Visceral leishmaniasis infection in a rheumatoid arthritis patient treated with infliximab

Anti-TNFalpha strategies can result in significant clinical benefits in rheumatoid arthritis (RA), but with an increased rate of opportunistic infections. Visceral leishmaniasis (VL) is a severe disease that can develop in immunocompromised hosts, principally in HIV patients. VL in RA patients treated with TNFalpha antagonists is an extremely rare event, and only one case has been described. Here we report a case of VL, occurring after 9 infusions of infliximab in association with azathioprine, in a patient who developed blood cytopenia, fluctuant fever, and splenomegaly.     

Efficacy of Prolonged Treatment With Pegylated Interferon (Peg-IFN) and Ribavirin in Thalassemic Patients With Hepatitis C Who Relapsed After Previous Peg-IFN-Based Therapy

Background:

Most thalassemic patients with chronic hepatitis C virus (HCV) infection do not respond to therapy with pegylated interferon (Peg-IFN) plus ribavirin (RBV) due to hepatic siderosis and RBV dose reduction caused by RBV-induced anemia.

Objectives:

In the present study, we recruited HCV genotype 1-infected thalassemic patients who had relapsed after a 48-week treatment with Peg-IFN plus RBV in order to evaluate the efficacy of a 72-week regimen of Peg-IFN plus RBV.

Patients and Methods:

In this retrospective study, 23 thalassemic patients with HCV genotype 1 infection who had prior relapse after treatment with Peg-IFN and RBV for 48 weeks were consecutively enrolled in this study for evaluation of the efficacy of a 72-week treatment regimen.

Results:

For the 21 included cases, mean age was 29.7 years; 81% were men and 28.6% had cirrhosis. At the end of the treatment, nine (42.9%) patients had an undetectable level of HCV RNA in their sera. However, six months after treatment completion four of these patients relapsed and a sustained virological response (SVR) was found in five (23.8%) patients. Undetectable HCV RNA level at week 4 (P = 0.03) and undetectable HCV RNA level at week 12 (P < 0.01) were found to be predictors of SVR. There was an average 47.9% increase in blood transfusion during therapy and treatment was discontinued for 12 (57.1%) patients prematurely.

Conclusions:

The present study suggests that thalassemic patients with chronic hepatitis C genotype 1 infection who did not achieve SVR after a course of therapy with Peg-IFN and RBV may benefit from being retreated with a 72-week regimen.     

复方鳖甲软肝片联合聚乙二醇干扰素α-2a治疗慢性乙型肝炎的疗效观察

目的探讨复方鳖甲软肝片联合聚乙二醇干扰素α-2a治疗慢性乙型肝炎(慢乙肝)患者的肝组织学变化.方法选取60例慢乙肝随机分为治疗组和对照组,每组30例.治疗组给予口服复方鳖甲软肝片4片/次,3次/d,同时皮下注射聚乙二醇干扰素α-2a 180 μg/次,1次/周;对照组给予皮下注射聚乙二醇干扰素α-2a 180 μg/次,1次/周,同时服用一般保肝药物(如甘草甜素等).2组均使用维生素B4和鲨肝醇行升白细胞治疗,疗程为48周.结果肝脏穿刺活体组织检查结果显示,治疗组肝纤维化及透明质酸程度有改善,均优于对照组(P＜0.05).2组炎症活动度改善无明显差异.结论复方鳖甲软肝片联合聚乙二醇干扰素α-2a治疗慢乙肝效果较聚乙二醇干扰素α-2a联合普通护肝药物好,值得进一步深入研究.     

Anti-Golgi complex antibodies during pegylated-interferon therapy for hepatitis C.

BACKGROUND/AIM: Pegylated interferon (Peg-IFN) plus ribavirin is the standard therapy for hepatitis C. Peg-IFN has several antiviral mechanisms, but its role in hepatitis C treatment seems to be related to its immunomodulatory effect. Ribavirin, an antiviral agent, potentiates IFN activity when added to it. Both drugs are associated with adverse reactions of different magnitudes. Autoimmune phenomena have been reported with this treatment. In this paper, we describe cases of ALT/GGT flares during Peg-IFN plus ribavirin treatment, which related to the appearance of anti-Golgi antibody and disease progress. METHODS: We investigated three patients with hepatitis C and severe ALT/GGT flares during Peg-IFN and ribavirin treatment coinciding with anti-Golgi complex antibody as the only marker of autoimmunity. We then reviewed the medical files and tested anti-Golgi antibody in stored sera from 25 patients treated with conventional IFN and in 14 patients treated with Peg-IFN. RESULTS: The three patients were male, over 45 years of age; all were relapsers and non-responders. Anti-Golgi antibody was positive during treatment coinciding with ALT/GGT flares but with hepatitis C virus (HCV)-RNA negativity, disappearing after stopping treatment, with normalization of ALT/AST levels. One patient had progression of fibrosis from F2 to F3 despite negativity of HCV-RNA. In the last group, only two patients treated with Peg-IFN experienced ALT/GGT flares but without anti-Golgi antibody CONCLUSIONS: The presence of anti-Golgi complex antibody could be a marker of a temporary autoimmune phenomenon and progressive disease.     

聚乙二醇干扰素α-2a治疗丙氨酸转氨酶异常但＜2倍正常值上限的HBeAg阳性慢性乙型肝炎患者24周临床研究

目的 观察聚乙二醇干扰素α-2a(Peg-IFN α-2a)治疗ALT＜2倍正常值上限(ULN)且肝组织学炎症活动度(G)≥2的HBeAg阳性慢性乙型肝炎患者的临床疗效.方法采用随机、开放、对照的研究方法,将55例ALT＜2×ULN且G≥2的HBeAg阳性慢性乙型肝炎患者分为Peg-IFN α-2a治疗组27例和恩替卡韦对照组28例,接受48周治疗,数据行卡方检验和t检验.结果治疗24周时,Peg-IFN α-2a组有8例患者HBeAg被清除,占29.6%(χ2=9.71,P＜0.01),其中6例HBeAg血清转换,占22.2%(χ2=6.98,P＜0.01);2例HBsAg被清除,占7.4%.Peg-IFN α-2a组与恩替卡韦组HBeAg滴度分别下降(1179.8±582.6) PEIU/mL和(441.5±258.8) PEIU/mL(t=2.66,P=0.01).恩替卡韦组和Peg-IFN α-2a组分别与其基线相比,HBV DNA分别下降(4.520±0.694)lg拷贝/mL和(3.520±1.442)lg拷贝/mL(t=2.45,P=0.029).Peg-IFN α-2a组G3患者较G2患者有更高的HBeAg阴转率(χ2=4.23,P=0.041).结论治疗24周时,Peg-IFN α-2a在HBeAg阴转、HBeAg血清转换、HBeAg滴度下降较恩替卡韦有明显优势,恩替卡韦降低HBV DNA载量更为有效.在基线肝组织炎症活动度较高患者中,Peg-IFN α-2a可能有更高的HBeAg清除率.     

Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin

Summary.  The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis ( P  =   0.002), the timing of HCV RNA negativiation ( P  <   0.001) and the mean doses of ribavirin ( P  <   0.001) were significantly associated with relapse, but those of Peg-IFN were not. Stepwise reduction of the ribavirin dose was associated with a stepwise increase in relapse rate from 11% to 60%. For patients with complete early virologic response (c-EVR) defined as HCV RNA negativity at week 12, only 4% relapse was found in patients given ≥12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 μg/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (≥12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in c-EVR patients.     

A killing disease epidemic among displaced Sudanese population identified as visceral leishmaniasis.

A fatal disease epidemic affected the Bentiu area in southern Sudan and led to a mass migration of the Nuer tribe searching for treatment. The initially available information revealed a high mortality rate due to a possible occurrence of tuberculosis, malaria, enteric fever or visceral leishmaniasis (VL). Serological screening of 53 of the most severely affected patients in an enzyme-linked immunosorbent assay (ELISA) or an improved direct agglutination test (DAT) revealed positivity for VL. In 39 of those patients, diagnosis was confirmed by identification of Leishmania donovani amastigotes in lymph node or bone-marrow aspirates. In a total of 2714 patients observed, 1195 (44.0%) had clinical symptoms suggesting VL: DAT positive titers (1:3200-greater than or equal to 1:12800) were obtained in 654 (24.1%), of whom 325 were confirmed parasitologically. Forty-two VL cases died before or during treatment, giving a mortality rate of 6.4%. Among the intercurrent infections diagnosed in the VL population (654), respiratory involvements (31.7%) and malaria (10.7%) were most prevalent. With the exception of four (0.6%), all other VL patients (509) responded readily to sodium stibogluconate. The factors initiating the outbreak are discussed. Malnutrition and nomadic movements to potential VL endemic areas appeared to be the most important. HIV infection as a possible predisposition seemed remote considering the clinical and epidemiological similarity to VL occurring in East Africa, adequate humoral response in DAT, and immediate positive response to specific anti-Leishmania chemotherapy.     

Effect of hepatitis C virus treatment in fibrosis progression rate (FPR) and time to cirrhosis (TTC) in patients co-infected with human immunodeficiency virus: a paired liver biopsy study

BACKGROUND/AIMS: Patients with hepatitis C and human immunodeficiency virus coinfection have rapid fibrosis progression. The effect on fibrosis progression rate and time to cirrhosis of HCV treatment has not been extensively studied. First aim of the study was to assess changes in FPR and TTC and staging after HCV therapy vs. no treatment. Secondary aim was to study changes in FPR/staging of sustained viral responders and non-responders to Peg-IFN alfa-2a and RBV. METHODS: Seventy-four (74) co-infected patients were grouped in three according to HCV treatment, Group 1 - None (n=9), Group 2 - IFN (n=30), Group 3-Peg-IFN alfa-2a (n=35). Paired liver biopsies were analyzed and FPR/TTC calculated for each biopsy. RESULTS: Baseline characteristics, duration of treatment and time between biopsies were similar among groups. HCV therapy, improved grading, but only Peg-IFN alfa-2a therapy resulted in staging decrease. Group 2 had significant staging increase and Group 1 had doubling of FPR and (TTC) reduction from 22.7 to 9.09 years. Peg-IFN alfa-2a treated patients had negative change in FPR and stabilization in TTC. SVR and NR with Peg-IFN alfa-2a/RBV had same FPR and staging. CONCLUSIONS: In patients with HIV/HCV co-infection Peg-IFN alfa 2a based treatment produced regression or stable fibrosis in contrast to accelerated progression in those without treatment.     

Visceral leishmaniasis in those infected with HIV: clinical aspects and other opportunistic infections

Cases of visceral leishmaniasis (VL) in HIV-positive individuals have been reported from most areas of the world where the geographical distributions of the two infections overlap. The majority of the co-infected cases that have been recorded, however, live around the Mediterranean basin. In these subjects, the length of the incubation period of VL is presumably very short, particularly in those who have severe immunodepression. At diagnosis, almost all cases of VL/HIV co-infection have been found to have fewer than 200 CD4+ cells/microl blood, and about 50% meet the AIDS-defining criteria during their first episode of VL. The clinical manifestations of VL in HIV-infected individuals may be similar to those seen in HIV-negative cases; fever, pancytopenia and hepato-splenomegaly, for example, are found in 75% of all the HIV-positive cases. Following the dissemination of the parasites, however, the HIV-positive cases may develop unusual, multi-organ pathology. Almost all the cases of co-infection are very prone to VL relapses, even after carefully managed antileishmanial treatment. The opportunistic infections that are often seen in HIV-positives frequently develop during VL episodes, the signs and symptoms of the leishmaniasis then confusingly overlapping with those of the other infections.     

Pegylated interferon alpha2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients

BACKGROUND: Hepatitis C virus (HCV) and HIV coinfection constitutes an important epidemiological and clinical problem. We evaluated the safety and efficacy of Pegylated interferon alpha2b (Peg-IFN) and a fixed dose of ribavirin in the treatment of chronic hepatitis C in HIV coinfection. METHODS: Open, prospective study in HCV-HIV coinfected patients with persistently elevated alanine aminotransferase (ALT) levels and a liver biopsy showing either portal or bridging fibrosis. Therapy included Peg-IFN (50 micro g weekly) with ribavirin 800 mg for 48 weeks. The primary end point was sustained virological response (SVR). Univariate and multivariate analyses were performed to determine factors associated with response. RESULTS: By intent-to-treat analysis, 11 of 35 patients (31%) reached SVR. SVR was significantly better for genotypes 2/3 than for genotype 1 (54% versus 21%; P < 0.05). By multivariate logistic regression analysis, only a non-1 genotype was an independent factor for SVR [odds ratio (OR), 6; 95% confidence interval (CI), 1.1-31.7; P < 0.005]. A decrease of at least 1.5 log10 HCV RNA at week 12 of therapy was highly predictive of SVR (OR, 49.9; 95% CI, 4.9-508.2; P < 0.001). Most patients developed adverse events, although only six patients (17%) discontinued treatment due to toxicity. CONCLUSIONS: The combination of low doses of Peg-IFN plus a fixed dose of ribavirin resulted in a rate of SVR similar to that obtained with higher doses of the drugs in HIV-infected patients and lower than those obtained in non-HIV patients. Response at week 12 may be useful to help guide therapy in HCV-HIV co-infected patients.     

Evaluation of a cyclophilin inhibitor in hepatitis C virus-infected chimeric mice in vivo

Cyclosporin A (CsA) inhibits replication of the HCV subgenomic replicon, and this effect is believed to not be mediated by its immunosuppressive action. We found that DEBIO-025, a novel non-immunosuppressive cyclophilin inhibitor derived from CsA, inhibited HCV replication in vitro more potently than CsA. We also examined the inhibitory effect of DEBIO-025 on naive HCV genotypes 1a or 1b in vivo using chimeric mice with human hepatocytes. These mice were treated for 14 days with DEBIO-025, pegylated-interferon alpha-2a (Peg-IFN), a combination of either drugs, or CsA in combination with Peg-IFN. In mice treated with Peg-IFN, serum HCV RNA levels decreased approximately 10-fold whereas DEBIO-025 treatment alone did not induce any significant change. In mice treated with both DEBIO-025 and Peg-IFN, HCV RNA levels decreased more than 100-fold. All mice treated with Peg-IFN combined with CsA died within 4 days. The combination treatment of DEBIO-025 and Peg-IFN reduced HCV RNA levels and core protein expression in liver, indicating that the HCV RNA levels reduction in serum was attributable to intrahepatic inhibition of HCV replication. CONCLUSION: We demonstrated that DEBIO-025 was better tolerated than CsA, and that its anti-HCV effect appeared to be synergistic in combination with Peg-IFN in vivo.     

Rapid reduction of hepatitis C virus-Core protein in the peripheral blood improve the immunological response in chronic hepatitis C patients

Aim: The extracellular hepatitis C virus (HCV)-antigen, including HCV-Core protein, can suppress immune cells. Recently, the efficacy of double filtration plasmapheresis (DFPP) for chronic hepatitis C (CHC) was reported. However, the mechanism of efficacy of DFPP might not be only the reduction of HCV but also the effect of immune cells via direct and/or indirect mechanisms. The aim of this study is to analyze the virological and immunological parameters of difficult-to-treat HCV patients treated with DFPP combined with Peg-interferon and RBV (DFPP/Peg-IFN/RBV) therapy. Methods: Twelve CHC patients were enrolled and treated with DFPP/Peg-IFN/RBV therapy. The immunological, virological and genetic parameters were studied. Results: All patients (4/4) treated with the major IL28B allele (T/T) could achieve complete early virological response (EVR). The amounts of HCV-Core antigen in the peripheral blood of EVR patients treated with DFPP/Peg-IFN/RBV rapidly declined in comparison to those of late virological response (LVR) patients treated with DFPP/Peg-IFN/RBV and EVR patients treated with Peg-IFN and RBV (Peg-IFN/RBV). The amount of IFN-γ produced from peripheral blood gradually increased. On the other hand, the amount of IL10 gradually decreased in the EVR patients. The frequencies of HCV-Core binding on CD3+ T cells rapidly declined in EVR patients treated with DFPP/Peg-IFN/RBV therapy. Moreover, the distributions of activated CD4(+) and CD8(+) T cells and CD16-CD56 high natural killer cells were significantly changed between before and after DFPP. Conclusions: The rapid reduction of HCV-Core antigens and changes in the distribution of lymphoid cells could contribute to the favorable immunological response during DFPP/Peg-IFN/RBV therapy.     

Influence of the type of pegylated interferon on the onset of depressive and neuropsychiatric symptoms in HIV-HCV coinfected patients

This is a prospective observational comparative 48-week study to assess the impact of the different types of Peg-IFN on depressive and neuropsychiatric symptoms during treatment in HIV-HCV coinfected patients. Thirty-one patients treated with Peg-IFN alpha-2b 1.5 microg/kg/w plus ribavirine (RBV) (Peg-IFN alpha-2b Group) and 32 patients receiving Peg-IFN alpha-2a 180 microg/w plus RBV (Peg-IFN alpha-2a Group) were included. Depressive and neuropsychiatric symptoms, quality of life and adherence were assessed. Fifteen subjects (23%) discontinued therapy (p = 0.3, between groups). Overall, 37 patients presented mild to moderate depressive symptoms, 9 moderate to severe and 3 severe, without differences between groups. Patients in Peg-IFN alpha-2b reported higher fatigue and dizziness at weeks 12 (p < 0.05) and 24 (p < 0.05), and irritability and memory loss at week 24 (p < 0.05) with respect to Peg-IFN alpha-2a Group. At week 12, role functioning, general health perception, vitality, emotional role, mental health and the summary areas of physical health and mental health were lower in Peg-IFN alpha-2b Group (p < 0.05). The same was observed in physical functioning (p = 0.05) and role functioning, general health perception, emotional role and mental health (p < 0.001) at week 24. Three months after finishing treatment, no patient had depressive or neuropsychiatric symptoms, and quality of life improved. Antiretroviral adherence was low but adherence to anti-HCV therapy remained high in both groups. According to our data, Peg-IFN alpha-2a and Peg-IFN alpha-2b exert a similar impact on the overall rate of depressive symptoms, although patients treated with Peg-IFN alpha-2a experience less fatigue and fewer neuropsychiatric symptoms and a lower impairment in their physical and mental quality of life.     

Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy

Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear. We enrolled 145 consecutive Taiwanese patients with CHC receiving Peg-IFN α-2a plus ribavirin for the study. Blood samples were taken more frequently at defined intervals in the first 3 d. Peg-IFN was administered at week 1. It was then administered weekly in combination with daily ribavirin for 24 or 48 wk. A mathematical model fitted to the observed HCV kinetics was constructed, which could interpret the transient HCV titer elevation after Peg-IFN treatment. The results demonstrated a comparable viral clearance rate (c = 3.45 ± 3.73) (day(-1), mean ± SD) but lower daily viral production rate (P = 10(6)-10(12)) in our patients than those reported previously in Western patients. Of 110 patients with a sustained virological response (SVR), 47 (43%) had a transient elevation of viral titer within 12 h (proportion of 12 h/3 d: 44% in non-SVR vs. 70% in SVR; P = 0.029). Among 91 patients with available rs8099917 data, patients with the TT genotype had an early surge of viral titer after therapy and a higher SVR and viral clearance rate than those with the GT genotype. In conclusion, Taiwanese patients with CHC receiving Peg-IFN plus ribavirin therapy have a lower daily viral production rate than Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance rate and better virological responses in these patients.     

Rapid clearance of circulating Leishmania kinetoplast DNA after treatment of visceral leishmaniasis

With the aim of evaluating the utility of the detection of Leishmania kDNA in peripheral blood for the cure assessment of visceral leishmaniasis (VL), a PCR based method was performed in patients with confirmed VL at three follow-up periods after specific chemotherapy with pentavalent antimonial. In 16 out of 17 (94.1%) patients with pre-treatment detectable kDNA that were clinically cured, the PCR turned negative up to 37 days after the initiation of treatment, remaining negative over 90 days after treatment. The clearance of Leishmania kDNA from peripheral blood of patients with VL hints to occur during or shortly after treatment concurring or preceding clinical recovery.     

Monotherapy with peginterferon alpha-2b {12 kDa} for chronic hepatitis C infection in patients undergoing haemodialysis.

BACKGROUND: A combination of Peginterferon and Ribavirin is the standard treatment for patients with chronic hepatitis C viral infection (HCV). Ribavirin is contraindicated in patients with chronic renal failure (CRF). Conventional Interferon monotherapy is effective in around 30% of such patients. There is scanty data on the use of Peginterferon monotherapy in them. METHODS: We describe our preliminary experience of monotherapy with Peginterferon alpha- 2b {12 kDa} (Peg-IFN) for HCV patients undergoing haemodialysis for CRF. They were treated with Peg-IFN 1 microg/kg body weight subcutaneously once a week for 24 weeks. In all patients, clinical (age, sex, mode of acquiring HCV, pattern of haemodialysis) and virological (HCV RNA quantitative-PCR and genotype) profile was noted at baseline. Early virological response at 12 weeks (EVR), end-of-treatment virological response at 24 weeks (ETVR) and sustained virological response after 6 months of stopping treatment (SVR) were noted during the follow-up period. RESULTS: The clinical and virological characteristics of patients were as follows: Of a total number of 6 patients, 5 were male and 1 was female with an age range of 35 to 62 years. The duration of haemodialysis was from between 5 and 12 months before the start of treatment and its frequency lay between 1 and 3 times a week. The mode of acquiring HCV was blood transfusion (100%). All 6 cases suffered from chronic hepatitis. The genotype distribution was genotype 3 in 3 (50%), genotype 1 in 1 (16.7%) and genotype none of 6 in 2 (33.3%) patients. All the patients (100%) completed treatment. EVR was seen in all 6 patients (100%). ETVR was seen in 5 of 6 patients (83.3%). A follow-up period of more than 1 year was available in 4 patients. 3 of these 4 patients (75%) had SVR. A virological response was maintained in all 3 (100%) patients with SVR even after 6 months of renal transplantation. CONCLUSION: Peg-IFN monotherapy is safe and effective in patients with HCV who are on haemodialysis for CRF.     

Serious underreporting of visceral leishmaniasis through passive case reporting in Bihar, India

OBJECTIVES: Visceral leishmaniasis (VL) is a major public health problem in Bihar, India. Unfortunately, accurate data on the incidence or prevalence of the disease are not available. This longitudinal study was undertaken to determine the incidence of VL in a Community Development Block area of the state of Bihar. Survey results were compared with official reports of the disease to assess the extent of underreporting by the Government health system. METHODS: Three health subcentre areas in Kanti Block, consisting of 14 villages with a total population of 26 444, were selected. Active surveillance was performed every month from January 2001 to December 2003 by house to house survey to detect cases of fever for more than 15 days. Patients clinically suspected of suffering from VL were subjected to parasitological examination for confirmation. Analysis of records of the reporting agencies in the district was undertaken to compare and assess the extent of underreporting. RESULTS: A total of 202 cases of VL were identified in 3 years giving an average annual incidence rate of 2.49/1000 population (95% CI = 2.15-2.83). As identification data of patients was not available with the official reporting agencies for 2001 and 2002, extent of underreporting could be assessed for 2003 only. In the study population, 65 cases of VL were detected during 2003 providing an annual incidence rate of 2.36/1000 population. Only eight (12.30%) cases were reported officially, resulting in underreporting by a factor of 8.13. In 2003, the official incidence rate of VL for Kanti Block was 0.31/1000 against the actual rate of 2.36/1000. As the constraints for official reporting at the block and the district levels are similar, the underreporting at district level was also assumed to be similar. This finding has significance in the preparation for elimination programme.     

Successful interferon treatment in a patient chronically infected with hepatitis B virus carrying unusual S- (and P-) mutants in the presence of anti-HBs antibodies.

BACKGROUND: Hepatitis B virus (HBV) immune escape mutants with point mutations within the S gene may arise during the natural course of HBV infection, due to a positive selection pressure exerted by the host immune response. Mutations within the immunodominant B and T cell epitopes of hepatitis B surface antigen (HBsAg) allow the resulting S-mutants to propagate even in the presence of neutralizing anti-HBs antibodies and the HBV-specific T-cell immune response. Aim: To study the antiviral effect of Pegylated-interferon (Peg-IFN) in a patient with chronic hepatitis B carrying unusual S-(and P-) mutants in the presence of anti-HBs antibodies. PATIENTS, METHODS AND RESULTS: We report on a 43-year-old male chronically infected with a genotype A HBV strain, with cocirculation of both HBsAg and anti-HBs antibodies, who received treatment with 120 mug of Peg-IFN for 24 weeks. HBeAg seroconversion and clearance of both HBV DNA by polymerase chain reaction and HBsAg were successfully achieved. Improved histology was observed in a biopsy performed 44 weeks after Peg-IFN therapy was completed. It seems plausible that the ascribed genotype A could have contributed to the effective response to Peg-IFN, even though the treatment was provided only throughout a 24-week period. CONCLUSION: To our knowledge, this is the first report regarding the successful result obtained by using Peg-IFN as a treatment for a chronically HBV-infected patient carrying HBsAg immune escape mutants.     

Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a-ribavirin combination therapy

BACKGROUND AND AIM: Elevated serum alpha-fetoprotein (AFP) levels are noted in patients with chronic hepatitis C (CHC) without hepatocellular carcinoma (HCC). The change in AFP levels after treatment with pegylated interferon and ribavirin (Peg-IFN/RBV) combination therapy is still unknown. The aim of this study was to investigate the predictors of elevated serum AFP in patients with CHC, and its change after Peg-IFN/RBV therapy. METHODS: A total of 123 patients, intended to receive pegylated interferon alfa-2a plus ribavirin therapy, were enrolled. Eighty-three patients had complete treatment and received follow up for and additional 24 weeks. The factors that may affect the elevation of pretreatment AFP and the normalization of post-treatment AFP were determined. RESULTS: The mean AFP level was 18.5 +/- 63.0 ng/mL (range, 1.3-676.0 ng/mL); 41 (33.3%) of the 123 patients had elevated serum AFP (more than 10 ng/mL) at baseline. A multivariate logistic regression analysis disclosed that older age (odds ratio [OR], 1.093; 95% confidence interval [CI], 1.015-1.177; P = 0.018), more advanced METAVIR fibrosis stage (OR, 5.237; 95% CI, 1.244-22.037; P = 0.024), a higher aspartate aminotransferase (AST) level (IU/L) (OR, 1.020; 95% CI, 1.008-1.033; P = 0.001), and lower platelet count (x10(9)/L, OR, 0.985; 95% CI, 0.968-0.994; P = 0.003) were independent determinants of pretreatment AFP elevation. After treatment, 72 of 83 (86.7%) cases were found to have normal post-treatment AFP levels (<10 ng/mL) at the end of follow up (EOF). Post-treatment negativity of the chronic hepatitis C virus (HCV)-RNA (OR, 10.014; 95% CI, 1.000-100.329; P = 0.050) and the post-treatment platelet count (x10(9)/L) (OR, 1.025; 95% CI, 1.001-1.050; P = 0.040) were associated with normal AFP at EOF. AFP progressively decreased with significant differences starting from the 12th week after treatment to the end of treatment, and was lowest at the EOF date for the sustained viral response (SVR) group. On the contrary, the non-SVR group did not have an AFP change during and after treatment. CONCLUSION: Older age, low platelet count, higher AST levels, and advanced fibrosis predisposed chronic hepatitis C patients without HCC to have elevated serum AFP levels. After Peg-IFN/RBV combination therapy, a higher platelet count and HCV viral eradication were determinants of normal AFP at EOF. Serial AFP levels decreased after treatment, presenting in a time-dependent manner, specifically for the SVR group.     

Development of visceral leishmaniasis in an HIV<Superscript>+</Superscript> patient upon immune reconstitution following the initiation of antiretroviral therapy

Case presentation

Here, we report on a case of VL in an HIV-infected patient from the Republic of Georgia who had moved to Germany 14 years before and who had travelled several times to southern Europe in between. After presenting with typical Pneumocystis jiroveci pneumonia, which was treated appropriately, the patient was started on antiretroviral therapy. Shortly thereafter, however, he developed fever of unknown origin. All laboratory assays for the diagnosis of various infectious agents including serological assays and polymerase chain reaction testing of bone marrow aspirate to diagnose VL did not yield positive results at first. Only upon repetition of these tests, diagnosis of VL could be made and the patient treated accordingly.

Case discussion

Visceral leishmaniasis (VL) is a common opportunistic infection in HIV-positive patients from endemic countries but occurs rarely following antiretroviral treatment. This case demonstrates that patients who develop VL upon immune reconstitution may not be diagnosed initially by standard laboratory assays for the diagnosis of VL and underlines the necessity to repeat serologic and molecular biologic testing for VL in cases of fever of unknown origin in patients from or with travel history to endemic countries.