Hepatocellular carcinoma in a transplanted donor liver and colon cancer developing in a patient with a complex background: A case report.

The development of tumors in livers transplanted from hepatitis B virus (HBV)-negative donors to patients with hepatitis B and cirrhosis is rare. The present study describes the case of a woman in her 60s who developed hepatocellular carcinoma (HCC) in her grafted liver, 19 years after transplantation, as well as a metachronous colorectal tumor. The pathological findings, including clinical, immunohistochemical and molecular results, are described in the present case report. The liver tumor was a conventional HCC and the colorectal tumor comprised a tubular adenocarcinoma. Immunohistochemistry of both tumors showed a loss of expression of mutL homolog 1 and postmeiotic segregation increased 2 in the tumor cells, confirming microsatellite instability-high (MSI-H) status. Furthermore, a molecular study detected the presence of genes located on the Y chromosome in the normal and tumor tissues of the liver, proving that the HCC occurred in the grafted liver. The present report also discusses that prolonged use of immunosuppressive drugs to prevent post-transplant rejection, poorly controlled diabetes mellitus and MSI-H may have contributed to the risk of tumor development.

Long term changes in thrombocytopenia and leucopenia after HCV eradication with direct-acting antivirals.

BACKGROUND: Thrombocytopenia due to hypersplenism is a major complication of hepatitis C virus (HCV)-associated cirrhosis. HCV eradication improves these complications in some patients, but the long-term effects of HCV eradication on these complications remain unclear, especially in patients treated with direct acting antivirals (DAAs). The aim was to evaluate long term changes in thrombocytopenia and leucopenia after HCV eradication with DAAs. METHODS: The present multicenter study retrospectively evaluated changes over 5 years in thrombocytopenia and leukocytopenia, as well as changes in liver fibrosis markers and spleen size, in 115 patients with HCV-cirrhosis treated with DAAs. RESULTS: Thrombocytopenia and leukocytopenia were improved 4 weeks after DAA administration, with thrombocytopenia show further gradual improvement over the next year. Fib-4 index was markedly reduced 1 year after DAA, followed by subsequent gradual reduction over the next 4 years. Spleen size showed gradual annual reductions, with patients experiencing spleen size reduction characterized at baseline by bilirubinemia. CONCLUSIONS: Rapid DAA-associated HCV eradication might lead to rapid disappearance of liver inflammation and bone marrow suppression due to HCV infection. HCV eradication may gradually improve portal hypertension, reducing spleen size.

Colonic TRPV4 overexpression is related to constipation severity.

BACKGROUND: Chronic constipation is prevalent and involves both colon sensitivity and various changes in intestinal bacteria, particularly mucosa-associated microflora. Here we examined regulatory mechanisms of TRPV4 expression by co-culturing colon epithelial cell lines with intestinal bacteria and their derivatives. We also investigated TRPV4 expression in colon epithelium from patients with constipation. METHODS: Colon epithelial cell lines were co-cultured with various enterobacteria (bacterial components and supernatant), folate, LPS, or short chain fatty acids. TRPV4 expression levels and promoter DNA methylation were assessed using pyrosequencing, and microarray network analysis. For human samples, correlation coefficients were calculated and multiple regression analyses were used to examine the association between clinical background, rectal TRPV4 expression level and mucosa-associated microbiota. RESULTS: Co-culture of CCD841 cells with P. acnes, C. perfringens, or S. aureus transiently decreased TRPV4 expression but did not induce methylation. Co-culture with clinical isolates and standard strains of K. oxytoca, E. faecalis, or E. coli increased TRPV4 expression in CCD841 cells, and TRPV4 and TNF-alpha expression were increased by E. coli culture supernatants but not bacterial components. Although folate, LPS, IL-6, TNF-alpha, or SCFAs alone did not alter TRPV4 expression, TRPV4 expression following exposure to E. coli culture supernatants was inhibited by butyrate or TNF-alphaR1 inhibitor and increased by p38 inhibitor. Microarray network analysis showed activation of TNF-alpha, cytokines, and NOD signaling. TRPV4 expression was higher in constipated patients from the terminal ileum to the colorectum, and multiple regression analyses showed that low stool frequency, frequency of defecation aids, and duration were associated with TRPV4 expression. Meanwhile, incomplete defecation, time required to defecate, and number of defecation failures per 24 h were associated with increased E. faecalis frequency. CONCLUSIONS: Colon epithelium cells had increased TRPV4 expression upon co-culture with K. oxytoca, E. faecalis, or E. coli supernatants, as well as TNFα-stimulated TNFαR1 expression via a pathway other than p38. Butyrate treatment suppressed this increase. Epithelial TRPV4 expression was increased in constipated patients, suggesting that TRPV4 together with increased frequency of E. faecalis may be involved in the pathogenesis of various constipation symptoms.

Impact of Post-progression Survival on Outcomes of Lenvatinib Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Retrospective Cohort Study.

BACKGROUND/AIM: Lenvatinib is a tyrosine kinase inhibitor (TKI) more effective against hepatocellular carcinoma (HCC) than sorafenib, making lenvatinib a first-line treatment option for patients with unresectable HCC. In patients treated with sorafenib, post-progression survival (PPS) rather than progression-free survival (PFS) is essential for overall survival (OS). However, the importance of PPS for OS in patients treated with lenvatinib is uncertain, and optimal treatment after lenvatinib failure has not yet been established. PATIENTS AND METHODS: The present study investigated the correlations of PFS and PPS with OS in studies of HCC patients treated with lenvatinib by weighted linear regression analysis. Furthermore, the contribution of treatment regimens after lenvatinib failure to OS were evaluated in daily clinical practice. RESULTS: An analysis of 20 studies with 4,054 patients found that PPS had a stronger correlation with OS (r=0.869, p<0.001) than did PFS (r=0.505, p=0.007). Analysis of 79 patients with unresectable HCC treated with first-line lenvatinib showed that subsequent treatment was the most significant contributor to OS. Second-line sorafenib was administered to 25 patients, with late transition to third-line treatment being highest among patients who received second-line treatment. CONCLUSION: PPS contributes significantly to OS in HCC treatment with TKIs, with multi-sequential treatment being a key determinant of longer OS.

Direct-acting antivirals for hepatitis C virus-infected patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients has a high risk of recurrence. Although eradication of HCV is expected to reduce this risk, the risk in patients with a history of HCC may be high after treatment with direct-acting antivirals (DAAs). AIM: To determine the risk factors for HCC recurrence in patients with HCV and a history of HCC. METHODS: The risk of HCC recurrence in patients with a history of HCC and/or of HCC occurrence in patients without a history of HCC after DAA therapy was retrospectively analyzed in 311 HCV patients treated at our institution and several neighboring hospitals. The frequency and predictors of HCC recurrence/ occurrence after DAA treatment were included in these analyses. The clinical course of HCC before and after DAA treatment was also evaluated. RESULTS: HCV patients with a history of HCC were older and had greater progression of liver fibrosis and diabetes than patients without a history of HCC. Median recurrence-free survival (RFS) was 1092 d in patients with a history of HCC, and post-DAA HCC recurrence/occurrence was observed in 29 patients (53.7%) with and 5 (1.9%) without a history of HCC over 6 years (P < 0.001). RFS in patients with a history of HCC did not differ significantly before and after DAA treatment. The frequency of HCC recurrence/occurrence in patients with a history of HCC was lower after than before DAA treatment. Multivariate analysis showed that the incidence rate of HCC recurrence/occurrence before DAA treatment was the only independent predictor of HCC recurrence/occurrence after DAA treatment. Liver function was well preserved and clinical course was good in patients with HCC recurrence/occurrence after DAA therapy. CONCLUSION: DAA therapy in patients infected with HCV is also effective in patients with a history of HCC. Curative treatment for HCC is desirable before DAA therapy. The frequency of HCC recurrence/occurrence before DAA therapy was associated with a significantly increased risk of HCC recurrence after DAA therapy. Careful observation after DAA therapy is required in patients with a history of HCC.

Chronic liver disease questionnaire to manage patients with chronic liver diseases.

BACKGROUND AND AIMS: Although patients with chronic liver disease (CLD) usually show few symptoms, they exhibit decreased health-related QOL (HRQOL) with occurrence complications including hepatocellular carcinoma (HCC). Health-related QOL is an important indicator in the management of CLD. The Chronic Liver Disease Questionnaire (CLDQ) was established as a tool for assessment of HRQOL. In this study, we evaluate its usefulness for the management of daily clinical practice. METHODS: Patients (N = 190, median age 70 years old) treated between 2016 and 2019 were registered and prospectively followed-up with annual CLDQ. Associations of liver function and development of factors for admission or death were evaluated. RESULTS: Of the 190 patients registered, median age 70 years old, 140 were Child-A, 121 were Fib-4 index >2.67 and showed 80 HCC. All 6 domains including Systemic Symptoms (SS) were negatively correlated with Child-Pugh score more than with albumin-bilirubin score and Fib-4 index. A hundred four admission events and 49 deaths were found during observation period, and median event-free survival was 34.3 months. Treatment for HCC was the most frequent cause of admission, and 37 liver-related deaths were found. Systemic Symptoms score 2 years after registration was decreased in both HCC- and non-HCC cohort. Systemic Symptoms decreased and SS < 4 might be predictive for event occurrence. CONCLUSIONS: CLDQ is useful to assess HRQOL in patients with CLD and is well correlated with liver function especially Child-Pugh. Chronic Liver Disease Questionnaire might be useful to predict the prognosis of CLD and can be a tool of management in clinical practice.

Endoscopic ultrasound-guided fine-needle biopsy for the diagnosis of gastric linitis plastica.

We report two cases of patients with gastric linitis plastica (GLP), in which the histopathological diagnosis was made by endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen-tip needle. Esophagogastroduodenoscopy findings showed mucosal swelling and poor distensibility of the gastric antrum. Abdominal computed tomography findings showed significant thickening of the gastric wall at the antrum. Conventional endoscopic and bite-on-bite biopsy were attempted but resulted in failure to diagnose the lesions. We performed EUS-FNB to obtain histopathological samples from a deeper site, which confirmed the diagnosis. We considered this method safe and effective for the diagnosis of GLP.

Discrepant Diagnostic Results of Nested Polymerase Chain Reaction-based Genotyping in a Patient with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection.

Accurate genotyping is important to improve the treatment of hepatitis C virus (HCV) infection. We herein report a 44-year-old Japanese man with hemophilia A and coinfection of HCV and human immunodeficiency virus (HIV) who was diagnosed with HCV genotype 4 by direct sequencing. Two genotyping tests based on the nested polymerase chain reaction method that we used misdiagnosed his genotype as 2b and 1b. Although several HCV genotyping tests are available in Japan, it is important to recognize that some cannot detect genotype 4. Care should be taken when genotyping HCV patients who have received non-heated coagulation factor preparations or were infected abroad.

Diagnostic Fine-Needle Biopsy of Small Solid Pancreatic Lesions Using a Franseen Needle during Endoscopic Ultrasound Examination.

BACKGROUND AND AIM: During endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNB), Franseen needles can help collect sufficient tissue to permit histopathological assessment. However, its efficacy might be limited by the size of the targeted lesion. This study aimed to evaluate the feasibility of histopathological assessment of small solid pancreatic lesions using a 22-gauge Franseen needle during EUS-FNB. METHODS: This retrospective study evaluated data from all patients who underwent EUS-FNB using a Franseen needle for solid pancreatic lesions at the University of Toyama Hospital between June 2018 and April 2020. RESULTS: The study included 159 patients who had 152 malignant lesions and 7 benign lesions. The malignant lesions included pancreatic cancers (n = 134), neuroendocrine neoplasms (n = 15), metastatic tumors (n = 2), and a solid pseudopapillary neoplasm (n = 1). The diagnostic accuracy of EUS-FNB (combining histology and cytology) was 98.7%. However, the histopathological diagnosis was only confirmed for 64.3% of small lesions (<10 mm), relative to 97.2% for larger lesions. Multivariate analysis also revealed that lesion size of <10 mm predicted a less accurate histopathological diagnosis (odds ratio: 6.97, 95% confidence interval: 1.02-47.67; p = 0.041). Further analyses revealed a failed histological diagnosis in 4 patients with lesions of <5 mm in size and accurate diagnoses in 9 out of 10 patients with lesions of 5-10 mm in size. CONCLUSIONS: The diagnostic accuracy for small lesions (<10 mm), especially for lesions of <5 mm, based on histological examination alone, was significantly lower than that for others (>10 mm). Furthermore, multivariate analysis revealed that only lesion size was an independent predictor of histopathological diagnosis accuracy.

Efficacy of on-demand intrahepatic arterial therapy in combination with sorafenib for advanced hepatocellular carcinoma.

PURPOSE: The purpose of this study was to evaluate the effectiveness and tolerability of "on-demand" combination therapy with sorafenib and hepatic arterial treatments, such as transarterial chemoembolization and hepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Eighty consecutive patients with advanced HCC, 58 administered sorafenib monotherapy and 22 administered on-demand combination therapy, were retrospectively evaluated. RESULTS: The disease control rate was significantly higher in the combination group than in the monotherapy group (86.3% vs 51.7%, p=0.01). Elevated alanine aminotransferase levels were significantly more frequent in the combination group (40.9% vs 12.1%, p=0.01), but it was tolerable. Progression-free survival (180 vs 45 days, p=0.045) and overall survival (983 vs 452 days, p=0.004) were significantly longer in the combination group, as was the duration of sorafenib treatment (367 vs 66 days, p<0.001). Multivariate analysis showed that hepatitis C virus infection, disease control, and combination therapy were positive independent prognostic factors for survival, whereas alpha-fetoprotein >400 ng/mL was negatively prognostic. In patients receiving combination therapy, male sex, hepatitis B virus infection, performance status deterioration, Barcelona clinic liver cancer-B, and major vascular invasion were prognostic of survival. CONCLUSION: On-demand combination therapy was tolerated and may be a therapeutic option for patients with advanced HCC.

Combined hepatocellular-cholangiocarcinoma successfully treated with sorafenib: case report and review of the literature.

Sorafenib, a multiple kinase inhibitor, has been established as first-line standard systemic chemotherapy for patients with advanced hepatocellular carcinoma (HCC). We encountered a patient with combined hepatocellular and cholangiocarcinoma (CHC) who achieved complete remission in response to sorafenib treatment. A 58-year old man with hepatitis C virus (HCV)-induced liver cirrhosis was diagnosed with CHC in segments 6th and 7th of the liver and underwent partial surgical resection. Three months later, CHC recurred as metastases at multiple intrahepatic sites, lymph nodes, and bones, making surgery impossible. Treatment with sorafenib was initiated at 400 mg b.i.d., later reduced to 400 mg/day. After 6 months of sorafenib administration, he no longer showed abnormal uptake on fluorodeoxyglucose positron emission tomography. He was continued on sorafenib for 2.5 years, but later discontinued due to adverse events. He has shown no evidence of tumor recurrence more than 1 year after sorafenib discontinuation. His HCV was eradicated by direct-acting antivirals, and he remains in good health.

L-Carnitine for the Treatment of Overt Hepatic Encephalopathy in Patients with Advanced Liver Cirrhosis.

Hepatic encephalopathy is a major complication in patients with advanced cirrhosis and is associated with poor prognosis. To evaluate the effectiveness of L-carnitine supplementation in patients with overt hepatic encephalopathy (OHE), outcomes were retrospectively analyzed in patients with OHE who were treated with intravenous branched-chain amino acids (BCAA), with or without intravenous L-carnitine. Twenty-six patients were treated with intravenous BCAA in addition to conventional agents such as lactulose and non-absorbable antibiotics (Group A), and 19 patients were treated with these agents plus intravenous L-carnitine (Group L). Changes in blood ammonia concentrations, hepatic coma grade and the Glasgow Coma Scale (GCS) were compared in the two groups. Recurrence-free survival (RFS) was evaluated in the two groups and in patients who were and were not administered oral L-carnitine supplementation. At baseline, GCS scores were significantly lower and deterioration in liver function greater in Group L. After 3 d of intravenous L-carnitine, however, GCS showed a significantly greater improvement in Group L than in Group A. Blood ammonia levels improved stably over time in Group L. Overall survival and RFS were similar in Group L and Group A, but median RFS was significantly longer in patients who did than did not receive oral L-carnitine supplementation (735 versus 497 d, p=0.03). Although these findings are preliminary, L-carnitine supplementation may be a therapeutic option for patients with OHE and disturbed consciousness.

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis.

AIMS: The study aimed to evaluate the effects of tolvaptan treatment on survival of patients with decompensated liver cirrhosis with refractory ascites. METHODS: This multicenter, retrospective, observational study included patients with cirrhosis who were treated with tolvaptan for hepatic ascites refractory to conventional diuretics. Patients who could and could not decrease accompanying diuretics within 1 month after tolvaptan administration were defined as the "Decreased" and "Not-decreased" groups, respectively. RESULTS: Median body weight change 1 week after tolvaptan treatment was -1.95 kg, with the 50% of patients experiencing a 2 kg/week reduction. Spot urinary sodium was found to be a better predictor of tolvaptan response than liver function and liver fibrosis markers. Median survival was significantly longer (not reached versus 116 days, p = 0.005) and serum creatinine concentrations 12 weeks after tolvaptan administration significantly lower (0.99 vs. 1.55 mg/dL, p < 0.05) in the Decreased than in the Not-decreased group. Multivariate analysis showed that the presence of viable hepatocellular carcinoma (hazards ratio [HR] 2.14, p = 0.02) and a decrease in diuretics were independently prognostic of survival (HR 0.36, p < 0.01). CONCLUSIONS: The maintenance of renal function is essential in enhancing survival of patients with cirrhosis. Doses of diuretics should be adjusted appropriately during tolvaptan treatment.

A Patient with Non-alcoholic Steatohepatitis Complicated by Multiple Myeloma.

A 68-year-old woman with liver dysfunction was diagnosed with nonalcoholic steatohepatitis (NASH) stage 1. Three years later, she showed massive ascites and jaundice. A trans-jugular liver biopsy confirmed advanced cirrhosis, suggesting that her liver fibrosis had progressed rapidly. At the same time, she was diagnosed with multiple myeloma (MM). In this case, the plasma levels of osteopontin (OPN), a proinflammatory cytokine that promotes liver fibrosis progression through the hedgehog pathway and is increased in patients with MM, were increased. This increased OPN expression was accompanied by the upregulation of the hedgehog pathway in this patient, suggesting that the MM-associated increase in OPN had promoted the progression of liver fibrosis through the hedgehog pathway. The progression of liver fibrosis should be monitored in patients with NASH if other diseases, such as MM, are present.

[Rhabdomyolysis associated with long-term treatment of esomeprazole].

Proton pump inhibitors (PPIs) have been widely used in the treatment of gastroesophageal reflux disease and peptic ulcer disease. Although they have a potent acid suppressive effect and excellent efficacy in acid-related diseases, PPI-induced rhabdomyolysis has been reported. Here, we report the case of a patient with reflux esophagitis who developed rhabdomyolysis after esomeprazole treatment. A 67-year-old man with reflux esophagitis who had started esomeprazole treatment for the preceding 10 months complained of back and limb fatigue and myalgia. His serum creatinine kinase (CK) level was markedly elevated, and CK isozyme exhibited an MM pattern. He was diagnosed with rhabdomyolysis induced by esomeprazole. The cessation of esomeprazole rapidly improved his symptoms, and the serum CK level was normalized within 16 days. PPI-induced rhabdomyolysis is a rare complication. In most cases, PPI-induced rhabdomyolysis occurs within 3 months after starting PPIs. However, rhabdomyolysis occurred at 10 months after starting esomeprazole treatment in our patient. Early diagnosis of PPI-induced rhabdomyolysis is required even in long-term PPI users.

Vanishing Tumor in a Liver Graft from a Hepatitis B Virus Surface Antigen-Positive Donor.

We report a case of vanishing tumor considered as inflammatory pseudotumor (IPT) found in the liver after living donor liver transplantation (LDLT) from a hepatitis B virus surface antigen-positive donor. The radiological findings were similar to those of hepatocellular carcinoma (HCC). However, the tumor disappeared completely within several months and was suggested to have been an IPT. IPT is known to be associated with biliary duct operation or biliary infection, and it can show various enhancement patterns in radiological studies, sometimes resembling HCC. It should be considered in the differential diagnosis of a liver tumor in patients with LDLT.

Serum microRNA profiles in patients with chronic hepatitis B, chronic hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis, or drug-induced liver injury.

PURPOSE: Some blood biomarkers or histological examination by liver biopsy are used for the diagnosis of liver diseases in clinics. However, conventional blood biomarkers show poor specificity and sensitivity, and liver biopsy is highly invasiveness. Therefore, to overcome such disadvantages, specific/sensitive and noninvasive options are desirable. In recent years, circulating microRNAs (miRNAs) have been acknowledged for their potential as disease markers. Actually, several miRNAs have been reported to be biomarker candidates of liver diseases. However, these earlier studies were performed for one disease. Therefore, the specificity as biomarkers was not guaranteed, because they didn't study for the other types of liver injury. In this study, we examined if circulating miRNA could distinguish different types of liver diseases. METHODS: Serum miRNA profiles in 28 patients with chronic hepatitis B, chronic hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis or drug-induced liver injury as well as 4 control subjects were determined by TaqMan MicroRNA Array analysis. Principal component analysis (PCA) of selected miRNAs was performed. RESULTS: We identified 37 miRNAs whose levels were significantly different between any of the groups. Although individual miRNAs could not distinguish different types of liver diseases, probably because of similar liver pathology, their profiling by PCA could classify different liver disease groups. CONCLUSIONS: The profiling of the selected miRNAs can be useful to distinguish different types of liver diseases.

Peritumoral Hyperplasia in Hepatic Sclerosed Hemangioma.

Peritumoral hyperplasia (PTH) is a hyperplastic lesion located around hypervascular tumors. Hepatic sclerosed hemangioma is a very rare form of hemangioma with sclerotic changes and is distinct from sclerosing hemangioma. We present a patient with non-alcoholic steatohepatitis-induced cirrhosis who presented with a hypervascular tumor. The tumor showed atypical findings of hemangioma and was treated with surgical resection because hepatic malignancy could not be ruled out. Histopathologic examination revealed the tumor was a sclerosed hemangioma with PTH. Lesions with carcinogenic potential were found in the PTH lesion. Sclerosed hemangioma should be observed and managed carefully.

Hyperbilirubinemia without Transaminitis during Combined Therapy with Daclatasvir and Asunaprevir.

Daclatasvir (DCV) and asunaprevir (ASV) are direct-acting antivirals (DAAs) used in the treatment of chronic hepatitis C virus (HCV) infection. Combined therapy with DCV and ASV shows high efficacy and safety even in patients with cirrhosis. We encountered a patient exhibiting severe hyperbilirubinemia during combined therapy, which is an unreported side effect of DCV and ASV. A 78-year-old woman with cirrhosis developed hyperbilirubinemia >10 mg/dl without transaminitis 3 weeks after starting combined therapy. We suspected DAAs-induced liver disorder and discontinued treatment, which resulted in the improvement of hyperbilirubinemia. Caution is required in the use of DAAs for patients with advanced cirrhosis.

Neutrophil-to-lymphocyte ratio predicts recurrence after radiofrequency ablation in hepatitis B virus infection.

BACKGROUND AND AIM: Radiofrequency ablation (RFA) is an established treatment for small hepatocellular carcinoma (HCC) wherein non-recurrence is essential for long-term survival. Recently, neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation that is associated with tumor-associated macrophages (TAMs), was suggested to be a prognostic marker of HCC treated with RFA. Therefore, we evaluated predictive factors, including NLR, associated with recurrence after curative RFA. METHODS: A total of 163 patients initially diagnosed with HCC and treated with RFA were enrolled. We retrospectively analyzed factors associated with recurrence and survival after RFA. Furthermore, TAMs were evaluated using surgically resected specimens. RESULTS: Hepatitis C virus (HCV) infection was the most frequent cause of HCC in this population (111 cases, 68.1%), whereas hepatitis B virus (HBV) infection accounted for 26 cases (16.0%). Recurrence, mostly intrahepatic distant recurrence, was found in 101 cases (61.9%). Recurrence and posttreatment NLR were independent prognostic factors related to survival, and male sex, HCV infection, serum des-γ-carboxy prothrombin >  40 AU/L, and posttreatment NLR were associated with recurrence. Pretreatment NLR showed no association with recurrence, whereas posttreatment NLR showed prognostic value. Interestingly, pretreatment NLR >  2.5 was significantly associated with recurrence in HBV-HCC patients (odds ratio 3.439, P = 0.037) not but HCV-HCC (odds ratio 1.430, P = 0.17). Furthermore, TAMs were increased in the peripheral area of HCCs with HBV infection compared with those with HCV. CONCLUSIONS: Recurrence of HCC after RFA was strongly associated with survival. NLR is useful as a predictive marker of recurrence, especially in HBV-HCC patients.