Should we change the treatment plan in early hepatocellular carcinoma with chronic kidney disease?

doi:10.21203/rs.3.rs-2103634/v1

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Research Article

Should we change the treatment plan in early hepatocellular carcinoma with chronic kidney disease?

https://doi.org/10.21203/rs.3.rs-2103634/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 11 Apr, 2023

Read the published version in BMC Surgery →

You are reading this latest preprint version

Background

Chronic kidney disease (CKD) has been considered to be a poor prognostic factor for hepatocellular carcinoma (HCC). However, few studies have focused on early HCC and the impact of CKD on survival, which should be considered in curative treatment for early HCC.

Materials and Methods

Patients with BCLC stage 0/A were enrolled from 2009 to 2019. A total of 383 patients were divided into CKD stages 1, 2 and CKD stages 3, 4, and 5, based on estimated glomerular filtration rate. Overall survival (OS) and disease-free survival (DFS) of different treatments were determined using the Kaplan–Meier method.

Results

The CKD1,2 group had a significantly better OS than the CKD3,4,5 group (72.6 months vs 56.7 months; p = 0.003). DFS was similar between the groups (62.2 months vs 63.8 months, p = 0.717). In the CKD1,2 group, the surgically treated (OP) group had significantly superior OS (65.0 months vs 80.0 months, p = 0.014) and DFS (50.9 months vs 70.2 months, p = 0.020) than the radiofrequency ablation-treated group. In the CKD3,4,5 group, the OP group showed a survival advantage in OS (70.6 months vs 49.2 months, p = 0.004), while DFS was similar between treatment groups (56.0 months vs 62.2 months, p = 0.097).

Conclusion

CKD should not be considered to be a poor prognostic factor in early HCC patients. However, liver resection provides a survival advantage in CKD patients with early HCC.

Hepatocellular carcinoma

chronic kidney disease

hepatectomy

radiofrequency ablation

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver in the modern era and is the second leading cause of cancer death in East Asia.[1, 2] Multiple risk factors have been associated with HCC, including alcohol addiction, non-alcoholic liver disease, cirrhosis, and particularly viral hepatitis, such as hepatitis B (HBV), C (HCV), and D.[3]

The management of HCC is multidisciplinary. Ablation, curative liver resection, and liver transplant are considered to be the standard curative treatment for early HCCs (Barcelona Clinic Liver Cancer Classification [BCLC] 0 and A).[4, 5] Treatment options are based on feasibility, surgical risk, and availability of liver donors. However, radiofrequency ablation (RFA) and surgery are used in the major proportion BCLC stage 0/A cases due to the scanty of liver donors.

Multiple prognostic factors for the treatment of HCC have been identified, including tumor staging, etiologies, liver function, and comorbidities.[6] Among these factors, chronic kidney disease (CKD) has long been considered to be a poor prognostic factor for HCC patients.[7, 8] Some studies have reported a higher post-operative complication rate in HCC patients with CKD than in those with preserved renal function.[9] Several studies from medical institutions in Taiwan have shown that HCC patients with renal dysfunction might have an inferior outcome.[10, 11] However, other studies have found an acceptable outcome in non-CKD as well as in CKD patients.[9, 12] In clinical practice, patients sometimes undergo RFA due to impairment of renal function. Evidence for guiding treatment options in early HCC patients with CKD is lacking.

Therefore, we conducted this retrospective study on early-stage HCC patients treated under BCLC guidelines and analyzed the impact of CKD and different interventions (RFA and surgery). This study sought to determine whether CKD is a poor prognostic factor for early HCC patients and whether surgery in early HCC patients with CKD patients provides survival advantages or only increases risk.

We retrospectively reviewed 1,180 patients diagnosed with HCC between January 2009 and December 2019. Data were recorded until December 2021. Among these, 445 patients were BCLC stage 0/A. After excluding cases under active surveillance and those with incomplete data, the remaining 383 patients, whom all underwent either surgery or RFA, were enrolled (Fig. 1).

The application of RFA or operation was based on BCLC stage and performance status after tumor board consensus and shared decision-making with the patient. If the patient met the criteria of RFA, they would undergo RFA by a hepatologist. Patients who were treated surgically underwent liver resection for curative treatment of HCC via either laparoscopic or an open approach.

These patients were followed-up by regular blood tests, tumor markers, and image studies every 3 months. Tumor recurrence was diagnosed when computed tomography or magnetic resonance imaging showed classic features of HCC, as reported by a radiologist.

Chronic kidney disease classification

CKD classification was based on the estimated glomerular filtration rate (eGFR, in ml/min/1.73²) based on the definition and classification recommended by Kidney Disease Quality Outcome Initiative (K/DOQI). eGFR was calculated by using the Simplified Modification of Diet in Renal Disease equation.[13] We divided the patients into two groups: the CKD1,2 group, with eGFR > 60, and the CKD3,4,5 group, with eGFR < 60, to investigate the effect of kidney dysfunction (Fig. 1).

Statistical analysis

Statistical analyses were performed using SPSS for Windows Ver. 25 (IBM SPSS Inc., Armon, NY, USA). Independent sample t-tests were used to compare the differences between the two groups. To overcome selection bias, a propensity score matching (PSM) was performed based on [list each variable] if group characteristics differed markedly. Survival curves, including overall survival (OS) and disease-free survival (DFS) were calculated according to the Kaplan–Meier method and statistical significance was accepted at the p < 0.05 level.

Patient characteristics and treatments

Based on the pre-treatment final renal function evaluation, 383 patients were divided into the CKD 1, 2 (n = 281) and CKD 3,4,5 (n = 102) groups. The pre-treatment characteristics of these two groups are shown in Table 1. The CKD 3, 4, 5 groups included older patients (64.00 vs 70.25 years, p < 0.001), while the CKD 1,2 groups had a greater proportion of patients with a history of alcohol consumption (30% vs 15%, p = 0.002). The CKD 1, 2 groups included more HBV carriers (49% vs 33%, p = 0.005), whereas the CKD 3, 4, 5 groups had more HCV carriers (30% vs 48%, p = 0.007). To avoid bias between these two groups, we performed PSM. The results are shown in the PSM column of Table 1. Ninety-eight patients could be matched, with no significant factor differences among the two groups.

Table 1

Baseline characteristic of BCLC 0/A hepatocellular carcinoma patients with chronic kidney disease at various stages, who received intervention (n = 383)
Variables	Original Groups			After PSM
Variables	CKD1,2 (n = 281)	CKD3,4,5 (n = 102)	p-value	CKD1,2 (n = 98)	CKD3,4,5 (n = 98)	p-value
Sex, female, n(%)	90 (32%)	44 (43%)	0.051	40 (41%)	41 (42%)	0.885
Age, year (mean ± SD)	64.00 (10.68)	70.25 (9.53)	< 0.001*	69.01 (10.30)	70.03 (9.54)	0.473
BMI, kg/m² (mean ± SD)	24.9 (4.44)	25.6 (3.72)	0.120	25.26 (5.34)	25.66 (3.73)	0.649
Tumor size (mm)	25.95 (13.95)	25.72 (11.27)	0.866	26.11 (15.1)	25.88 (11.3)	0.902
BCLC stage, A, n (%)	202 (72%)	79 (77%)	0.249	80 (82%)	75 (77%)	0.382
Alcohol consumption	87 (31%)	15 (15%)	0.002*	20 (20%)	15 (15%)	0.354
ECOG PS, n (%)
0	274 (97.5%)	94 (92%)	0.017*	93 (94.9%)	91 (92.8)	0.554
1	5 (1.8%)	8 (8%)	0.004*	4 (4.1%)	7 (7.2%)	0.354
≥ 2	2 (0.7%)	0	0.079	1 (1.0%)	0	0.319
AFP > 20 ng/ml, n (%)	55 (20%)	15 (15%)	0.139	18 (18%)	15 (15%)	0.569
Child–Pugh Class, n (%)
A	273 (97%)	97 (95%)	0.193	93 (95%)	93 (95%)	1
B	8 (3%)	5 (5%)	0.193	5 (5%)	5 (5%)	1
HBV, n (%)	138 (49%)	34 (33%)	0.005*	29 (30%)	34 (35%)	0.447
HCV, n (%)	93 (33%)	49 (48%)	0.007*	49 (50%)	47 (48%)	0.776
HBV&HCV co-infection, n (%)	13 (4.6%)	6 (5.9%)	0.637	7 (7%)	6 (6%)	0.775
BMI: Body mass index; ECOG PS: Eastern Cooperative Oncology Group performance status; AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PSM: Propensity score matching

With a view to evaluating the impact of RFA and surgery on OS and DFS, we further divided the CKD 1, 2 and CKD 3, 4, 5 groups into RFA and surgery groups. The preoperative characteristics of these two groups are shown in Table 2. In the CKD 1, 2 groups, BCLC stage was significantly advanced in the OP subgroup (66% vs 77%, p = 0.038). The CKD 1, 2 OP subgroups also had a higher proportion of patients with elevated alpha-fetoprotein level (13% vs 29%, p = 0.005) and HCV carriers (49% vs 33%, p = 0.007). However, the RFA subgroup had a more advance Child–Pugh class (Class B: 5% vs 0%, p = 0.004) and more HBV carriers (40% vs 58%, p = 0.003) than the OP subgroup.

Table 2

Baseline characteristics of CKD1,2 and CKD3,4,5 hepatocellular carcinoma patients
Variables	CKD1,2			CKD3,4,5
Variables	RFA (n = 134)	OP (n = 147)	p-value	RFA (n = 69)	OP (n = 33)	p-value
Sex, female, n (%)	50 (37%)	40 (27%)	0.070	34 (49%)	10 (30%)	0.072
Age, year (mean ± SD)	64.54 (10.18)	63.50 (11.14)	0.410	71.33 (8.74)	67.97 (10.80)	0.124
BMI, kg/m² (mean ± SD)	24.8 (4.83)	25.0 (4.08)	0.732	25.6 (3.67)	25.7 (3.90)	0.916
Tumor size (mm)	28.8 (8.8)	29.7 (16.55)	0.907	22.97 (7.78)	31.45 (14.90)	0.004*
BCLC stage, A, n (%)	88 (66%)	113 (77%)	0.038*	50 (72%)	29 (8%)	0.083
Alcohol consumption	44 (33%)	43 (29%)	0.441	9 (13%)	6 (18%)	0.521
ECOG PS, n (%)
0	131 (97.7%)	143 (97.3%)	0.796	67 (97.1%)	27 (81.8%)	0.007*
1	1 (0.8%)	4 (2.7%)	0.212	2 (2.9%)	6 (18.2%)	0.007*
≥2	2 (1.5%)	0	0.138	0	0	-
AFP > 20 ng/ml, n (%)	17 (13%)	38 (29%)	0.005*	11 (16%)	4 (12%)	0.601
Child–Pugh Class, n (%)
A	126 (94%)	147 (100%)	0.003*	65 (94%)	32 (97%)	0.549
B	8 (5%)	0	0.004*	4 (6%)	1 (3%)	0.549
HBV, n (%)	54 (40%)	85 (58%)	0.003*	23 (33%)	11 (33%)	1
HCV, n (%)	50 (37%)	43 (29%)	0.153	32 (46%)	17 (52%)	0.633
HBV&HCV co-infection, n (%)	5 (4%)	7 (5%)	0.910	3 (4%)	3 (9%)	0.406
BMI: Body mass index; ECOG PS: Eastern Cooperative Oncology Group performance status; AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PSM: Propensity score matching

The pre-treatment characteristics of the RFA and OP subgroups in the CKD3,4,5 group are shown in Table 2. In the CKD3,4,5 group, tumor size was much bigger in the OP subgroup (22.97 mm vs 31.45 mm, p = 0.004). The OP subgroup also had an inferior performance status (Eastern Cooperative Oncology Group Performance Status 0: 97.1% vs 81.8%, p = 0.007). Other tumor factors and liver functions showed no significant difference.

Advantages of preserved renal function are reduced in overall survival after PSM and have no effect on disease-free survival

The OS and DFS rates of patients with CKD1,2 and CKD3,4,5 are compared in Fig. 2. The CKD1,2 group had significantly better OS than the CKD3,4,5 group (72.6 months vs 56.7 months, p = 0.003). DFS was similar between these groups (62.2 months vs 63.8 months, p = 0.717). However, there was no significant difference in OS between the groups after PSM reduced the age differences (66.6 months vs 57.6 months p = 0.152). DFS consistently showed no significant differences after PSM, similar to before PSM (58.2 months vs 66.3 months, p = 0.721)

OP consistently results in superior OS in both CKD1,2 and CKD3,4,5 groups

The OS and DFS rates of the patients who underwent RFA and surgery in the CKD1,2 group are shown in Fig. 3. The OP subgroup had a significantly superior OS (65.0 months vs 80.0 months, p = 0.014) and DFS (50.9 months vs 70.2 months, p = 0.020) as compared to the RFA group. In the CKD3,4,5 group shown in Fig. 4, the OP group showed a consistent survival advantage in terms of OS (70.6 months vs 49.2 months, p = 0.004), but there was no significant difference in DFS (56.0 months vs 62.2 months, p = 0.097).

In this study, we showed that patients with early HCC and CKD in different stages who underwent curative treatments had similar survival outcomes after PSM. Patients with CKD 1, 2 had a superior OS outcome as compared to patients with CKD 3, 4, 5 before PSM, while there was no significant difference in the DFS.

Our initial data comparing OS and DFS between CKD1,2 and CKD3,4,5 among BCLC 0&A HCC patients was similar to those of previous studies that concluded that CKD was a poor prognostic factor in HCC patients. Liu et al. reported that CKD was not only a poor prognostic factor but was also a significant factor for post-operative complications for patients who underwent hepatectomy as treatment.[14] Furthermore, Lee et al. demonstrated that HCC patients with CKD stages 4 and 5 had inferior survival compared to those with CKD stages 1 and 2.[15] CKD and end-stage renal disease have long been considered to be risk factors for HCC. Several hypotheses have been proposed regarding this relationship, including a dysregulated immune system, defective DNA repair mechanism, and impaired antioxidant defense; however, further evidence is required to prove these links.[7, 16]

Previous studies were not filtered by the HCC stage. We assumed that CKD had more of an impact on survival in patients being treated for moderate and advanced HCCs. We found few reports that focused on CKD in patients with early-stage HCC. These patients should undergo curative treatments to potentially have a longer survival outcome. When we studied the baseline characteristic of these patients in our study, we noticed that the CKD3,4,5 group was significantly older than the CKD1,2 group (CKD1,2 to CKD3,4,5: 64.00 vs 70.25, p < 0.001). It is natural that eGFR declines with age. The process is believed to be related to multiple factors, including systemic disease and environmental factors.

Interestingly, after we minimized the age difference between the two CKD groups by PSM, the OS was no longer significantly different between the groups (p = 0.152). This result was similar to that of Yoshikawa et al., which showed no significant difference between groups separated by a cutoff eGFR value of 45 ml/min/1.73². However, their study only included patients undergoing hepatectomy.[12] Thus, a CKD bias in HCC patients might be due to age and result in differences in OS. Taiwan had a high prevalence of CKD stages 3–5 (9.06%), with age, male sex, and systemic diseases (such as diabetes mellitus, metabolic syndrome, and hypertension) being significant risk factors.[17, 18] This would had an impact on survival.

We further studied the impact of surgery and RFA on the different CKD groups and found that surgery provided a superior OS and DFS in patients with preserved renal function. These data suggested that, in the CKD1,2 group, liver resection is the standard treatment option for early-stage HCC if the surgical risk is tolerable.[5, 19] DFS also benefited from surgical resection, with clearer and safer margins, resulting in a superior outcome.

In the CKD3,4,5 group, the OS was consistently superior in the OP subgroup (p = 0.004), even though ECOG and tumor size were more unfavorable in the OP subgroup. However, the advantage in terms of DFS vanished in advanced CKD patients. It is well-established that patients with impaired renal function have an increased cancer risk. Their pathophysiology might contribute to the accumulation of uremic toxins, which promote the development of liver fibrosis and cirrhosis.[20, 21] High inflammation status caused by impaired renal function might also play a critical role in the high recurrence rate. Renal dysfunction has been proven to increase the cytokines level in our body, including interleukin[19]-1, IL-6, and tumor necrosis factor-α.[22] These cytokines are associated with HCC risk by accumulating errors and mutations in the cell cycle during necrosis and regeneration, giving hepatocytes more potential for carcinogenesis.[23] The DFS results could also be related to a higher ratio of HBV infection in the OP subgroup, rather than to uremic toxins, as mentioned by Hwang mentioned in his research.[24] The molecular pathways need to be identified clearly, and larger samples, without bias, need to be evaluated in future studies.

In our study, the results indicated that CKD should not be considered as a poor prognostic factor, which deprived early HCC patients from curative treatment. Our data suggested that liver resection for patients with early HCC and CKD at different stages could obtain a better survival. Thus, our data imply that we should no longer consider CKD as a poor prognostic factor in HCC patients, as the prior conclusion might have been due to the confounding effect of age on CKD.

Limitations

This was a small sample-size study involving fewer than 400 patients from a single center. Although the size limited the strength of this study, a specialized liver team and tumor board could minimize the associate bias. The comparison between the OP and RFA subgroups within the CKD1,2 group reveals worse liver function (Child–Pugh class) in the RFA group but a more advanced tumor stage (BCLC) in the surgical subgroup, which could be a bias in our study. We could only divide the CKD stages into two groups due to the sample size. Further studies should be performed to divide CKD patients into more groups with a higher sample size.

CKD should not be considered a poor prognostic factor in early HCC patients scheduled to undergo curative treatments. Liver resection provides superior survival for HCC patients with CKD, even in late disease stages.

Ethics approval and consent to participate

This study was conducted under the approval of the Institutional Ethics Review Board of Keelung Chang Gung Memorial Hospital (IRB number:191218044). All enrolled subjects had provided informed consent.
Consent for publication

Not applicable.
Availability of data and materials

The datasets used during the current study are available from the corresponding autho on reasonable request.

Competing interests

The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

Funding

This research received no specific grant from any funding agency in the public,

commercial, or not-for-profit sectors.

Authors' contributions

Conceptualization: W-P. C.; methodology: R.-S. S.; software: W-P. C.; validation: R-S. S.; formal analysis: W-P. C.; investigation: P-H. C.; resources: R.-S. S., Y.-C. C.; data curation: R.-S.S., P.-H. C., S.-W. C.; writing original draft preparation: W-P. C., R.-S.S.; writing review and editing, R-S, S. All authors have read and agreed to the published version of the manuscript
Acknowledgements

We are particularly grateful to the tumor registration team in Chang Gung Memorial Hospital ,Keelung for collecting the data and CMRPG2L0091.
Authors' information

Wu-Po Chao, MD ^a; Shion-Wei Chai, MD ^a; Po-Hsing Chiang, MD ^a ; Ta-Chun Chou, MD ^a; Yi-Chan Chen, MD ^a ; Ruey-Shyang Soong, MD ^b,c,d,e^＊

^a Division of General Surgery, Department of Surgery, Keelung Chang Gung Memorial Hospital, No. 222, Maijin Rd., Anle Dist., Keelung City 204201, Taiwan

b Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, No.111 Sec.3, Xinglong Rd., Wenshan Dist., Taipei City 116, Taiwan

^cCollege of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei City, 110, Taiwan

^dDivision of Transplantation Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

^eTMU Research Center for Organ Transplantation, Taipei Medical University

College of Medicine, Taipei, Medical University,

*Corresponding author:

Dr. Ruey-Shyang Soong

Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, No.111 Sec.3, Xinglong Rd., Wenshan Dist., Taipei City 116, Taiwan

E-mail: [email protected]; Telephone: +886-936170198

ORCID ID: https://orcid.org/0000-0001-7245-9505

Rawla P, Sunkara T, Muralidharan P, Raj JP: Update in global trends and aetiology of hepatocellular carcinoma. Contemp Oncol (Pozn) 2018, 22(3):141-150.
McGlynn KA, Petrick JL, El-Serag HB: Epidemiology of Hepatocellular Carcinoma. Hepatology 2021, 73 Suppl 1:4-13.
Ghouri YA, Mian I, Rowe JH: Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog 2017, 16:1.
Reig M, Forner A, Rimola J, Ferrer-Fabrega J, Burrel M, Garcia-Criado A, Kelley RK, Galle PR, Mazzaferro V, Salem R et al: BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022, 76(3):681-693.
Llovet JM, Bru C, Bruix J: Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999, 19(3):329-338.
Tandon P, Garcia-Tsao G: Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies. Liver Int 2009, 29(4):502-510.
Yeh H, Chiang CC, Yen TH: Hepatocellular carcinoma in patients with renal dysfunction: Pathophysiology, prognosis, and treatment challenges. World J Gastroenterol 2021, 27(26):4104-4142.
Orii T, Takayama T, Haga I, Fukumori T, Amada N: Efficacy of a liver resection for hepatocellular carcinoma in patients with chronic renal failure. Surg Today 2008, 38(4):329-334.
Toshima T, Shirabe K, Yoshiya S, Muto J, Ikegami T, Yoshizumi T, Maehara Y: Outcome of hepatectomy for hepatocellular carcinoma in patients with renal dysfunction. HPB (Oxford) 2012, 14(5):317-324.
Chen YC, Su YC, Li CY, Wu CP, Lee MS: A nationwide cohort study suggests chronic hepatitis B virus infection increases the risk of end-stage renal disease among patients in Taiwan. Kidney Int 2015, 87(5):1030-1038.
Chen YC, Lin HY, Li CY, Lee MS, Su YC: A nationwide cohort study suggests that hepatitis C virus infection is associated with increased risk of chronic kidney disease. Kidney Int 2014, 85(5):1200-1207.
Yoshikawa T, Nomi T, Hokuto D, Kamitani N, Matsuo Y, Sho M: Outcomes in Patients with Chronic Kidney Disease After Liver Resection for Hepatocellular Carcinoma. World J Surg 2021, 45(2):598-606.
Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G: Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005, 67(6):2089-2100.
Liu X-Y, Zhao Z-Q, Cheng Y-X, Tao W, Yuan C, Zhang B, Wang C-Y: Does Chronic Kidney Disease Really Affect the Complications and Prognosis After Liver Resection for Hepatocellular Carcinoma? A Meta-Analysis. Frontiers in Surgery 2022, 9.
Lee CH, Hsieh SY, Lin JL, Liu MS, Yen TH: Hepatocellular carcinoma in patients with chronic kidney disease. World J Gastroenterol 2013, 19(16):2466-2472.
Lin HF, Li YH, Wang CH, Chou CL, Kuo DJ, Fang TC: Increased risk of cancer in chronic dialysis patients: a population-based cohort study in Taiwan. Nephrol Dial Transplant 2012, 27(4):1585-1590.
Tonelli M, Riella M: Chronic kidney disease and the aging population. Int J Organ Transplant Med 2014, 5(1):1-6.
Tsai MH, Hsu CY, Lin MY, Yen MF, Chen HH, Chiu YH, Hwang SJ: Incidence, Prevalence, and Duration of Chronic Kidney Disease in Taiwan: Results from a Community-Based Screening Program of 106,094 Individuals. Nephron 2018, 140(3):175-184.
Tsilimigras DI, Bagante F, Sahara K, Moris D, Hyer JM, Wu L, Ratti F, Marques HP, Soubrane O, Paredes AZ et al: Prognosis After Resection of Barcelona Clinic Liver Cancer (BCLC) Stage 0, A, and B Hepatocellular Carcinoma: A Comprehensive Assessment of the Current BCLC Classification. Ann Surg Oncol 2019, 26(11):3693-3700.
Sun CY, Chang SC, Wu MS: Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS One 2012, 7(3):e34026.
Nitta T, Kim JS, Mohuczy D, Behrns KE: Murine cirrhosis induces hepatocyte epithelial mesenchymal transition and alterations in survival signaling pathways. Hepatology 2008, 48(3):909-919.
Ebert T, Neytchev O, Witasp A, Kublickiene K, Stenvinkel P, Shiels PG: Inflammation and Oxidative Stress in Chronic Kidney Disease and Dialysis Patients. Antioxid Redox Signal 2021, 35(17):1426-1448.
Rico Montanari N, Anugwom CM, Boonstra A, Debes JD: The Role of Cytokines in the Different Stages of Hepatocellular Carcinoma. Cancers (Basel) 2021, 13(19).
Hwang JC, Weng SF, Weng RH: High incidence of hepatocellular carcinoma in ESRD patients: caused by high hepatitis rate or 'uremia'? a population-based study. Jpn J Clin Oncol 2012, 42(9):780-786.

No competing interests reported.

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Editorial decision: Major revision
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You are reading this latest preprint version

Should we change the treatment plan in early hepatocellular carcinoma with chronic kidney disease?

Status:

Journal Publication

Version 1

Abstract

Background

Materials and Methods

Results

Conclusion

Figures

Introduction

Material And Methods

Chronic kidney disease classification

Statistical analysis

Results

Patient characteristics and treatments

OP consistently results in superior OS in both CKD1,2 and CKD3,4,5 groups

Discussion

Limitations

Conclusion

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1