Prevalence of hepatitis B or C virus infections in patients with non-Hodgkin's lymphoma

BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) are not only hepatotropic, but also lymphotropic viruses. Recently, some reports suggested that these viruses may participate in the development of malignant lymphoproliferative disorders. METHODS: We investigated the prevalence of HCV or HBV infection in 348 patients with non-Hodgkin's lymphoma (NHL). We also compared these prevalences with those in blood donors as a control group representing the general population in our area (n= 1,513,358). Next, we evaluated the clinical and pathologic characteristics of HCV- or HBV-infected NHL cases. Non-Hodgkin's lymphoma was classified according to the Working Formulation classification. RESULTS: Thirty-seven cases (14.9%) were found to be infected with HCV or HBV; of these, 20 (8.1%) were infected with HCV, and 17 (6.9%) with HBV. In male NHL patients, the rate of HCV infection was significantly higher than in an age- and sex-matched population in the same area (P < 0.001, Mantel-Haenszel test). The rate of HBV infection also tended to be higher in the population (P = 0.0551). In contrast, in female NHL patients, the rate of HCV or HBV infection was not higher than in the general population. In HCV-infected cases, 15 cases (75%) had B-cell NHL and 16 cases (80%) were classified as being in the intermediate grade; B-cell NHL comprised 83% of all NHL cases. In HBV-infected NHL cases, 11 (65%) were of B-cell type and 10 (58%) were classified as being in the intermediate grade. CONCLUSIONS: The high prevalence of HCV or HBV infections in our study population provides epidemiologic evidence suggesting that HCV and HBV infections may be involved in the development of a subgroup of NHL in males. Our investigation also revealed that both HCV- and HBV-infected NHL patients showed certain similarities in clinical and pathologic manifestations.     

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%).     

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 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.     

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.     

Subacute hepatic failure due to hepatitis E

Background and Aim:  The data available on subacute hepatic failure due to hepatitis E virus is scarce. The aim of this study is to analyze the clinical spectrum and outcome of this condition.
Methods:  This is a retrospective hospital-based study of patients with acute hepatitis E and subacute hepatic failure from January 2001 to June 2006.
Results:  We encountered 12 patients with this condition during the study period. There were four females and eight males (age 39 ± 16). Jaundice and ascites were present in all. The model for end stage liver disease (MELD) score was 25 ± 8. All of them had normal-sized liver on ultrasonogram. Transjugular liver biopsies were done in nine patients and revealed extensive bridging, submassive necrosis and cholestasis. Complications included spontaneous bacterial peritonitis (four) and urinary tract infections (two), renal failure (three) and encephalopathy (three). The in-hospital mortality was 25% (3/12). The remaining nine patients left the hospital alive with normalization of liver functions in eight of them over the next few months.
Conclusion:  Subacute hepatic failure caused by hepatitis E is a distinct entity with a better prognosis compared with the previously published series of subacute hepatic failure. Liver biopsy is useful to differentiate from hepatitis E virus superinfection on underlying chronic disease. Poor prognostic factors were female sex, younger age, encephalopathy and persistent renal failure. These patients should be considered for liver transplantation.     

Late onset hepatic failure due to hepatitis B virus with mutations in the pre-core region

A 60-year-old man complained of severe general fatigue on October 11, 1992. Pertinent laboratory findings were: aspantate aminotransferase (AST) 1920 IU, alanine aminotransferase (ALT) 2050 IU, and total bilirubin (T.Bil) 124 micromol/l (normal range, 0–17 micromol/l). Virological assay revealed that hepatitis B surface antigen (HBsAg), anti-hepatitis B e (HBe), anti-HBc, and immunoglobulin M (IgM) anti-HBc were positive, and anti-HBs, HBeAg, and anti-delta antibody were negative. A diagnosis of acute hepatitis due to hepatitis B virus was made. Despite a decrease in transaminase, jaundice worsened and prothrombin time was prolonged. On the 60th day of hospitalization, massive ascites developed, but the patient's consciousness was not impaired. Although albumin and diuretics were given, the ascites further increased. Paracentesis of 2000ml of ascitic fluid was performed twice a week. On the 120th day of hospitalization, the patient passed black stools and he exhibited renal failure 3 weeks later. Although severe jaundice persisted, he was still alert. On the 150th day of hospitalization, massive gastrointestinal bleeding occurred, due to hemorrhagic gastritis. Despite receiving intensive care, the patient died. Determination of the HBV DNA sequence revealed two point mutations in the pre-core region; these have not been reported elswwhere.     

Excellent prognosis and prevalence of HCV infection of primary hepatic and splenic non-Hodgkin's lymphoma

Background: Primary Hepatic (PHL) and Primary Splenic (PSL) non‐Hodgkin’s Lymphoma are rare entities. Small series of PHL and PSL have been reported, suggesting a non‐fortuitous association with Hepatitis C Virus (HCV) infection. The prognosis is believed to be dismal, with early recurrence and short survival. Patients: We retrospectively reviewed all PHL and PSL patients diagnosed at our institution between 1990 and 2005. Results: Twenty‐five adult patients were identified, six with PHL and 19 with PSL. Twenty‐four patients had a B‐cell lymphoma, defined as Diffuse Large B‐cell lymphoma in 18. The prevalence of HCV infection was 68% among PSL and 66% among PHL. Combination chemotherapy was the mainstay of treatment for PHL and PSL; all but one patient with PSL underwent splenectomy before chemotherapy. Complete remission was achieved in all the cases after frontline therapy; only four patients relapsed but responded to additional chemotherapy courses. Most patients presented with aggressive histological subtypes; 92% were alive at a median follow up of 79 months. HCV infection did not appear to influence the results of therapy. Conclusion: Our study confirms the rarity of PHL and PSL, shows a high prevalence of HCV infection, and demonstrates that the outcome of patients with PHL and PSL may be favourable.     

Hepatitis C virus and non-Hodgkin's lymphomas

Hepatitis C virus (HCV) seems to be the aetiologic agent of mixed cryoglobulinaemia, and as this 'benign' lymphoproliferative disorder can frequently develop into more aggressive haematological disorders, this study was undertaken to determine the prevalence of HCV infection in non-Hodgkin's lymphomas. 199 unselected subjects treated by three haematological centres in Northeast Italy were investigated for the presence of HCV infection. As controls, the prevalence of HCV infection was determined in a group of patients affected by other haematological malignancies (153 subjects) and in the general population of the same geographical area in the cohort study called the Dyonisos project (6917 subjects).
The presence of anti-HCV antibodies was determined by a commercial kit and, in positive cases, by PCR amplification of the 5' untranslated region of the virus. The HCV genotype was also obtained by PCR amplification of the Core region with type-specific primers. The presence of serum cryoglobulins was determined in each case of NHL.
HCV infection was significantly ( P <0.00000001) higher in patients with non-Hodgkin's lymphomas (28.0%) when compared with that of the general population (2.9%), and with the group of patients affected by other malignancies (3.1%). The prevalence is particularly high in low-grade (38.4%), as compared with intermediate (11.4%), or high-grade (15.2%) lymphomas. The presence of the virus is significantly ( P <0.000001) associated with the presence of detectable levels of cryoglobulins. On the basis of these findings, HCV seems to play an important role in the development of low-grade non-Hodgkin's lymphomas.     

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.     

Prevalence of TT virus in patients with fulminant hepatic failure in Japan

A novel virus (TT virus) was isolated from patients with posttransfusion hepatitis of unknown etiology. We studied the prevalence of TT virus in 26 patients with fulminant hepatic failure without risk factors, including blood transfusion, and also examined 106 healthy blood donors as controls. We assayed serum TT virus DNA by seminested polymerase chain reactions and also examined the genotypes of this virus. Serum was obtained at admission from patients with fulminant hepatic failure. Serum samples at admission from seven (27%) of the 26 patients were positive for TT virus DNA. There were no differences in clinical findings, duration from onset to coma, or results of laboratory tests in patients with and without TT virus DNA. However, all 7 patients with TT virus died, whereas 9 of the 19 patients without TT virus died. The outcome for patients with fulminant hepatic failure and TT virus was significantly worse than for patients without the virus (P = 0.0227). TT virus was also detected in 29 (27%) of the 106 healthy blood donors. The genotype of the TT virus was mainly 1a in both groups. There were no differences in the rate of positivity and the genotypes of TT virus between patients with fulminant hepatic failure and healthy blood donors. TT virus infection may not cause severe hepatitis, such as fulminant hepatic failure, but it may indicate a poor outcome in such patients. Received: September 14, 1998 / Accepted: May 28, 1999     

Coexistence of B-cell non-Hodgkin lymphoma and cutaneous T-cell lymphoma in a patient with chronic hepatitis C and cryoglobulinaemia

The coexistence of chronic active hepatitis C with cryoglobulinemia and B-cell lymphoma has been presented in numerous case reports. However, the combination of these conditions with T-cell lymphoma has never been described before. We present the case of a patient who suffered chronic active hepatitis C, cryoglobulinaemia and B-cell lymphoma and was later complicated by cutaneous T-cell lymphoma (CTCL).     

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV+ patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.     

Hepatitis C virus risk: a hepatitis C virus related syndrome

BACKGROUND: The association between mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection has been recently described in many reports. OBJECTIVE: The aim of this study was to evaluate the long-term prognosis of hepatitis C virus-positive patients affected by mixed cryoglobulinemia with or without kidney involvement. PATIENTS: At total of 119 hepatitis C virus-positive patients affected by mixed cryoglobulinemia were divided in two groups. Group A: mixed cryoglobulinemia without kidney involvement (103 cases); group B: mixed cryoglobulinemia with glomerulonephritis (GN) (16 cases). A further 37 patients affected by mesangio-proliferative glomerulonephritis (MPGN) were evaluated as controls (group C). METHODS: Anti-hepatitis C virus antibodies were determined by commercial kits and hepatitis C virus-RNA was detected by polymerase chain reaction (PCR) amplification of the 5' untranslated region (5'UTR) of the virus. The hepatitis C virus genotype was determined according to Okamoto. Liver biopsy was performed in 62 patients, bone marrow biopsy in 65 patients, and kidney biopsy in all patients with proteinuria. RESULTS: In group A, 46 patients (45%) were affected by chronic liver disease (CLD), 21 (20%) by low-grade non-Hodgkin's lymphoma (NHL) and 16 (15%) by both diseases. All patients of group B were affected by type I membrano-proliferative glomerulonephritis, 3 (19%) by chronic liver disease, 6 (37%) by low-grade non-Hodgkin's lymphoma, and 7 (44%) by both diseases. Several genotypes of hepatitis C virus were found, but Type 1b was prevalent. In group C, no patient showed chronic liver disease or non-Hodgkin's lymphoma. Younger age, higher mean blood pressure, lower C4 serum level, and poorer survival significantly distinguished group B from group A. Survival rates at 5 years were: 87.4% for group A, 89.5% for group C, and 50.0% for group B. None of the patients of group B developed kidney failure requiring dialysis, whilst infections were the leading cause of death. CONCLUSIONS: In hepatitis C virus-positive patients, the presence of mixed cryoglobulinemia associated with kidney involvement seems to indicate a new syndrome characterized by immune system impairment, lack of progression to kidney failure, and poor survival (hepatitis C virus-Risk syndrome).     

Diffuse large B-cell non-Hodgkin's lymphoma in a patient with autoimmune lymphoproliferative syndrome

Mutations of Fas or Fas ligand genes result in the autoimmune lymphoproliferative syndrome (ALPS) in humans. We report here a diffuse large B-cell non-Hodgkin's lymphoma occurring in a man with ALPS. Fas-mediated lymphocyte apoptosis was defective in vitro, owing to a mutation within the death domain of the Fas molecule. High-dose methotrexate and doxorubicin-based chemotherapy led to complete remission of lymphoma.     

New infection with heterotypic hepatitis C virus in a patient with long-term hepatitis C virus eradication

BACKGROUND: Experimental hepatitis C virus infection in chimpanzees has shown that natural hepatitis C virus infection does not induce protective immunity and reinfection can occur in seroconverted animals. AIM: To study the clinical, virological and histological outcome of a new infection sustained by a different hepatitis C virus strain after a primary infection with eradication of the original virus. PATIENTS AND METHODS: A young Italian man with chronic hepatitis C virus type 4 hepatitis was treated with Interferon therapy and achieved a sustained biochemical and virological response. After long follow-up, an asymptomatic flare-up of alanine transaminase occurred. This alanine transaminase increase was associated with serum hepatitis C virus RNA positivity and a low viral load, and the infecting hepatitis C virus genotype was type 3. The clinical and virological course of this new infection is described. RESULTS AND CONCLUSIONS: This report shows that there is no protective immunity against hepatitis C virus type 3 after infection by hepatitis C virus type 4 strain.     

Detection of hepatitis C virus RNA in paraffin-embedded tissues from patients with non-Hodgkin's lymphoma

The aim of this study is to detect the possible role of hepatitis C Virus (HCV) in lymphomagenesis. HCV-RNA and anti-HCV antibodies were studied in tissue and serum samples taken from patients with non-Hodgkin's Lymphoma (NHL). The prevalence of HCV, the clinical presentation of these cases, and association with histologic subtypes were determined. RT-PCR was used to detect the HCV-RNA in serum and tissue samples. The anti-HCV antibodies were tested with microparticle enzyme immunoassay. Immunohistochemistry with the ABC method was used to detect the HCV core protein in HCV-RNA(+) cases. RNA could be detected in 30 of 35 cases, and other tests were performed in these 30 samples. HCV-RNA was detected in 11 tissue samples (11/30, 37%). HCV core protein was studied in 10 of 11 HCV-RNA(+) cases, and 1-3% nuclear staining was found in only 2 samples. Serologically, HCV-RNA was detected in 7 of 30 samples (23.3%) and anti-HCV antibody was detected in 3 of 30 samples (10%). Detection of HCV-RNA in 37% of the lymphoma tissue samples suggests that HCV may have a role or is a contributing factor in the pathogenesis of lymphoma. The very low HCV core protein in lymphoma tissues may be due to the low viral load in lymphoid tissues and/or higher sensitivity of the PCR method. Detection of anti-HCV antibody in only three cases may be associated with undetectable levels of antibodies due to the immune deficiency in cases with NHL.