Jianpi Huayu Decoction Enhances the Effect of Sorafenib and Alleviates Adverse Events in Hepatocellular Carcinoma by Remodeling the Gut Microbiota

2021 ◽  
Author(s):  
Xue Deng ◽  
Yingjie Xie ◽  
Yantong Lu ◽  
Xueyan Li ◽  
Xuan Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Gut Microbiota

scholarly journals Synergistic Sorafenib with Jianpi Huayu Decoction Resulted in Tumor Regression and Prevented Adverse Events in Hepatocellular Carcinoma by Remodeling the Gut Microbiota

2021 ◽  
Author(s):  
Xue Deng ◽  
Yingjie Xie ◽  
Yantong Lu ◽  
Xueyan Li ◽  
Xuan Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Gut Microbiota ◽  
Tumor Regression ◽  
Acquired Resistance ◽  
Xenograft Model ◽  
Body Weight Loss ◽  
Complementary Therapy ◽  
Clinical Dose ◽  
Stat3 Signaling

Abstract Background: There is an urgent need for effective treatments for hepatocellular carcinoma (HCC). Sorafenib is first-line treatment for HCC, which has a modest efficacy due to severe adverse effects(AE), acquired resistance and others. Combination therapy may be able to overcome this limitation. Jianpi Huayu Decoction (JHD) is a traditional Chinese medicine formulation, which has been shown to be effective as an alternative and complementary therapy of HCC. We investigated the synergistic effect of JHD with sorafenib by a xenograft model.Methods: Growth of mouse-derived HCC cells and adverse events(AE) of treatment were evaluated in a subcutaneous model with JHD and clinical-dose sorafenib combination treatment. Diarrhea, the most frequently reported AE, was evaluated by diarrhea score. The gut microbiota(GM) composition of the mice was analyzed by Illumina NovaSeq. Results: JHD administration in mice synergistically enhanced the anti-tumor response, thereby suppressing HCC, and prevented occurrence of the most common AEs(diarrhea and body weight loss) of sorafenib. Sorafenib induced increased proinflammatory GM(Helicobacter) which promoted the progression of HCC and against anti-tumor treatment. JHD reduced the abundance of anti-inflammatory microbiota Muribaculum, Fusicatenibacter, and Dorea. Following the modulation of GM, the proinflammatory signaling interleukin 6/signal transducer and activator of transcription-3 pathway was downregulated by JHD.Conclusions: Our finding suggested that differences in the microbial gut flora may modulate resistance to sorafenib through IL-6/STAT3 signaling. JHD with microbiota modulation properties could potentiate sorafenib and provided a promising approach for HCC treatment.

Analysis of monitoring adverse events and problems in the treatment with sorafenib for hepatocellular carcinoma

Kanzo ◽  
2013 ◽  
Vol 54 (4) ◽  
pp. 249-256
Author(s):  
Keiko Komori ◽  
Chie Mochizuki ◽  
Yoshie Masu ◽  
Noriko Hasegawa ◽  
Akio Ishihara ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events

scholarly journals Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

2021 ◽  
Vol 13 ◽  
pp. 175883592110311
Author(s):  
Chiun Hsu ◽  
Lorenza Rimassa ◽  
Hui-Chuan Sun ◽  
Arndt Vogel ◽  
Ahmed O. Kaseb
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Healthcare Providers ◽  
Safety Data ◽  
Standard Of Care ◽  
Antiangiogenic Agents ◽  
Efficacy And Safety ◽  
First Line

In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.

The interplay between gut microbiota and the immune system in liver transplant recipients and its role in infections

2021 ◽  
Author(s):  
Giuseppe Ancona ◽  
Laura Alagna ◽  
Andrea Lombardi ◽  
Emanuele Palomba ◽  
Valeria Castelli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Liver Transplant ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Transplant Recipients ◽  
Liver Transplant Recipients

Liver transplantation (LT) is a life-saving strategy for patients with end-stage liver disease, hepatocellular carcinoma and acute liver failure. LT success can be hampered by several short-term and long-term complications. Among them, bacterial infections, especially due to multidrug-resistant germs, are particularly frequent with a prevalence between 19 and 33% in the first 100 days after transplantation. In the last decades, a number of studies have highlighted how gut microbiota (GM) is involved in several essential functions to ensure the intestinal homeostasis, becoming one of the most important virtual metabolic organs. GM works through different axes with other organs, and the gut-liver axis is among the most relevant and investigated ones. Any alteration or disruption of GM is defined as dysbiosis. Peculiar phenotypes of GM dysbiosis have been associated to several liver conditions and complications, such as chronic hepatitis, fatty liver disease, cirrhosis and hepatocellular carcinoma. Moreover, there is growing evidence of the crucial role of GM in shaping the immune response, both locally and systemically, against pathogens. This paves the way to the manipulation of GM as a therapeutic instrument to modulate the infectious risk and outcome. In this minireview we provide an overview of the current understanding on the interplay between gut microbiota and the immune system in liver transplant recipients and the role of the former in infections.

scholarly journals Early Exposure to Gut Microbiome Reduces Hepatocellular Carcinoma Risks in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yang-Ming Lee ◽  
Wei-Chun Chang ◽  
Fu-Ju Lei ◽  
Chew-Teng Kor ◽  
Hsueh-Chou Lai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Liver Tumors ◽  
Male Mice ◽  
Germ Free ◽  
Housing Environment ◽  
Male Sex ◽  
Group 10 ◽  
Group 5

Aims. Liver cancer is a multietiological disease that has multiple factors contributing to the hepatocarcinogenic process, e.g., hepatitis viruses, carcinogens, male sex, or metabolic factors. Notably, emerging evidence reported that gut microbiota is crucial to the pathogenesis of hepatocellular carcinoma (HCC) via activation of innate immunity. However, the effect of time to gut microbiota exposure after birth is unknown. Using a germ-free animal housing environment, instead of antibiotics, we examined the effects of various time-to-exposure (TTE) to gut microbiota durations on HCC risk. Methods. HBV or carcinogen-mediated spontaneous HCC models were implemented in this study. The HCC incidence rates in mice either kept germ-free (GF; that is, with no exposure to gut microbiota) or exposed to gut microbiota after being moved to a specific pathogen-free (SPF) housing environment and with various time-to-exposure (TTE) durations, namely, 5 weeks after birth, 10 weeks after birth, or since conception (that is, 5-week TTE group, 10-week TTE group, and SPF group, respectively), were recorded. The mice were sacrificed at 30 or 40 weeks after birth, and macro-/microscopic observations and pathological diagnosis were performed. Results. The incidence of liver tumors among the male mice was higher than that among the female mice in the carcinogen-induced HCC mice sacrificed at 40 weeks after birth (with P=0.011, 0.035, 0.0003, and 0.012, respectively, in the GF group, 5-week TTE group, 10-week TTE group, and SPF group). Similarly, in the HBV-HCC model, the incidence of liver tumors among the male mice was significantly higher than that among the female mice (with P=0.013, 0.020, 0.012, and 0.002, respectively, in the GF group, 5-week TTE group, 10-week TTE group, and SPF group). These results suggest that gut microbiota exposure is irrelevant to the male sex preference of HCC. Surprisingly, when comparing carcinogen-induced HCC male mice in the 10-week TTE group (90%; n=10), 5-week TTE group (56%; n=9), and SPF group (30%; n=10) (P=0.020), we found that the incidence of liver tumors was higher in the mice with later exposure to gut microbiome. Similarly, when comparing HBV-HCC male mice in the 10-week TTE group (100%; n=11), 5-week TTE group (70%; n=10), and SPF group (33%; n=9) (P=0.080), we also found that the incidence of liver tumors was higher in the mice with later exposure to gut microbiome. Conclusions. Early (prepubertal) exposure to gut microbiome reduces the risk of HCC development, indicating a potentially important factor for cancer surveillance. Exploring the mechanisms by which such exposure affects HCC risk might lead to novel cancer vaccines.

scholarly journals How Much Time Should Be Waited and What Are the Main Findings to Evaluate the Hepatocellular Carcinoma Response to Regorafenib? A Real-Life Experience

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Gustavo Hideki Kawanami ◽  
Leopoldo Katsuda ◽  
Thiara Barcelos Rocha ◽  
Fabio da Silva Yamashiro ◽  
Leonardo Pelafsky ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Kinase Inhibitors ◽  
Life Experience ◽  
Real Life ◽  
Treatment Modalities ◽  
Screening Methods ◽  
Second Line ◽  
Imaging Findings ◽  
Sorafenib Treatment

Background. Hepatocellular carcinoma is a relevant cause of mortality worldwide, mainly among patients who have a prior liver disease. In spite of clear recommendations regarding surveillance and screening methods, most patients are still diagnosed only when they are no longer candidates to curative treatment modalities, while others do not achieve the goals of such treatments, thus increasing the need of anticancer drugs. Moreover, when cirrhotic patients begin to receive these drugs, many types of adverse events are seen as a reason to withdrawal, even when there are findings suggesting a good response to the treatment. Case Summary. This case report is about a cirrhotic patient who received many types of treatment, from surgery and chemoembolization during early stages to first- and second-line systemic therapy when the disease turned to be advanced. Since he had no signs of liver dysfunction and suffered tumor progression during sorafenib treatment, regorafenib was initiated. The main findings that make this case important are the adverse events after taking this second-line agent, which would certainly be considered unacceptable and would lead to the drug withdrawal. The reasons why regorafenib was maintained are explained based on clinical and imaging findings, showing how this decision led to an excellent response. Conclusions. The knowledge of the main adverse events described in the pilot clinical trials can avoid unnecessary withdrawal of regorafenib. In addition, some clinical and imaging findings can be deemed as predictors of good response to tyrosine kinase inhibitors.

scholarly journals Gut microbiota, fatty liver disease, and hepatocellular carcinoma

2018 ◽  
Vol 2 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Huikuan Chu ◽  
Brandon Williams ◽  
Bernd Schnabl
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease

Stereotactic Body Radiation Therapy as a Salvage Treatment for Single Viable Hepatocellular Carcinoma at the Site of Incomplete Transarterial Chemoembolization

2021 ◽  
Author(s):  
Sumin Lee ◽  
Jinhong Jung ◽  
Jin-hong Park ◽  
So Yeon Kim ◽  
Jonggi Choi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiation Therapy ◽  
Adverse Events ◽  
Transarterial Chemoembolization ◽  
Stereotactic Body Radiation Therapy ◽  
Medical Center ◽  
Salvage Treatment ◽  
Iodized Oil ◽  
Stereotactic Body Radiation

Abstract Background: To evaluate the clinical outcomes of patients who received stereotactic body radiation therapy (SBRT) for single viable hepatocellular carcinoma (HCC) at the site of incomplete transarterial chemoembolization (TACE).Methods: Incomplete TACE was defined as (1) evidence of viable HCC at the site of TACE on follow-up images following one or more consecutive TACEs, (2) no definite tumor staining on celiac angiogram, or (3) no definite iodized oil uptake on post-embolization angiogram or computed tomography. A total of 302 patients were treated between 2012 and 2017 at Asan Medical Center (Seoul, South Korea). Doses of 10–15 Gy per fraction were given over 3–4 consecutive days. Treatment-related adverse events were evaluated according to the common terminology criteria for adverse events, version 4.03.Results: The median follow-up duration was 32.9 months (interquartile range [IQR], 23.6–41.7) and the median tumor size was 2.0 cm (range, 0.7–6.9). The local control (LC) and overall survival rates at 3 years were 91.2% and 72.7%, respectively. 95.4% of the tumors reached complete response (CR) during the entire follow-up period (anyCR). The median interval from SBRT to anyCR was 3.4 months (IQR, 1.9–4.7), and 39.9% and 83.3% of the lesions reached CR at 3- and 6-months after SBRT, respectively. Radiation-induced liver disease was observed in 8 (2.6%) patients. No patients experienced gastroduodenal bleeding within the radiation field.Conclusion: SBRT should be considered a feasible salvage treatment option for HCC after incomplete TACE.

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