HEPATITIS C LYMPHOGENSIS

Clinical scenario : 

Clinical scenario An 48-years man suffering from compensated cirrhosis caused by HCV had regular follow up monthly since 2003. In March 2009 ,splenic vein thrombosis was detected during routine follow up by abdominal ultrasonography. The patient was asymtomatic and a febriale with mild heptomegaly .Lab .tests showed decreased platelet count and serum albumine level ,one –two fold raiase in serum ALT all of which had been nearally unchanged for several years.CT with contrast was done and documented a filling defect in splenic vein originating form the splenic hilum.based on diagnosis of splenic vein thrombosis,warfarin administration was strated after heparin infusion to maintain INR approximately 2.0.

Clinical scenario : 

Clinical scenario Few months later, abdominal CT showed, further extension of the thrombus to the portal vein with small tumor mass apear in splenic hilum with marked enlargment of the splenic size and moderate increase in size of liver. Serum alpha feto protein ,CEA and CA19-9. histopathologic examination revised the diagnosis of lage B-cell lymphoma.

Introduction : 

Introduction

Introduction : 

Introduction

Introduction : 

Introduction

Risk of Lymphoma Increases with Hepatitis C Virus Infection : 

Risk of Lymphoma Increases with Hepatitis C Virus Infection

INTRODUCTION : 

INTRODUCTION Recent studies have confirmed that hepatitis C virus (HCV) is not only a hepatotropic, but also a lymphotropic and sialotropic viru. *This virus can be isolated from hepatocytes, hepatic lymphocytes, peripheral mononuclear cells, bone marrow and lymphoid tissues in infected people.

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The HCV Connection It is not fully understood how HCV causes NHL. There are theories that the virus might be the causative agent, or that the constant immune system stimulation from hepatitis C triggers NHL. However, we do know that the incidence of NHL in people with hepatitis C is higher than in the general population

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One very large study from Sweden of 27,150 HCV infected persons found that the incidence of NHL was nearly double in persons with hepatitis C who had been infected with hepatitis C for longer than 15 years. Other studies have found a similar or even a higher risk for HCV infected patients developing NHL. Smoking cigarettes also has been found to increase the risk of NHL even without hepatitis C.

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In 2005 a study from Italy linked smoking to the development of NHL. The same study found that people with hepatitis C who are heavy smokers have about a 4-fold increased risk for developing NHL.

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Particles of viral genome were found in T and B cells of patients with chronic hepatitis and infected with HCV (2). Recently, HCV infection was found in most of the type 2 mix cryoglobulinemia patients. This is a lymphoproliferative disease of the gland characterized by heat sensitive protein complexes derived from polyclonal Ig G and monoclonal Ig M. It is known that it progresses to Bcell non-Hodgkin lymphoma (NHL) in some cases (1). In rare B lymphocyte neoplasms associated with monoclonal Ig M production (Waldenstrom's macroglobulinemia), HCV infection is found in substantial proportion of cases, indicating a possible role for the virus in neoplastic Ig M gammopathies (3). Recent finding of HCV genome and anti-HCV in the sera of B-NHL cases not associated with mixed cryoglobulinemia suggests that HCV may be responsible for B cell-clonal proliferation

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Particles of viral genome were found in T and B cells of patients with chronic hepatitis and infected with HCV (2). Recently, HCV infection was found in most of the type 2 mix cryoglobulinemia patients. This is a lymphoproliferative disease of the gland characterized by heat sensitive protein complexes derived from polyclonal Ig G and monoclonal Ig M. It is known that it progresses to Bcell non-Hodgkin lymphoma (NHL) in some cases (1). In rare B lymphocyte neoplasms associated with monoclonal Ig M production (Waldenstrom's macroglobulinemia), HCV infection is found in substantial proportion of cases, indicating a possible role for the virus in neoplastic Ig M gammopathies (3). Recent finding of HCV genome and anti-HCV in the sera of B-NHL cases not associated with mixed cryoglobulinemia suggests that HCV may be responsible for B cell-clonal proliferation

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Studies have demonstrated that hepatitis B is a moderately lymphotropic disease.

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The correlation between HCV infection and non – Hodgkin’s lymphoma is no doubt at present. However, the reports on the correlation between HCV infection and Hodgkin’s lymphoma are still controversy. Hepatitis C virus (HCV) six times likely to develop non-Hodgkin's .

Hepatitis C Infection Increases Risk of Lymphoma and Multiple Myeloma : 

Hepatitis C Infection Increases Risk of Lymphoma and Multiple Myeloma According to the results of a recent study published in Hepatology, individuals with the Hepatitis C virus have a significantly increased risk of developing non-Hodgkin’s lymphoma (NHL) and multiple myeloma. Duberg A, Nordstom M, Torner A, et al. Non-Hodgkin’s Lymphoma and Other Nonhepatic Malignancies in Swedish Patients with Hepatitis C Virus Infection. Hepatology. 2005;41: 652-659.

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Apart from its well known role as an etiological agent for non-A and non-B viral hepatitis, there is growing evidence that hepatitis C virus is associated to B-cell non-Hodgkin lymphoma. The association between HCV and lymphoproliferative disorders has been recently postulated based on epidemiological data, biological studies and clinical observations. Although various subtypes of lymphomas appear to be associated to HCV, diffuse large B-cell lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia and marginal zone lymphoma appeared to be particularly represented among HCV-positive patients.

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The causative role of HCV in those disorders has been further supported by the response to anti-viral therapy. Despite a better understanding of pathophysiological processes at stake leading from HCV infection to overt lymphoma, many issues still need to be further elucidated

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Although HCV has been demonstrated to directly infect peripheral blood mononuclear cells both in vitro and, in some cases, in vivo, a strong body of evidence rather supports the hypothesis of an indirect transformation mechanism by which sustained antigenic stimulation leads from oligoclonal to monoclonal expansion and sometimes to lymphoma, probably through secondary oncogenic events.

A Lymphoma Linked to Hepatitis C Responds to Interferon Therapy : 

A Lymphoma Linked to Hepatitis C Responds to Interferon Therapy Hepatitis C virus (HCV) infection is a known cause of mixed cryoglobulinemia, which is characterized by chronic polyclonal B-cell stimulation, and has also been epidemiologically linked to B-cell non-Hodgkin's lymphomas. A new study provides evidence that 1 form of B-cell lymphoma -- splenic lymphoma with villous lymphocytes -- can respond to interferon therapy for HCV disease.

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a group of French oncologists started a trial of antiviral therapy in 8 additional patients with this malignancy and concurrent HCV infection. All patients had a therapeutic response to 3 million units of recombinant interferon alfa given 3 times weekly, either alone or with ribavirin. In all patients, splenomegaly resolved progressively, and levels of circulating abnormal villous lymphocytes decreased. After a median follow-up of 27 months, 7 patients remained in complete remission. One patient who relapsed had a complete hematologic response when antiviral therapy was restarted. A retrospective analysis of 6 other patients with splenic lymphoma with villous lymphocytes who did not have HCV infection found no evidence of response to interferon therapy. Hermine O et al. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002 Jul 11; 347:89-94

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Diagnosis

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There are also various types of infections that increase the risk of NHL including: • Human immunodeficiency virus (HIV) • Epstein-Barr virus (EBV) • Helicopter pylori (H. pylori – a bacteria that can cause stomach ulcers) • Human T-cell leukemia/lymphoma virus (HTLV-1) • Hepatitis C virus (HCV)

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Symptoms The most common symptoms of NHL include: • Swollen but painless lymph nodes (generally in the neck, armpits and groin) • Unexplained weight loss • Fever Alan Franciscus, Editor-in-Chief HCSP • VERSION 2.1 • February 2009 1 HCSP • VERSION 2.1 • February 2009 2 • Night sweats • Coughing, trouble breathing, or chest pain • Constant weakness and fatigue • Pain, swelling, or a feeling of fullness in the abdomen