Hepatitis C Virus Reactivation Research Articles

Reactivation of hepatitis C virus caused by steroid monotherapy for sudden deafness.

Hepatitis C virus (HCV) reactivation has been reported to be caused due to several anticancer drugs and immunosuppressive agents; however, HCV reactivation after steroid monotherapy has rarely been reported. Here, we report the case of a 65-year-old Japanese man with HCV infection who developed HCV reactivation after the administration of prednisolone (PSL) for 6days for sudden deafness. In the patient history, the positivity for anti-HCV antibody was observed, but serum level of HCV RNA was not measured. Two months after PSL administration, the patient experienced an alanine aminotransferase (ALT) flare and the serum level of HCV RNA was observed to be 6.2 log IU/mL; then, the patient was admitted to our hospital for hepatitis treatment. Based on the clinical course and laboratory findings, the patient was diagnosed with HCV reactivation. Although the ALT levels decreased spontaneously during follow-up, they did not drop to normal range; subsequently, sofosbuvir and ledipasvir treatments were started. A sustained virological response 24weeks after the end of treatment was achieved. This case study suggests that HCV reactivation with hepatitis flare can occur even after a steroid monotherapy, and doctors should pay attention to HCV reactivation when administering PSL for patients with HCV infection.

Frequency of Type 2 Diabetes Mellitus among Patients with Hepatitis C Virus Infection

Background: Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) have established themselves as significant global health concerns, with a notable co-prevalence that suggests a potential pathophysiological connection. The increasing incidence of T2DM, particularly in developing countries, alongside the significant burden of HCV, poses challenges for healthcare systems and necessitates deeper understanding of their interrelation. Objective: This study aimed to ascertain the frequency of T2DM among patients with HCV infection and to investigate the potential association between HCV reactivity and the incidence of T2DM. Methods: A cross-sectional analysis was conducted at a molecular pathology laboratory in Lahore, Pakistan. Patients aged 18-60 years without cirrhosis or pre-existing T2DM were consecutively enrolled over a six-month period. Exclusion criteria included liver cancer, interferon therapy, end-stage renal disease, other viral hepatitides, and pregnancy. Data were collected via questionnaires after informed consent, with serum and hemoglobin A1c (HbA1c) levels measured. HCV reactivity was confirmed via real-time polymerase chain reaction (RT-PCR), and the frequency of T2DM was assessed by HbA1c criteria. Statistical analysis involved univariate analysis using SPSS version 25.0. Results: Among the 300 HCV-reactive patients, the frequency of T2DM was found to be 49.33% (148 patients). The mean age of participants was 42.71 ± 6.808 years, with 53.0% males and 47.0% females. Urban and rural participants were nearly equally represented. A significant association was noted between HCV reactivity and T2DM (p=0.001), while no significant relationship was found with gender, residence, marital status, or family history of T2DM. Conclusion: The study highlights a substantial frequency of T2DM in HCV-reactive patients and a significant association between HCV infection and the development of T2DM. Regular HbA1c monitoring in HCV-reactive patients is recommended for the early identification and management of T2DM.

Management of Hepatitis B Virus and Hepatitis C Virus Infections in Patients with Cancer Receiving Immune Checkpoint Inhibitors

ABSTRACT Background Patients with cancer with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded from many cancer clinical trials of immune checkpoint inhibitors (ICIs). Therefore, data are limited regarding the management of HBV and HCV infections in patients with cancer treated with ICIs. To address this gap, we reviewed the literature on management of HBV and HCV infections in patients with cancer receiving ICIs. Methods We searched MEDLINE and PubMed for all original research articles, case reports, and systematic reviews published in English between Jul 2013 and Jul 2023 on patients with cancer with HBV or HCV infection receiving ICIs. Results We found 28 studies (three prospective clinical trials, seven retrospective cohort studies, nine retrospective case series, and nine case reports) that evaluated the safety of ICI therapy in patients with HBV infection and cancer. The overall rate of HBV reactivation was 1.4% (38/2799), and no HBV-related deaths were reported. The frequency of HBV reactivation in patients with chronic and past HBV infections was 2% (35/1667) and 0.3% (3/1132), respectively. The risk of HBV reactivation was significantly higher among patients with chronic HBV infection not receiving antiviral prophylaxis than among those receiving antivirals (17% vs 1%, p < 0.05). Based on high-quality evidence, for patients with chronic HBV infection, antiviral prophylaxis is recommended before ICI therapy initiation. For patients with past HBV infection, monitoring and on-demand antiviral treatment are sufficient. We found 11 studies (five clinical trials, five retrospective studies, and one prospective observational study) that evaluated the safety of ICI therapy in patients with HCV infection and cancer. The overall rate of HCV reactivation was 0.5% (2/387), and no HCV-related deaths were reported. HCV reactivation occurs primarily in patients receiving immunosuppressants for ICI-related toxic effects. ICIs are safe for HCV-infected patients with solid tumors. Conclusions Chronic HBV or HCV infection should not be considered a contraindication for ICI therapy. Specific risk assessment, monitoring, and management strategies are necessary to reduce the risk of ICI-related liver injury in patients with cancer and chronic HBV or HCV infection.

Management of autoimmune and viral hepatitis in immunotherapy: a narrative review.

Cancer immunotherapy has firmly established itself as a pillar of cancer care due to its advantages over traditional anti-tumor therapy but also carries limitations due to potential for severe adverse reactions. This review highlights the current understanding and management of patients with autoimmune and viral hepatitis immune in the setting of immune checkpoint inhibitor (ICI) therapy. A literature search was conducted on PubMed, Scopus, Google Scholar SEER*Stat databases (from inception to December 2022) using search terms: "immune checkpoint inhibitor", "autoimmune hepatitis", "viral hepatitis", "HBV pathogenesis", "HCV pathogenesis", "HBV reactivation", "HCV reactivation", "cancer immunotherapy", "immune related adverse events", "immune related hepatitis". Pre-existing autoimmune disease (AD), whether active or inactive, can predispose patients receiving ICI therapy to develop autoimmune disease flares or immune-related adverse events (irAEs). Thus, patients with AD have routinely been excluded from clinical trials and data on safety of ICI therapy are limited. Hepatic irAE can be seen in ICI therapy and is a distinct entity from autoimmune hepatitis (AIH). ICI therapy alters the immune environment in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Patients who had prior exposure to HBV are at risk for viral reactivation. However, the prevalence of viral hepatitis in patients receiving immunotherapy is underrecognized and can lead to increases in liver biochemical tests as well as deterioration of liver function ultimately limiting treatment. The high morbidity and mortality associated with immune-related hepatitis emphasizes the need for screening of underlying diseases, including autoimmune and viral hepatitis, prior to initiation of ICI. Presence of AIH or chronic viral hepatitis is the most important risk factor for hepatic adverse events in ICI therapy. Screening for AIH, HBV and HCV is paramount in patients who will undergo ICI therapy.

Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) As a Biomarker for Lymphoid Malignancy with HCV Infection.

The hepatitis C virus (HCV) is potentially associated with liver cancer, and advances in various drugs have led to progress in the treatment of hepatitis C and attempts to prevent its transition to liver cancer. Furthermore, reactivation of HCV has been observed in the treatment of lymphoma, during which the immortalization and proliferation of lymphocytes occur, which leads to the possibility of further stimulating cytokines and the like and possibly to the development of lymphoid malignancy. There are also cases in which the disappearance of lymphoid malignancy has been observed by treating HCV and suppressing HCV-Ribonucleic acid (RNA), as well as cases of recurrence with an increase in HCV-RNA. While HCV-associated lymphoma has a poor prognosis, improving the prognosis with Direct Acting Antivirals (DAA) has recently been reported. The reduction and eradication of HCV-RNA by means of DAA is thus important for the treatment of lymphoid malignancy associated with HCV infection, and HCV-RNA can presumably play a role as a biomarker. This review provides an overview of what is currently known about HCV-associated lymphoma, its epidemiology, the mechanisms underlying the progression to lymphoma, its treatment, the potential and limits of HCV-RNA as a therapeutic biomarker, and biomarkers that are expected now that DAA therapy has been developed.

S3234 A Cancer Encasing the Porta Hepatis: An Aggressive Intra-Abdominal B Cell Lymphoma Presenting as a Post-Obstructive Jaundice With Reactivation of Hepatitis C Virus

Introduction: Hepatitis C virus (HCV) is a lymphotropic virus that promotes HCV-mediated B-cell proliferation and transformation to Non-Hodgkin Lymphoma (NHL). Here we present a case of reactivation of HCV presenting as an aggressive intra-abdominal B cell lymphoma. Case Description/Methods: A 68-years-old-male with history of eradicated HCV with recombinant interferon-alfa and resolved HBV infection presented with painless jaundice and pruritus. CT abdomen revealed a 9.6 x 11.5 x 9.5 cm heterogeneous mass causing CBD and intrahepatic biliary duct dilation. Labs revealed reactivation of HCV infection with worsening of liver function tests with total bilirubin of >40mg/dl. FNA biopsy confirmed mature B-cell lymphoma. Given persistent worsening jaundice despite biliary stent, trial of high dose steroid was initiated to improve lymphoma burden in order to get a window to initiate chemotherapy. After tumor board discussion, he received radiation therapy for tumor shrinkage for this aggressive lymphoma. Prior to initiation of planned R-CHOP chemotherapy, he developed severe sepsis with hepatic abscess. Patient and family opted for hospice care and comfort care was initiated. Discussion: Chronic HCV is a fast-growing epidemic in the U.S.A which carries an enormous threat to general population and healthcare. HCV becomes chronic in >70% of infected patients with risk for cirrhosis, hepatocellular carcinoma and lymphoma. HCV can cause NHL via lymphocyte proliferation from viral antigenic stimulation, HCV replication inside B-cell and mutation via B-cell damage. Among patient who achieve sustained viral response (SVR), reactivation occurs in 1%, 11% and 15% among low-risk monoinfected HCV, high-risk monoinfected HCV and HIV/HCV coinfected group respectively. Treatment of HCV with resolution of NHL has been reported and there is some literature with sequential chemotherapy followed by antiviral therapy (AVT) showing promising results in HCV-NHL cases. Concurrent use of AVT and chemotherapy is primarily discouraged due to hematological toxicity. More evidence and studies need to be explored for such aggressive HCV-NHL management. Patient with SVR should have at least an annual testing and periodic follow-up to access for HCV reactivation or reinfection. Hepatitis C education regarding risk factors reduction and transmission prevention should be encouraged at every healthcare level and in general community and only then we can achieve WHO aim of eradication by 2030.

Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab

Introduction: In the Phase 3 IMbrave150 trial (NCT03434379), atezolizumab + bevacizumab demonstrated a clinically meaningful survival benefit over sorafenib in patients with unresectable hepatocellular carcinoma (HCC), including those with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. We used IMbrave150 data to investigate the safety and risk of viral reactivation or flare in infected patients treated with atezolizumab + bevacizumab or sorafenib. Methods: Patients with unresectable HCC not previously treated with systemic therapy were randomized 2:1 to atezolizumab + bevacizumab or sorafenib. In this exploratory analysis, safety was continually evaluated, including for hepatic adverse events. Patients were monitored for HBV and HCV reactivation and flare at screening, the beginning of Cycles 5 and 9, and at treatment discontinuation. Results: Of 501 enrolled patients, 485 were included in the safety population; 329 (68%) received atezolizumab + bevacizumab, and 156 (32%) received sorafenib. Overall, 150 (31%) and 58 (12%) patients had HBV and HCV infections, respectively. The safety profiles of atezolizumab + bevacizumab and sorafenib were consistent across patients, regardless of viral infection. Overall, hepatic serious adverse events occurred in 11% of patients receiving atezolizumab + bevacizumab and 8% receiving sorafenib. HBV or HCV reactivation occurred in 2% or 16% of atezolizumab + bevacizumab-treated patients, respectively, versus 7% or 14% with sorafenib. There were no instances of hepatitis flare with atezolizumab + bevacizumab. Conclusions: Atezolizumab + bevacizumab had a similar hepatic safety profile in patients with and without HBV or HCV infection. Viral reactivation rates were similar between arms. Overall, these data support the use of atezolizumab + bevacizumab in patients with HCC and HBV or HCV infection without any special precaution.

Hepatitis C Virus Reactivation in Anti-HCV Antibody-Positive Patients with Chronic Hepatitis B Following Anti-HBV Therapies.

Background and Aims: Whether hepatitis C virus (HCV) reactivation occurs and how the viral load evolves in anti-HCV antibody-positive chronic hepatitis B (CHB) patients who underwent nucleos(t)ide analogue (Nuc) therapies remain unsolved. Methods: A cohort of 66 such patients was studied. Results: At the start of Nuc treatment (baseline), all patients had detectable hepatitis B virus (HBV) DNA levels (6.05 ± 1.88 log IU/mL), while HCV RNA levels (3.79 ± 1.43 log IU/mL) were detected (i.e., chronic hepatitis C (CHC)) in only 13 patients (19.7%). Following Nuc therapies, HBV DNA levels reached the nadirs at end of therapy (EOT) (6.05 ± 1.88 vs. 0.25 ± 0.99 log IU/mL, p < 0.0001) and relapsed at 6 months after EOT (6mEOT) at a level of 3.45 ± 2.64 log IU/mL compared with EOT (p < 0.0001). Among the 13 CHC patients, a non-significant decrease in HCV RNA was noted at EOT (3.52 ± 1.71 vs. 2.77 ± 2.63 log IU/mL, p = 0.166) but tended to decrease further at 6mEOT (2.77 ± 2.63 vs. 1.89 ± 2.06 log IU/mL, p = 0.063). Two of the thirteen CHC patients showed an increase in HCV-RNA ≥ 1 log10 IU/mL at EOT, and one of the fifty-three patients with undetectable HCV RNA at baseline (i.e., resolved past HCV infection) showed detectable HCV RNA at year 1 (3200 IU/mL) and year 2 (1240 IU/mL) following entecavir therapy. Conclusions: HCV reactivation did occur during HBV suppression, and the rate was 4.5% (3/66), 15.4% (2/13), and 1.9% (1/53), for all patients, CHC patients, and patients with resolved past HCV infection, respectively. The reverse HBV and HCV viral evolutions at 6mEOT indicate that HBV relapse may suppress HCV replication again.

Reactivation rates of hepatitis B or C or HIV in patients with psoriasis using biological therapies: a systematic review and meta-analysis.

Some biological therapies for psoriasis can cause the reactivation of viral infections. Although recent studies suggest no increased rate of reactivation with biological therapies, some life-threatening cases have been reported. Therefore, this meta-analysis examined the rate of virus reactivation in patients with psoriasis with biological therapies and concurrent hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. PubMed, Embase, and the Cochrane Library were searched for available papers from inception to December 2021. The outcome was the number of patients with virus reactivation after using biological therapies. The random-effect model was used in all analyses. Fourteen reports (1033 patients) were included. The pooled overall rate of virus reactivation was 0.04 (95%CI 0.01-0.09; I2 = 67.7%, P < 0.001). The pooled rates of HBV, HCV, and HIV reactivation were 0.04 (95%CI 0.00-0.10; I2 = 79.9%, P < 0.001), 0.07 (95%CI 0.02-0.14; I2 = 23.7%, P = 0.24), and 0.12 (95%CI 0.00-0.40), respectively. The pooled rates of HBV and HCV reactivation were 0.10 (95%CI 0.03-0.19) and 0.08 (95%CI 0.03-0.15) in Asia, but 0.00 (95%CI 0.00-0.01) and 0.04 (95%CI 0.00-0.21) in Europe. The publication type also influenced the results. The use of biological therapy in patients with psoriasis and HBV, HCV, or HIV infection might be associated with the rate of viral reactivation, but this meta-analysis had limitations, and the evidence might be weak. Nevertheless, it might suggest that at least a consultation with an infection specialist might be warranted in patients with psoriasis in whom biological therapies are considered.

Safety of direct acting antiviral treatment for hepatitis C in oncologic setting: A clinical experience and a literature review.

With a globally estimated 58 million people affected by, chronic hepatitis C virus (HCV) infection still represents a hard challenge for scientific community. A chronic course can occur among patients with a weak innate ad adaptive response with cirrhosis and malignancies as main consequences. Oncologic patients undergoing chemotherapy represent a special immunocompromised population predisposed to HCV reactivation (HCVr) with undesirable changes in cancer treatment and outcome. Aim of the study highlight the possibility of HCVr in oncologic population eligible to chemotherapy and its threatening consequences on cancer treatment; underline the importance of HCV screening before oncologic therapy and the utility of direct aging antivirals (DAAs). A comprehensive overview of scientific literature has been made. Terms searched in PubMed were: “HCV reactivation in oncologic setting” “HCV screening”, “second generation DAAs”. Pharmacokinetic and Pharmacodynamics characteristics of DAAs are reported, along with drug - drug interactions among chemotherapeutic drug classes regimens and DAAs. Clinical trials conducted among oncologic adults with HCV infection eligible to both chemotherapy and DAAs were analyzed. Viral eradication with DAAs in oncologic patients affected by HCV infection is safe and helps liver recovery, allowing the initiation of cancer treatment no compromising its course and success.

Screening and prevention of hepatitis C virus reactivation during chemotherapy.

Hepatitis C virus (HCV) reactivation occurs in 23% of HCV-infected cancer patients receiving chemotherapy. Forty-three percent of the patients with reactivation of HCV during chemotherapy develop a hepatitis flare. Most of the cancer patients with HCV reactivation have an unremarkable clinical course following an HCV-related hepatitis flare during chemotherapy. However, 26%–57% of the cancer patients developing an acute flare of chronic hepatitis C during chemotherapy require unanticipated discontinuation or dose reduction of chemotherapy, which results in deleterious changes in the cancer treatment plan. Although an optimal strategy for HCV screening in cancer patients receiving chemotherapy has not been established, universal pre-chemotherapy HCV testing for patients with hematological malignancies is recommended by current guidelines. All the currently approved direct-acting antivirals (DAAs) can be used in cancer patients, but the use of DAAs during chemotherapy should avoid drug–drug interactions between chemotherapy and antiviral agents. If there are no contraindications or anticipated drug–drug interactions, DAAs treatment can be administered before, during, or after chemotherapy. In conclusion, HCV reactivation occurs in approximately one-fourth of HCV-infected cancer patients receiving chemotherapy. An HCV-related hepatitis flare during chemotherapy may lead to the discontinuation of potentially life-saving chemotherapy. Currently, universal HCV screening is recommended in hematological malignancy patients before chemotherapy, but there is no evidence-based guideline for other cancer patients. DAAs treatment can cure HCV infection and prevent HCV reactivation during chemotherapy.

Reactivation of hepatitis C virus with severe hepatitis flare during steroid administration for interstitial pneumonia.

Hepatitis C virus reactivation (HCVr) was defined previously as an increase in HCV RNA level of ≥ 1 log10 IU/mL from baseline HCV RNA level after chemotherapies or immunosuppressive therapies, but HCVr during a steroid monotherapy has rarely been reported. Here we report a 75-year-old Japanese female with chronic hepatitis C (genotype 2a) who developed HCVr after the administration of prednisolone for interstitial pneumonia. She experienced alanine aminotransferase (ALT) flare with icterus, but after the tapering of prednisolone and a liver supporting therapy, levels of HCV RNA and ALT were gradually decreased. Then, she received an anti-viral therapy with sofosbuvir/ledipasvir. Although HCV relapsed 4 weeks after the therapy, a second therapy with glecaprevir/pibrentasvir was successful. This case suggests that HCVr with hepatitis flare can occur even after a steroid monotherapy, and we should pay attention to HCVr when we administer prednisolone for patients with HCV chronic infection.

The clinical impact of hepatitis C virus infection in Egyptian multiple myeloma patients

BackgroundMultiple myeloma (MM) is a human B cell neoplasia characterized by the clonal proliferation of malignant plasma cells in the bone marrow. Worldwide, hepatitis C virus (HCV) infection is a public health problem. For MM patients, the clinical impact of preexisting HCV infection is still unclear. We aim to assess the clinical characteristics and the prevalence of the HCV infection in Egyptian MM patients. This observational study included 81 MM patients. HCV antibody assay was performed, and positive cases were confirmed using a reverse transcription-quantitative PCR (RT-PCR) method.ResultsFifteen (18.5%) patients were anti-HCV antibody positive. Only 6/15 (7.4%) patients were HCV RNA positive by RT-PCR. Liver affection in the form of hyperbilirubinemia with grade 4 adverse events was significantly higher in the anti-HCV positive/HCV RNA positive group versus anti HCV negative group (16.7% vs. 1.5%, p value = 0.005). The median HCV-RNA before the initiation of chemotherapy was 2.5 log IU/ml with mean ± SD = 4.25 ± 1.6 with no HCV reactivation. In the univariate and multivariate analysis, HCV infection was not an independent factor related to DFS. Low hemoglobin level < 10 g/dL (HR 0.59, 95% CI, 0.36–0.97, p value = 0.037) and abnormal serum total bilirubin level (HR 1.9, 95% CI 1.03–3.5, p value = 0.039) influenced DFS in the univariate analysis. However, in the multivariate analysis, serum calcium level greater than 12 mg/dL (HR 7.04, 95% CI 1.12–44.45, p value = 0.038) and abnormal serum total bilirubin level (HR 10.9, 95% CI 2.92–41.02, p value = < 0.001) remained statistically significant worse prognostic factors.ConclusionIn conclusion, our study revealed the prevalence of HCV infection in Egyptian MM patients. Serologic tests at diagnosis are necessary to identify these patients, and confirmation of positive cases by molecular techniques should be mandatory, with regular follow-up for liver dysfunction. Finally, further larger studies explaining the molecular mechanisms linking HCV and the MM pathogenesis are warranted.

Risks of hepatitis C virus reactivation in a real-life population of oncology patients treated in an academic center.

Chemotherapy has been associated with a theoretical risk of hepatitis C virus (HCV) reactivation. However, little is known about the amplitude of viral replication and the incidence of subsequent hepatic exacerbation. We aimed to describe the occurrence of hepatitis flare and HCV reactivation at our center. We included, over a period of 5 years, adult patients with chronic HCV receiving intravenous chemotherapy. We excluded patients with undetectable HCV RNA, hepatocellular carcinoma, liver metastases or other etiologies of hepatic disease. The primary objective was to identify hepatic flares (elevation of alanine aminotransferase 3 times above the upper limit of normal). Secondary objectives were to assess viral reactivation (HCVr, HCV-RNA ≥1 log10 IU/mL when compared to baseline value), hepatic decompensation, mortality and the impact on the chemotherapy. Descriptive statistics were used. A total of 11 patients with chronic HCV were identified among the 5761 oncology patients. Five patients experienced a hepatic flare with median maximal ALT value of 139 U/L (IQR 133-237). Only 2 patients met criteria for HCVr with a median RNA increase of 1.16 log IU/mL (IQR 1.1-1.2). One patient presented with both HCVr and a hepatic flare. Only one patient required chemotherapy discontinuation following hepatic flare. No hepatic decompensation or related mortality were observed. We identified a very small number of HCV cases among our population. We observed HCVr and hepatic flares, but only one consequence on cancer treatment. Nonetheless, HCV screening is encouraged among patients undergoing chemotherapy to allow close follow-up of hepatic function.

Virologic Impact of Radiotherapy in Hepatitis C Virus-Infected Patients With Hepatocellular Carcinoma.

Hepatitis B virus (HBV) reactivation had been reported following radiotherapy in patients with hepatocellular carcinoma (HCC) along with limited data focused on patients infected with hepatitis C virus (HCV). Herein, we aimed to examine the virologic impact of radiotherapy in HCV-infected patients with HCC. In this case-control study, we identified all patients with unresectable HCC who received radiotherapy directed to the liver at MD Anderson from March 2009 through November 2018. Cases were defined as patients with HCV infection; controls were defined as patients without HCV infection. The case to control ratio was 1:3, and the subjects were matched by age, radiation dose, and fractionation or biologically effective dose of the radiation to the normal liver (α/β=2.5) and tumor (α/β=10). Thirty-two patients were studied, including 8 cases and 24 controls. No HCV reactivation was observed among the cases. Hepatitis flare was observed in 2 (25%) of 8 cases and 2 (8%) of 24 controls (p=0.25). The peak alanine aminotransferase level within 6 months after radiotherapy did not differ significantly between the cases and controls. Radiotherapy completion rates were similar in the two groups. This is the first report analyzing changes in HCV RNA levels after radiation for HCV-associated HCC. Our results suggest that the effects of radiotherapy on the liver function of HCV-infected patients with HCC do not differ from the HCV-uninfected patients. Therefore, it may not be necessary to monitor for HCV replication in HCV-infected patients receiving radiotherapy for HCC or to incorporate a biological variable based on HCV infection status in mathematical models of liver dose-volume constraints that predict radiation-induced liver disease.

High rate of hepatitis C virus and human immunodeficiency virus false-positive results in serologic screening in sub-Saharan Africa: adverse impact on the blood supply.

False positivity in blood screening may cause unnecessary deferral of healthy donors and exacerbate blood shortages. An international multicenter study was conducted to estimate the frequency of HCV and HIV false seropositivity in seven African countries (Burundi, Cameroon, Democratic Republic of Congo, Madagascar, Mali, Mauritania, and Niger). Blood donations were tested for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) with rapid detection tests (RDTs), third-generation enzyme immunoassays (EIAs), or fourth-generation EIAs. HCV (456/16,613 [2.74%]) and HIV (249/16,675 [1.49%]) reactive samples were then confirmed with antigen/antibody assays, immunoblots, and nucleic acid testing. Partial viral sequences were analyzed when possible. The HCV reactivity rate with RDTs was significantly lower than with EIAs (0.55% vs. 3.52%; p < 0.0001). The HIV reactivity rate with RDTs was lower than with third-generation EIAs (1.02% vs. 2.38%; p < 0.0001) but similar to a fourth-generation assay (1.09%). Only 16.0% (57/357) and 21.5% (38/177) of HCV and HIV initial reactive samples, respectively, were repeatedly reactive. HCV and HIV infections were confirmed in 13.2% and 13.7%, respectively, of repeated reactive donations. The predominant HCV genotype 2 and 4 strains in West and Central Africa showed high genetic variability. HIV-1 subtype CRF02_AG was most prevalent. High rates (>80%) of unconfirmed anti-HCV and anti-HIV reactivity observed in several sub-Saharan countries highlights the need for better testing and confirmatory strategies for donors screening in Africa. Without confirmatory testing, HCV and HIV prevalence in African blood donors has probably been overestimated.

PB1832 MATRIX CHEMOTHERAPY FOR PRIMARY CNS LYMHPOMA COMPLICATED WITH HCV INFECTION AND SUCCESSFUL ERADICATION OF BOTH DISEASES

Background:There is a well‐known connection between Hepatitis C virus (HCV) infection and B‐cell lymphomas (BCL). HCV infected patients have an increased risk of developing BCL. Hypothetically, lymphomagenesis can be induced by chronic antigen stimulation (analogous to Helicobacter pylori associated gastric marginal zone lymphoma) and/or a direct pro‐oncogenic effect of intracellular HCV proteins. Several studies have demonstrated that antiviral therapy may induce remission and improve prognosis of HCV‐associated lymphomas. On the other hand, HCV infection can cause sever complication during the immunochemotherapy and stem cell transplantation. These patients are at risk for HCV reactivation, accelerated liver disease progression, drug‐induced liver toxicity. Thus, HCV‐infected patients often suffer treatment delays, reduced dose intensity, and many times are excluded from bone marrow transplantation. Accordingly, there is some evidence of negative prognostic impact of HCV infection on survival.Aims:To draw attention to the HCV caused complications during lymphoma treatment.Methods:Here we present the case of a HCV‐infected patient with primary central nervous system (CNS) lymphoma complicated with HCV infection and review the relevant literature.Results:A 56‐year old woman with CNS lymphoma was treated with MATRIX (methotrexate, cytarabine, thiotepa, and rituximab). Initial serum serology showed reactivity to HBcAg and HCV. Polymerase chain reaction (PCR) detected no hepatits B virus DNA, however the copy number for hepatitis C virus (HCV) RNA was 104 850 000 IU/ml. She received HBV prophylaxis with lamivudine and subsequently entecavir against reactivation of HBV. After the 2nd cycle of chemotherapy her liver function tests became severely abnormal (AST: 514 U/L ALT: 264 U/L, ALP: 145 U/L, GGT: 1328 U/L, total Bi: 74.6 umol/L, conjugated Bi: 63.5 umol/L). The patient was asymptomatic regarding the lymphoma and in complete remission according to MRI scans. Further systemic chemotherapy had to be halted. The HBV DNA was still undetectable by PCR. Drug induced or mechanical cholestasis and the role of ongoing HCV infection was contemplated. The biliary tracts were not dilated on ultrasound scans. She had an ERCP with sphincterotomy and sofosbuvir plus ledipasvir plus ribavirin treatment for HCV was started. Meanwhile, intrathecal methotrexate therapy was administered 3‐weekly to bridge till next chemotherapy. The antiviral therapy was completed without any side effects and at 3 months, her HCV RNA PCR was negative with entirely normal liver function. The patient achieved sustained virological response. Two more cycles of MATRIX was delivered and an autologous stem cell transplantation with BCNU and thiothepa conditioning. Liver function remained normal ever since.Summary/Conclusion:This is a rare case where the role of HCV infection in liver damage during systemic chemotherapy is highly possible. We would like to draw attention to the liver vulnerability caused by chronic HCV infection. Nowadays HCV eradication is feasible with novel direct acting antiviral therapies, HCV‐infection should not contraindicate the adequate chemotherapy.

Hepatitis C virus infection and non-hepatocellular malignancies in the DAA era: A systematic review and meta-analysis.

Direct antiviral agents have greatly improved therapeutic options for chronic hepatitis C. Indeed, former "difficult-to-treat" patients can now be treated and can achieve sustained response. Hepatitis C virus (HCV) is associated with hepatocellular carcinoma and with B-cell non-Hodgkin lymphoma (B-NHL). Other malignancies have been reported to be associated with HCV infection albeit with various grades of evidence. Antineoplastic treatment is often reduced or suspended in HCV-positive cancer patients to avoid "HCV reactivation." In this setting, antiviral therapy combined with antineoplastic protocols may improve the outcome. For this reason, we conducted a systematic review and a meta-analysis to update the association between HCV infection and non-hepatocellular malignancies, and to shed light on the effects exerted by antiviral treatment on the natural history of oncological diseases. Relevant studies were identified by searching PUBMED, EMBASE and MEDLINE up to 1 August 2018. Pooled risk estimates were calculated with random-effects models according to PRISMA guidelines. A total of 58 studies were included in the analysis: 27 studies of the association between HCV and B-NHL(OR 3.36; 95% CI 2.40-4.72;P<0.00001);13 studies of the association between sustained virological response and progression-free survival (PFS) in B-NHL patients(OR 9.34; 95% CI 4.90-17.79; P<0.00001); 13 studies of the association between HCV and intrahepatic-cholangio-carcinoma (OR 3.95;95% CI 2.25-6.94; P<0.00001); and 5 studies of the association between HCV infection and pancreatic adeno-carcinoma(OR 1.60; 95% CI:1.25-2.04; P=0.0002). This study updates the strong association between B-NHL and HCV infection, confirms the association between HCV and non-hepatocellular tumours, and demonstrates a very strong association between viral eradication and a better outcome of HCV-positive B-NHL.

Hepatitis B virus and hepatitis C virus infection in immunocompromised patients.

To provide an update on recent studies of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in cancer patients with an emphasis on viral reactivation after cancer treatment, new antiviral therapies, and safety concerns. The diagnostic criteria for HBV reactivation in patients receiving cancer therapy were revised in 2018. HBV reactivation in these patients is preventable, even with the use of new cancer therapies. HCV reactivation also has been reported in cancer patients, particularly those with hematologic malignancies, and is not a virologic condition usually associated with poor outcome. Prophylaxis to prevent HCV reactivation is not recommended because therapy with direct-acting antivirals eradicates the infection in the majority of cancer patients. Cancer patients with HBV or HCV infection are at risk for viral reactivation, with many similarities between these two infections. Patients at high risk for reactivation will benefit significantly from taking oral antivirals, which will reduce the risk of HBV reactivation or prevent development of HCV reactivation following its virologic cure.

2226. Immune Checkpoint Inhibitors in Solid Tumor Patients with Chronic Hepatitis C Virus Infection: A Prospective Case-Series

BackgroundImmune checkpoint inhibitors are a novel class of targeted therapy that activates T cell-mediated tumor cell death. Controversies exist about the safety and efficacy of immunotherapy in patients with chronic viral infections affecting T cells, such as hepatitis C virus (HCV). Herein, we analyzed the effect of immune checkpoint inhibitors on HCV viremia and HCV-related hepatic outcome.MethodsHCV-infected patients with solid tumors seen at MD Anderson Cancer Center (November 2012–April 2018) were enrolled in a prospective observational study. Patients were monitored for the development of HCV reactivation (HCV-RNA ≥1 log10IU/mL over baseline), hepatitis flare (alanine transaminase increase to ≥3 times upper limit of normal) and HCV-associated hepatitis (HCV reactivation and hepatitis flare) while on cancer treatment.ResultsOut of 205 chronically infected patients with solid tumors, 12 (6%) received immunotherapy and were seen in the HCV clinic, but only four (2%) returned for regular monitoring (Table 1). They were followed for 9 months. None of the four patients received concomitant chemotherapy or steroids. Hepatitis flare occurred in three patients, but HCV reactivation or HCV-associated hepatitis was not detected in any study patient. Immune checkpoint inhibitors were discontinued in one patient (25%) due to hepatitis flare unrelated to HCV.ConclusionThe use of immune checkpoint inhibitors appears to be safe in solid tumor patients with HCV infection.Table 1.Demographics, Types of Cancer, Immunotherapy Received, and Changes in Serum HCV-RNAPatientAge, yearsSexHCV GenotypeCirrhosisType of CancerImmunotherapyBaseline HCV-RNA (log 10IU/mL)Highest HCV-RNA After Baseline (log 10IU/mL)Hepatitis Flare 1 67Male1aYesHepatocellular carcinomaNivolumab + ipilimumab5.455.08Yes a 2 52Male1aNoMelanomaNivolumab + ipilimumab6.976.95Yes b 3 57Male3NoMelanomaPembrolizumab5.726.39No 4 55Male1aNoMelanomaIpilimumab5.757.18 cYes c a After partial hepatectomy. b Negative infectious work-up including hepatitis A, B, E, cytomegalovirus, and herpes simplex virus. c Six months after completing immunotherapy, HCV-associated hepatitis occurred after starting high-dose steroids for brain metastasis.Disclosures H. Torres, Gilead Sciences, Merck & Co., Inc.: Grant Investigator, Grant recipient. Vertex Pharmaceuticals: Grant Investigator, Grant recipient.