Bimodal peaks of liver stiffness in a case of drug-induced liver injury.

A 69-year-old male complained of general fatigue and presented with elevation of liver enzymes without any cause of liver injury. We diagnosed him with hepatocellular drug-induced liver injury (DILI). Liver stiffness, which was evaluated according to the shear wave velocity (SWV) using virtual touch tissue quantification, was serially observed during hospitalization. A fast SWV was noted on the date of admission, indicating a "hard" degree of liver stiffness. The SWV gradually decreased until the 20th hospital day. However, the patient's liver enzymes again became elevated on the 20th hospital day, and the SWV simultaneously increased in association with a rise in the total bilirubin level. The laboratory data for the second peak of the SWV indicated mixed-type DILI; therefore, the patient's pathological state transitioned from the hepatocellular type to the mixed type. A liver biopsy performed before discharge revealed a state of recovery from acute inflammation without fibrotic changes. We conclude that the second peak of the SWV may be affected by the presence of intrahepatic cholestasis. We herein report the occurrence of bimodal peaks of liver stiffness in a patient with DILI. In such cases, each peak of liver stiffness may be the result of a different pathological mechanism, namely acute inflammation versus acute intrahepatic cholestasis. Although the detailed mechanisms underlying the development of liver stiffness due to intrahepatic cholestasis remain unclear, this case presented a limitation of virtual touch tissue quantification for evaluation of liver stiffness as fibrosis marker in the liver with intrahepatic cholestasis.

Efficacy of hepatic arterial infusion chemotherapy using 5-fluorouracil and systemic pegylated interferon α-2b for advanced intrahepatic cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is categorized into intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). The prognosis of ICC is far worse than that of ECC. In this pilot trial, the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) combined with subcutaneous administration of pegylated interferon (PEG-IFN) α-2b in patients with advanced ICC was evaluated. METHODS: The subjects were 20 advanced ICC patients treated using subcutaneous PEG-IFNα-2b (50-100 µg on day 1 of every week, for 4 weeks) and intra-arterial infusion of 5-FU (250 mg/day for 5 h on days 1-5 of every week, for 4 weeks). One treatment cycle lasted 4 weeks. Therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for ≥1 cycle. RESULTS: The objective early response rate was 60.0 %. Cumulative survival rates were 71.6 % at 6 months, 53.7 % at 12 months, 28.6 % at 18 months, and 14.3 % at 24 months. Median survival time was 14.6 months. All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatment-related deaths were not observed. CONCLUSIONS: The combination therapy of PEG-IFNα-2b and 5-FU for advanced ICC seems not to be worse than the results of the previous studies. Furthermore, most adverse effects are transient and well tolerated. Based on the present findings, this combination therapy may be useful for patients with advanced ICC as one of the therapeutic option.

Therapeutic efficacy of combination therapy with intra-arterial 5-fluorouracil and systemic pegylated interferon α-2b for advanced hepatocellular carcinoma with portal venous invasion.

BACKGROUND: The prognosis of advanced hepatocellular carcinoma (HCC) remains poor, particularly among patients with portal vein tumor thrombosis (PVTT). This study evaluated the efficacy of combined 5-fluorouracil and pegylated interferon (PEG-IFN) α-2b in patients with advanced HCC. METHODS: Subjects comprised 59 HCC patients with PVTT treated using subcutaneous administration of PEG-IFNα-2b (50-100 µg on day 1 of each week for 4 weeks) and intra-arterial infusion of 5-fluorouracil (250 mg/d for 5 hours on days 1-5 of each week for 4 weeks). One treatment cycle lasted 4 weeks. The current therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for ≥1 cycle. The primary efficacy endpoint was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival. RESULTS: Objective early response rate was 73.0%. Cumulative PFS rates were 67.4% at 6 months, 30.2% at 12 months, 25.9% at 18 months, and 20.7% at 24 months. Median PFS was 9.7 months. Cumulative survival rates were 82.4% at 6 months, 73.6% at 12 months, 52.8% at 24 months, and 44.0% at 36 months. Median survival time was 29.9 months. All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatment-related deaths were not observed. CONCLUSIONS: Although a prospective randomized controlled trial using a larger population of patients with advanced HCC is needed to evaluate combination therapy with 5-fluorouracil and PEG-IFNα-2b, this new combination therapy may be useful for patients with advanced HCC.

Serial changes of liver stiffness measured by acoustic radiation force impulse imaging in acute liver failure: a case report.

Acoustic radiation force impulse (ARFI) imaging is a new technology used to determine liver elasticity. We report the case of a patient that survived hyperacute-type acute liver failure (ALF) and who showed a dramatic change in the value of shear wave velocity (SWV) measured by ARFI, which corresponded with the severity of her liver damage. The value of SWV increased significantly up to 3.6 ± 0.3 m/s during the encephalopathy phase and then decreased along with the recovery of liver function, the blood flow of the right portal vein, and the liver volume. These findings suggest the value of SWV in ALF as a reliable marker of liver tissue damage. Further investigations of the pathophysiological significance of SWV in ALF are warranted.

Conservative treatment of an aortoesophagial fistula after endovascular stent grafting for a thoracic aortic aneurysm.

BACKGROUND: Aortoesophageal fistula (AEF) is an uncommon condition that presents a problem in therapy because of the high rate of morbidity and mortality associated with its surgical management and the uniformly fatal outcome of medical treatment. In this article we describe a case of secondary AEF after endoluminal stent grafting of the thoracic aorta, which was observed by only conservative management and followed up for 14 months with no signs of recurrent hemorrhage or chronic mediastinitis. CASE REPORT: A 54-year old man with hepatocellular carcinoma (HCC) was admitted to our hospital because of tarry stool. He had a history of traumatic aneurysm, and undergone segmental replacement with a stent graft three years ago. After admission, Esophagogastroduodenoscopy and computed tomography identified AEF. He was treated conservatively, because his stage of HCC was advanced. Oral intake was prohibited, and the patient received proton pump inhibitors, intravenous hyperalimentation and antibiotics. Afterwards, no signs of hemorrhage were observed. Although oral intake was resumed after that, another bleeding event or development of mediastinitis was not observed. Subsequently, He was received chemotherapy for advanced HCC, and we observed downstaging of his advanced HCC. CONCLUSIONS: Although we observed 14 months survival in our case under conservative management of secondary AEF, it seems that the treatment of secondary AEF should do the operative management.

Combination therapy of intra-arterial 5-fluorouracil and systemic pegylated interferon α-2b for advanced hepatocellular carcinoma.

BACKGROUND: This study evaluated the efficacy of combined 5-fluorouracil (5-FU) and pegylated interferon (PEG-IFN) α-2b in patients with advanced hepatocellular carcinoma (HCC). METHODS: Fifty patients with portal vein tumor thrombosis were enrolled. Of these, 21 patients were treated using subcutaneous administration of PEG-IFNα-2b and intra-arterial infusion of 5-FU (5-FU/PEG-IFN group), 12 patients were treated using intramuscular administration of IFNα-2b and intra-arterial infusion of 5-FU (5-FU/IFN group), and 17 patients received intra-arterial infusion chemotherapy with lipiodol-cisplatin (CDDP) suspension (CDDP group). RESULTS: The objective early response rate was significantly higher in the 5-FU/PEG-IFN group than in the 5-FU/IFN or CDDP groups (71.4 vs. 8.3% and 17.6%, respectively; P < 0.0001). Cumulative survival rates at 6 and 12 months were 83.8 and 77.8% in the 5-FU/PEG-IFN group, 60.8 and 16.2% in the 5-FU/IFN group, and 58.4 and 12.5% in the CDDP group, respectively. The cumulative survival rate was significantly higher in the 5-FU/PEG-IFN group than in the other 2 groups (P = 0.0272). Serious complications and treatment-related deaths were not observed in any of the 3 groups. CONCLUSION: Although a prospective randomized controlled trial using a larger population of patients with advanced HCC is needed to evaluate combination therapy with 5-FU and PEG-IFNα-2b, this new combination therapy may be useful for patients with advanced HCC.

Effects of branched-chain amino acid-enriched nutrient for patients with hepatocellular carcinoma following radiofrequency ablation: a one-year prospective trial.

BACKGROUND AND AIM: This prospective control study examined whether supplementation with branched-chain amino acid (BCAA)-enriched nutrients can help maintain and improve residual liver function and nutritional status in cirrhotic patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). METHODS: Subjects were 49 patients with hepatitis C-related HCC who underwent RFA. Two groups were formed: BCAA group (BCAA-enriched nutrient, aminoleban EN) and controls (standard diet only). Event-free survival rate, liver function tests, and Short Form (SF)-8 scores were evaluated in both groups before and one year after RFA. Energy metabolism using indirect calorimetry was measured before and after 3 months. RESULTS: Complete data were obtained from 35 patients (BCAA group, n = 20; controls, n = 15). Six events (death, recurrence of HCC, rupture of esophageal varices and liver failure) occurred during the observation period, but frequencies of these events did not differ between groups. Event-free survival rate tended to be higher in the BCA group than in controls. Among the parameters of liver function, serum albumin level was only significantly increased over 6 months, and remained at similar values for one year (P < 0.05). SF-8 scores for general health, physical functioning, and social functioning were significantly elevated in the BCAA group (P < 0.05). Non-protein respiratory quotient was significantly improved in the BCAA group (P < 0.01). CONCLUSION: Supplementation with BCAA-enriched nutrients for one year in cirrhotic patients with HCC after RFA therapy can perform safety and improve both nutritional state and quality of life.

Non-invasive evaluation of liver fibrosis using acoustic radiation force impulse imaging in chronic hepatitis patients with hepatitis C virus infection.

BACKGROUND/AIMS: Acoustic radiation force impulse (ARFI) imaging is a new technology for performing liver elastography. However, use of this technique to estimate the degree of fibrosis in chronic liver disease (CLD) related to hepatitis C virus (HCV) infection has not yet been established. We evaluated the validity, accuracy and flexibility of the ARFI method in CLD. METHODOLOGY: Subjects comprised 30 patients with chronic hepatitis (CH), 30 patients with liver cirrhosis (LC) and 10 healthy subjects (controls). All patients had HCV infection. Elastography of the liver was performed at different sites using the ARFI method. Relationships between shear wave velocity (SWV) obtained by ARFI, clinical diagnosis, serum parameters of liver function and fibrosis in the liver were evaluated. Moreover, cut-off values for differential diagnosis between CH and LC were estimated using area under the receiver operating characteristics (AUROC). RESULTS: Mean SWV (+/- standard deviation) was 2.67 +/- 1.18 m/s, 1.33 +/- 0.54 m/s and 0.99 +/- 0.21 m/s in the LC, CH and control groups, respectively. SWV was significantly higher in the LC group than in the CH and control groups (p < 0.0001), and in the CH group than in the control group (p = 0.0023). SWV in each stage of fibrosis was 1.09 +/- 0.22 m/s in F0-1, 1.24 +/- 0.52 m/s in F2, 1.61 +/- 0.79 m/s in F3, and 2.35 +/- 1.11 m/s in F4. SWV correlated significantly with serum total bilirubin, alanine aminotransferase, cholesterol, albumin, platelet counts, prothrombin time, fibrosis markers, hyaluronic acid and type IV collagen. A steady stepwise increase in elasticity correlated significantly with severity of hepatic fibrosis (p = 0.9772; p = 0.002). Diagnostic ability for LC was superior in ARFI (AUROC, 0.930 in ARFI; 0.846 in aspartate aminotransferase to platelet ratio index; 0.829 in Forns' index; and 0.785 in platelet count). CONCLUSIONS: ARFI is extremely useful for distinguishing between CH and LC, and SWV might correlate significantly with degree of progression in CLD with HCV infection.

Interferon-gamma down-regulates expression of tumor necrosis factor-alpha converting enzyme/a disintegrin and metalloproteinase 17 in activated hepatic stellate cells of rats.

Interferon-gamma (IFN-gamma) is a potent cytokine that exerts antiproliferative and antifibrogenic effects on hepatic stellate cells (HSCs). Although therapeutic application of IFN-gamma for chronic liver diseases is anticipated, the responses of activated HSCs to IFN-gamma have not been fully elucidated. To seek unknown molecules and pathways that might be responsive to IFN-gamma treatment in activated HSCs, we examined global protein expression profiles using two-dimensional gel electrophoresis combined with peptide mass fingerprint. We identified 76 increased and 59 decreased spots (>3-fold increase or decrease, total 135 spots). Database analysis suggested that the following four pathways were involved in alteration of HSCs toward a quiescent phenotype in response to IFN-gamma: i) down-regulation of the TGF-beta and PDGF signaling pathways; ii) reorganization of intermediate filaments; iii) up-regulation of fatty acid metabolism; iv) decreased expression of TNF-alpha converting enzyme (TACE)/a disintegrin and metalloproteinase 17 (ADAM17), which is responsible for shedding of the proinflammatory cytokine TNF-alpha. We confirmed down-regulation of both ADAM17 expression and soluble TNF-alpha secretion by Western blotting and real-time PCR. TNF-alpha mRNA/protein expression was not altered by IFN-gamma treatment. Our data suggest that IFN-gamma stimulation suppresses the activated phenotype of HSCs in vitro through multiple pathways. Of these pathways, down-regulation of ADAM17 expression may play a role in blocking the auto-activation mechanism of cultured HSCs through activation of the TNF-alpha signaling and shedding pathways.

Comparison of Predicted Energy Expenditure in Japanese Patients with Non-Alcoholic Fatty Liver Disease to Establish a Suitable Nutrition Intervention.

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing in Western and Asian countries, including Japan. NAFLD includes the condition of non-alcoholic steatohepatitis, which can progress to end-stage liver disease. Weight reduction based on basal energy expenditure (BEE) is considered to be the only established treatment for patients with NAFLD. However, a formula that is suitable for predicting BEE in Japanese patients with NAFLD remains to be determined. We enrolled 77 Japanese patients who were diagnosed with NAFLD according to histological findings. Their BEE was measured (mBEE) by indirect calorimetry. Physical findings, laboratory data and their predicted BEE (pBEE) values were compared with the mBEE values. All pBEE values were evaluated as a root mean squared error (RMSE) and an accurate estimation. The mBEE values correlated with the patient's weight, skeletal muscle mass, and age. Most of predictive formulae overestimated BEE in NAFLD patients in the present study. In contrast, the Kyoto equation provided an accurate prediction. Most prediction formulae included body weight as a reference of the skeletal muscle mass and were established using data from a healthy study population. However, differences in muscle mass exist among different races, and body composition differs between healthy individuals and those with high BMIs. The improved accuracy of the Kyoto equation is likely due to the similar backgrounds of the patients in the present study. The Kyoto equation is the most suitable formula for estimating BEE in Japanese patients with NAFLD.

Liver cirrhosis induced by long-term administration of a daily low dose of amiodarone: a case report.

The anti-arrhythmic agent amiodarone (AD) is associated with numerous adverse effects, but serious liver disease is rare. The improved safety of administration of daily low doses of AD has already been established and this regimen is used for long-term medication. Nevertheless, asymptomatic continuous liver injury by AD may increase the risk of step-wise progression of non-alcoholic fatty liver disease. We present an autopsy case of AD-induced liver cirrhosis in a patient who had been treated with a low dose of AD (200 mg/d) daily for 84 mo. The patient was a 85-year-old male with a history of ischemic heart disease. Seven years after initiation of treatment with AD, he was admitted with cardiac congestion. The total dose of AD was 528 g. Mild elevation of serum aminotransferase and hepatomegaly were present. Liver biopsy specimens revealed cirrhosis, and under electron microscopy numerous lysosomes with electron-dense, whorled, lamellar inclusions characteristic of a secondary phospholipidosis were observed. Initially, withdrawal of AD led to a slight improvement of serum aminotransferase levels, but unfortunately his general condition deteriorated and he died from complications of pneumonia and renal failure. Long-term administration of daily low doses of AD carries the risk of progression to irreversible liver injury. Therefore, periodic examination of liver function and/or liver biopsy is required for the management of patients receiving long-term treatment with AD.

Proliferation of mouse liver stem/progenitor cells induced by plasma from patients with acute liver failure is modulated by P2Y2 receptor-mediated JNK activation.

BACKGROUND: We recently reported that acute liver failure plasma (ALF-P) promotes the proliferation of mouse liver oval cells (OCs) through c-jun N-terminal kinase (JNK) activation. The aim of this study was to investigate the mechanism by which ALF-P induces JNK activation and OC proliferation. METHODS: OCs and primary hepatocytes were exposed to ALF-P or normal control plasma (NC-P). Cell proliferation and activation of JNK and other JNK signaling molecules were detected subsequently. Next, we determined the effects of extracellular adenosine triphosphate (ATP) and ATP receptors on ALF-P-stimulated cell growth. Finally, the relationship between the tumor necrosis factor alpha (TNFα) and ATP receptor pathways was investigated. RESULTS: Cell proliferation accompanied by JNK activation was only observed in ALF-P-stimulated OCs. ALF-P stimulated the activation of SEK1/MKK4 and ATF2, but not c-Jun. Both PPADS (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) treatment and P2Y2 (G-protein-coupled) small interfering RNA (siRNA) transfection blocked the effects of ALF-P on cell proliferation and JNK activation. However, ATP levels in ALF-P were significantly lower than that in NC-P, and ATP did not stimulate the proliferation of OCs. On the other hand, TNFα stimulated JNK activation and proliferation of OCs. TNFα receptor antagonist partly inhibited the ALF-P-stimulated proliferation of OCs. Moreover, PPADS significantly inhibited TNFα-stimulated cell proliferation, induced apoptosis, and inhibited the activation of JNK. However, our data showed no significant difference in plasma TNFα levels between the NC-P and ALF-P samples. CONCLUSIONS: JNK activation induced by P2Y2 receptor crosstalk with the TNFα signaling pathway is important in mediating the effects of ALF-P on the proliferation and survival of OCs.

A disintegrin and metalloproteinase 17 (ADAM17) mediates epidermal growth factor receptor transactivation by angiotensin II on hepatic stellate cells.

AIMS: Epidermal growth factor receptor (EGFR) transactivation induced by angiotensin II (Ang II) participates in the progression of various diseases. A disintegrin and metalloproteinase 17 (ADAM17) is thought to promote renal fibrosis, cardiac hypertrophy with fibrosis and atherosclerosis by activation of the EGFR through secretion of EGFR ligands. The purpose of this study was to investigate whether Ang II-induced EGFR transactivation occurs on hepatic stellate cells (HSCs) and whether the reaction is mediated via ADAM17. MAIN METHODS: Ang II-induced EGFR transactivation and cellular proliferation of the human HSC line LI90 were investigated using Western blotting and ATP assay, respectively. Ang II-induced secretion of mature amphiregulin into the cell culture medium was evaluated by enzyme-linked immunosorbent assay (ELISA). KEY FINDINGS: An inhibitor of ADAM17, TAPI-1, as well as antagonists of EGFR and angiotensin II type-1 receptor (AT1), attenuated Ang II-induced EGFR transactivation and proliferation of LI90 cells. Furthermore, silencing of ADAM17 inhibited Ang II-induced secretion of mature amphiregulin in addition to EGFR transactivation. SIGNIFICANCE: These results indicate that ADAM17 mediates Ang II-induced EGFR transactivation on HSCs, and that this process may participate in the progression of liver fibrosis.

Therapeutic efficacy of transarterial chemo-embolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma.

AIM: To evaluate the efficacy of transarterial chemoembolization (TACE) using a suspension of a fine-powder formulation of cisplatin (DDPH) in lipiodol (LPD) in the treatment of hepatocellular carcinoma (HCC). METHODS: The subjects were 262 HCC patients treated with TACE using a DDPH-LPD suspension. The DDPH-LPD suspension was prepared by mixing 50 mg of DDPH into 10 mL of LPD. TACE was repeated when treated lesions relapsed and/or new hepatic lesions were detected. These patients received additional TACE using the same agent. TACE was repeated until complete regression of the tumor was obtained. The primary efficacy endpoint of the current study was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival. RESULTS: The objective early response rate was 43.6%. Cumulative PFS rates were 56.7% at 6 mo, 23.1% at 12 mo, 13.4% at 18 mo, and 10.5% at 24 mo. The median PFS was 6.6 mo. Cumulative survival rates were 90.6% at 6 mo, 81.9% at 12 mo, 70.5% at 24 mo, and 58.8% at 36 mo. Median survival time was 46.6 mo. All adverse reactions were controllable by temporary suspension of treatment. No serious complications or treatment-related deaths were observed. CONCLUSION: TACE using a suspension of DDPH in LPD may be a useful treatment for HCC.

Non-invasive determination of hepatic steatosis by acoustic structure quantification from ultrasound echo amplitude.

AIM: To use leptin-deficient (ob/ob) mice with demonstrated differences in steatosis levels to test a new diagnostic method using the acoustical structure quantification (ASQ) mode and the associated analytical parameter, "focal disturbance ratio" (FD-ratio). METHODS: Nine ob/ob mice, at 5, 8, and 12 wk of age (n = 3 in each age group), were used as models for hepatic steatosis. Echo signals obtained from ultrasonography in the mice were analyzed by ASQ, which uses a statistical analysis of echo amplitude to estimate inhomogeneity in the diagnostic region. FD-ratio, as calculated from this analysis, was the focus of the present study. FD-ratio and fat droplet areas and sizes were compared between age groups. RESULTS: No fibrosis or inflammation was observed in any of the groups. The fat droplet area significantly (P < 0.01) increased with age from 1.25% ± 0.28% at 5 wk to 31.07% ± 0.48% at 8 wk to 51.69% ± 3.19% at 12 wk. The median fat droplet size also significantly (P < 0.01) increased with age, from 1.33 (0.55-10.52) µm at 5 wk, 2.82 (0.61-44.13) µm at 8 wk and 6.34 (0.66-81.83) µm at 12 wk. The mean FD-ratio was 0.42 ± 0.11 at 5 wk, 0.11 ± 0.05 at 8 wk, and 0.03 ± 0.02 at 12 wk. The FD-ratio was significantly lower at 12 wk than at 5 wk and 8 wk (P < 0.01). A significant negative correlation was observed between the FD-ratio and either the fat droplet area (r = -0.7211, P = 0.0017) or fat droplet size (r = -0.9811, P = 0.0052). CONCLUSION: This tool for statistical analysis of signals from ultrasonography using the FD-ratio can be used to accurately quantify fat in vivo in an animal model of hepatic steatosis, and may serve as a quantitative biomarker of hepatic steatosis.

Transcatheter arterial chemoembolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma.

AIM: To evaluate the efficacy of transcatheter arterial chemoembolization (TACE) using a suspension of a fine-powder formulation of cisplatin (DDPH) for hepatocellular carcinoma (HCC). METHODS: The study population was comprised of 164 patients who were treated by TACE alone. Of these patients, 76 underwent TACE using a suspension of DDPH in lipiodol (LPD) (DDPH group), and the remaining 88 underwent TACE with an emulsion of doxorubicin (ADM) with LPD (ADM group). We compared the DDPH group with the ADM group in terms of the objective early response rate, progression free survival (PFS) and overall survival (OS). RESULTS: The objective early response rate in the DDPH group was significantly higher than that in the ADM group (54% vs 24%, P < 0.001). The PFS rate in the DDPH group was also significantly higher than that in the ADM group (P < 0.001). Moreover, the OS in the DDPH group was significantly longer than that in the ADM group (P = 0.002). Although the incidence rate of nausea or vomiting in the DDPH group was higher than that in the ADM group, the ADM group showed a higher incidence rate of the adverse events of hepatic arterial damage and leucopenia. No other serious complications were observed in either group. CONCLUSION: We conclude that TACE using a suspension of DDPH in LPD could be a useful treatment for HCC.

Changes in liver function parameters after percutaneous radiofrequency ablation therapy in patients with hepatocellular carcinoma.

AIM: To evaluate changes in liver function parameters and risk factors 1 year after percutaneous radiofrequency ablation (RFA) therapy in patients with hepatocellular carcinoma (HCC). METHODS: Subjects in this retrospective study comprised 45 patients with HCC who underwent RFA therapy (RFA alone, n = 25; transcatheter arterial embolization therapy before RFA, n = 20) and showed no recurrence of HCC 1 year after RFA. Serial changes in serum total bilirubin, albumin, prothrombin time and Child-Pugh score (CPs) were evaluated before and after RFA. In addition, Cox proportional hazards regression analysis was used to clarify risk factors for aggravation of liver function after RFA therapy. RESULTS: Serum albumin levels showed a significant decrease from before (3.6 +/- 0.4 g/dL) to 12 months after RFA therapy (3.2 +/- 0.4 g/dL; P