Gene/Protein Disease Symptom Drug Enzyme Compound
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According to previous reports, the prevalence of hepatitis B virus (HBV) infection in patients with systemic lupus erythematosus (SLE) is varied. There has been no report on Taiwan, a hyperendemic area for HBV infection. Furthermore, impaired production of interferon (IFN) in peripheral blood mononuclear cells (PBMC) has been reported to be potentially pathogenic to both chronic HBV infection and SLE. However, the production of IFN in patients with both diseases coexisting is unknown. The aims of this study were to evaluate the prevalence of HBV infection in lupus patients in Taiwan and to measure the production of IFN in patients with both diseases coexisting. One hundred and seventy-three consecutive lupus patients and a control group of 692 age- and sex-matched healthy subjects were included for evaluation of the prevalence of HBsAg. Four groups of subjects (patients with SLE and HbsAg, SLE, chronic hepatitis B and normal controls) were selected for evaluation of the in vitro production of IFN-alpha and -gamma. Six (3.5%) of the 173 SLE patients were positive for HBsAg, which was significantly lower than that of controls (14.7%; P < 0.0001). Patients with coexistent SLE and chronic HBV infection had less lupus activity, including less proteinuria (P = 0.02) and a lower serum titre of anti-double stranded DNA antibodies (anti-dsDNA; P = 0.04), than HBsAg-negative lupus patients. The in vitro production of IFN-alpha in patients with chronic hepatitis B was significantly lower than in those patients with SLE or in the normal control group (P < 0.01). The yields of IFN-alpha and -gamma in patients with coexistent SLE and chronic HBV infection were significantly different from those patients with SLE alone (P < 0.05), but close to those of patients with chronic HBV infection. In conclusion, the prevalence of HBsAg carriers is significantly lower in lupus patients in Taiwan. Patients with coexistent SLE and chronic HBV infection had less lupus activity. Interferon-alpha and -gamma may play a role in the above phenomenon.
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PMID:Hepatitis B infection and changes in interferon-alpha and -gamma production in patients with systemic lupus erythematosus in Taiwan. 919 65

We report here a case of membranous glomerulonephritis associated with chronic hepatitis B (HB) virus infection and describe differential localization of HB antigens in glomeruli. The patient showed mild proteinuria and was positive for hepatitis B surface (HBs) antigen, hepatitis B envelope (HBe) antigen, and antibody to hepatitis B core (HBc) antigen in the serum. The antibody against hepatitis C was negative. A renal biopsy revealed membranous glomerulonephritis with mesangial proliferation. The immunohistochemical studies using monoclonal antibodies localized the HBe antigen along the capillary wall and the HBs antigen in the mesangial area. The immunoelectron microscopic study confirmed the localization of HB antigens: HBe antigen was located in the subepithelial and intramembranous electron dense deposits and HBs antigen in the mesangial deposits. Our present results provide the first report of the differential localization of HB antigens in glomeruli at both the light and electron microscopic levels. The differential localization of HB antigens will provide insight into the pathogenesis of membranous glomerulonephritis.
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PMID:Differential localization of s and e antigens in hepatitis B virus-associated glomerulonephritis. 924 78

We report a 50-year-old male patient with hepatitis C virus (HCV)-associated membranous glomerulonephritis (MN), for which he had been treated with corticosteroid therapy for one and a half years. This patient received blood infusion at 38 years of age. He visited our hospital because of liver dysfunction at 42 years. One year later, proteinuria and microhematuria were pointed out (43 years). Renal biopsy revealed MN with focal fibrocellular crescents. HBsAg, cryoglobulin, rheumatoid factor were all negative. Prednisolone was administered at the dose of 30 mg/day for 4 weeks and tapered subsequently. The steroid treatment was effective (urinary protein excretion: 4.2-->0.3 g/day, serum albumin: 2.4-->4.0 g/dl, 3 months later), and transaminase slightly elevated (GPT 50-->60-80 IU/l). One and a half years later he proved to be positive for HCV antibody, and corticosteroid administration was terminated. Subsequently proteinuria increased, and reached 3.0 g/day 6 years later. However, serological markers and ultrasonographic study for chronic hepatitis revealed mild changes of the liver. These findings suggest that corticosteroid therapy is not contraindicated against HCV-associated MN, and may possibly be used as the treatment for this condition.
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PMID:[A case of hepatitis C virus associated membranous glomerulonephritis ameliorated by corticosteroid therapy]. 965 13

Hepatitis C viral infection occurs relatively low in Korea compared to hepatitis B. However, it progresses into chronic hepatitis and cirrhosis more frequently than HBV. It may be associated with cryoglobulinemia and glomerulonephritis, both in native and transplanted kidneys. We report three cases of membrano-proliferative glomerulonephritis type I in anti-HCV positive, but cryoglobulin-negative patients, presenting massive proteinuria, two in native kidneys and one in an allograft. HCV-RNA was positive in sera of two patients. Two were cirrhotic and ALT was mildly elevated in two. In addition to the characteristic membranoproliferative feature, two native kidneys overlapped with features of diabetic nephropathy. Immunofluorescence demonstrated mainly IgM and C3 deposits along the peripheral capillary walls. Subendothelial electron dense deposits were present in the glomeruli of all three cases with subepithelial and intramembranous deposits in two. HCV-RNA was associated not only with a greater amount of immune deposits but also with subepithelial and intramembranous deposits, indicating the role of active infection.
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PMID:Membranoproliferative glomerulonephritis associated with HCV infection in native kidneys and renal allograft. 988 79

Cryoglobulins are a group of proteins with the common property of precipitating from cooled serum. Cooled cryoglobulinemia is a classic disease caused by immune complexes which subside on vessel walls and produce a clinical picture represented by recurrent purpura, asthenia, arthralgias, Raynaud's phenomenon, glomerulonephritis and sensorimotor neuropathy. The authors describe a case of a patient C.M., 37 years old, with cryoglobulinemia, chronic hepatitis C and gravidic cholestasis at 28 weeks' gestation. The clinical picture worsened with the appearance of mild hypertension with proteinuria and hypochromic anaemia. At 31 weeks' the arthralgic symptomatology and pruritus revealed degeneration with an alteration of glycemic profile values and treatment with rapid human insuline was started. The cardiotocography began to be pathologic and a cesarean section was performed; the newborn weighted 1570 g. Cooled cryoglobulinemia is a pathology which worsens in a gravidic state and can impair the outcome of pregnancy.
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PMID:Essential mixed type II cryoglobulinemia in a HCV positive pregnant woman: case report. 998 69

To improve the efficacy of interferon (IFN) in the treatment of chronic hepatitis C, administration of IFN-beta twice per day was evaluated. Thirty-eight patients with chronic hepatitis C (26 males and 12 females, aged 25-67 years) were included. Patients were treated with a new protocol that included twice-daily treatment with IFN-beta. Three million units (MU) of IFN-beta was administered twice daily every day for 4 weeks followed by 10 MU of IFN-alpha2b, every day for 2 weeks and then three times a week for 18 weeks (total IFN-beta, 148 MU; IFN-alpha2b, 680 MU). Complete responders (CR) were defined by alanine aminotransferase levels that normalized within 6 months after completion of IFN therapy and remained normal for more than 6 months, and by serum hepatitis C virus (HCV) RNA levels that became negative as determined using the Amplicor assay. Twenty-one of 38 (55.3%) patients were CR. Nine of 21 (42.9%) patients with HCV serotype 1 were responders compared with nine of 12 (75.0%) patients with HCV serotype 2. In patients with an HCV titre greater than 1 million equivalents ml-1 (1 MEq ml-1), nine of 24 (37.5%) responded, and in patients with HCV titres less than 1 MEq ml-1, 12 of 14 (85.7%) responded. In patients with HCV serotype 1 and greater than 1 MEq ml-1 HCV RNA, four of 15 (26.7%) responded to IFN. Two-thirds (66.7%) of the patients who became negative for HCV RNA after 2 weeks of therapy responded, while 72.7% of those with positive HCV RNA after 2 weeks of therapy were non-responders. Proteinuria was frequently observed as an adverse effect of twice-daily administration of IFN-beta. The combination of twice-daily administration of IFN-beta for 4 weeks followed by IFN-alpha showed a high response rate in patients with chronic hepatitis C, but in patients with both serotype 1 and a high titre of HCV RNA, response rates were still low. Thus, the HCV RNA titre 2 weeks after starting therapy with IFN was useful for predicting the eventual response to IFN.
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PMID:Evaluation of twice-daily administration of interferon-beta for chronic hepatitis C. 1060 46

Cryofiltration, which has developed from double filtration plasmapheresis (DFPP) with a cooling unit, is an on-line technique to remove cryoglobulin. We report on a patient who suffered from progressive edema and renal insufficiency caused by cryoglobulinemic membranoproliferative glomerulonephritis (MPGN), probably due to chronic hepatitis C virus (HCV) infection. To remove cryoglobulins and terminate the HCV infection, we utilized combination therapy with cryofiltration and interferon-alpha injection with corticosteroids. Interferon-alpha was capable of decreasing proteinuria but not diminishing cryoglobulin. Additional cryofiltration could remove cryoglobulin to an undetectable level. This combination therapy was partially successful to reduce proteinuria and prevent the progressive deterioration of renal function. The major adverse effects of this therapy were bleeding and myelosuppression. We conclude that this combination therapy may be effective and should be considered as treatment for cryoglobulinemic MPGN.
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PMID:The effect of combination therapy with interferon and cryofiltration on mesangial proliferative glomerulonephritis originating from mixed cryoglobulinemia in chronic hepatitis C virus infection. 1060 30

The characteristics and prevalence of hepatitis C virus (HCV)-associated glomerulopathy remain to be determined. To analyze the relationship between HCV infection and glomerulopathy, we enrolled three groups of individuals or patients. The first group consisted of 7776 individuals who were seen for routine checkups. The second group consisted of 86 patients with chronic hepatitis C, 40 patients with chronic hepatitis B, and 51 patients with non-viral liver diseases. The third group consisted of nine patients with HCV association glomerulopathy who underwent renal biopsy. Of the 7776 individuals undergoing medical checkups, 142 (1.8%) were positive for HCV antibody. The positive rate of proteinuria was significantly higher (P<0.030) in individuals with HCV antibody (2.1%) than in those without the antibody (0.6%). Abnormal levels of serum creatinine (5.8 vs. 0%, P=0.025) and complications of cryoglobulinemia (45 vs. 5%, P<0.001) were significantly more common in the 86 patients with chronic hepatitis C (5.8%) than in the 91 patients with other liver diseases. All patients with abnormal levels of serum creatinine had concomitant cryoglobulinemia. Of the nine patients with histologically proven HCV-associated glomerulopathy, four had cryoglobulinemia (all were type II). Elevations of serum creatinine level (4/4 vs. 0/5, P=0.048) and a glomerular legion of membranoproliferative glomerulonephritis (3/4 vs. 0/5, P=0.048), a severe type of glomerulonephritis, were more common in the four patients with cryoglobulinemia than in the remaining five patients. In conclusion, HCV infection was found to be significantly associated with glomerulopathy. In addition, the presence of cryoglobulinemia, which usually accompanies membranoproliferative glomerulonephritis, was found to be an indicator of renal insufficiency in patients with HCV-associated glomerulopathy.
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PMID:The role of hepatitis C virus infection in glomerulopathy. 1105 24

There is an increasing recognition of the association between chronic hepatitis C virus infection and glomerular diseases. Renal complications may be the presenting manifestation of hepatitis C virus infection. Patients may present with signs and symptoms of cryoglobulinemic systemic vasculitis, proteinuria, microscopic hematuria, acute renal failure, or nephrotic syndrome. The pathogenesis of hepatitis C virus associated with renal disease remains incompletely understood; however, deposition of circulating immune complexes in the subendothelial space and mesangium in the glomeruli seems to play a major role. The most common renal pathology associated with hepatitis C virus infection is type I membranoproliferative glomerulonephritis with or without cryoglobulinemia. In patents who do not have significant renal impairment, combination therapy with interferon alfa (IFN-alpha) and ribavirin seems to be the treatment of choice, although the experience with this combination is quite limited in patients with renal involvement. A prolonged course of high-dose IFN-alpha has been most commonly used for these patients with significant success, but relapse of hepatitis C viremia and renal disease after discontinuation of therapy have frequently occurred.
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PMID:Kidney disease in patients with chronic hepatitis C. 1117 99

Focal segmental glomerulosclerosis (FSGS) is a renal disease characterized by sclerotic segmentary lesions, involving a few glomeruli. Male-female ratio is >1 and, in the majority of cases, the patients are aged between 25 to 35 years. The clinical picture is similar to a nephrotic syndrome with non-selective proteinuria poorly sensitive to steroids and often associated with microhematuria. The etiology is still unknown, even in a prevalence in drug addicts, patients with AIDS and subjects with recurrent urological infections with vesico-ureteral reflux was observed. Recent reports showed that chronic infection Hepatitis C Virus (HCV)-related may be associate with or responsible for onset of some syndrome involving the kidney but not the liver. We report the case of a young woman with HCV-Ab positive chronic hepatitis that, during the disease, showed clinical findings of renal involvement, histologically related to a FSGS. We administered to her alpha-IFN at doses of 3 Mega Units thrice-a-week for six months. Serum HCV-RNA, proteinuria and hematuria disappeared simultaneously after the treatment. We underline that the lack of finding of HCV antigens or HCV-RNA in glomerular lesions (as occurred in our patient) does not rule out the virus role in pathogenesis of immunological nephritis. The recovery of our patient as well as the disappearance of proteinuria and hematuria during IFNalpha treatment may be further evidence that FSGS and chronic hepatitis HCV-related are not associated by chance. Further observations and perfectioning of diagnostic techniques are required to clarify the pathogenetic relationship between HCV and renal immunological syndromes.
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PMID:Focal segmental glomerulosclerosis and hepatitis C virus: a case report. 1131 19


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