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PubMed1993

Prevention of hepatitis B virus infection.

Hepatitis B virus infection is the most important cause of acute and chronic liver disease worldwide. The Immunization Practices Advisory Committee has proposed a comprehensive strategy to eliminate the transmission of hepatitis B virus in the United States. The three phases of this strategy are prevention of perinatal transmission of the hepatitis B virus, universal vaccination of all infants against hepatitis B virus infection and selected vaccination of high-risk adolescents and adults. Because family physicians provide obstetric, perinatal, adolescent and adult care, they can have a major influence on the success of this strategy.

Adolescent↗

PubMed2000

Natural history of hepatitis C virus infection.

Hepatitis C is a heterogeneous disease whose natural history is controversial and perplexing. However, it can be a pernicious disease and is responsible for considerable mortality and morbidity. More than 80% individuals infected with the hepatitis C virus (HCV) develop chronic infection; the remaining 10-20% develop spontaneous clearance with natural immunity. The majority of patients who develop chronic HCV infection are asymptomatic; but 60-80% develop chronic hepatitis as indicated by elevated ALT; around 30% maintain normal ALT. One-third of chronically infected patients develop progressive liver injury, fibrosis and cirrhosis over a period of 20-30 years, and 15% develop hepatocellular carcinoma. Acquiring infection after the age of 40 years, male sex, excessive alcohol-consumption, HBV or HIV co-infection and the immunosuppressive state have been identified as factors associated with progression of fibrosis and development of cirrhosis. The relationship between virus load, HCV genotype I and quasispecies variability and progression of live disease is controversial. In the present study on 141 patients with chronic HCV infection and established chronic liver disease, the median time to develop cirrhosis was 20 years. Progression to cirrhosis was faster (16 vs 20 years) in those who acquired infection after the age of 35 years, and in immunosuppressed patients (8 vs 21 years), whereas diabetes, sex and HBV co-infection were not associated with faster progression.

Acute Disease↗

PubMed2002

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation evolving to an overt lymphoma. Recently, CD81 was identified as an HCV receptor on B-lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. In addition, expansion of CD5+ B lymphocytes was described to be associated with various non-HCV related autoimmune disorders. Therefore, we studied the possible role of peripheral B cells CD81 and CD5 over-expression in the development of HCV-related autoimmunity and their association with disease severity in chronic HCV infection. Peripheral B cells CD5 expression and mean fluorescence intensity (MFI) of CD81 were determined in 30 HCV-infected patients, 30 healthy controls and 15 patients with hepatitis B virus infection using fluorescence-activated cell scan (FACS). We have also investigated the association between peripheral CD5 and CD81 B-cell over-expression and markers of autoimmunity and disease severity in patients chronically infected by HCV. CD5+ B-cells were increased in chronic HCV infection (23.2 +/- 7.2%) compared with those of healthy controls (15 +/- 5.5%) (P < 0.0001) and chronic HBV infection (19 +/- 3.7%) (P = 0.08). CD81 MFI was significantly higher in HCV-infected compared to HBV-infected patients and healthy controls. Both increased CD81 MFI and CD5+ B-cell expansion were associated with the production of rheumatoid factor and mixed cryoglobulins and positively correlated with HCV viral load and histological activity index. The overexpression of CD81 and the expansion of CD5+ peripheral B-cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.

Adult↗

PubMed1997

Cutaneous necrotizing vasculitis associated with hepatitis A virus infection.

Hepatitis A virus has been recognized as an etiologic factor of cutaneous necrotizing vasculitis in only 2 adult cases. We describe a 2-year-old Bedouin girl who developed cutaneous necrotizing vasculitis during the acute phase of hepatitis A infection. The cutaneous punch biopsy from an ecchymotic lesion revealed microscopic findings of a necrotizing vasculitis process involving the superficial and deep blood vessel plexuses. Fibrin thrombi were present in the lumen of a few blood vessels. She was treated with 2 mg/kg/day, tapered during 5 weeks. Serum liver enzymes returned to the normal range within 6 weeks of the first presenting symptom. A few skin scars were noted in previously necrotic areas. Hepatitis A is one of many viruses that may be an etiologic factor in development of cutaneous necrotizing vasculitis in children.

Acute Disease↗

PubMed2002

Acute renal failure associated with nonfulminant hepatitis A virus infection.

Hepatitis A is usually a mild self-limiting infection of the liver. Nonfulminant acute renal failure very rarely complicates type A viral hepatitis. An unusual case, a 32-year-old female with serologically proven acute hepatitis A infection, was complicated by acute renal failure and the patient in this study is the first case associated with Cushing's disease. She recovered, and the laboratory tests returned normal one month after initial hospitalization. Although the mechanism responsible for renal failure in acute hepatitis A virus infection is still uncertain, possible causes are discussed with the review of literature.

Acute Kidney Injury↗

PubMed2003

Anemia in the treatment of hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a significant worldwide health care problem. Nearly one-third of all patients infected with human immunodeficiency virus (HIV) are coinfected with HCV. Compared with HIV-monoinfected persons, coinfected individuals experience more rapid progression of fibrosis and higher incidence of cirrhosis and death as a result of liver disease. Treatment for HCV infection includes ribavirin (RBV) plus interferon alfa (IFN-alpha) or pegylated IFN, a combination treatment associated with anemia that may require RBV dose reduction or discontinuation. IFN-RBV-associated anemia is more profound among coinfected patients, who have a high prevalence of pretreatment anemia and may also be taking other medications causing anemia. Epoetin alfa administration to HCV-infected patients with IFN-RBV-related anemia can significantly increase hemoglobin levels and maintain significantly higher RBV doses compared with patients treated with RBV dose reduction alone. Higher RBV doses and adherence to HCV therapy have been associated with higher sustained virologic response (SVR) rates. Maintenance of RBV dose with epoetin alfa may improve adherence, thereby affecting SVR.

Anemia↗

PubMed2006

Response to combined interferon and ribavirin is better in patients infected with hepatitis C virus genotype 6 than genotype 1 in Hong Kong.

Data on the treatment efficacy of interferon (IFN)-alpha and ribavirin in patients with chronic hepatitis infected with hepatitis C virus (HCV) of genotype 6 are lacking. A study has been reported from Hong Kong which compared the treatment efficacy of IFN-alpha and ribavirin in the treatment of chronic HCV infection with genotypes 1 and 6. Twenty-four patients with HCV genotype 1 and 16 patients with HCV genotype 6 were studied. The baseline demographic data including median age, gender ratio, alanine aminotransferase levels, bilirubin levels, HCV RNA levels and histological scores were comparable between the two groups of patients. All patients received IFN-alpha 5 million units three times per week and ribavirin (1,000 mg for those weighing </=75 kg and 1,200 mg for those weighing >75 kg) for 1 year. Patients infected with HCV genotype 6 achieved virological response significantly higher than those with HCV genotype 1 (67 vs. 33% at week 24, p = 0.02; 75 vs. 42% at the end of treatment, p = 0.05; 63 vs. 29% at 6 months after completion of treatment, p = 0.04). Histological improvement in inflammatory activity and fibrosis in the liver were observed in 25% and 25% of patients infected with HCV genotype 6 in contrast to only 13 and 8% in patients infected with HCV genotype 1; however, the differences were not statistically significant. In conclusion, patients with HCV genotype 6 gain a better response to combined treatment with IFN-alpha and ribavirin than those with HCV genotype 1 and achieve a significantly higher rate of sustained virological response.

Antiviral Agents↗

PubMedDate not supplied

[Usefulness of the PCR technique (polymerase chain reaction) in the follow-up of patients infected with hepatitis C virus. Preliminary communication].

UNLABELLED: In the study we show the usefulness of PCR (polymerase chain reaction) to follow patients with chronic hepatitis, infected with hepatitis C virus (HCV) of Centro Médico de Caracas. The study included 14 patients: 12 anti-HCV positive, 1 with chronic autoimmune hepatitis and 1 classified as non B-non C hepatitis. The patients were divided in 3 groups: Group 1 (5 pretreatment patients, anti-HCV+), 4 with increase in ALT and PCR positive, 1 with normal ALT and PCR negative. Group 2 (7 treated with recombinant interferon alpha 2b), 4 without normalization of ALT and PCR positive, 3 with normalization of ALT and PCR negative. Group 3 (control) 2 patients anti-HCV negative and PCR negative. Two posttreatment patients could be genotyped: one patient was infected with 1a and showed an early relapse with treatment and the other was infected with genotype 1b, which is reported to be more refractory to antiviral treatment. CONCLUSIONS: the results show a 100% correlation between biochemical markers of HCV infected patients and the presence of viral RNA detected by PCR. the usefulness of determination of genotype to assess any prognostic value of this parameter in Venezuela is discussed.

Follow-Up Studies↗

PubMed1996

Hepatitis C virus RNA in peripheral blood mononuclear cells: comparing acute and chronic hepatitis C virus infection.

Hepatitis C virus (HCV) can infect peripheral blood mononuclear cells (PBMC) of patients with chronic HCV infection. No data are available on PBMC testing for HCV RNA in acute hepatitis C. This study investigated the presence of HCV RNA in PBMC of patients with acute posttransfusion hepatitis C, compared with those with chronic HCV infection. Nested polymerase chain reaction (PCR) was applied to detect HCV RNA in 111 and 48 paired samples of serum and PBMC of 11 patients with acute posttransfusion hepatitis C and 48 patients with chronic HCV infection, respectively. In patients with acute posttransfusion hepatitis C, HCV RNA was detected in 17 of 29 (59%) and 67 of 82 (82%) serum samples collected during the incubation period and acute phase, respectively. Meanwhile, of the 48 patients with chronic HCV infection, 41 had serum HCV RNA (85%). HCV RNA was not detected in PBMC samples from incubation period or from acute-phase hepatitis, although it was detected in 12 of the 48 PBMC samples of chronically infected patients (25%) P < .005). Of the 12 PBMC specimens positive for positive-stranded HCV RNA, 6 were also positive for negative-stranded HCV RNA. Among patients with chronic HCV infection, HCV infection of PBMC was not related to age, sex, blood transfusion, serum alanine transaminase (ALT) levels, or serum virus titers. In conclusion, HCV infection of PBMC rarely exists in patients with acute hepatitis C. As HCV infection persists, the incidence of HCV infection of PBMC becomes higher.

Acute Disease↗

PubMed2005

Hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a major public health problem. Up to 3% of the world's population is infected with HCV, and at least 200 000 adults in the UK carry the virus. Of those exposed to HCV, 80% become chronically infected, and at least 30% of carriers develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. This review provides an overview of selected features of the molecular biology and pathogenesis of HCV infection, and thereafter discusses in detail the epidemiology of HCV, the hepatic and extra-hepatic diseases caused by the virus, and the current treatment options for both acute and chronic virus infection. The special cases of healthcare workers, prison inmates and individuals coinfected with human immunodeficiency virus and HCV are considered in detail.

HIV Infections↗

PubMed2000

Impact of acute hepatitis B virus superinfection on chronic hepatitis C virus infection.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is not uncommon, but the impact of acute HBV superinfection in patients with chronic HCV infection is still unknown. Two patients with well documented chronic HCV infection were hospitalized for acute hepatitis, which was serologically confirmed to be acute HBV superinfection. One patient who was seropositive for both HBV-DNA and HCV-RNA upon admission died of hepatic failure. The other became seronegative for HCV-RNA and recovered with alanine aminotransferase normalization, seroclearance of HBsAg, and antibodies to HCV. These findings confirm that acute superinfection in patients with chronic hepatitis may increase the risk for severe hepatitis, and suggest that HBV as the newcomer may suppress the pre-existing HCV. Together with the earlier observation that acute HCV superinfection suppresses pre-existing HBV, it seems that the timing or sequence of infection is a factor influencing the outcome of viral interactions.

Acute Disease↗

PubMed2003

The epidemiology and natural history of hepatitis C virus infection.

Hepatitis C virus (HCV) infection is the most common chronic blood-borne infection in the United States. HCV infection is generally benign in its acute stage but tends to become chronic in more than 70% of patients, at which stage it can induce liver cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Approximately 2.7 million Americans are estimated to have chronic HCV infection. Although the incidence of HCV infection is believed to be falling, the prevalence of HCV-related liver disease is rising. Better identification of risk factors for HCV transmission and improved understanding of the infection's natural history should refine measures for preventing the spread of infection and preventing complications in those infected.

Hepatitis C↗

PubMed1993

Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B virus infection.

OBJECTIVE: To investigate the possible interference with acute hepatitis B virus infection by co-infection with hepatitis C virus. DESIGN: Analysis of stored sera collected for transfusion transmitted viruses study in 1970s. SETTING: Four major medical centres in the United States. PATIENTS: 12 recipients of blood infected with hepatitis B virus. MAIN OUTCOME MEASURES: In 1970s, presence of antibodies in hepatitis B virus and raised serum alanine aminotransferase concentration; detection of antibodies to hepatitis C virus with new enzyme linked immunoassays. RESULTS: Five of the 12 patients were coinfected with hepatitis C virus. Hepatitis B surface antigen was first detected at day 59 in patients infected with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C virus (p = 0.01); median durations of antigenaemia were 83 and 21 days respectively (p = 0.05), and the antigen concentration was lower in the coinfected patients. Alanine aminotransferase patterns were uniphasic when hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in patients with combined acute infection (no value > 380 IU/l; p = 0.0025). Four coinfected recipients developed chronic hepatitis C virus infection. The fifth patient was followed for only four months. CONCLUSIONS: Acute coinfection with hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in humans, and onset of hepatitis B may reduce the severity of hepatitis C virus infection but not frequency of chronicity. Alanine aminotransferase concentration showed a biphasic pattern in dual infection.

Acute Disease↗

PubMed1984

[Anti-HBc IgM in acute and chronic hepatitis B virus infection].

Hepatitis B core antigen (HBcAg) synthesized in E. coli was used for determination of immunoglobulin M class-specific antibodies against HBcAg. It was found that 98% of cases with acute hepatitis B surface antigen (HBsAg) positive hepatitis type B were anti-HBc immunoglobulin M (IgM) positive. Atypical hepatitis B was detected in 33% of anti-HBc-positive HBsAg-negative cases with acute hepatitis. Anti-HBc IgM was positive for 6 months in acute resolving hepatitis type B, whereas cases resulting in chronic hepatitis B remained anti-HBc IgM-positive for up to 900 days. Chronic HBsAg carriers with severe liver disease had anti-HBc IgM more often than individuals with minor liver damage; 83% of HBsAg-positive liver cirrhoses, 63% of chronic aggressive hepatitis, 50% of HBsAg-positive liver carcinoma, but only 17% of chronic persistent hepatitis or 7% of healthy blood donors were anti-HBc IgM-positive. Determination of anti-HBc IgM is useful in detecting atypical hepatitis B virus infections without HBsAg in serum and, with some restrictions, in discriminating acute and chronic hepatitis type B.

Acute Disease↗

PubMed1996

Hepatitis C virus infection.

Hepatitis C, previously termed parenterally transmitted NANB hepatitis, is caused by a single-stranded RNA virus (HCV). Infection with this virus has epidemiologic characteristics similar to hepatitis B, with infection from contaminated blood appearing to be a primary source of disease. Although 80% to 90% of the viral hepatitis associated with blood transfusions used to be the most common mechanism for HCV transmission, parenteral drug abuse has become the major documented risk factor in the United States. Health care workers face occupational hazards for HCV infection primarily through needlestick and other contaminated sharps accidents, although the risks are much lower than those historically documented for HBV. Current universal bloodborne precautions for infection control appear to be effective against occupational cross-infection in patient care settings. Ongoing studies in patients with long-term persistent hepatitis C are investigating the usefulness of prolonged interferon therapy to reduce hepatic damage and HCV chronicity.

Dentistry↗

PubMed2003

Immune-based novel therapies for chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a great public health problem, with an estimated 200 million chronically infected patients worldwide. No vaccines are currently available for HCV, and only a subset of HCV patients responds to interferon-alpha (IFN-alpha) and Ribavirin treatment. Substantial evidence has emerged recently to support the role of the host immune response in the outcome and pathogenesis of HCV infection. Our aims of this article are to present the immune-based novel therapeutic options for HCV infection and the evidence supporting their use in patients with chronic hepatitis C. There is a growing consensus that acute control of HCV infection is associated with a vigorous intrahepatic antiviral CD4+ and CD8+ T cell response. IFN-gamma was detectable in the livers of the chimpanzees that cleared or controlled the virus, raising the possibility that IFN-gamma might perform antiviral effector functions during HCV infection. Based on these observations, therapeutic induction of intrahepatic IFN-gamma by adoptive immunotherapy might be able to control chronic HCV infection. Immune-based novel therapies appear to hold great promise in treating chronic HCV infection.

Animals↗

PubMedDate not supplied

[Interferon alpha in the treatment of prolonged hepatitis A virus infection].

Hepatitis A viral infection usually lasts up to 12 weeks, but in 3-16% of patients relapses may occur and the course of the disease is protracted. The outcome of hepatitis A is always good, so that antiviral therapy is not necessary. However, from the aspect of patients with protracted course of the disease up to a year, it might be important to restore clinical recovery in a shorter period of time. Knowing about antiviral and immunomodulatory effects of endogenous interferon (virally activated) in treatment of protracted hepatitis A, we introduced interferon-alpha in the 12th week of the disease and followed-up its effects on the further course of the disease. The study comprised 80 patients with established diagnosis of acute protracted hepatitis A, excluding hepatitis B, Epstein-Barr, cytomegalovirus, adenovirus or toxic liver lesion. In 40 patients treated with interferon we followed up the activity of aminotransferases and persistence of IgM-anti-HAV in correlation with the same parameters in 40 patients treated symptomatically. The registered persistence of aminotransferases' pathological activity was 20:30 weeks (interferon: symptomatic therapy). In greater doses interferon affected the length of persistence IgM-anti-HAV, 20:34 weeks (interferon: symptomatic therapy).

Antiviral Agents↗

PubMed2003

Immune responses in hepatitis B virus infection.

Hepatitis B virus infection is one of the most frequent causes of chronic liver disease worldwide. Even though a preventive vaccine is available, the search for a cure for chronically infected patients remains a high priority to reduce the morbidity and mortality from liver cirrhosis and hepatocellular carcinoma. This review summarizes the immune response in acute, self-limited and chronic hepatitis B; its differential effects on viral replication and liver injury; and prospects for immunotherapy.

Antibody Formation↗