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PubMed1993

Monitoring of early events of experimental woodchuck hepatitis infection: studies of peripheral blood mononuclear cells by cytofluorometry and PCR.

The peripheral blood mononuclear cells (PBMC) of woodchucks experimentally infected by woodchuck hepatitis virus (WHV) were examined simultaneously for the presence of membrane associated WHV antigens by cytofluorometry, and for WHV DNA and RNA sequences by the polymerase chain reaction (PCR). Four woodchucks were inoculated: two with a well-defined infectious inoculum and two with an inoculum obtained from an animal at the late incubation phase, which was positive for WHV DNA by PCR but still devoid of WHV markers. Infection was demonstrated in all four inoculated woodchucks by the appearance at different times of WHV DNA and WHV antigens in both leucocytes and serum. WHV DNA was first detected by PCR either in the serum (two cases) or in leucocytes (two cases). The mean percentage of cells positive for membrane associated WHsAg or WHcAg detected by cytofluorometry were 37% +/- 25 and 17% +/- 15 respectively. After 8 weeks, all inoculated animals were WHsAg positive in serum. These data suggest that PBMC are involved in the early events of hepadnavirus infection. They also show that sera which are positive by PCR for WHV DNA may transmit viral infection even while still seronegative for WHV markers and for WHV DNA by dot blot.

Animals↗
PubMed2001

Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection.

Entecavir (ETV) is a guanosine nucleoside analogue with potent antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus. To explore the consequences of prolonged virus suppression, woodchucks received ETV orally for 8 weeks and then weekly for 12 months. Of the 6 animals withdrawn from therapy and monitored for an additional 28 months, 3 had a sustained antiviral response and had no evidence of hepatocellular carcinoma (HCC). Of the 6 animals that continued on a weekly ETV regimen for an additional 22 months, 4 exhibited serum viral DNA levels near the lower limit of detection for >2 years and had no evidence of HCC. Viral antigens and covalently closed circular DNA levels in liver samples were significantly reduced in all animals. ETV was well tolerated, and there was no evidence of resistant variants. On the basis of historical data, long-term ETV treatment appeared to significantly prolong the life of treated animals and delay the emergence of HCC.

Animals↗
PubMed2000

Replication status and histological features of patients with triple (B, C, D) and dual (B, C) hepatic infections.

In patients with multiple hepatotropic viral infections (B and C, or B, C and D), the reciprocal influence of each virus remains controversial. The aims of this study were twofold: first, to determine the impact of multiple infection on the replication status of B, C and D viruses and on histological features; and second, to compare patients with multiple infection to patients infected only with the hepatitis C virus (HCV). We retrospectively included 50 patients with multiple infection and 50 control HCV patients, who were matched on independent factors associated with fibrosis, such as age, gender, alcohol consumption and duration of infection. The replication status of hepatitis B virus (HBV), HCV and hepatitis D virus (HDV), and histological lesions, were determined. In patients with multiple infection, HCV RNA was present less frequently (44% vs 98%, P < 0.001) and the prevalence of cirrhosis was higher (35% vs 8%, P < 0.001). Among patients with triple infection (n = 16), HBV replication was observed in 25%, HCV RNA was detectable in only two (P < 0.0001) and HCV viremia was significantly lower than in the matched HCV patients (0 vs 54.7, P < 0.0001). Among patients with dual infection (n = 34), HCV RNA was present less frequently in those with serological markers of active HBV infection than in those without (30% vs 79%, P = 0.01). Hence, multiple infection is associated with a decrease of HCV replication. Cirrhosis seems to be more frequently observed in patients with multiple infection. In patients with triple infection, serum HCV RNA and markers of HBV replication were absent in 80%, suggesting that HDV acts as a dominant virus. In patients with dual infection, HBV and HCV exert an alternative, dominant replication.

Adult↗
PubMed1976

Detection of core antibody in hepatitis B infection.

Hepatitis B core antigen (HBcAg) is found on the decoated Dane particle and on a morphologically similar particle detected mainly in the nucleus of hepatocytes of patients with hepatitis B. HBcAg prepared from the liver of a chimpanzee infected with hepatitis B virus was used to test human serum for core antibody (anti-HBc) by complement fixation. Anti-HBc was found in serum collected from patients with hepatitis B in both the acute and convalescent stages, from carriers of hepatitis B surface antigen (HBsAg) and from patients with chronic liver or renal disease who were carriers of HBsAg. It was not found in patients with hepatitis A or infectious mononucleosis, or in healthy persons who were not carriers of HBsAg.

Adult↗
PubMed1988

Pre-ALL and non-A, non-B hepatitis infection.

We report a case of acute lymphoblastic leukaemia which presented as hypoplastic anaemia following Non-A, Non-B viral hepatitis infection. The role of infection and the mechanisms involved in the evolution of pre-ALL to overt leukaemia remain speculative. However, it is of practical importance to distinguish pre-ALL from aplastic anaemia and the myelodysplastic syndromes during the early pancytopenic phase to avoid inappropriate management.

Anemia, Aplastic↗
PubMed1995

Role of hepatitis C virus in dual and triple hepatitis virus infection.

Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) share same transmission routes, thus dual or triple infection may occur and even persist in the same patients. A significant amount of literature has accumulated since the advent of HCV assays. It is pertinent to review and evaluate the clinical and virological significance of HCV in multiple hepatotropic viral infection. The reported series on seroprevalence of HCV indicate that HCV is found in more than 10% of HBV- or HDV-infected patients worldwide. Of the patients with dual or triple infection involving HCV, those having coreplication of viruses tend to have severe and progressive liver disease that is resistant to interferon therapy, in contrast with patients having a single virus infection. Paradoxically, dual or triple hepatitis virus infections are associated with viral interference. In particular, HCV exerts a suppressive effect on HBV and HDV and may enhance seroclearance of HBV antigens or even usurp the role of preexisting virus as the agent for continuing hepatitis. Although HBV and HDV may also suppress HCV, it appears to be less effective. These findings clearly suggest the necessity of monitoring patients with HBV or HDV infections. In view of complex dynamism of viral interaction in multiple hepatotropic virus infection, the importance of HCV assay in the clinical studies can not be overemphasized. The basic mechanisms that regulate the viral interactions, in particular the impact of HCV in dual or triple virus infections, remain to be investigated.

Antiviral Agents↗
PubMed1996

Acquired osteosclerosis associated with intravenous drug use and hepatitis C infection.

Hepatitis C has recently been recognized as a secondary cause of osteosclerosis; a further example, the first outside of North America, is described. A 37-year-old man with a history of intravenous drug use and known to be hepatitis C antibody positive presented with bone pain. Radiographs and magnetic resonance imaging demonstrated an increase in cortical and trabecular bone that on biopsy was of a normal lamellar pattern but markedly sclerotic. Biochemical markers of bone formation (serum osteocalcin) and resorption (urinary hydroxyproline excretion rate) were both markedly elevated. Pain lessened following administration of pamidronate. Biochemical markers of bone turnover fell towards their reference ranges 12 months after initiating pamidronate therapy but without significant change in bone mineral density. Osteosclerosis is a rare complication of hepatitis C infection, the symptoms of which are controllable with diphosphonate therapy.

Adult↗
PubMed1999

Renal manifestations of hepatitis C infection.

Hepatitis C is an important cause of renal disease, and renal complications may be the presenting manifestation of hepatitis C infection. About half of patients present with evidence of renal insufficiency, and up to one quarter present with nephrotic syndrome. Others present with proteinuria or evidence of diminished renal function. The pathogenesis of hepatitis C-associated renal disease remains incompletely defined, but most evidence suggests that glomerular injury results from deposition of circulating immune complexes in the subendothelium and mesangium. Membranoproliferative glomerulonephritis, with or without cryoglobulinemia, is the most common renal lesion. Interferon alpha-2b is currently the treatment of choice. However, success is limited, with many patients failing to respond or suffering relapse upon discontinuation of therapy. Studies of newer treatment modalities, such as longer courses of interferon or the use of ribavirin or immunosuppressive agents, are underway. Hepatitis C-associated renal disease may progress to end-stage renal failure requiring dialysis in about 10% of patients.

Antiviral Agents↗
PubMed2000

Molecular biology of hepatitis C infection.

Hepatitis C infection (HCV) is an emerging epidemic. Liver specialists are managing this disease with limited scientific information about the underlying pathogenesis and treatment. The current review offers a molecular dissection of infection, a snapshot of the HCV life cycle, and emerging strategies for antiviral therapy.

Animals↗
PubMed2000

Commentary: Iron metabolism in hepatitis C infection.

Hepatitis C virus (HCV) infections have started to decline, but up to 10,000 deaths each year are the consequence of chronic liver disease, following the infection. Laboratory testing identifies HCV-infected individuals using positive recombinant immunoblot assays to detect the presence of the antibody; the diagnosis is confirmed by detecting HCV RNA in serum. HCV-infected patients who have large accumulations of hepatic iron have not responded well to interferon therapy, compared to patients with normal hepatic iron stores. Physicians who treat patients infected with HCV should be aware of the detrimental effect of excess liver iron on interferon therapy. The degree of hepatic iron overload should be assessed and the reason for the excess iron should be investigated. Phlebotomy is the most practical method for iron removal and is well tolerated by patients with HCV infection.

Hepatitis C↗
PubMed1999

Agreement in pathologic interpretation of liver biopsy specimens in posttransplant hepatitis C infection.

Hepatitis C virus-related disease is rapidly becoming the most common indication for orthotopic liver transplant (OLT) in the United States. Although post-OLT hepatitis C viremia is universal, 40% to 60% of patients develop recurrent chronic hepatitis C. Distinguishing recurrent chronic hepatitis C infection from acute rejection may be difficult because of overlapping histopathologic features. To improve our diagnostic accuracy we undertook a study to determine interobserver and intraobserver agreement between pathologists examining post-OLT liver biopsy specimens in patients from our transplant database. Clinical data and microscopic sections from 26 patients with hepatitis C virus-related OLT were reviewed. Biopsy specimens were obtained because of abnormal liver enzymes (21/26) or routine post-OLT follow-up (5/26), representing both early (18+/-11 days) and late (252+/-206 days) post-OLT periods. Unidentified sections were examined by an experienced pathologist in a randomly assigned order and reexamined 6 weeks later in the same fashion by the initial reviewer and a second experienced pathologist. Interobserver and intraobserver agreement was calculated using K statistic. The intraobserver agreement was 81 % with a kappa coefficient of 0.67 (P = .001). The interobserver agreement was 78% with a kappa coefficient of 0.60 (P < .001). The early post-OLT biopsy specimens (18+/-11 days) were the most difficult to interpret.

Adult↗
PubMed1986

The prophylaxis of hepatitis B infection.

Hepatitis B is a common viral infection that is increasing in incidence. The emergency physician is often responsible for administering prophylactic measures against hepatitis B infection to hospital employees who have sustained percutaneous exposure to blood or blood products and to members of the community who come to the emergency department because of exposure to hepatitis B. Therefore, the emergency physician must be familiar with the current data on the safety and efficacy of available prophylactic measures, hepatitis B immune globulin and hepatitis B vaccine, and any protocols for hepatitis B prophylaxis in effect in the institution. The data supporting current recommendations for hepatitis B prophylaxis are reviewed, and a sample protocol is given.

Cross Infection↗
PubMed1999

Opportunistic hepatic infections in AIDS patients with fever of unknown origin.

The clinical features and histopathologic manifestations of hepatic opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) in Taiwan remain unexplored. We report 28 AIDS patients (25 men, 3 women; mean age, 34 years) with fever of unknown origin who underwent 31 liver biopsies from December 1995 to May 1997. In most cases, the biochemical tests showed moderate to markedly elevated alkaline phosphatase concentrations, but normal or mildly elevated aminotransferase concentrations. The most common histopathologic finding was macrosteatosis, which was noted in 15 of the 28 patients. Another important histopathologic finding indicating the etiology of hepatic opportunistic infection was granuloma, which was found in 11 patients. Histochemical stain and culture of liver specimens yielded Mycobacterium avium complex (MAC) in eight patients, Mycobacterium tuberculosis in two patients, Histoplasma capsulatum in one patient, and cytomegalovirus in one patient with concomitant MAC infection. Therefore, a definitive diagnosis in AIDS patients with fever of unknown origin was made in 11 of the 28 cases with the assistance of liver biopsy. During follow-up, late extrahepatic involvement by the same infectious agents was found in six patients. Thus, hepatic manifestations could be a harbinger of disseminated opportunistic infections in AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed2000

Risk factors for recurring hepatocellular carcinoma differ according to infected hepatitis virus-an analysis of 236 consecutive patients with a single lesion.

Patients with hepatocellular carcinoma (HCC) frequently experience intrahepatic HCC recurrence even after complete ablation of primary lesions. Because the oncogenic process may be different for hepatitis B viral (B-viral) and hepatitis C viral (C-viral) HCC, the present study was conducted to elucidate the factors contributing to HCC recurrence with respect to the infected hepatitis virus. Two hundred thirty-six patients with a single HCC lesion who underwent complete ablation of the tumor by PEIT and/or PMCT or surgical resection at Tokyo University and its affiliated hospitals from 1993 to 1997 were enrolled. The patients were classified into 3 groups: the B-viral group, C-viral group, and NBNC group. After complete removal of tumors, the patients were followed for a mean period of 39 months. The factors contributing to HCC recurrence were analyzed by univariate and multivariate analysis using the Cox proportional hazard model. The rate of intrahepatic recurrence in enrolled patients at 1, 3, and 5 years was 19%, 50%, and 64%, respectively. The intrahepatic recurrence rate in C-viral and B-viral HCC was higher than that in the NBNC-related HCC. Fibrosis staging, pathological grading of HCC, and serum AFP levels were significantly linked to intrahepatic recurrence by univariate analysis, and fibrosis staging was strongest in the multivariate analysis for C-viral HCC (P = .004). In contrast, fibrosis staging did not affect the recurrence in B-viral (P = .51) and NBNC-related (P = .77) HCC. Risk factors for HCC recurrence differed according to the infected viral state.

Aged↗
PubMed1998

Simultaneous amoebic liver abscess and hepatitis A infection.

Hepatitis A virus (HAV) infection and amoebic liver abscess have an identical mode of transmission (fecal-oral route) and similar epidemiology. Either of these diseases might be considered in patients presenting with clinical signs and symptoms of liver disease in areas of the world where hepatitis and Entamoeba histolytica are endemic. The following two cases describe patients with simultaneous infection of HAV and amoebic liver abscess. This report emphasizes the role of dual infection in patients from endemic areas. It also challenges the assumption that jaundice in patients with amoebic liver abscess is due to amoebic hepatitis, rather than co-infection with viral hepatitis.

Acute Disease↗
PubMed1993

Infected hepatic Echinococcus cyst presenting as recurrent Escherichia coli empyema.

An 81-year-old man, previously a shepherd in Italy, presented with recurrent Escherichia coli empyema over an 8-month period. His empyema was caused by an infected, nonviable hepatic Echinococcus cyst that eroded the diaphragm and led to intermittent spillage and pleural seeding. This case demonstrates that when dealing with Escherichia coli empyema, a subdiaphragmatic source ought to be suspected, and among immigrants from areas with prevalent hydatid disease, infected hepatic Echinococcus cyst might rarely be the cause.

Aged↗
PubMed1996

Treatment of a patient with an infected hepatic cyst.

Symptomatic hepatic cysts are infrequently seen by family physicians. We review the literature and describe the diagnosis and management of a patient with cystic liver disease and a dominant infected hepatic cyst. The treatment included percutaneous drainage, intravenous antibiotic therapy, and sclerotherapy infusion using sterile alcohol (95% ethanol).

Aged↗