Hepatitis C virus infection in patients with B-cell non-Hodgkin's lymphoma

OBJECTIVE: As a causative role of hepatitis C virus (HCV) in B-cell lymphoproliferative disorders (LPD) has been suggested by several reports, we investigated the prevalence of HCV infection among patients with LPD at our hospital with the aim of clarifying the clinical features and the outcome for HCV antibody-positive patients with non-Hodgkin's lymphoma (NHL). METHODS: Retrospective chart review. PATIENTS: A total of 123 patients with B-cell LPD (4 with chronic lymphocytic leukemia, 17 with multiple myeloma, and 100 with B-cell NHL), 38 patients with non-B-cell LPD (5 with adult T-cell lymphoma, 8 with Hodgkin's disease, and 25 with non-B-cell NHL) and 516 patients with miscellaneous diseases other than liver diseases or LPD (control) were studied. RESULTS: HCV infection was detected in 17 of 100 patients with B-cell NHL versus none of 25 patients with non-B-cell NHL (p=0.023) and in 34 patients (6.6%) in the control group with miscellaneous diseases (p=0.0011). In HCV-positive B-cell NHL, primary liver involvement was detected in 3 of 17 patients compared to none of 83 HCV-negative patients (p=0.0019). Intermediate-grade lymphoma (Working Formulation) was the most frequent histology. Eleven of 15 HCV-positive patients achieved complete remission after chemotherapy, and 6 of 7 deaths were caused by liver-related diseases. CONCLUSION: The prevalence of HCV infection was higher in patients with B-cell NHL than in those with non-B-cell NHL and the control group. Primary liver involvement and liver-related causes of death were frequent in HCV-positive patients with B-cell NHL.     

Hepatitis C virus infection in patients with non-Hodgkin's lymphoma

Summary. Hepatitis C virus (HCV), which is both a hepatotropic and a lymphotropic virus, has been proposed as a possible causative agent of mixed cryoglobulinaemia. This 'benign' lymphoproliferative disorder can switch over to a malignant B-cell non-Hodgkin's lymphoma (NHL). Therefore HCV infection has been investigated in a series of 50 unselected Italian patients with B-cell NHL. Antibodies against HCV were found in 30% of NHL and HCV viraemia in 32% of cases. HCV-related markers were detected in 34% (17/50) of our NHL patients; this prevalence is particularly significant when compared with HCV seropositivity in Hodgkin's lymphoma (3%) and healthy controls (1.3%).     

Hepatitis B and C virus infection in Romanian non-Hodgkin's lymphoma patients

We determined the hepatitis C virus (HCV) antibodies (anti-HCV) and the hepatitis B virus (HBV) surface antigen (HBsAg) in a cohort of 68 consecutive non-Hodgkin's lymphoma (NHL) patients diagnosed and treated in our institution between December 1997 and March 1999. 27 cases were diagnosed as low-grade, 33 as intermediate-grade, and eight as high-grade NHL. In 35 cases (51.4%) we found evidence of either HCV or HBV infection. Anti-HCV antibodies were found in 20 patients (29.5%) and HBsAg was found in 21 patients (30.8%). In six patients both anti-HCV and HBsAg were present. Anti-HCV were present in 12/27 low-grade NHL cases (44.4%) and in 8/41 intermediate/high-grade (aggressive) NHL cases (19.5%, P < 0.03). HBsAg was found in 10/27 low-grade NHL cases (37%) and in 11/41 aggressive NHL cases (26.8%). Evidence of liver disease, as reflected by elevated aminotransferases or typical alterations at liver biopsy, was present in eight patients. Cryoglobulins were present in six patients, all anti-HCV positive and with low-grade NHL. The prevalence of both HCV antibodies and HBsAg was significantly higher (P < 0.0001) in our NHL cases than in a sample of the general Romanian population, where the prevalence of anti-HCV was 4.9% and that of HBsAg was 6.3%. It is difficult to say whether either HCV or HBV had actually been involved in lymphomagenesis or if alpha-interferon treatment would be effective in this subset of patients.     

Hepatitis C virus infection prevalence and liver dysfunction in a cohort of B-cell non-Hodgkin's lymphoma patients treated with immunochemotherapy

Several studies have reported a higher prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) than in the general population. Treatment for NHL includes the use of chemotherapeutic agents such as cytotoxic drugs, corticosteroids, and rituximab, which can be immunosuppressive and hepatotoxic. While reactivation of hepatitis B virus (HBV) when undergoing immunosuppressive therapy for haematological malignancies is a well-documented complication, data on HCV reactivation or liver function impairment after chemotherapy for NHL are controversial. From January 2006 to December 2009, 207 consecutive NHL patients treated with chemotherapy without rituximab (CHOP) or with rituximab (R-CHOP) were observed; screening for HCV infection and baseline liver function tests were performed in all patients. The prevalence of HCV infection was 9.2%. This prevalence is higher than that observed in the general population in Italy (3%). Among the HCV-infected subjects, the incidence of hepatitis flares was 26.3% vs 2.1% among the HCV-uninfected individuals. Although less frequent and less severe than in HBV-infected subjects, liver dysfunction can occur as a consequence of rituximab-containing regimens in HCV-infected patients with NHL. In the cases considered in this study, no patient treated with chemotherapy without rituximab developed hepatitis flares. The frequency and the severity of this complication vary in different reports. Therefore, we recommend the assessment of liver function and the screening of all patients with NHL for HCV infection before starting chemotherapy; we also recommend monitoring of liver function tests and HCV-RNA serum levels during treatment.     

Prevalence of hepatitis C virus infection in B-cell non-Hodgkin's lymphoma: systematic review and meta-analysis

BACKGROUND & AIMS: The aim of our study was to conduct a systematic review of studies evaluating prevalence of hepatitis C virus (HCV) infection in B-cell non-Hodgkin's lymphoma (B-NHL) and to perform a meta-analysis of case-control studies comparing this prevalence with that of a reference group. METHODS: Data sources: Electronic databases and the Cochrane Controlled Trials Register. Study selection: Studies evaluating prevalence of HCV infection in patients with B-NHL. Studies comparing HCV prevalence in B-NHL (cases) and in a reference group (controls) were included in the meta-analysis. Data extraction: Author/country, diagnostic method (serology/PCR), control type, matching/design, and VHC prevalence. Data synthesis: Prevalence of HCV infection and meta-analysis combining the odds ratios (OR). RESULTS: Forty-eight studies (5542 patients) were identified. Mean HCV infection prevalence was 13% (95% CI: 12%-14%), which was higher in Italy (20%) and Japan (14%). Ten studies compared HCV prevalence in B-NHL (17%) and healthy controls (1.5%) (OR: 10.8; 95% CI: 7.4-16), results being homogeneous; OR increased up to 14.1 when only Italian studies were considered. Sixteen studies compared HCV prevalence in B-NHL (13%) and in other hematologic malignancies (2.9%) (OR: 4.2; 95% CI: 2.5-7), also with homogeneous results; OR increased up to 7.8 when subanalysis included only Italian studies. CONCLUSIONS: HCV prevalence in patients with B-NHL is approximately 15%, higher than that reported not only in general population (1.5%) but also in patients with other hematologic malignancies (2.9%), suggesting a role of HCV in the etiology of B-NHL. The striking geographic variation in this association suggests that genetic and/or environmental factors are also involved in the pathogenesis of this disorder.     

Hepatitis C virus infection and non-Hodgkin's lymphoma: a review and case report of nine patient

The role of hepatitis C virus (HCV) is well established in the development of chronic hepatitis, cirrhosis and hepatic carcinoma, as well as in mixed type II cryoglobulinemia, membranoproliferative glomerulonephritis(MPGN) and porphyria cutanea tarda (PCT). Increasing evidence has been reported of a close association of HCV infection with autoimmune and hematological processes, mainly cytopenias and lymphoproliferative disorders such as B cell non-Hodgkin's lymphoma. We describe the demographic, clinical and histopathological findings of nine patients from the Mexican population with non-Hodgkin's lymphoma and HCV infection.     

Hepatitis C virus and non-Hodgkin's lymphoma 10 years later

Hepatitis C virus is associated with chronic liver disease as well as with lymphoproliferative disorders such as mixed cryoglobulinemia and, likely, non-Hodgkin's lymphomas. The association between hepatitis C virus infection and B-cell lymphoma is controversial since it shows a strong regional variation. In fact, the prevalence of hepatitis C virus infection in non-Hodgkin's lymphoma shows a prevalence ranging between 7.4 and 37.0%. However, the intimate pathogenetic mechanism involved in hepatitis C virus-associated lymphomas remains considerably unknown. Hepatitis C virus may exert its oncogenic potential via an indirect mechanism or utilise other pathways directly. It is reasonable to assume that several different pathogenetic mechanisms operate in the wide spectrum of hepatitis C virus-related lymphoproliferative disorders, which include the intermediate to high-grade lymphoma, and the more common indolent, low-grade lymphoma, preceded by long standing symptomatic mixed cryoglobulinemia Type II. In this review, the etiopathogenetic role of hepatitis C virus in non-Hodgkin's lymphoma is discussed on the basis of molecular, clinical and epidemiological considerations.The management of hepatitis C virus-associated non-Hodgkin's lymphoma is similar to that of conventional lymphoma, although viral reactivation or the underlying chronic liver disease can complicate chemotherapy. Whether to treat low-grade hepatitis C virus-related lymphomas with anti-viral therapy is still debatable, but encouraging data emerge from some recent studies.     

High prevalence of hepatitis B virus infection in B-cell non-Hodgkin's lymphoma

In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.     

Hepatitis C and B-cell lymphoma

Hepatitis C virus (HCV) infection is a major public health problem worldwide. HCV, a lymphotropic and hepatotropic virus, is clearly associated with cirrhosis, end-stage liver disease, autoimmune phenomena, hepatocellular carcinoma, and essential mixed cryoglobulinemia. Recently, there have been increasing reports of B-cell lymphomas in patients with HCV infection, and epidemiologic data from several sources have demonstrated high rates of HCV seroprevalence in patients with B-cell malignancies. This review describes a case report of a patient with HCV and chronic lymphocytic leukemia, followed by a summary of the literature on this rapidly evolving area.     

Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis,behavior and treatment

A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.     

Hepatitis C virus infection and lymphoproliferative diseases: prospective study on 1,576 patients in France

CONTEXT: Discordant data have been reported about the prevalence of hepatitis C virus (HCV) infection in patients with lymphoproliferative diseases and the putative role of HCV in lymphomagenesis. OBJECTIVE: To assess the prevalence of HCV infection in patients admitted to a hematology department in Paris, France. DESIGN: Prospective, controlled study. SETTING: University medical center. PATIENTS: 813 patients admitted to the Hematology department (164 B-cell non-Hodgkin's lymphoma, 34 Hodgkin's diseases, 107 chronic lymphocytic leukemia, 54 multiple myeloma, 12 Waldenstr?m's macroglobulinemia, 17 acute lymphoblastic leukemia, 6 hairy cell leukemia, 189 myeloproliferative diseases, 6 solid organ tumors, and 224 nonmalignant diseases) and 694 patients admitted to the Internal Medicine department (control group). MEASUREMENTS: All patients were tested for antibodies to HCV by a third-generation enzyme-linked immunosorbent assay. RESULTS: HCV antibodies were detected in 20 of 813 (2.46%) patients in Hematology including 11 of 394 (2.79%) patients with lymphoproliferative diseases, 3 of 164 (1.83%) B-cell non-Hodgkin's lymphoma, 2 of 107 (1.87%) chronic lymphocytic leukemia, 1 of 54 (1.85%) multiple myeloma, 1 of 189 (0.5%) myeloproliferative diseases, and 8 of 224 (3.57%) nonmalignant hematologic diseases. HCV antibodies were detected in 3 of 694 (0.43%) patients in the control group. HCV contamination preceded B-cell non-Hodgkin's lymphoma only in 2 of 3 HCV-positive patients. CONCLUSION: The prevalence of HCV infection was low (1.83%) in patients with B-cell non-Hodgkin lymphoma. HCV seems not to play a major role in the pathogenesis of B-cell lymphoma in France. Cofactors should be stressed to explain geographical discrepancies.     

Hepatitis C virus infection and lymphoproliferative diseases in France: a national study. The GERMIVIC Group

The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by North American and southern European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). In order to evaluate the situation in France, we conducted a retrospective national study about the association of chronic HCV infection and LPD. 72 Internal Medicine and Infectious Diseases departments were contacted. Response rate was 51.4%. We recorded 43 LPD (19 males, 24 females): 31 B-cell-NHL, 4 Waldenstr?m's macroglobulinemia, 3 chronic lymphocytic leukemia, 2 multiple myeloma, 2 lymphomas of the mucosa-associated lymphoid tissue, and 1 Hodgkin's disease. Mean age at HCV diagnosis was 62 years (range 33-84). In 16 cases, LPD occurred in patients known to be HCV-infected. For 11 patients, LPD diagnosis preceded the diagnosis of HCV infection, whereas diagnosis was done simultaneously in 11 patients. For those with accurate infection date, mean interval between both events was 15.2 years. Fourteen patients had HCV extrahepatic manifestations: 9 mixed cryoglobulinemia, including 7 with NHL, 5 sicca syndrome (5 NHL), and both in one patient. Cohort of HCV-infected patients could be accurately determined for 16 departments, totaling 1,485 patients and 37 cases. Thus, from our data the frequency of LPD among HCV-infected patients approximates 2. 49%. Despite possible bias inherent to this retrospective study, our data support the hypothesis of HCV-associated LPD and particularly B-cell-NHL. In France, this association is much lower than in Italy. Further studies are needed to assess the precise role of HCV in the multistep process leading to monoclonal proliferation.     

'Les liaisons dangereuses': Hepatitis C, Rituximab and B-cell non-Hodgkin's lymphomas

Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkin’s lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with Rituximab-containing regimens. In this paper we review the recent data regarding the effects of Rituximab in NHL patients with HCV infection. We also added a section devoted to improving communication between oncohaematologists and hepatologists. Furthermore, we propose a common methodological ground to study hepatic toxicity emerging during chemotherapy.