Mice subjected to partial hepatectomy ate approximately two-thirds as much food over the first 24 hours after surgery as did

controls (Supporting Fig. 1A). Thus, the decline in body mass observed after partial hepatectomy (Fig. 1) exceeds that predicted based on decreased caloric intake alone (6% to 7% after 24-hour fast; D.A.R., unpublished observations). These results demonstrate the induction of Selleck Copanlisib a reproducible systemic catabolic response after partial hepatectomy in mice. To investigate whether the systemic metabolic response described above is specific for partial hepatectomy or a more common response to hepatic insufficiency, changes in body mass were determined in another model of hepatic regeneration, that induced by administration of CCl4.15, 16 As seen after partial hepatectomy, CCl4 treatment induced specific catabolic changes in total, lean, and fat mass prior to onset of hepatocellular proliferation, with earlier recovery of lean versus fat tissue stores (Fig. 2A-F). Mice treated with CCl4 took in approximately one-fourth as much food over the initial 24 hours (Supporting Fig. 1B). Together, these data show that systemic catabolism prior to the onset of hepatocellular proliferation occurs in two different models of liver regeneration. The data described above raise the possibility

that the systemic catabolic Torin 1 clinical trial response to a hepatic regenerative stimulus (e.g., partial hepatectomy or CCl4 exposure) might contribute to regulation of liver regeneration. If so, then the

extent of this response—like regeneration itself—should occur in proportion to the magnitude of the regenerative stimulus. One-third partial hepatectomy induces significantly less hepatocellular proliferation compared to removal of two-thirds of the liver.17, 18 Therefore, the systemic response to two-thirds partial hepatic resection was compared to that seen after one-third hepatectomy. The development of hypoglycemia and accumulation 3-mercaptopyruvate sulfurtransferase of hepatic triglycerides, which we previously reported as regulated during and important for normal liver regeneration,8, 9 was examined first. The results showed that the degree of hypoglycemia was significantly less severe (Fig. 3B) and the magnitude of hepatic triglyceride accumulation much lower (Fig. 3C) after one-third versus two-thirds hepatic resection. Further analysis showed that removal of one-third of the liver was also associated with significantly less decline in total and fat mass (Fig. 3A). The decline in lean mass after one-third hepatectomy was not significantly different than that seen after two-thirds hepatectomy (P = 0.3). These data show that catabolism of total body and fat mass after partial hepatectomy occurs in proportion to the degree of induced hepatic insufficiency.

Quantification of the gelatinolytic areas was measured with ImageJ (National Institutes of Health, Bethesda, MD). Frozen liver sections from TLR4-WT and TLR4-MT mice were incubated in 1% agarose fortified with fluorescent gelatin (Molecular Probes, Invitrogen). The sections were then incubated at 37°C in a substrate

development buffer, and ethylene diamine tetraacetic acid was used as a negative control as previously described.25 Primary LECs were cultured for 24 and 48 hours and subsequently incubated with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) reagent (Promega, Madison, WI). The absorbance of the plate was read colorimetrically at an optical density of 490 nm. Dabrafenib chemical structure Standardization and other steps were performed according to the manufacturer’s instructions. Data are expressed as means and standard errors of the mean (SEMs) of at least three independent ITF2357 purchase experiments. Groups were compared by a two-tailed Student t test. A P value less than 0.05 was considered statistically significant. As a first step in exploring a role for TLR4 in liver fibrosis–associated angiogenesis, we determined

the expression of TLR4 in LECs from both humans and mice. Confirming prior studies,26 quantitative RT-PCR analysis detected TLR4 mRNA levels in both human and murine LECs; levels were substantially elevated in comparison with other systemic human endothelial cells such as human umbilical vein endothelial cells (HUVECs), although they were less elevated than the levels of lymphocyte-positive control Raji cells (Fig. 1A). This observation was substantiated by detection of a specific immunofluorescence signal for TLR4 in isolated mouse and human LECs (Fig. 1B); this CHIR-99021 in vivo indicated that TLR4 was expressed in both

murine and human LECs. Although other TLR molecules were also expressed within LECs (data not shown), they were not pursued in further detail in this work. Instead, the present study was focused in a hypothesis-based manner on the recognition of TLR4 by LPS and its potential relevance to liver injury, fibrosis, and vascular integrity due to the proposed links of LPS with these processes. Reorganization of endothelial cells into tubelike vascular structures in Matrigel, which is called tubulogenesis, provides an in vitro estimation of the angiogenic capacity of vascular cells because a number of steps required for angiogenesis in vivo are required for tubulogenesis in vitro.15 To test TLR4 functional relevance in angiogenesis, we isolated LECs from TLR4-MT or TLR4-WT mice and measured tubulogenesis. As shown in Fig. 2A,B, although LPS prominently stimulated tubulogenesis in WT mice, both basal tubulogenesis and LPS-stimulated tubulogenesis were markedly attenuated in TLR4-MT mice. The antibiotic polymyxin-B inhibited tubulogenesis in all groups, and this further supports the role of basal LPS and TLR4 in this process.

An alternative approach would have been to examine severity of phenotypes within the NAFLD sample alone. The case-control approach provided greater power: with fewer than 600 cases of NAFLD, we were able to show genetic associations of rs738409 with P values ranging from 1 × 10−38 to 1 × 10−47, whereas in a case-only analysis, our lowest P value was 5 × 10−11. This increased power

by adding MIGen is due to the increased overall sample size as well as increased phenotypic breadth of the samples since few or no individuals in the NASH CRN just have just steatosis or no steatosis, respectively. The addition of these ancestry-matched controls did not appear to generate large numbers of false positives in that only variants near PNPLA3 strongly associated with NAFLD, whereas the other tested variants see more did not. Limitations of this work include the ascertainment of the NASH CRN on the basis of NAFLD at DAPT one timepoint and the analysis of individuals of European ancestry; thus, results may not be directly translatable to differently ascertained samples of other ancestries or be the same over time. Although we have tried to assess the effect of the G allele of rs738409 in PNPLA3 in large meta-analyses, a small

effect on metabolic syndrome components cannot be ruled out. Further the results may be affected by unmeasured confounders but the results are undiminished when controlling for measured confounders. The presence of liver disease in MIGen would cause misclassification and would bias our results towards the null, slightly reducing power compared with an equivalently sized sample known to be free of liver disease. However, this misclassification would not cause spurious associations, so the strong association between PNPLA3 and NAFLD/NASH remains valid even in this setting.

Finally, because many of the histologic subphenotypes of NAFLD are highly intercorrelated Aldehyde dehydrogenase in the NASH CRN sample, further work will be needed to better characterize and possibly distinguish the specific effects of rs738409 on these phenotypes in patients with histologic NAFLD. This is to our knowledge the first well-powered assessment of the effects on histology-based NAFLD of genetic variants previously associated with liver enzyme levels. Our results suggest that variation at PNPLA3 specifically and strongly influences the development of advanced NAFLD including NASH, fibrosis and cirrhosis. Given that PNPLA3 appears to be part of a family of enzymes that affect lipid metabolism, this suggests that altering lipid metabolism, particularly within the liver, can affect accumulation of fat and subsequent development of NAFLD. These results therefore suggest that certain inherited variations in lipid metabolism precede and could lead to the development of liver disease.

2 [95% CI, 4.8-7.8] local; 25.3 [95% CI, 22.5-28.3] limited nonlocal; and 9.7 [95% CI, 8.0-11.7] advanced nonlocal). The 3- and 5-year cumulative incidences of first recurrence were 70.8% (95% CI, 66.8-74.7) and 81.7% (95% CI, 77.7-85.3) (Fig. 1A,B). Median time to first recurrence was 18 (IQR, 7-42) months. Multivariate analysis identified age (P = 0.030), tumor size (P = 0.047), and number of nodules (P < 0.001) as significant predictors

of first recurrence (Table 2). All three variables were independent predictors of local recurrence (Supporting Appendix 1), but only age and number of nodules Selleckchem Ibrutinib correlated with nonlocal recurrences (Supporting Appendix 2). Table 3 shows the type of first recurrence as a function of time of detection and initial HCC nodule/s size. Figure 2 summarizes the events observed during follow-up and their management (details in Supporting Appendix 3). Three-fourths of the patients whose HCC recurred experienced multiple episodes of local and/or limited nonlocal recurrence, and about one-third of these ultimately developed advanced nonlocal recurrences. The median times to second, third, and fourth recurrences (measured from CRs of the previous recurrence) were 6.5 (IQR, 2.0-16.0), 4.4 (IQR, 1.0-10.0), and 2.0 (IQR, 1.0-6.0) Small molecule library months, respectively. Altogether, there were 877 episodes of recurrence: 134 (15.7%) local, 513 (58.1%) limited nonlocal

and 230 (26.2%) advanced nonlocal. Of the 134 local recurrences, 7 (4.4%) were observed in 159 HCC nodules ≤2.0 cm, 49 (12.9%) in 378 nodules > 2.0 ≤3.0 cm, and 78 (25.0%) in 312 nodules >3.0 ≤3.5 cm. Details are shown in Supporting Appendix 3. Briefly, RFA was used to treat 110 (82.0%) of the 134 local and 467 (91.0%) of the 513 limited nonlocal recurrences. CRs were obtained in 102 (92.7%) and 455 (97.4%)

cases, respectively. Of the 102 local recurrences that exhibited CRs, only seven (6.8%) had a TF. Local recurrence was detected in 54 (11.8%) of the 455 limited nonlocal recurrences with CRs. In all, 315 patients died (incidence rate: 15.4 per 100 person-years). Overall, 127 (40.3%) deaths were unrelated to the tumor (Supporting Appendix 4); there were 188 (59.7%) Nintedanib (BIBF 1120) HCC-related death (incidence rate: 9.2 per 100 person-years). Estimated cumulative overall survival rates at 3 and 5 years were 67.0% (95% CI, 62.7-70.9) and 40.1% (95% CI, 35.0-45.1) (Fig. 3A-C) and median overall survival was 43 (IQR, 12-124) months. Multivariate analysis identified Child-Pugh class B (P = 0.013), first recurrence ≤24 months after RFA (P < 0.001), local recurrence (P < 0.001), and advanced nonlocal recurrence (P < 0.001) as independent predictors of death (Table 4). Estimated 3- and 5-year cumulative tumor-specific survival rates were 78.6% (95% CI 74.5-82.1) and 56.6% (95% CI 50.6-62.1), and median tumor-specific survival was 71 (IQR: 41-124) months (Fig. 3D). Multivariate analysis identified local (P < 0.001) and advanced nonlocal recurrences (P < 0.

Itching was the most bothersome symptom reported by all patients and caregivers, across all ages. Other symptoms included xanthomas (n=6; 18%), poor nutrition/ growth (n=11; 33%), jaundice (n=9; 27%), GI/heart problems (n=6; 18%; n=5 (15%)) bone density (n=4; 12%) and pain (n=4; 12%). The most important and relevant itching impact concepts were skin damage (10 (76%) patients; 16 (80%) caregivers), difficulty staying asleep (3 (23%) patients; 16 (80%)

caregivers); difficulty falling asleep (7 (54%) patients; 11 (55%) caregivers), and mood disturbances (7 (54%) patients; 13 (65%) caregivers). To ascertain itching severity, caregivers used observation of behaviors (frequency or intensity of scratching or rubbing), impacts (sleep Palbociclib research buy disturbance, skin damage due to scratching, mood changes) and reports by the children about their symptoms to their parents. The caregiver observations were particularly valuable for children from infancy through 8 years of age, as patients in these age groups had difficulty adequately reporting symptoms. By the final three interviews, limited new information was gained about the majority of itching, impact and observation concepts, thereby http://www.selleckchem.com/products/Romidepsin-FK228.html indicating that saturation was achieved. Conclusions: In these ALGS patients with pruritus, itching was the most

impactful and bothersome symptom. Based on these data, a new instrument to assess itch severity in ALGS, the ItchRO, has been developed and is currently being validated in the context of treatment response to novel therapies. Disclosures: Linda Abetz-Webb – Consulting: Lumena Ciara Kennedy – Employment: Lumena Pharmaceuticals Bonnie Hepburn – Consulting: Lumena Pharmaceuticals Nathan Johnson – Consulting: Endpoint Outcomes Sharon Medendorp – Consulting: Lumena Pharmaceuticals Alejandro Dorenbaum – Employment:

Lumena Pharmaceutical, Stanford University; Stock Shareholder: BioMarin Pharmaceutical Benjamin L. Shneider – Consulting: Bristol Myers Squibb, Vertex; Grant/Research Support: Hyperion Therapeutics; Stock Shareholder: Bristol Myers Squibb The following people have nothing to disclose: Martha Gauthier, Binita M. Kamath Background: NAFLD is the most common chronic liver disease in children. Liver biopsy remains the standard for assessing steatosis but is limited by invasiveness, cost, and the potential Methisazone for sampling error. FibroScan® (Echosens, Paris, France) is an ultrasound-based technology used to assess fibrosis using transient elastography (TE). Recently, a new FibroScan® measurement called “”controlled attenuation parameter”" (CAP) has been developed to detect and quantify steatosis. CAP represents the ultrasonic attenuation coefficient during TE, expressed as dB/m. There are no data regarding use of CAP in the pediatric population. Objective: To assess whether the degree of steatosis as determined by liver biopsy correlates with CAP measurements in a pediatric and young adult cohort.

7, 8 Finally, the increase in the rate of hepatic encephalopathy (HE) by the shunt, the strongest argument against the TIPS treatment, was not confirmed by the study of García-Pagán et al.1 If this finding were extended to patients with Child-Pugh class A or B disease, they might also be regarded as candidates for early TIPS treatment. Because of the great influence of find more this study on the treatment strategy for variceal bleeding, specific attention should be paid to those results differing from previous studies or experiences. The results of the medical group are largely as expected.9, 10 In contrast, some results of the early TIPS group are unexpected. The fact that the authors used bleeding

and not survival as the primary endpoint reveals that they expected a small difference in survival requiring an impossibly high sample size. Indeed, the patients had advanced disease

and a mean bilirubin concentration of 3.7± 4.8 mg/dL at the baseline. Thus, approximately half of the patients had a bilirubin concentration greater than 3 mg/dL, which predicts reduced survival after TIPS.4, 11, 12 When such patients are treated electively, they have 6-week and 1-year survival rates of only 85% and 75%, respectively.13 Survival rates were, however, comparable between Child-Pugh class BTK activity inhibition A and B patients treated electively (95% and 85%) and the early TIPS group (97% and 86%). It can be speculated that bleeding might cause an acute but transient deterioration that upgrades a patient’s Child-Pugh score, which does not reliably reflect the baseline liver function.

In contrast to the study under discussion, randomized studies of secondary prophylaxis did not find a survival benefit for TIPS patients.4, 9 This may be due to the fact that these studies excluded acute bleeders and thus selected survivors with a lower risk of bleeding-related deaths. In addition, the previous studies used uncovered stents with a high rate of shunt insufficiency, which led to a higher rate of recurrent bleeding. As for HE, the results of the study by García-Pagán et al.1 and the studies of secondary prophylaxis are also different. Although TIPS increased the incidence next of HE in patients treated for secondary prophylaxis,4, 9 this was not observed in the study by García-Pagán et al. (8 patients with early TIPS and 12 patients with medical treatment). The lower rate of HE, as expected, may be due to the fact that in the study by García-Pagán, stents were initially dilated to 8 mm, and a further dilatation to 10 mm was performed only if the gradient did not decrease below the threshold of 12 mm Hg. Despite this, the mean pressure gradient after TIPS of 6.2 ± 3 mm Hg was lower than that needed and provided the chance for a further reduction in the incidence of HE with even smaller shunts.

6B,C). CL58 is therefore unlikely to inhibit HCV entry by interfering with TJ function at its antiviral dose. In order to investigate the possible interaction between CL58 and HCV envelope proteins, we performed coimmunoprecipitation

experiments using Flag-tagged CL58. Interestingly, CL58 tagged at its C terminus but not its N Ibrutinib mouse terminus was able to precipitate with both HCV glycoproteins (Fig. 7). Consistently, the antiviral effect of synthetic FLAG-tagged CL58 on HCVpp entry was confirmed (Supporting Fig. 4). This observation implies that CL58 might exert its effect via potential interaction with HCV glycoproteins. The topology/structure of the overexpressed fusion polypeptide is important for its association with HCV E1 and E2. HCV entry is a multistep event involving a number of host factors, including heparan sulfate proteoglycan, LDLR, SR-BI, CD81, CLDN1, and OCLN,8, 18 all of which are located on the plasma membrane of permissive cells. These cellular

factors now offer promising targets for novel antiviral treatments ICG-001 mw because viral entry is necessary for disease initiation, spreading, and transmission. For example, antibodies against CD81, SR-BI, and CLDN1 extracellular regions have been shown to block viral entry.19, 20 Further, compounds such as ITX 5061, a SR-BI antagonist, or atriazine compound called EI-1 also inhibit HCV entry at a postbinding step.21 More strikingly,

a novel peptide derived from the N terminus of HCV NS5A protein exerts a broad spectrum of virocidal effect on HCV and several other enveloped viruses.22 Through peptide library screening and rational design, we obtained a novel peptide, CL58, derived from check details human CLDN1, which potently inhibited HCV entry at a postbinding step. Together, our findings provide a proof of principle that a new class of inhibitors that block virus-host interactions may be developed. The finding that CL58 inhibits HCV entry is interesting for two reasons. First, a number of peptides derived from OCLN ELs have been reported to induce endocytosis of TJ proteins and interfere with TJ integrity.13-16, 23 Similarly, addition of a CLDN1 EL1 peptide (residues 53-80) to polarized cells interferes with epithelial barrier function.17 These findings make CLDN1 a relatively less attractive target for anti-HCV therapies, because reagents targeting CLDN1/OCLN ELs will likely cause leakage of important cellular barriers due to disrupted TJs. In sharp contrast, CL58 contains the first 18 aa of the CLDN1 N terminus but has no effect on CLDN1/OCLN distribution and is noncytotoxic at doses that exert potent antiviral activity. Thus, CL58 can potentially be a lead peptide for further design of useful therapeutics. Second, the observed inhibitory kinetics of CL58 suggests that CL58 acts at a postbinding stage of virus entry.

It is hoped Small molecule library purchase that the consensus strategies will be updated regularly and adopted by health authorities to improve the care of patients with HCCA in many other countries outside the Asia–Pacific region as well. “
“We read the excellent article by Harrison et al.,1 who showed that elevated baseline low-density lipoprotein levels are associated with higher sustained virological response (SVR) rates. In our experience with 32 transplant patients who suffered hepatitis C recurrence and were treated with peginterferon

alfa-2b and ribavirin, the total cholesterol (TC) levels (mg/dL) did not influence SVR.2 In this particular group of patients, the importance of parameters such as the body mass index (BMI; kg/m2), triglyceride (TGC) levels (ng/mL), and hepatic percentage of steatosis in the response to antiviral therapy was demonstrated. Ten patients (31.2%) stopped their therapy because of side effects. The observed BMI values, TC levels, TGC levels, and percentages of steatosis were confirmed to be normally distributed by the one-sample Kolmogorov-Smirnov

goodness-of-fit test procedure. Comparisons of the BMI values, TC levels, TGC levels, and percentages of steatosis ICG-001 nmr between nonresponse (NR), SVR, and sustained biochemical response (SBR) groups were analyzed by analysis of variance with the post hoc Bonferroni test, and correlations between variables were tested with the Pearson test. A univariate analysis was

performed to estimate the chance of a response according to the aforementioned variables. The BMI values (26.8 ± 3.3 kg/m2), TGC levels (245.3 ± 84.4 ng/mL), and percentages of steatosis (26.8% ± 23.6%) in the NR group (nine cases) were higher than those observed in the SVR group [six cases; 20.4 ± 2.6 kg/m2 (P < 0.001), 108.3 ± 48.4 ng/mL (P = 0.002), and 5.75% ± 2.2% (P = 0.027), respectively] and in the SBR group [seven cases; 21.5 ± 1.6 kg/m2 (P = 0.003), 132.4 ± 51.2 ng/mL (P = 0.008), and 6.2% ± 2.4% (P = 0.033), respectively]. The differences Methocarbamol between the SVR and SBR groups were not significant for the aforementioned variables. As for cholesterol, no significant differences were registered between the NR group (197.6 ± 47.3 mg/dL), the SVR group (149.3 ± 37 mg/dL), and the SBR group (153.4 ± 41.5 mg/dL). The Pearson correlation test (correlation coefficient >0.7, P < 0.001 for every correlation) showed a strong correlation between the BMI values, cholesterol levels, TGC levels, and percentages of steatosis. For patients with a BMI <25 kg/m2 and TGC levels < 160 ng/mL, the chance of SVR was 48 times higher than the chance of NR.

1 years (range 0.6-18.7 years) that included both pre- and post-LT patients.[52] For children with acute renal injury, the pediatric modified RIFLE (Risk for renal GDC-0973 supplier dysfunction, Injury to the kidney, Failure of the kidney, Loss of kidney function, and Endstage renal disease) criteria utilizes a combination of the eCCL by the Schwartz method and urine output to inform the severity of renal injury.[54] Renal insufficiency that would necessitate combined liver and kidney transplant (CLKT) is less common in children than adults.[55] Renal dysfunction among children with chronic liver disease can be quite variable. For example,

children with biliary atresia tend to have good renal function prior to and following liver transplant,[56, 57] while those with tyrosinemia may have a glomerular filtration rate of less than 55 mL/min/1.73 m2.[58] Significant renal disease can be associated with primary hyperoxaluria, congenital hepatic fibrosis, and methylmalonic acidemia. Renal dysfunction prior to LT can be exacerbated following LT, particularly in children with inborn errors CYC202 mw of metabolism, alpha-1-antitrypsin deficiency (A1ATD), and Alagille syndrome (AGS).[59-62] Increased susceptibility to renal toxicity caused by calcineurin inhibitors may be attributed to associated genetic polymorphisms

in the ABCB1 gene.[63] 16. Renal function should be assessed in all patients, with special emphasis on those with metabolic liver diseases associated with renal dysfunction (1-B) and those at increased risk for calcineurin inhibitor toxicity. (2-B) 17. Serum creatinine alone should not be used to assess renal function (1-B); either cystatin C (2-B) or the revised Schwartz Formula (2-C) should be used to estimate the glomerular filtration rate in children with chronic liver disease. see more 18. The modified Risk for Renal Dysfunction, Injury, Failure, Loss, and Endstage

renal disease could be used to assess the degree of acute renal injury. (2-B) Dental caries due to frequent and prolonged bottle-feeding occur in children with endstage liver disease.[64, 65] A survey of transplant centers in the United States noted that a dental infection prior to transplantation resulted in cancellation or postponement of LT (38% of responding sites) and post-LT sepsis from a suspected dental source (27% of sites).[66] Preventive oral health care strategies are important in this patient population.[66, 67] 19. Children with endstage liver disease should receive a careful oral examination looking for evidence of dental caries, gingival disease, or dental abscess; referral to a pediatric dentist should occur if abnormalities are identified. (2-B) General anesthesiology assessment should include determination of venous access, review of cardiovascular, respiratory, gastrointestinal, renal, central nervous system, hepatic, and hematological systems.

51 In patients with TERT or TERC mutations, aplastic PR-171 order anemia or pulmonary fibrosis may be the only clinical presentation.11, 12 Most patients with telomerase mutations and aplastic anemia do not have respiratory failure, and most patients with pulmonary fibrosis do not have cytopenias, suggesting that environmental factors contribute to disease development in a susceptible patient; for example, most patients with telomerase mutations and pulmonary fibrosis are smokers.12, 13 In pedigrees of telomerase mutations, liver disease and aplastic anemia presented alone in different affected individuals, further suggesting a role for environmental factors. In one study, ≈3%

of patients with idiopathic pulmonary fibrosis also had cryptogenic cirrhosis, indicating some overlap between clinical features.52 Wnt inhibitor review In conclusion, telomerase mutations resulting in telomere erosion appear to be a genetic risk factor for human cirrhosis and may predispose affected subjects to disease progression in combination with environmental injury, further supporting telomere attrition as a causal event in cirrhosis pathophysiology. Establishing how shortened telomeres increase the risk of cirrhosis may allow for the design of future therapies to reduce the risk of hepatic fibrosis in susceptible populations. Patients with mutations

also may be appropriate targets for more aggressive forms of therapy to treat their primary disease given their increased risk of cirrhosis. Additional Supporting Thiamet G Information may be found in the online version of this article. “
“Aim:  Several investigators have shown that interferon (IFN) therapy can suppress the recurrence of hepatocellular carcinoma (HCC) after curative treatment. We investigated the effect of IFN therapy on the first and second HCC recurrence following hepatic resection of

hepatitis C virus (HCV)-related HCC. Methods:  Subjects included 166 patients who had undergone curative resection for a single HCV-related HCC. We analyzed the outcome after initial hepatic resection and risk factors of a second HCC recurrence following treatment for the first HCC recurrence. Results:  Using multivariate analysis, a non-sustained virological response (non-SVR) was significantly associated with a high incidence of first HCC recurrence. The rate of second HCC recurrence tended to be higher in the non-SVR group than in the SVR group. In the patients with recurrence of multiple tumors or who received non-curative treatment for recurrent HCC, the second HCC recurrence rates were significantly higher. Multivariate analysis demonstrated that non-curative treatment for first HCC recurrence was an independent risk factor for a second HCC recurrence. Among the patients who received curative treatment for their first HCC recurrence, the rates of second recurrence were significantly higher in the non-SVR group than in the SVR group.