Histiocytic necrotising lymphadenitis in mediastinum mimicking thymoma or lymphoma - case presentation and literature review of Kikuchi Fujimoto disease.

Kikuchi Fujimoto disease (KFD) as a rare self-limiting lymphadenopathy of short and benign course concerns most frequently the lymph nodes of the neck. The most common symptoms are painfulness of the diseased area, fever and night sweating. The etiology is not well understood, but in the role of pathogenesis viral, autoimmune and genetic factors are taken into account. In the presented case of 37-year-old female it was necessary to exclude diseases such as lymphoma or thymoma because of atypical mediastinal location of Kikuchi Fujimoto disease. After multidisciplinary consultation the lymph node was resected from the mediastinum with videothoracoscopic approach. The diagnosis was difficult for the pathologist because of the large percentage of necrosis of the lymph node but the image was typical for histiocytic necrotizing lymphadenitis. Two cases of patients with KFD limited to the mediastinum have been previously reported in the literature. This article presents the world's first reported case of this disease in the topographic location of the thymus. Furthermore, a review of current literature was made.

Diagnosis of chronic hepatitis.

In this brief review the basic information concerning diagnosis of chronic hepatitis is presented. The evaluation of patient with chronic hepatitis must consider a number of possible etiologies. In some chronic hepatitis cases hepatic injury may be due to more than one agent. Because the clinical signs of chronic hepatitis are not characteristic or the course of disease may be asymptomatic special attention should be dedicated to biochemical, immunological and virological tests. The most sensitive and specific tests and techniques should be used in differential diagnosis. The knowledge about extrahepatic manifestations of liver diseases, mainly due to immunological disorders, is also very important. However, the role of liver biopsy in chronic hepatitis cases is essential to confirm the diagnosis and indicate the possible etiology.

[Biochemical markers of fibrosis in chronic hepatitis and liver cirrhosis of viral origin]. / Biochemiczne wykladniki wlóknienia w przewleklym zapaleniu watroby i w marskosci watroby o etiologii wirusowej.

OBJECTIVE: Usefulness of three selected extracellular matrix components as markers of hepatic fibrosis in patients with chronic viral hepatitis and post inflammatory liver cirrhosis. METHODS: 91 patients with chronic HBV or HCV infection were divided into four groups; chronic hepatitis--group O; cirrhosis classes A, B and C (Child-Pugh classification)--groups A, B and C, respectively. The serum levels of: N-terminal peptide of type III procollagen (PIIIP), laminin (LP1) and hyaluronic acid (HA) in these patients were measured using commercial radioimmunological and radiometric tests. RESULTS: The mean values of the investigated markers increased in patients with cirrhosis according to the stage of the disease (thus group A showed the least level while the highest was exhibited in group C). Between all the groups: O, A, B and C, HA was the marker showing the greatest difference. The only marker with a greater mean level in group O than group A, was PIIIP. Substantially higher levels of the investigated markers were found in the patients with HCV than in those with HBV, but only within group A. CONCLUSIONS: 1) The values of the studied markers increased in various degree with the cirrhosis progress. 2) LP1 and HA measurements have particular value in the clinical estimation of cirrhotic advancement. 3) HA measurement may be helpful in differentiating between cirrhosis and chronic hepatitis. 4) The course of hepatic fibrosis may be influenced by the etiological factor as the values of the studied markers are higher in patients with HCV than in patients with HBV, in the early stage of cirrhosis.

[Immunological disorders in patients with chronic viral hepatitis type C]. / Zaburzenia immunologiczne u chorych z przewleklym wirusowym zapaleniem watroby typu C.

UNLABELLED: Various immunological disorders have been observed frequently in patients with chronic viral hepatitis C. Hepatitis C virus has been implicated in the pathogenesis of: essential mixed cryoglobulinemia, cryoglobulinemic vasculitis glomerulonephritis, thrombocytopenia, porphyria cutanea tarda, autoimmune thyroiditis (among others). AIM OF THE STUDY: Was to determine the prevalence and clinical meaning of immunological disorders in HCV infected patients. METHODS: 93 HCV infected patients were studied with regard to the presence of cryoglobulins, autoantibodies, rheumatoid factor (RF) and circulating immunological complexes (CIC). RESULTS: 35 patients out of 93 (38%) had detectable cryoglobulins. Cryoglobulins in 90 cases were of type III and in 3--of type II. CIC /by immunoelectrophoresis of the PEG sediments/ were found in sera of 87 patients (93.5%). 38 persons (41%) had detectable rheumatoid factor. Antinuclear antibodies were found in sera of 15 patients (16%), anti-smooth muscles antibodies--in 21 persons (23%) and anti-LKM1 antibodies--in 5 (5%). Titers of autoantibodies were usually low. The most frequent clinical manifestations were arthralgia and skin changes. CONCLUSION: Immunological disorders /circulating immune complexes (93.5%), autoantibodies (60%), rheumatoid factor (41%), cryoglobulinemia type III (38%)/ are frequently found in HCV infected patients. Age, gender, histological score and clinical evidence of liver cirrhosis do not influence on rate of these abnormalities. Clinical manifestations of immunological disorders are usually mild.

[Central nervous system disorders in AIDS patients]. / Zmiany w osrodkowym ukladzie nerwowym (oun) u chorych z AIDS: material wlasny.

A number of 95 AIDS patients with neurological signs and symptoms hospitalised at the Department of Hepatology and AIDS (in the years 1989-97) were analysed. Sixty patients showed abnormal EEG. Computer assisted tomography (CT) revealed organic changes in them. The remaining 35 patients showed no changes in EEG and CT scan but in 22 of them examination of cerebro-spinal fluid revealed meningoencephalitis of different origin. Moreover, central nervous system autopsy of 55 patients (who had died of AIDS in the years 1986-97) showed macroscopic and/or microscopic changes in 48 out of them (87%).

[Effectiveness of antiviral treatment of patients with chronic hepatitis C (a Polish multicenter study)]. / Efektywnosc leczenia przeciwwirusowego przewleklego zapalenia watroby typu C (wieloosrodkowe badania pòlskie).

Interferon alpha (INF) is routine treatment in patients with chronic hepatitis C. Many controlled investigations were evaluated to establish the optimal schedule of treatment with sustained virological and biochemical response. Recently, multicentre meta-analyses suggest that combination therapy (INF + Ribavirin) was more effective than treatment with interferon alone. The aim of this study was to compare the efficacy of four schedules of antiviral treatment in 445 patients with chronic hepatitis C. Combination therapy (INF + Ribavirin) given for 6 mo. and monotherapy (INF) for 18 mo. were more effective than interferon alone given for 6 mo. Treatment with INF alone for 6 mo. was demonstrated to be insufficient.

Detection of active hepatitis C virus and hepatitis G virus/GB virus C replication in bone marrow in human subjects.

We have analyzed the presence of hepatitis C virus (HCV) and hepatitis G virus (HGV) sequences in bone marrow and serum samples from 48 patients of a hematologic outpatient clinic. HCV RNA was detected in 18 (38%) and 15 (31%) and HGV RNA was detected in 6 (13%) and 9 (19%) of serum and bone marrow samples, respectively. In 3 patients, HGV RNA was detectable in bone marrow but not in the serum; 2 of these patients were negative for the presence of specific antibodies. Using a highly strand-specific Tth-based reverse transcriptase-polymerase chain reaction (RT-PCR), the presence of HCV RNA and HGV RNA negative strand was demonstrated in 4 and 5 bone marrow samples, respectively. Our study shows that HCV and HGV can replicate in bone marrow; in the case of HGV, analysis of serum may underestimate the true prevalence of infection. (Blood. 2000;95:3986-3989)

Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial.

UNLABELLED: BACKGROUND, AIM, AND METHODS: Alpha interferon is the generally approved therapy for HBe antigen positive patients with chronic hepatitis B, but its efficacy is limited. Lamivudine is a new oral nucleoside analogue which potently inhibits hepatitis B virus (HBV) DNA replication. To investigate the possibility of an additive effect of interferon-lamivudine combination therapy compared with interferon or lamivudine monotherapy, we conducted a randomised controlled trial in 230 predominantly Caucasian patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis B. Previously untreated patients were randomised to receive: combination therapy of lamivudine 100 mg daily with alpha interferon 10 million units three times weekly for 16 weeks after pretreatment with lamivudine for eight weeks (n=75); alpha interferon 10 million units three times weekly for 16 weeks (n=69); or lamivudine 100 mg daily for 52 weeks (n=82). The primary efficacy end point was the HBeAg seroconversion rate at week 52 (loss of HBeAg, development of antibodies to HBeAg and undetectable HBV DNA). RESULTS: The HBeAg seroconversion rate at week 52 was 29% for the combination therapy, 19% for interferon monotherapy, and 18% for lamivudine monotherapy (p=0.12 and p=0.10, respectively, for comparison of the combination therapy with interferon or lamivudine monotherapy). The HBeAg seroconversion rates at week 52 for the combination therapy and lamivudine monotherapy were significantly different in the per protocol analysis (36% (20/56) v 19% (13/70), respectively; p=0.02). The effect of combining lamivudine and interferon appeared to be most useful in patients with moderately elevated alanine aminotransferase levels at baseline. Adverse events with the combination therapy were similar to interferon monotherapy; patients receiving lamivudine monotherapy had significantly fewer adverse events. CONCLUSIONS: HBeAg seroconversion rates at one year were similar for lamivudine monotherapy (52 weeks) and standard alpha interferon therapy (16 weeks). The combination of lamivudine and interferon appeared to increase the HBeAg seroconversion rate, particularly in patients with moderately elevated baseline aminotransferase levels. The potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy.

Hepatitis A shifting epidemiology in Poland and Eastern Europe.

The clinical morbidity of hepatitis A probably only represents 20% of cases of hepatitis A virus (HAV) infection. When it became possible to determine specific antibodies, a seroepidemiological survey of anti-HAV was undertaken in Poland, which showed that between 1979 and 1997 there was a shift in the peak age of infection from childhood to adulthood, concomitant with a substantial decline in the incidence of HAV infection. Data from the World Health Organization also indicate that there has also been a decline in the incidence of hepatitis A in Eastern European countries in general, over the 3 years from 1994 to 1996. The potential risk of epidemics still exists, however, when appropriate conditions are created. The available data show that fewer young people are becoming infected with HAV, and general preventive measures, including vaccination of children and high-risk groups (e.g. healthcare and childcare personnel and those living in 'closed communities') are needed to deal with HAV infections in Eastern Europe.

Hepatitis C virus in lymphoid cells of patients coinfected with human immunodeficiency virus type 1: evidence of active replication in monocytes/macrophages and lymphocytes.

It has been reported that hepatitis C virus (HCV) may be lymphotropic in the setting of human immunodeficiency virus type 1 (HIV-1) coinfection. The present study was undertaken to determine the phenotype of lymphoid cells harboring replicating HCV in HIV-1-positive subjects. By means of highly strand-specific thermostable enzyme Tth-based reverse-transcriptase polymerase chain reaction, the presence of viral RNA-negative strand was sought in different subpopulations of peripheral blood mononuclear cells from 10 HIV-positive patients. HCV RNA-negative strand was most commonly present in monocytes/macrophages (4 cases), followed by CD8+ and CD4+ lymphocytes (2 cases) and CD19+ cells (1 case). In 2 cases that were further analyzed, viral-negative strand remained detectable in monocytes/macrophages cultured for 3 weeks. Moreover, monocyte/macrophage- and serum-derived viral sequences differed in the 5' untranslated region. These findings imply that, in HIV-infected subjects, HCV may replicate in the same cells as HIV-1, which raises the possibility of direct interactions between these pathogens.

Anti-HCV RIBA/LiaTek reactivity and HCV genotype in EIA-negative patients with viremia.

Individuals infected with hepatitis C virus (HCV) usually produce anti-HCV antibodies detectable by enzyme immunoassay (EIA); however, in certain viremic cases this antibody does not appear. To investigate whether anti-HCV in these cases is detectable by Western blot (WB), 38 HCV RNA positive/anti-HCV EIA-negative sera were tested by RIBA 3.0 or LiaTek III. The HCV genotypes (INNO-LiPA) were analyzed to determine whether the variance in these genotypes can be the reason for the late, weak antibody production or its absence. As the control group, 282 EIA-positive/HCV RNA-positive patients were examined. A single band reactivity of various intensities by RIBA or LiaTek was observed in 16/38 EIA negative sera. Positive results with NS3 were detected in 4 sera and weak positive (+/-) with core, NS3, and NS5 in 5, 6, and 1 sera, respectively. In 3 cases with anti-NS3, the seroreversion was observed in follow-up. The distribution of genotypes in anti-HCV-negative versus anti-HCV-positive groups was: 1b alone, 50.0% vs. 78.0%; 3a alone, 13.2% vs. 15.6%; and mixed (1b+3a), 36.8% vs. 5.0%, respectively. The follow-up studies showed that viremia was lost spontaneously in 12/35 patients. In some patients infected with two genotypes, the spontaneous loss of the 3a genotype was observed. The study showed that WB tests are useful for serological confirmation of HCV infection in some EIA negative/HCV RNA-positive patients but, because seroreversion may occur, sequential sera samples should be tested. No unusual HCV genotype was detected in anti-HCV-negative/HCV RNA-positive cases, but the frequency of mixed infection with the 1b+3a genotypes in this group was found to be higher than that in anti-HCV-positive hepatitis patients.

Analysis of hepatitis G virus/GB virus C quasispecies and replication sites in human subjects.

Although the hepatitis G virus is unlikely to be a primary hepatotropic virus, its replication sites remain unclear. Using highly strand-specific Tth-based reverse transcriptase PCR we searched for the presence of the viral RNA negative strand in various autopsy tissues in two patients who died of end-stage liver disease. In addition, amplified viral sequences were compared in the 5' untranslated and the putative capsid regions by the single-strand conformation polymorphism (SSCP). Negative strand HGV RNA was detected in bone marrow and spleen from both patients and in lymph node tissue from one. All amplified sequences from a given patient were identical when compared by SSCP and direct sequencing. This lack of difference in the composition of quasispecies recovered from various tissues suggests the presence of a single, common viral compartment in the infected host.

Hepatitis G virus coinfection in chronic hepatitis B and C patients in Poland.

This study evaluated the epidemiology and impact of hepatitis G virus (HGV) infection in patients with chronic hepatitis B and C. Serum samples were obtained from 128 consecutive untreated patients with chronic hepatitis B (72 cases) or C (56 cases). The presence of HGV RNA was determined by PCR amplification of the 5'untranslated region; the sensitivity of the assays was ten template copy equivalents. The prevalence of HGV RNA in hepatitis B and C was found to be 25% and 34%, respectively. HGV-positive and HGV-negative patients did not differ with respect to risk factors for infection, age, sex, or alanine aminotransferase activity. Similarly, there was no difference in the severity of liver disease, as assessed with HAI score. In conclusion, we found a very high prevalence of HGV infection in chronic hepatitis B and C patients in Poland. Nevertheless, no evidence was found that HGV coinfection has any impact on the severity of the underlying disease.

Hepatitis C virus negative strand RNA is not detected in peripheral blood mononuclear cells and viral sequences are identical to those in serum: a case against extrahepatic replication.

Peripheral blood mononuclear cells (PBMCs) from 27 hepatitis C virus (HCV)-infected patients were analysed for the presence of HCV negative strand RNA with strand-specific Tth-based RT-PCR. No negative strand RNA was detected in any sample, and positive strand HCV sequences amplified from PBMCs were identical to those found in serum. These findings suggest that HCV does not replicate in PBMCs, and the presence of HCV sequences at this site is compatible with passive virus adsorption and/or contamination by circulating virus.

Comparison of hepatitis B virus core promoter sequences in peripheral blood mononuclear cells and serum from patients with hepatitis B.

It has been reported that hepatitis B virus (HBV) DNA is present in peripheral blood mononuclear cells (PBMCs), although it is unclear whether it actually replicates there or is adsorbed from serum. HBV DNA sequences from the core promoter and precore regions were amplified from PBMCs and serum taken from 13 patients with hepatitis B infection. Analysis by single strand conformation polymorphism, direct sequencing and cloning revealed identical HBV DNA sequences in both PBMCs and serum from five patients with acute hepatitis and in five out of eight patients with chronic hepatitis. However, in the remaining three chronic hepatitis cases, HBV DNA sequences in both PBMCs and serum were different: two patients harboured HBV DNA sequences from their PBMCs with deletions/insertions in the core promoter region and one patient harboured HBV DNA sequences from their PBMCs with two nucleotide substitutions. These findings point to a possible presence of independent HBV DNA replication in PBMCs.

[Selected diagnostic and clinical aspects of chronic viral hepatitis type C]. / Wybrane zagadnienia diagnostyczne i kliniczne przewleklego wirusowego zapalenia watroby typu C.

The aim of this study was to evaluate selected diagnostic and clinical aspects of chronic hepatitis C (CH-C) in the group of 80 patients: 68 males aged 24-65 (mean 39.8 +/- 10,5) and 12 females aged 35-66 (mean 48.7 +/- 12.6). The epidemiological data allowed to divide the basic group into 3 subgroups: patients with transfusion-associated CH-C (subgroup I: 12 males, mean age 38 +/- 6.7 and 2 females aged 40 and 46), CH-C patients with parenteral hepatitis C virus exposure-other than blood transfusion (subgroup II: 25 males, mean age 40.6 +/- 8.2 and 5 females aged 43 +/- 15.1) and sporadic cases with unknown HCV exposure (subgroup III: 31 males, mean age 38.2 +/- 11.2 and 5 females, mean age 50.5 +/- 10.3). The duration of the disease (CH-C) was calculated from the incident of acute viral hepatitis or the first signs of liver damage caused by HCV to the confirmation of CH-C by liver biopsy. The following data were analyzed: a frequency of acute viral hepatitis with jaundice at the beginning of the disease, ALT flare-ups, mean highest activities of ALP and GGT, frequency of hypergammaglobulinaemia and sings of fatty liver in ultrasonographic finding (USG). In all patients but one anti-HCV antibodies (ELISA 2nd generation test by Abbott) were detected. In 64/80 subjects antibodies to HCV antigens: 5-1-1, C 100-3, C 33c and C 22 were determined by RIBA-2 test (Ortho). In 62/80 patients HCV-RNA in serum was determined by RT PCR. Liver biopsy was performed in 71/80 patients. Other co-existent liver diseases were excluded. The similarity between 3 subgroups was shown: similar percentage of males and females, similar patients mean age and the duration of the disease. It was shown that the acute beginning of the disease with jaundice has been observed twice as frequent in subgroups I and II compared with subgroup III. The same frequency of ALT flare-ups in all subgroups was observed (25-28.6%). No differences in mean highest ALP and GGT activities in 3 subgroups were observed. It was shown, however, that hypergammaglobulinaemia was detected more frequently in subgroup III (30.5%) compared with subgroup I (7.1%) and II (16.7%). The signs of fatty liver in ultrasonographic findings were also observed more frequently in subgroup III (30.5%) than in subgroup I (14.3%) or II (16.7%). In all patient but one, in which anti-HCV antibodies by ELISA test were detected, anti-C 33c and anti-C 22 antibodies by RIBA were present. HCV-RNA in serum was detected in 77.8% subjects from subgroup I. 73.9%-from subgroup II and 66.7%-from subgroup III. In all HCV-RNA positive patients anti-HCV antibodies were detected. The evidence of chronic active hepatitis confirmed by liver biopsy was shown in 63.6%, 67.8% and 71.8% of patients from subgroup I, II and III, respectively. In no case normal liver morphology was present. Authors concluded the distressing fact of the high incidence of chronic active hepatitis in patients unaware of HCV infection, without the incident of acute hepatitis at the beginning of the disease (over 1/3 of all described subjects). The differences of the clinical course of the disease between subgroups 1 + II and subgroup III suggest two different routes of HCV infection or the presence of two different HCV mutants in Polish population. Authors emphasise the necessity of HCV gene typing in CH-C patients, which might explain the surprisingly high incidence of chronic active hepatitis in the reported group. The use of the presented data for the general practitcioner making the diagnosis of crytogenetic liver disease is also accentuated.