SCT) patients. Seventy-four patients were monitored during the first 3 months after SCT using a qualitative polymerase chain reaction (PCR) for HHV-6 DNA. HHV-6 was detected in 181 out of 494 samples (36%) from 58 (78%) patients. These 181 samples were analysed using a quantitative competitive PCR. DNA could be quantified from 146 out of 181 samples (80.6%). The HHV-6 viral load was highest at 4 weeks compared with 8 weeks (P < 0.001) and 12 weeks (P = 0.01) after SCT. Three patients had HHV-6 encephalitis and one patient had hepatitis. The HHV-6 DNA levels were higher in patients with HHV-6 than in those without HHV-6 (P = 0.01). Patients who received grafts from unrelated or HLA-mismatched family donors had significantly higher HHV-6 DNA levels than patients who received grafts from matched sibling donors (P < 0.001). In a multiple regression model, unrelated donor grafts (P < 0.001) and use of intravenous immunoglobulin prophylaxis (P = 0.04) influenced HHV-6 DNA levels. HHV-6 viral load was significantly correlated with delayed platelet engraftment in both univariate (P < 0.01) and multivariate analysis, and to the number of platelet transfusions.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Blood Platelets; Bone Marrow Transplantation; Central Nervous System Diseases; Child; Child, Preschool; Cytomegalovirus; DNA, Viral; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hepatitis; Herpesviridae Infections; Herpesvirus 6, Human; Histocompatibility Testing; Humans; Immunoglobulins, Intravenous; Leukocytes; Male; Middle Aged; Multivariate Analysis; Platelet Transfusion; Polymerase Chain Reaction; Postoperative Period; Prospective Studies; Transplantation, Homologous; Viral Load

We report a Chinese girl with Epstein-Barr virus (EBV) associated aplastic anaemia and hepatitis. Epstein-Barr virus genome was demonstrated in her bone marrow cells and EBV-specific serology suggested reactivation of EBV infection. She was initially treated with anti-thymocyte globulin (ATG) and methylprednisolone but with no haematologic response, and liver function continued to deteriorate. She was then treated with acyclovir. Her aplastic anaemia improved and hepatitis resolved, and there was eradication of EBV genome from her bone marrow cells.

Topics: Acyclovir; Anemia, Aplastic; Child; Female; Hepatitis; Herpesviridae Infections; Herpesvirus 4, Human; Humans

To determine the incidence and clinical course of veno-occlusive disease of the liver (VOD) after bone marrow transplantation and to analyze risk factors for severe VOD.. Cohort study of 355 consecutive patients.. A bone marrow transplantation center.. Each patient was prospectively evaluated for VOD, and many risk factors for severe VOD were analyzed using logistic regression models. The relation of VOD to renal and cardiopulmonary failure was analyzed using time-dependent proportional hazards models.. Veno-occlusive disease developed in 190 of 355 patients (54%; 95% CI, 48% to 59%): Fifty-four patients had severe VOD and 136 had mild or moderate VOD. Independent variables derived from a multivariate model for predicting severe VOD included elevated transaminase values before transplantation (relative risk, 4.6; P < 0.0001); vancomycin therapy during cytoreductive therapy (relative risk, 2.9; P = 0.003); cytoreductive therapy with a high-dose regimen (relative risk, 2.8; P = 0.01); acyclovir therapy before transplantation (relative risk, 4.8; P = 0.02); mismatched or unrelated donor marrow (relative risk, 2.4; P = 0.02); and previous radiation therapy to the abdomen (relative risk, 2.2; P = 0.04). Vancomycin therapy was a marker for persistent fever. Multiorgan failure was more frequent among patients with VOD and usually followed the onset of liver disease.. Veno-occlusive disease, which developed in 54% of bone marrow transplant recipients, is frequently associated with renal and cardiopulmonary failure. Pretransplant transaminase elevations, use of high-dose cytoreductive therapy, and persistent fever during cytoreductive therapy are independent predictors of severe VOD.

Topics: Acyclovir; Adolescent; Adult; Aged; Blood Component Transfusion; Bone Marrow Transplantation; Child; Child, Preschool; Female; Hepatic Veno-Occlusive Disease; Hepatitis; Humans; Incidence; Infant; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Prospective Studies; Risk Factors; Transaminases; Vancomycin

We report a rare adult case of chronic active Epstein-Barr virus (EBV) infection. A 54-year-old woman was admitted to our hospital with intermittent fever, weight loss, hepatosplenomegaly, pancytopenia and liver disturbance. In serological tests for EBV, anti-virus capsid antigen (VCA)-IgG antibody and anti-early antigen (EA)-IgG antibody were markedly elevated and anti-EBV nuclear antigen (EBNA) antibody was negative. EBV genome was detected in the bone marrow nucleated cells and peripheral lymphocytes by Southern blot hybridization. The patient developed left facial edema, bilateral breast tumor and pneumonia. She died one year after admission in spite of the administration of prednisolone, interferon and acyclovir.

Topics: Acyclovir; Antigens, Viral; Blotting, Southern; Breast Neoplasms; Capsid Proteins; Chronic Disease; DNA-Binding Proteins; Edema; Epstein-Barr Virus Nuclear Antigens; Female; Hepatitis; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Interferon-alpha; Liver; Middle Aged; Prednisolone

Topics: Acyclovir; Azathioprine; Chronic Disease; Drug Evaluation; Drug Therapy, Combination; Hepatitis; Hepatitis, Chronic; Hepatitis, Viral, Human; Humans; Prednisone; Vidarabine