Case Report: Primary splenic non-Hodgkin's B cell lymphoma in a patient with chronic hepatitis C

A case of primary splenic lymphoma in a patient with chronic hepatitis C is reported. A 69-year-old man with chronic hepatitis C was admitted to Fukuoka City Hospital for evaluation of an enlarging splenic tumour. In the spleen, ultrasonographic examination revealed a hypoechoic tumour and computed tomography demonstrated a non-enhancing low density area measuring 7 cm in diameter; coeliac angiography revealed a hypovascular tumour. Gallium scintigraphy showed uptake of the radioisotope in the splenic tumour. A splenectomy was performed and the morphological and immunohistochemical findings of this tumour were compatible with those of non-Hodgin's B cell lymphoma. Recently, cases of malignant B cell lymphoma associated with hepatitis C virus infection have been reported. Lymphotropism of hepatitis C virus may play a pathological role in the development of non-Hodgkin's lymphoma. We emphasize the importance of considering lymphoma in the differential diagnosis of extrahepatic disorders during the course of chronic hepatitis C virus infections.     

Primary hepatic lymphoma in a patient with chronic hepatitis B

Primary hepatic lymphoma is a rare disorder and the clinical behavior remains unknown. We report a patient with primary hepatic lymphoma who had chronic hepatitis B. She was asymptomatic; however, a solitary tumor in the left lobe was incidentally detected. After left hepatic lobectomy was performed, a diagnosis of non-Hodgkin's lymphoma was made. No tumor was found except in the liver. Immunohistochemical stains for hepatitis B surface and core antigens were positive in hepatocytes; however, both were negative in the tumor tissue. The patient received no chemotherapy and the tumor relapsed. After chemotherapy, the tumor disappeared. However, exacerbation of hepatitis occurred after the fourth chemotherapy. The patient was followed up without chemotherapy, and she remains in apparent remission. Chemotherapy is effective against primary hepatic lymphoma and, if possible, patients with this disorder should be treated with chemotherapy postoperatively.     

Accelerated hepatitis C virus replication with rituximab treatment in a non‐Hodgkin's lymphoma patient

The treatment of patients with non‐Hodgkin's lymphoma (NHL) may be complicated by concomitant chronic hepatitis C virus (HCV) infection. Recent data suggest that HCV may also be a contributing factor to the development of this disease. Although antiviral treatment has occasionally been reported to result in the regression of lymphoma in patients with HCV infection, the importance of the control of this infection on the prognosis of lymphoma needs to be defined. Here we report a patient with diffuse large B‐cell lymphoma who presented with a mass in her left breast. She had had HCV‐related liver cirrhosis for 6 years. She was given rituximab monotherapy for three consecutive weeks, but treatment had to be discontinued as a result of hematological toxicity. HCV viral load also increased, but then decreased gradually after rituximab was stopped. She could be given no further therapy. Six months later she presented with spinal involvement with infiltration of the cauda equina. Though cranial–spinal radiotherapy and steroids were started, she died shortly thereafter. Though rituximab is an invaluable drug in the treatment of B‐cell lymphomas, we believe that the use of such agents with potentially long‐lasting effects on B lymphocytes requires extended vigilance for accelerated replication of hepatitis B and C viruses.     

Primary hepatic lymphoma in a patient with chronic hepatitis C

The case is presented of a woman with chronic active hepatitis C who developed primary hepatic lymphoma. The possible roles of viral hepatitis and therapeutic interferon in the pathogenesis and progression of this unusual maligancy are discussed. In addition, the importance of accurate tissue diagnosis to identify potentially treatable hepatic tumours is emphasized.     

Acute hepatitis B after autologous stem cell transplantation in a man previously infected by hepatitis B virus

We report a case of acute hepatitis B after autologous stem cell transplantation (ASCT) in a patient with low-grade non-Hodgkin's lymphoma. At diagnosis of the hematological disease, the patient had the characteristic serology of a previous hepatitis B infection, being Ag HBs negative, hepatitis B virus core antibody positive (anti-HBC) and hepatitis B virus surface antibody weakly positive. He developed fatal hepatitis B after autologous stem cell transplantation, suggesting reactivation consequent to immunosuppression.     

High-dose therapy with autologous stem cell transplantation in first response in mantle cell lymphoma

We retrospectively investigated the outcome of 30 newly diagnosed patients with mantle cell lymphoma treated with high-dose therapy and autologous stem cell transplantation in first response. With a median follow-up of 55 months, the 5-year overall-survival is 62%, the 5-year progression-free-survival is 40% and no secondary malignancy has occurred.     

Coexistence of hepatoma with mantle cell lymphoma in a hepatitis B carrier

The coexistence of hepatocellular carcinoma (HCC) and non-Hodgkin’s lymphoma (NHL) in the liver is rare. Reports show that these patients have cirrhotic livers or hepatitis virus infections before they develop HCC and NHL. We present a patient with hepatitis B virus infection who was transferred to our hospital with a newly detected liver mass; abdominal computed tomography examination showed one hypodense mass of 7 cm in diameter and multiple mesenteric and mediastinal lymph nodes. A liver tumor biopsy showed a hepatoma, and the pathologic findings from an inguinal lymph node excision showed mantle cell lymphoma. An immunohistochemical stain confirmed that the atypical lymphoid cells within the HCC were positive for the CD20, CD5 and cyclin D1 antigens. Taking these findings into account, the hepatic tumor was determined to be a HCC infiltrated by mantle cell lymphoma.     

Reactivation of hepatitis B virus during interferon‐free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co‐infection

Direct‐acting antiviral agents (DAA) for hepatitis C virus (HCV) are not effective for hepatitis B virus (HBV), which may be suggestive of reactivation of anti‐HBe hepatitis during interferon (IFN)‐free DAA therapy in HBV/HCV co‐infected patients with inactive HBV. A 69‐year‐old male patient was diagnosed with chronic hepatitis due to HBV/HCV co‐infection with serum levels of alanine aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log copies/mL. HCV was thought to be responsible for the hepatitis activity because of low level of HBV core‐related antigen (3.1 log U/mL). He was treated with combination therapy of daclatasvir and asunaprevir. Serum ALT gradually increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was stopped due to suspicion of drug‐induced liver injury and/or HBV reactivation. Administration of entecavir reduced HBV DNA levels, followed by improvement in ALT levels. This report proposes that close monitoring of HBV DNA during the anti‐HCV DAA therapy and the commencement of anti‐HBV therapy with nucleoside analogs after the increase of HBV DNA should be considered in patients with HBV/HCV co‐infection.     

Tuberculous hepatic abscess appearing after liver transplantation in a patient with human immunodeficiency virus and hepatitis B and C virus co‐infection

M. Rodríguez‐Framil, A. Antela, A. Prieto, E. Otero, E. Molina, E. Varo. Tuberculous hepatic abscess appearing after liver transplantation in a patient with human immunodeficiency virus and hepatitis B and C virus co‐infection.
Transpl Infect Dis 2011: 13: 515–519. All rights reserved Abstract: Tuberculosis infection occurs relatively frequently in solid organ transplant recipients, although the occurrence of tuberculous hepatic abscesses is uncommon. Anti‐tuberculous therapy has several concerns in transplant recipients, including an increased risk of cellular rejection and potential hepatotoxicity. We present the case of a human immunodeficiency virus‐infected liver transplant patient who developed multiple tuberculous liver abscesses. Treatment with isoniazid, ethambutol, pyrazinamide, and moxifloxacin was efficacious, well tolerated, and safe.     

慢性乙型肝炎患者病毒准种特性的初步研究

目的 探讨慢性乙型肝炎(CHB)患者血清中乙型肝炎病毒(HBV)是否存在准种特性,并初步了解HBV准种的复杂性和遗传差异性。 方法用多聚酶链反应(PCR)技术从1例CHB患者血清中扩增HBV整个PreC/C基因区,然后用T载体克隆PCR产物,从转化阳性的克隆中随机选出34个克隆进行核酸序列分析。结果在34个测序克隆中发现存在28种不同的序列,序列间差异性介于0.2％～2.1％。变异位点分布于整个区域。所有序列nt1896位均无变异。 结论 在CHB患者体内HBV存在复杂的准种特性。     

Suppression of hepatitis C virus (HCV) replication by hepatitis D virus (HDV) in HIV-infected hemophiliacs with chronic hepatitis B and C

Most hemophiliacs who are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have high serum levels of HCV RNA. To study the impact of multiple hepatitis virus infections, we evalated all eight chronic carriers of hepatitis B surface antigen (HBsAg) from a previously studied cohort of 99 hemophiliacs with chronic HIV and HCV infections. Stored serum or plasma samples were tested for antibody to hepatitis D virus (anti-HDV) by ELISA; qualitatively for HCV RNA, HBV DNA, and HDV RNA by the polymerase chain reaction (PCR); and quantitively for HIV RNA, HCV RNA, and hepatitis B virus (HBV) DNA by a quantitative branched DNA signal amplification assay. HCV RNA was detected in only one of five patients with HDV infections on a cross-sectional study, and this individual had low levels (<3.5×10⁵ genome eq/ml) of HCV RNA. In contrast, all three without HDV infections had high levels (>1.5×10⁷ genome eq/ml) of HCV RNA. HIV RNA was present in all eight patients. There was no correlation between the level of HIV RNA and the presence of hepatitis viruses. Three of the eight patients (38%) died of liver failure and another has hypersplenism with hypoprothrombinemia. We conclude that HDV infection appears to suppress HCV replication and that liver failure is common in adult HIV-infected hemophiliacs with chronic HCV and HBV infections. These findings have implications for the therapy of HCV-infected hemophiliacs who are HBsAg positive.This study was supported by the Brandywine Valley Hemophilia Foundation, and the Alice Livingston Trout Family Fund.Dr. Battegay was supported by the Swiss National Science Foundation, the Conrad Gessner Stipendium, and the Schweizerische Stiftung fur medizinisch biologische stipendien.     

Impact of prior rituximab on outcomes of autologous stem‐cell transplantation in patients with relapsed or refractory aggressive B‐cell lymphoma: a multicentre retrospective Spanish group of lymphoma/autologous bone marrow transplant study

The use of highly effective rituximab‐containing therapy for treating diffuse large B‐cell lymphoma (DLBCL) makes it more difficult to salvage relapsed or refractory patients. Autologous stem‐cell transplantation (ASCT) is the reference treatment for these patients, but the impact of previous exposure to rituximab on the subsequent results of ASCT remains unknown. We analysed 248 patients with relapsed or refractory DLBCL or grade 3B follicular lymphoma pre‐treated with rituximab as part of first‐line therapy (R+ group) who received ASCT, in comparison with a control group of 127 patients without previous exposure to rituximab (R? group). The complete remission (CR) rates were similar in both groups. Multivariate analysis identified age‐adjusted International Prognostic Index at diagnosis, extranodal involvement and disease status at transplant, and the number of previous chemotherapy lines as independent factors with a negative influence on CR rate. Compared with R? patients, those in the R+ group had a significantly better progression‐free survival (63% vs. 48% at 5 years) and overall survival (72% vs. 61% at 5 years). This observation was independent of other prognostic factors that affected these outcomes. In conclusion, ASCT is no less effective in patients with relapsed or refractory aggressive B‐cell lymphoma pre‐treated with first‐line rituximab‐containing therapy than in rituximab‐naive patients.     

A new hepatitis B virus strain in patients with severe anti-HBe positive chronic hepatitis B

In hepatitis B virus carriers who are anti-HBe positive despite ongoing viral replication (HBcAg in liver and HBV-DNA in serum) the natural course of hepatitis is severe and the response to interferon is low. We investigated whether a new hepatitis B virus (HBV) strain could be involved. A translational termination codon at the carboxyterminal end of the pre-C region responsible for the lack of HBeAg secretion was found in 18 of 19 HBV clones isolated from seven pedigreed patients with this clinical syndrome. The same findings were confirmed by direct sequencing. One of these patients underwent a liver transplant and HBV infection of the new liver resulted in high titered viremia and intrahepatic expression of HBcAg, without detectable HBeAg in serum. Another patient was superinfected by hepatitis delta virus (HDV) and developed high titres of total and IgM anti-HD. In spite of this, chronic hepatitis remained unchanged during 7 years of follow-up. These data strongly suggest that a viable precore minus mutant of hepatitis B virus is responsible for the lack of HBeAg in the serum of these patients. The HBV variant may explain the peculiar geographic distribution of anti-HBe positive hepatitis. The variations in the virus genome sequence may cause the more severe form of liver disease and modify the pathogenicity in the case of HDV superinfection.     

Natural killer (NK) cell leukaemia in a patient with a B cell non‐Hodgkin’s lymphoma

Summary We describe a 74‐year‐old woman with the diagnosis of natural killer (NK)‐cell leukaemia and autoimmune pathology. Four years previously, a diffuse large B cell non‐Hodgkin’s lymphoma had been diagnosed and treated effectively. Although NK‐cell leukaemia has been thought to be a distinct highly aggressive clinicopathological entity, our case shows no further evolution at the present time. As far as we know, this association has not been previously described in the literature.     

High‐dose CD20‐targeted radioimmunotherapy‐based autologous transplantation improves outcomes for persistent mantle cell lymphoma

Autologous stem cell transplant (ASCT) can improve outcomes for mantle cell lymphoma (MCL) patients, yet relapses are frequent. We hypothesized that high‐dose anti‐CD20 radioimmunotherapy (RIT)‐based conditioning could improve results in this setting. We thus assessed 162 consecutive patients with MCL at our centre undergoing ASCT following high‐dose RIT‐based (n = 61) or standard (n = 101) conditioning. RIT patients were less likely to be in first remission (48% vs. 72%; P = 0·002), be in complete remission (CR) (26% vs. 61%; P < 0·001) and have chemosensitive disease (84% vs. 96%; P = 0·006). RIT‐based conditioning was associated with a reduced risk of treatment failure [hazard ratio (HR) 0·40; P = 0·001] and mortality (HR 0·49; P = 0·01) after adjusting for these imbalances. This difference increased as disease status worsened (from CR to partial remission to stable/progressive disease), with respective HRs of 1·14, 0·53 and 0·04 for mortality, and 0·66, 0·36 and 0·14 for treatment failure. RIT‐based conditioning appears to improve outcome following ASCT for MCL patients unable to achieve CR after controlling for imbalances in important risk factors. These data support the further study of RIT and radiation‐based strategies in a risk‐adapted approach to ASCT for persistent MCL.     

Efficacy of autologous stem cell transplantation in mantle cell lymphoma: a 3-year follow-up study

This study was designed to evaluate the efficacy of therapeutic intensification with autologous stem cell transplantation (ASCT) for mantle cell lymphomas (MCL) in terms of response rate, duration of response, and event-free and overall survivals. Twenty-four patients with confirmed MCL responding to chemotherapy received a high-dose chemo-radiotherapy regimen followed by ASCT. Transplantation was performed during first-line therapy in nine cases, second-line in 13 cases and third-line in two cases. The source of hematopoietic stem cells was peripheral blood for 19 cases. At the time of ASCT, eight patients were in complete remission (33%). Seventeen of the 24 cases received an intensified regimen with TBI and seven received the BEAM or the BEAC regimen. After transplantation, 19 patients were in CR (79%). Nine of these were alive in continued CR at a median follow-up of 34 months, while seven relapsed at a median of 18 months. One patient died from Pneumocystis carinii interstitial pneumonitis and five patients developed secondary malignancies. With a median follow-up after transplantation of 34 months, the 3-year event-free survival was 55% and the 3-year overall survival was 68%. These results indicate that therapeutic intensification with ASCT might be an effective treatment for mantle cell lymphomas. Bone Marrow Transplantation (2000) 25, 251-256.