Ratio between estimated glomerular filtration rates of creatinine and cystatin C predicts overall survival in patients with hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) patients with sarcopenia have a poor survival, but there are no predictive markers for survival relating to muscle mass and liver function. Therefore, we investigated whether the ratio between estimated glomerular filtration rates of serum creatinine (Scre) and serum cystatin C (Scys) (eGFRcre/eGFRcys) can be used as a predictive marker of survival in HCC patients. METHODS: First, the correlation between Scre/Scys ratio and muscle mass was examined in 50 patients with chronic liver disease. Second, a change in Scre/Scys ratio relating to liver function was investigated in cirrhotic rats. Finally, the relationship between the eGFRcre/eGFRcys ratio and survival was assessed in 86 HCC patients. RESULTS: The Scre/Scys ratio was correlated with skeletal muscle mass index (r = 0.331, P = 0.019) and psoas muscle area index (r = 0.397, P = 0.004) in chronic liver disease patients. In cirrhotic rats, Scre and Scre/Scys ratio were decreased corresponding with liver function. Thirty-five of 86 HCC patients died within the average follow-up period of 35 months. The patients with an eGFRcre/eGFRcys ratio <1.26 had significantly longer rates of survival compared to patients with an eGFRcre/eGFRcys ratio ≥1.26 (28.8 vs. 18.5 months, P = 0.001). Using multivariate Cox regression analyses, the patient-related eGFRcre/eGFRcys ratio (hazard ratio [HR], 4.178; P = 0.007), as well as the tumor-related factors α-fetoprotein (HR, 1.000; P < 0.001) and Barcelona Clinic Liver Cancer stage (HR, 2.589; P < 0.001), were independent predictors of survival. CONCLUSION: The Scre/Scys ratio is associated with muscle mass and liver function. Furthermore, the eGFRcre/eGFRcys ratio could serve as a useful predictive marker for survival of HCC.

Changing clinical and molecular characteristics of hepatitis E virus infection in Mie Prefecture, Japan: Disappearance of indigenous subtype 3e strains.

AIM: To evaluate the clinical and molecular characteristics of hepatitis E virus (HEV) infection in Mie Prefecture, Japan, from 2004 through 2018. METHODS: The clinical information of hepatitis E cases was collected from 21 medical institutions in Mie Prefecture. The nucleotide sequences of infecting HEV strains were determined for cases with available serum samples. The origins or transmission routes were inferred from phylogenetic analyses of the nucleotide sequences. RESULTS: Fifty-three patients were diagnosed with HEV infection. The number of cases increased each year through 2012 and then decreased. Analyses of the clinical characteristics of the cases indicated that even mild cases were detected in the latter 10 years of the study. Nucleotide sequence analyses were undertaken on 38 of the 53 cases. The HEV subtype 3e (HEV-3e) strains identified for 13 cases were closely related to a swine HEV-3e strain that was isolated from the liver of a pig bred in Mie Prefecture. The number of cases infected with the indigenous Mie HEV-3e strains increased until 2012 but have not been reported since 2014. In the latter half of the study, cases involving various HEV strains of different genotypes and subtypes emerged. CONCLUSIONS: The disappearance of indigenous Mie HEV-3e strains appeared to be the primary cause for the decrease in hepatitis E cases in Mie Prefecture. The disappearance might have been associated with improved hygienic conditions on pig farms or the closure of contaminated farms. The results suggest that indigenous HEV strains can be eradicated by appropriate management.

Changes in liver function and body composition by direct-acting antiviral therapy for hepatitis C virus infection.

AIM: Management of low skeletal muscle mass (LSM) is a very important topic as LSM affects patient mortality in liver diseases. Changes in body composition are unexplored in chronic hepatitis C virus (HCV) patients, including those with liver cirrhosis, who receive direct-acting antiviral (DAA) therapy. Body composition measurements and liver function tests were carried out before and after DAA therapy. METHODS: Blood examination, visceral fat area (VFA) and extremity skeletal muscle mass were measured using the multifrequency bioelectrical impedance analysis method: (i) at 24 weeks before DAA therapy; (ii) at the start of DAA therapy; (iii) at the end of DAA therapy; (iv) at 24 weeks after DAA therapy; and (v) at 48 weeks after DAA therapy. RESULTS: Serum albumin (Alb) levels were significantly increased at 48 weeks post DAA therapy, especially in patients with LSM. Skeletal muscle mass index (SMI) was significantly increased after DAA therapy (at 24 weeks and 48 weeks post DAA therapy) in patients with LSM (P < 0.05). An increase in SMI was associated with an increase in body weight or a decrease in VFA. CONCLUSIONS: We continuously measured body composition in HCV-infected patients who received DAA therapy and found that skeletal muscle mass was significantly increased, associated with an elevation of serum Alb levels and/or body weight or reduction in VFA, but only in patients who presented with LSM before DAA therapy.

Factors contributing to the development of overt encephalopathy in liver cirrhosis patients.

The aim of this study was to clarify the relationships among psychometric testing results, blood ammonia (NH3) levels, electrolyte abnormalities, and degree of inflammation, and their associations with the development of overt hepatic encephalopathy (HE) in liver cirrhosis (LC) patients. The relationships between covert HE and blood NH3, sodium (Na), and C-reactive protein (CRP) were examined in 40 LC patients. The effects of elevated NH3, hyponatremia, and elevated CRP on the development of overt HE were also investigated. The covert HE group had significantly lower serum Na levels and significantly higher serum CRP levels. During the median observation period of 11 months, 10 patients developed overt HE, and the results of multivariate analysis showed that covert HE and elevated blood NH3 were factors contributing to the development of overt HE. Electrolyte abnormalities and mild inflammation are involved in the pathogenesis of HE. Abnormal psychometric testing results and hyperammonemia are linked to subsequent development of overt HE.

A case of a solitary Mycobacterium avium complex lesion of the liver.

A 70-year-old woman was admitted to our hospital on suspicion of liver tumor on regular abdominal ultrasonography. The abdominal ultrasonography identified a solitary, low-echoic lesion measuring 17mm in diameter in S7. This lesion was not enhanced in any phase of contrast-enhanced computed tomography (CT), and thus we performed a liver biopsy. Histopathological examination revealed a caseating granuloma. The chest CT showed pulmonary nodules, and Mycobacterium intracellulare was cultured from the bronchoalveolar lavage fluid. We diagnosed the individual with a Mycobacterium avium complex infection, and suspected that this was the cause of the solitary liver lesion.

Resveratrol sensitizes HepG2 cells to TRAIL-induced apoptosis.

Resveratrol is a natural polyphenol found in a wide variety of plants, including grapes, berries, and peanuts. Resveratrol can modulate a wide spectrum of molecular targets, including those involved in cancer signaling pathways. Here, we evaluated the role of resveratrol in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and examined the molecular mechanisms in the human hepatocellular carcinoma cell line HepG2. We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay to assess cell viability, flow cytometry to analyze cell cycle and apoptosis, and immunoblotting to detect protein expression. Resveratrol decreased cell viability at a concentration of 100 µmol/l or higher. At a concentration of 50 µmol/l, resveratrol induced S phase arrest of the cell cycle without apoptosis. In addition, phospho-AMPK increased significantly in a dose-dependent manner. Resveratrol was found to synergistically augment TRAIL-induced apoptosis. The rates of early apoptosis were 3.4, 9.6, and 49.6% on treatment with 50 µmol/l resveratrol, 10 ng/ml TRAIL, and both reagents, respectively. Resveratrol significantly downregulated the expression of survivin in a dose-dependent manner. In conclusion, we found that that resveratrol could augment TRAIL sensitivity by downregulating survivin. These results suggest that combination resveratrol with TRAIL may be an effective new strategy for the treatment of hepatocellular carcinoma.

Splenectomy increases the number of circulating hematopoietic stem/progenitor cells in patients with hepatitis C virus-associated liver cirrhosis.

AIM: The spleen is not believed to contribute to hematopoiesis in healthy adults. However, several reports have demonstrated that the spleen in adults contains a large number of hematopoietic stem/progenitor cells (HSC). Although splenectomy increases platelet and leukocyte counts, the effects of splenectomy on circulating HSC have not been elucidated. In this study, we evaluated the association between the number of circulating HSC and splenectomy in patients with hepatitis C virus (HCV)-associated liver cirrhosis (LC). METHODS: In 48 patients with various stages of HCV-associated chronic liver disease and seven patients with LC who underwent splenectomy, and 10 healthy volunteers, we determined the numbers of circulating CD34+ cells and colony-forming unit culture by flow cytometry and methylcellulose culture, respectively. Plasma stromal cell-derived factor-1α (SDF-1α) concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: The numbers of circulating CD34+ cells and colony-forming unit culture decreased but the plasma SDF-1α concentration increased with the progression of liver disease. There was an inverse correlation between the number of circulating HSC and the plasma SDF-1α concentration. The numbers of circulating HSC and platelets were determined before and after splenectomy in seven patients with LC. In these patients, the numbers of circulating HSC and platelets increased significantly after splenectomy and the enhancing effect persisted for a long time. CONCLUSION: Our data suggest that the spleen plays an important role in modulating HSC dynamics in patients with HCV-associated chronic liver disease. Our results also imply that splenectomy may improve liver function in patients with LC.

A case of refractory hepatic hydrothorax due to pleuroperitoneal communication successfully controlled by diaphragmatic plication and subsequent peritoneovenous shunting.

In general, control of hepatic hydrothorax is difficult, and patients have a poor prognosis. A case in which hepatic hydrothorax was well controlled for a long time after diaphragm plication and subsequent Denver shunt placement is reported. A 70-year-old man with decompensated liver cirrhosis presented with progressive exertional dyspnea. 5 years before admission, hepatic ascites associated with portal hypertension appeared, and a left pleural effusion subsequently developed. The pleural effusion was not controlled by salt restriction and diuretics. Based on the clinical findings, the existence of pleuroperitoneal communication was strongly suspected, and surgical diaphragmatic plication was performed. After the treatment, the pleural effusion did not accumulate, but ascites increased significantly, and conservative therapy was ineffective. For the treatment of massive ascites, a peritoneovenous shunt (Denver shunt®) was placed. Although more than 2 years have passed, the thoracoabdominal effusions have not accumulated, and the patient has been asymptomatic. The present case suggests that multidisciplinary treatment may improve the prognosis of patients with refractory thoracoabdominal effusions.

Des-γ-carboxy prothrombin ratio measured by P-11 and P-16 antibodies is a novel biomarker for hepatocellular carcinoma.

Serum tumor markers, including α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), are currently used in the diagnosis of hepatocellular carcinoma (HCC). There is, however, an aberrant increase in serum DCP in patients with obstructive jaundice, vitamin K deficiency or who are taking warfarin, resulting from a problem with the current methodology for measurement of this marker. This study aimed to elucidate the utility of a new biomarker, NX-PVKA, for early diagnosis of HCC. A total of 96 patients were included in the HCC group. The control group included 138 liver cirrhosis (LC) patients without HCC. Serum concentrations of conventional DCP, AFP, AFP-L3 and NX-PVKA were measured. The NX-PVKA ratio was calculated by dividing DCP by NX-PVKA. In patients not taking warfarin, the area under the curve values of DCP, NX-PVKA ratio, AFP and AFP-L3 were 0.715, 0.690, 0.737 and 0.654, respectively, confirming the clinical utility of these markers in detecting HCC. In cases with DCP > 35 mAU/mL in particular, a significant increase in the NX-PVKA ratio was observed in patients with HCC. In those cases, the cut-off value for the NX-PVKA ratio that was optimized by the receiver operating characteristic (ROC) curve was 1.15. In addition, the sensitivity and specificity for diagnosing HCC were 69.2% and 75.9%, respectively. Patients with HCC had higher NX-PVKA ratios compared to patients with LC taking warfarin (P = 0.063). These results suggest that, when used in combination with DCP, the NX-PVKA ratio is a promising novel marker for the detection of HCC.

Immunological aspects in late phase of living donor liver transplant patients: usefulness of monitoring peripheral blood CD4+ adenosine triphosphate activity.

AIM: To evaluate whether the combination of the peripheral blood CD4+ adenosine triphosphate activity (ATP) assay (ImmuKnow assay: IMK assay) and cytochrome P450 3A5 (CYP3A5) genotype assay is useful for monitoring of immunological aspects in the patient followup of more than one year after living donor liver transplantation (LDLT). METHODS: Forty-nine patients, who underwent LDLT more than one year ago, were randomly screened by using IMK assay from January 2010 to December 2011, and the complete medical records of each patient were obtained. The CYP3A5 genotypes were examined in thirty-nine patients of them. RESULTS: The mean ATP level of the IMK assay was significantly lower in the patients with infection including recurrence of hepatitis C (HCV) (n = 10) than in those without infection (n = 39): 185 versus 350 ng/mL (P < 0.001), while it was significantly higher in the patients with rejection (n = 4) than in those without rejection (n = 45): 663 versus 306 ng/mL (P < 0.001). The IMK assay showed favorable sensitivity/specificity for infection (0.909/0.842) as well as acute rejection (1.0/0.911). CYP3A5 genotypes in both recipient and donor did not affect incidence of infectious complications. CONCLUSIONS: In the late phase of LDLT patients, the IMK assay is very useful for monitoring immunological aspects including bacterial infection, recurrence of HCV, and rejection.

Impact of body composition on patient prognosis after SARS-Cov-2 infection.

BACKGROUND: Since the first outbreak of coronavirus disease 2019 (COVID-19), it has been reported that several factors, including hypertension, type 2 diabetes mellitus, and obesity, have close relationships with a severe clinical course. However, the relationship between body composition and the prognosis of COVID-19 has not yet been fully studied. METHODS: The present study enrolled 76 consecutive COVID-19 patients with computed tomography (CT) scans from the chest to the pelvis at admission. The patients who needed intubation and mechanical ventilation were defined as severe cases. Patients were categorized into four groups according to their body mass index (BMI). The degree of hepatic steatosis was estimated by the liver/spleen (L/S) ratio of the CT values. Visceral fat area (VFA), psoas muscle area (PMA), psoas muscle mass index (PMI), and intra-muscular adipose tissue content (IMAC) were measured by CT scan tracing. These parameters were compared between non-severe and severe cases. RESULTS: Severe patients had significantly higher body weight, higher BMI, and greater VFA than non-severe patients. However, these parameters did not have an effect on disease mortality. Furthermore, severe cases had higher IMAC than non-severe cases in the non-obese group. CONCLUSIONS: Our data suggest high IMAC can be a useful predictor for severe disease courses of COVID-19 in non-obese Japanese patients, however, it does not predict either disease severity in obese patients or mortality in any obesity grade.

Recurrent hepatocellular carcinoma with osteoclast-like giant cells: a case report.

BACKGROUND: Hepatocellular carcinoma with osteoclast-like giant cells is very rare and has an extremely poor prognosis. Here, we report a case of hepatocellular carcinoma with osteoclast-like giant cells that had a relatively better prognosis. CASE PRESENTATION: A 70-year-old Japanese man with hepatitis B virus-related liver cirrhosis was admitted to our hospital for the treatment of recurrent hepatocellular carcinoma. At the age of 60 years, he was first diagnosed as having hepatocellular carcinoma in the right lobe (9 cm in diameter), and liver resection of segment 7/8 was performed. Histological findings showed well-differentiated hepatocellular carcinoma. Since then, imaging studies have been performed every 3 or 4 months. One year later, hepatocellular carcinoma recurred in the lateral segment, and radiofrequency ablation was performed. Nine years after the first presentation, hepatocellular carcinoma recurrences were detected in the caudate lobe and segment 5 by imaging studies. Surgical resection of the caudate lobe was performed, and ultrasonography-guided radiofrequency ablation was subsequently performed for the segment 5 tumor. The resected tumor was simple nodular, well-differentiated HCC; it measured 21 × 21 mm and contained many osteoclast-like giant cells. As neither vascular nor bile duct invasion was found, we believe that radical resection was achieved. Since then, the hepatocellular carcinoma has not recurred for over a year and a half. CONCLUSION: Hepatocellular carcinoma with osteoclast-like giant cells is very rare and the prognosis is extremely poor, but early detection can lead to a better clinical course.

Subphrenic versus nonsubphrenic hepatocellular carcinoma: combined therapy with chemoembolization and radiofrequency ablation.

OBJECTIVE: This retrospective study was conducted to evaluate the clinical utility of the combination of chemoembolization and real-time CT fluoroscopically guided radiofrequency ablation in the treatment of patients with subphrenic hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients who had a single HCC with a maximum diameter of 5 cm or less were included in the study. None of the patients was a candidate for surgery, and all underwent combination therapy as initial treatment. The patients were divided into two groups based on tumor location. In all, the 93 men and 38 women (mean age, 67.9 +/- 9.4 years; range, 43-83 years) had 46 subphrenic HCCs and 85 nonsubphrenic HCCs. No differences were found in the pretreatment baseline characteristics of the two patient groups. Safety profiles, local tumor progression rates, and prognoses were compared. RESULTS: Tumor enhancement disappeared after 58 radiofrequency sessions (1.3 sessions/tumor) in patients with subphrenic HCC and after 104 radiofrequency sessions (1.2 sessions/tumor) in patients with nonsubphrenic HCC. The 5-year local tumor progression rates (subphrenic, 3% [95% CI, 0.2-12%]; nonsubphrenic, 9% [95% CI, 3-20%]; p = 0.31) and survival rates (subphrenic, 63% [95% CI, 36-81%]; nonsubphrenic, 69% [95% CI, 53-81%]; p = 0.55) were similar for the two patient groups. Although the incidence of self-limited pneumothorax was significantly higher among the patients with subphrenic HCC (13.8% vs 3.85%; p < 0.03), other complication rates were similar for the two patient groups. CONCLUSION: Combination therapy with chemoembolization and real-time CT-guided radiofrequency ablation is safe and useful even when HCC is in the subphrenic region.

Expression Pattern of Plexin Domain Containing 2 in Human Hepatocellular Carcinoma.

Plexin domain containing 2 (PLXDC2) is expressed in endothelial cells of tumor stroma, neural progenitor cells, and pluripotent stem cells, but their respective tissue expression pattern is not fully understood. In this study, we investigated the expression pattern of PLXDC2 in human hepatocellular carcinoma (HCC) tissues using a highly specific anti-PLXDC2 rabbit monoclonal antibody, which was recently developed. PLXDC2 was expressed in human HCC tissues including HCC cells, tumor vascular endothelial cells, and some infiltrating cells. The developed anti-PLXDC2 antibody allowed for highly specific and low background staining. Based on these current findings of PLXDC2 expression in human HCC tissues, the window may now be open to explore the role of PLXDC2 in human HCC.

Radiofrequency ablation combined with chemoembolization for the treatment of hepatocellular carcinomas larger than 5 cm.

PURPOSE: To evaluate survival, recurrence-free survival, technical success, technique effectiveness, and safety of radiofrequency (RF) ablation combined with chemoembolization in patients with hepatocellular carcinomas (HCCs) larger than 5 cm. MATERIALS AND METHODS: Patients with Child-Pugh class A or B cirrhosis and three or fewer HCCs with a maximum tumor diameter of 5.1-10 cm were included. Twenty patients with 32 HCCs were included. There were 16 men and four women with mean age of 69 years +/- 7.4 (range, 46-79 years).The maximum mean tumor diameter was 6.2 cm (range, 5.1-9.5 cm). RF ablation was performed under computed tomographic (CT) fluoroscopic guidance 1-2 weeks after chemoembolization. The primary endpoint of this study was survival. RESULTS: RF electrodes were placed in the planned sites, and RF ablation was completed with a planned protocol (technical success rate, 100%). Tumor enhancement was eradicated in all patients after 32 RF sessions. The primary and secondary technique effectiveness rates were 40% and 100%, respectively. There were two major complications in the 32 RF sessions (6%)--hepatic abscess and diaphragm perforation. Local tumor progression developed in five of the 20 patients (25%) during the mean follow-up of 30 months. The overall and recurrence-free survival rates were, respectively, 100% and 74% at 1 year, 62% and 28% at 3 years, and 41% and 14% at 5 years. The serum bilirubin level of 1.0 mg/dL (17.1 micromol/L) or less was a significantly better prognostic factor in the univariate analysis. CONCLUSIONS: This combination therapy may enhance survival in patients with HCCs larger than 5 cm.

Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma: differential signaling mechanisms of TLR3-induced NF-kappaB activation and apoptosis.

Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). TLR3 expression and function in cancer cells are not well understood. We investigated the expression of TLR3 in hepatocellular carcinoma (HCC) cells and the function of TLR3 signaling by stimulation and transfection with polyinosinic-polycytidylic acid (Poly I:C), a synthetic form of dsRNA. TLR3 mRNA was expressed in HCC tissues as well as in non-tumor tissues. Positive immunohistochemical staining for TLR3 was observed in 52.7% of HCC tissues, and in HCC cells we found both membranous and cytoplasmic expression of TLR3. While cell surface stimulation of TLR3 with Poly I:C did not affect cell viability, it did activate NF-kappaB levels. In contrast, cytoplasmic stimulation with transfected Poly I:C significantly induced apoptosis accompanied by the down-regulation of anti-apoptotic protein. Transfected Poly I:C also synergistically augmented TRAIL-induced apoptosis, but only with low levels of transfected Poly I:C was IFN-beta production not observed. In conclusion, our results indicate that TLR3 expression in HCC plays an important role with regard to cell survival and proapoptotic activity. Endogenously expressed TLR3 may provide new clinical prospects for TLR3 agonists as cytotoxic agents in HCC.

Obesity as a risk factor for GERD in Japan.

BACKGROUND: In Europe and the United States, it is known that obesity, which is increasing, is closely associated with gastroesophageal reflux disease (GERD), but in Japan no definite consensus has been reached on this relationship. Clarification of the relationship between the two is an important issue. METHODS: After screening, gastrointestinal endoscopic examinations were conducted on 1813 subjects who were surveyed using a questionnaire in which they recorded body weight, height, weight loss or gain, chief complaints, and underlying disease to prospectively examine the relationship between obesity and GERD. Differences in GERD prevalence and esophageal hiatal hernia prevalence in thin (body mass index less than 18.5 kg/m2), normal (18.5 to 25.0), and obese (greater than 25.0) subjects were examined, and the differences in GERD prevalence in patients with weight loss or gain were also investigated. RESULTS: GERD prevalence was 20.96% in the thin group, 24.42% in the normal group, and 31.86% in the obese group, indicating a significantly higher prevalence in the obese group compared with the other groups. The prevalence of hernia was also significantly higher in the obese group. GERD prevalence in the weight gain group was significantly higher than in the unchanged weight group and weight loss group. CONCLUSIONS: Both GERD prevalence and the prevalence of hernia were significantly higher in obese subjects, and the prevalence of GERD in subjects who had gained weight was also significantly higher. From these results, it was concluded that obesity is a risk factor for GERD in Japan.

Protective role of interleukin-18 against Fas-mediated liver injury.

Interleukin (IL)-18 plays an important role in the pathogenesis of several liver diseases as well as Fas-mediated apoptosis. However, the effects of IL-18 on Fas-mediated liver injury have not been well elucidated. Therefore, we examined the effects of IL-18 on Fas-mediated apoptosis in in vitro and in vivo experiments. We found that recombinant IL-18 protected mouse hepatocellular carcinoma cell lines, BNL5, from Fas-mediated apoptosis in a dose-dependent manner with up-regulation of both nuclear factor (NF) kappaB and X-linked inhibitors of apoptosis (XIAP). IL-18 transgenic (Tg) mice were also protected from Fas-mediated liver injury and this was further confirmed by histological study and TUNEL staining. In IL-18 Tg mice, up-regulation of XIAP and down-regulation of caspase 3 were observed after injection of anti-Fas, which was consistent with the in vitro findings. These results suggest that IL-18 suppresses Fas-mediated apoptosis of hepatocytes by up-regulation of NFkappaB and XIAP, following inhibition of caspase-3 activity. This observation raises the possibility that IL-18 could be a therapeutic strategy for Fas-mediated liver injury as a negative regulator of XIAP.

Histologically confirmed case of complete atrioventricular block due to hepatocellular carcinoma.

A 72-year-old man, who had been diagnosed as having hepatocellular carcinoma (HCC) with multiple extrahepatic metastasis, complained a general fatigue which appeared 2 weeks before admission. Because bradycardia was detected on physical examination, ECG was performed which revealed the complete atrioventricular (AV) block. We stopped Ca-blocker and ß-blocker, but the bradycardia persisted. He was admitted to our hospital for an emergent pacemaker implantation. On admission, he complained dyspnoea. After the surgery, he died due to deterioration of heart failure. The autopsy revealed cardiac metastasis of HCC on AV node, so it was suspected that cardiac metastasis caused the AV block. We thought that the cause of his death was the exacerbation of heart failure associated with bradycardia. It was likely that complete AV block as a very rare complication caused by cardiac metastasis of HCC influenced the prognosis of this patient.