https://www.gastrojournal.org/article/S0016-5085(16)00230-4/pdf

Extrahepatic Manifestations of Hepatitis C: A Meta-analysis of Prevalence, Quality of Life, and Economic Burden.

Importance Hepatitis B virus (HBV) reactivation is a serious complication for patients with lymphoma treated with rituximab-containing chemotherapies, despite lamivudine prophylaxis treatment. An optimal prophylactic antiviral protocol has not been determined. Objective To compare the efficacy of entecavir and lamivudine in preventing HBV reactivation in patients seropositive for the hepatitis B surface antigen with untreated diffuse large B-cell lymphoma receiving chemotherapy treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Design, Setting, and Patients Randomized, open-label, phase 3 study conducted from February 2008 through December 2012 at 10 medical centers in China. This study was a substudy of a parent study designed to compare a 3-week with a 2-week R-CHOP chemotherapy regimen for untreated diffuse large B-cell lymphoma. Patients enrolled in the parent study who were seropositive for the hepatitis B surface antigen and had normal liver function, serum HBV DNA levels of less than 10 3 copies/mL, and no prior antiviral therapy were randomized to entecavir (n = 61) or lamivudine (n = 60). Interventions Daily entecavir (0.5 mg) or lamivudine (100 mg) beginning 1 week before the initiation of R-CHOP treatment to 6 months after completion of chemotherapy. Main Outcomes and Measures The primary efficacy end point was the incidence of HBV-related hepatitis. The secondary end points included rates of HBV reactivation, chemotherapy disruption due to hepatitis, and treatment-related adverse events. Results There were 121 patients randomly assigned to receive entecavir (n = 61) or lamivudine (n = 60). The date of last patient follow-up was May 25, 2013. The rates were significantly lower for the entecavir group vs the lamivudine group for HBV-related hepatitis (0% vs 13.3%, respectively; difference between groups, 13.3% [95% CI, 4.7% to 21.9%]; P  = .003), HBV reactivation (6.6% vs 30%; difference, 23.4% [95% CI, 10.2% to 36.6%]; P  = .001), and chemotherapy disruption (1.6% vs 18.3%; difference, 16.7% [95% CI, 6.4% to 27.0%]; P  = .002). Of the 61 patients in the entecavir group, 15 (24.6%) experienced treatment-related adverse events. Of 60 patients in the lamivudine group, 18 (30%) experienced treatment-related adverse events (difference between entecavir and lamivudine groups, 5.4% [95% CI, −10.5% to 21.3%]; P  = .50). Conclusions and Relevance Among patients seropositive for the hepatitis B surface antigen with diffuse large B-cell lymphoma undergoing R-CHOP chemotherapy, the addition of entecavir compared with lamivudine resulted in a lower incidence of HBV-related hepatitis and HBV reactivation. If replicated, these findings support the use of entecavir in these patients. Trial Registrations clinicaltrials.gov Identifier:NCT01793844; Chinese Clinical Trial Registry Identifier: CTR-TRC-11001687

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Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial.

The clinical course of chronic hepatitis C virus (HCV) infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinico-epidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells non-Hodgkin’s lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCV-related thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients’ populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases.

Hepatitis C virus syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin’s lymphoma, and cancer

Malignant lymphoma encompasses a wide variety of distinct disease entities. It is generally more common in developed countries and less common in developing countries. The East Asia region has one of the lowest incidence rates of malignant lymphoma. The incidence of malignant lymphoma around the world has been increasing at a rate of 3-4% over the last 4 decades, while some stabilization has been observed in developed countries in recent years. The reasons behind this lymphoma epidemic are poorly understood, although improving diagnostic accuracy, the recent AIDS epidemic, an aging world population and the increasing adoption of cancer-causing behaviors are suggested as contributing factors. Etiologies of malignant lymphoma include infectious agents, immunodeficiency, autoimmune disease, exposure to certain organic chemicals, and pharmaceuticals. The distribution of many subtypes exhibit marked geographic variations. Compared to the West, T/natural killer (NK) cell lymphomas (T/NK-cell lymphoma) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are relatively more common, whereas other B-cell lymphomas, particularly follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, are less common in Asia. Some subtypes of T/NK-cell lymphomas defined by Epstein-Barr virus association are predominantly Asian diseases, if not exclusively so. Both ethnic and environmental factors play roles in such diversity. In this review, we discuss the geographic distribution and etiology of malignant lymphoma, as well as the trend.

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Epidemiologic overview of malignant lymphoma

Hepatitis C virus (HCV) infection is associated with substantial clinical and economic burden and is an important public health issue in Asia. The objective of this review was to characterize HCV epidemiology and related complications in China, Japan, South Korea and Taiwan. A search of electronic databases and conference abstracts identified 71 potentially relevant articles. Of those, 55 were included in the epidemiology review and 9 in the review of HCV-related complications. HCV prevalence in the general population was 1.6% in China, 0.6-0.9% in Japan, 0.6-1.1% in South Korea and 1.8-5.5% in Taiwan. Prevalence was higher for injecting drug users (48-90%) and those with human immunodeficiency virus coinfection (32-85%) and was lower for blood donors (<1%). Annual incidence of HCV in China was 6.01 per 100,000. HCV genotype 1b was associated with the highest incidence of hepatocellular carcinoma (HCC). Five-year survival for patients with liver cirrhosis was 73.8%, decreasing to 39.2% following liver transplantation; the majority of deaths were attributable to HCC. Limitations were that the majority of studies included in the epidemiology review were small, regional studies conducted in specific populations, and there was an absence of large population-based studies. Thus, estimates may not be representative of the epidemiology of HCV for each country. The prevalence HCV in China and HCV incidence in the Asian region remain largely unknown, and they are likely underestimated. Further epidemiologic and clinical data are needed to provide more precise estimates for use by public health agencies.

A review of the burden of hepatitis C virus infection in China, Japan, South Korea and Taiwan

We performed a large case–control study (3,932 cases, 15,562 controls) to investigate the association of hepatitis B virus (HBV) and hepatitis C virus (HCV) with hematopoietic malignancies in Korea, where HBV is endemic. HBV was present in 636 control patients (4.1%), 333 lymphoma patients (12.4%), and 75 leukemia patients (6.0%). HCV infection was present in 173 control patients (1.1%), 76 lymphoma patients (2.8%), and 18 leukemia patients (1.4%). Co-infection of HBV and HCV was present in one (0.007%) control patient, seven lymphoma patients (0.3%), and one leukemia patient (0.08%). HBV infection was associated with increased risks for most subtypes of B and T/NK-cell lymphomas, Hodgkin’s lymphoma, and acute myeloid leukemia. HCV infection was associated with increased risks for diffuse large B cell lymphoma, extranodal marginal zone B cell lymphoma, peripheral T cell lymphoma, and acute lymphoid leukemia B cell early pre-B type. HBV seems to have a more important role than HCV in the pathogenesis of specific hematologic malignancies in Korea.

Sung Soo Jang

Papers

High prevalence of hepatitis B and hepatitis C virus infections in Korean patients with hematopoietic malignancies