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Post-induction hypotension (PIH) during general anesthesia is a serious concern due to its high incidence and association with adverse postoperative outcomes and prognosis. We prospectively enrolled consecutive 1,603 patients scheduled for non-cardiac and cardiac surgery under general anesthesia. The primary outcome was defined as the lowest mean blood pressure from induction of general anesthesia to the start of surgery: post-induction blood pressure (PIB). Multivariable regression analysis was used to investigate the relationships between PIB and preoperative echocardiographic measurements, types and doses of anesthetic agents, and preoperative comorbidities and oral medication. Left ventricle regional wall motion abnormality (RWMA) and lower estimated glomerular filtration rate significantly associated lower PIB. Factors significantly associated with higher PIB were high BMI, beta blockers, high pre-induction mean blood pressure, and starting induction in the afternoon. Sevoflurane and prophylactic norepinephrine use were associated with higher PIB as anesthetic interventions. Significant interactions were found between sevoflurane and RWMA (P for interaction: 0.01). This is the first study to demonstrate the feasibility of intervening in the selection of anesthetic agents based on echocardiographic findings and to recommend the use of sevoflurane and prophylactic norepinephrine for the prevention of PIH, especially in patients with RWMA., (© 2024. The Author(s).)

Purpose: Nurses routinely assess respiration of hospitalized children; however, respiratory rate measurements are technically difficult due to rapid and small chest wall movements. The aim of this study is to reveal the respiratory status of small children undergoing minor surgery with load cells placed under the bed legs, and to test the hypothesis that respiratory rate (primary variable) is slower immediately after arrival to the ward and recovers in 2 h., Methods: Continuous recordings of the load cell signals were performed and stable respiratory waves within the 10 discriminative perioperative timepoints were used for respiratory rate measurements. Apnea frequencies were calculated at pre and postoperative nights and 2 h immediately after returning to the ward after surgery., Results: Continuous recordings of the load cell signals were successfully performed in 18 children (13 to 119 months). Respiratory waves were appraisable for more than 70% of nighttime period and 40% of immediate postoperative period. There were no statistically significant differences of respiratory rate in any timepoint comparisons (p = 0.448), thereby not supporting the study hypothesis. Respiratory rates changed more than 5 breaths per minute postoperatively in 5 out of 18 children (28%) while doses of fentanyl alone did not explain the changes. Apnea frequencies significantly decreased 2 h immediately after returning to the ward and during the operative night compared to the preoperative night., Conclusion: Respiratory signal extracted from load cell sensors under the bed legs successfully revealed various postoperative respiratory pattern change in small children undergoing minor surgery., Clinical Trail Registration: UMIN (University Hospital Information Network) Clinical Registry: UMIN000045579 ( https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000052039 )., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Background: Severe hypotension immediately after induction of general anesthesia (post-induction hypotension) is a common complication and is associated with a poor postoperative outcome. We hypothesized that post-induction hypotension results from cardiac dysfunction which can be assessed by preoperative echocardiography., Methods: We retrospectively enrolled 200 patients who had undergone elective surgery within 6 months after preoperative transthoracic echocardiography. The incidence of post-induction hypotension identified from anesthesia records was defined as a decrease in mean blood pressure to ≤50 mmHg after injection of induction anesthetics prior to surgery. Logistic regression analysis of patient characteristics and echocardiographic variables was used to identify the independent factors for post-induction hypotension., Results: Post-induction hypotension was found in 63 of the 200 cases (incidence 32%). Independent risk factors for post-induction hypotension were the presence of a regional wall motion abnormality (RWMA) [odds ratio (OR), 6.65.; 95% confidence interval (CI), 1.76 - 25.10], an elevated E/e' (OR, 1.13; 95% CI, 1.00 - 1.28), female gender (OR, 3.61; 95% CI, 1.37 - 9.56), and the use of an angiotensin II receptor blocker (OR, 3.17; 95% CI, 1.12 - 8.96)., Conclusions: Assessment of RWMA and E/e' with preoperative transthoracic echocardiography might be helpful for stratification of patients at a risk of post-induction hypotension in general anesthesia., Competing Interests: Declaration of Competing Interest The authors declares that there is no conflict of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Background: In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. In the surveillance of very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona clinical stage 0), we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-Ⅱ are not so useful. Therefore, we must survey with imaging modalities. The superiority of magnetic resonance imaging (MRI) over ultrasound (US) to detect HCC was confirmed in many studies. Although enhanced MRI is now performed to accurately diagnose HCC, in conventional clinical practice for HCC surveillance in liver diseases, unenhanced MRI is widely performed throughout the world. While, MRI has made marked improvements in recent years., Aim: To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously., Methods: In 394 patients with very small HCC nodules, those who underwent MRI and US at nearly the same time (on the same day whenever possible or at least within 14 days of one another) at the first diagnosis of HCC were selected. The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US., Results: The sensitivity of unenhanced MRI for detecting very small HCC was 95.1% (97/102, 95% confidence interval: 90.9-99.3) and that of unenhanced US was 69.6% (71/102, 95% confidence interval: 60.7-78.5). The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US ( P < 0.001). Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful, S 7-8 was identified in 51.7%., Conclusion: Currently, unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The oral nucleos(t)ide analogue, entecavir (ETV) was demonstrated to reduce the rate of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis. However, the reduction of HCC differs in various regions of the world., Aim: To investigate the reduction of HCC development due to ETV therapy by meta-analysis., Methods: We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed (2004-2019)., Results: The regions with the most marked reduction in HCC development due to ETV therapy were Spain (1.0%/year) and Canada (Southern part, 1.3%/year), and the most ineffective areas were South Korea (3.6%-3.8%/year), China (3.3%/year), Taiwan (2.4%-3.1%/year), and Hong Kong (2.8%/year). Following ETV administration, the incidence of HCC in genotype D regions (1.89% ± 0.28%/year, mean ± SE) was significantly lower than that in genotype C regions (2.91% ± 0.24%/year, P < 0.01). With regard to the initial HBV-DNA level, in genotype C patients (average: 5.61 Log 10 IU/mL) this was almost the same as that in genotype D patients (average: 5.46 Log 10 IU/mL). Moreover, there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment., Conclusion: The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent., Competing Interests: Conflict-of-interest statement: Nozaki A has received research funding from Gilead Sciences and Abb Vie. Tarao K, Chuma M, Maeda S, Taguri M declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are relevant as a larger tumor size is more frequently associated with microvascular invasion and/or satellites., Aim: To examine the impact of the tumor marker alpha-fetoprotein (AFP) or PIVKA-II in detecting very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona stage 0) in the large number of very small HCC. The difference in the behavior of these tumor markers in HCC development was also examined., Methods: A total of 933 patients with single-nodule HCC were examined. They were subdivided into 394 patients with HCC nodules ≤ 2 cm in maximum diameter and 539 patients whose nodules were > 2 cm. The rates of patients whose AFP and PIVKA-II showed normal values were examined., Results: The positive ratio of the marker PIVKA-II was significantly different ( P < 0.0001) between patients with nodules ≤ 2 cm in diameter and those with nodules > 2 cm, but there was no significant difference in AFP ( P = 0.4254). In the patients whose tumor was ≤ 2 cm, 50.5% showed normal levels in AFP and 68.8% showed normal levels in PIVKA-II. In 36.4% of those patients, both AFP and PIVKA-II showed normal levels. The PIVKA-II-positive ratio was markedly increased with an increase in the tumor size. In contrast, the positivity in AFP was increased gradually and slowly., Conclusion: In the surveillance of very small HCC nodules (≤ 2 cm in diameter, Barcelona clinical stage 0) the tumor markers AFP and PIVKA-II are not so useful., Competing Interests: Conflict-of-interest statement: Tanaka K has received research funding from Bristol-Myers Squibb and Abb Vie; Nozaki A has received research funding from Gilead Sciences; Tarao K, Komatsu H, Komatsu T, Taguri M, Chuma M, Numata K and Maeda S, declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Coagulation function dynamically changes during cardiac surgery and is normalized after surgery. The authors investigated changes of coagulation function during cardiac surgery and after mimicked salvaged blood transfusion (SBT), and determined background risk factors for coagulation dysfunction by thromboelastmetry including maximum clot firmness of fibrinogen assay (FIBTEM-MCF: primary variable)., Design: Prospective observational study with ex vivo laboratory experiment., Setting: University hospital., Participants: Consecutive 65 adult elective cardiac surgery patients being scheduled to use cell salvage technique., Interventions: Arterial blood sampling (preoperative: after anesthesia induction, and postoperative: after reversal of heparin), and ex vivo dilution of postoperative blood with salvaged blood (7.4%: 2.5 mL + 0.2 mL and 18.5%: 2.2 mL + 0.5 mL)., Measurements and Main Results: Thromboelastometry was performed for the preoperative blood sample, and postoperative blood samples mixed with different amount of the salvaged blood. Preoperative FIBTEM-MCF significantly decreased after cardiac surgery (16.5 [95% confidence interval (15.4-17.6)] mm to 9.5 [8.4-10.6] mm, p < 0.0001). In vitro 7.4% and 18.5% salvaged blood addition dose-dependently reduced FIBTEM-MCF (9.1 [95% confidence interval (8.0-10.1)] mm, 7.9 [6.8-9.0] mm, respectively, p < 0.0001). Preoperative FIBTEM-MCF and changes of FIBTEM-MCF during cardiac surgery were independent risk factors for development of the FIBTEM-MCF 8 mm or less after in vitro salvaged blood addition. Furthermore, residual heparin within salvaged blood was indicated by significant increase of intrinsic assay-clotting time/ heparin assay-clotting time after 18.5% in vitro salvaged blood addition (p < 0.0001)., Conclusions: Salvaged blood transfusion of more than 18.5% whole blood volume may impair coagulation function particularly in patients with lower FIBTEM-MCF before and after cardiac surgery., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It is well known that the incidence of developing hepatocelluler carcinoma (HCC) is increased in liver cirrhosis of different etiologies. However, comparison of HCC incidence in various liver diseases has not yet been estimated. We surveyed this comparison., Methods: The PubMed database was examined (1989-2017) for studies published in English language regarding the prospective follow-up results for the development of HCC in various liver diseases. A meta-analysis was performed for each liver disease., Results: The annual incidence (%) of HCC in the non-cirrhotic stage and cirrhotic stage, and the ratio of HCC incidence in the cirrhotic stage/non-cirrhotic stage were as follows. (a) hepatitis B virus liver disease: 0.37%→3.23% (8.73-fold), (b) hepatitis C virus liver diseases: 0.68%→4.81% (7.07-fold), (c) primary biliary cholangitis (0.26%→1.79%, 6.88-fold), (d) autoimmune hepatitis (0.19%→0.53%, 2.79-fold), and (e) NASH (0.03%→1.35%, 45.00-fold). Regarding primary hemochromatosis and alcoholic liver diseases, only follow-up studies in the cirrhotic stage were presented, 1.20% and 2.06%, respectively., Conclusions: When the liver diseases advance to cirrhosis, the incidence of HCC is markedly increased. The development of HCC must be closely monitored by ultrasonography, magnetic resonance imaging, and computed tomography, irrespective of the different kinds of liver diseases., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: To survey the efficacy and safety of dual therapy with daclatasvir and asunaprevir in the elderly hepatitis C virus (HCV) patients multicentricity., Methods: Interferon-ineligible/intolerant patients and non-responders to previous pegylated-interferon/ribavirin therapy with chronic HCV genotype 1b infection were enrolled. Child B, C cirrhotic patients were excluded. Patients received oral direct acting antiviral treatment consisting of 60 mg daclatasvir once daily plus 200 mg asunaprevir twice daily for 24 wk. We divided the patients into two groups of 56 elderly patients (≥ 75 years-old) and 141 non-elderly patients (< 75 years old) and compared the efficacy and safety., Results: Ninety-one point one percent of elderly patients and 90.1% of non-elderly patients achieved sustained virological response at 24 wk (SVR 24 ). In the former, 1.8% experienced viral breakthrough, as compared with 3.5% in the latter (not significant). Adverse events occurred in 55.4% of the former and 56.0% of the latter. In the former, 7 cases (12.5%) were discontinued due to adverse events, and in the latter 9 cases were discontinued (6.4%, not significant)., Conclusion: Dual therapy with daclatasvir and asunaprevir achieved the same high rates of SVR 24 in HCV elderly patients without more adverse events than in the non-elderly patients., Competing Interests: Conflict-of-interest statement: Tanaka K has received research funding from Bristol-Myers Squibb and AbbVie; Nozaki A has received research funding from Gilead Sciences; Tarao K, Sato A, Ishii T, Komatsu H, Ikeda T, Komatsu T, Matsushima S and Oshige K declare that have no conflict of interest.

Objective: Right-sided type colonic diverticulosis has been predominant in Japan, in contrast to European counties where the left-sided type is predominant. Considering the recent change in the dietary habits of Japanese people to a more Western diet in urban areas of Japan, the features of colonic diverticulosis may also change to reflect a more Western type. Therefore, we attempted to clarify the current situation., Methods: A total of 435 consecutive outpatients who agreed to a barium enema and complete examination were enrolled in this study., Results: 113 patients (26.0%) revealed colon diverticulosis; 50.4% of the patients had more than ten diverticula. The percentage of man with ten or more diverticula (67.4%) was significantly higher than that of women patients (40.0%, p<0.01). Among the 88 patients who had four or more diverticula, 39 patients (44.3%) were right-side dominant, 27 (30.7%) left-side dominant and 22 (25.0%) were both-sides. Thirteen (68.4%) of the 19 patients who had more than 30 diverticula were left-side dominant., Conclusion: The clinical features of colon diverticulosis in the patients living in Yokohama may be changing to reflect a more Western type, in particular decreased right-side dominance, increases in the left-side and both-sides dominant patients, and the emergence of patients with crowded diverticula in the left-side colon was observed.

Objective: It is accepted that inflammation promotes malignant progression in the development of cancers. Whether, this is true for hepatocellular carcinoma (HCC) remains as an open question. We examined the relationship between the inflammatory histology activity index (HAI) in the background liver cirrhosis (LC) and the histological grading of the HCC in the hepatectomized HCC patients with HCV-associated LC., Material and Methods: Out of 264 HCC patients who underwent curative hepatic resection, 197 had HCV-associated LC. Among them, 52 patients with a small solitary HCC nodule (< 5 cm in diameter) were studied. Inflammation in the background LC was evaluated by modified Knodell's HAI. To evaluate the inflammation, piece meal necrosis, intra lobular cellular degeneration and focal necrosis, portal cellular inflammation (0-4, each) were estimated. The average HAI was calculated. The grade of malignancy of HCC was determined by WHO classification., Results: The average HAI in the 15 patients with moderately differentiated HCC (4.3 ± 0.8, mean ± SD) was significantly larger than that in 11 patients with well differentiated HCC (3.5 ± 0.6, p = 0.036). The HAI in the 24 patients whose HCC nodules contained poorly differentiated HCC (5.2 ± 1.1) was significantly larger than that in patients with moderately differentiated HCC (p = 0.025). Thus, the HAI order was well differentiated group < moderately differentiated group < poorly differentiated group., Conclusions: Inflammation in the background non-cancerous cirrhotic portion would evoke malignant progression in HCC development from HCV-associated LC.

Contrast-induced nephropathy (CIN) is an important complication of coronary angiography (CAG) and percutaneous coronary intervention (PCI). The aim of this study was to examine the effect of CAG and PCI to renal function in patients with a low risk of CIN by measuring serum cystatin C concentration. The patients were classified into 3 groups; CAG group, elective PCI group, and emergency PCI group. Enrolment continued until 100 patients were included in each of the 3 groups. The exclusion criteria were as follows; (1) serum creatinine concentration >1.5 mg/dL, (2) age >80 years, (3) cardiogenic shock, (4) use of mechanical ventilation or intra-aortic balloon pump, (5) history of renal failure, and (6) quantity of contrast used > maximum radiographic contrast dose. Blood samples for serum cystatin C analysis were collected before and 3 months after the index procedure. Two patients in the CAG group, 4 patients in the elective PCI group, and 12 patients in the emergency PCI group developed CIN. Multivariate analysis identified the predictors of CIN: pre-procedural cystatin C concentration >1.04 mg/L, contrast volume >150 mL and emergency procedure. In the elective PCI group and emergency PCI group, serum cystatin C concentration was significantly increased 3 months after PCI procedure. Even patients with a low risk of CIN developed CIN after CAG and PCI, which caused increase of serum cystatin C concentration. We should become more aware of the possible development of CIN and avoid performing unnecessary CAG and PCI procedure as far as possible.

Objective: Whether severe inflammation in the background liver cirrhosis might correlate with the development of poorly differentiated human hepatocellular carcinoma (HCC) was studied in hepatitis C virus (HCV)-associated liver cirrhosis., Methods: Out of 214 HCC patients who underwent curative hepatic resection, 148 patients were HCV-associated liver cirrhosis (LC) patients. Out of these 148, 31 patients with small solitary HCC nodule (diameter ≤ 3 cm) were included in this study. Inflammation in the background LC was evaluated by modified histology activity index (HAI). To evaluate the inflammation, piece meal necrosis, intra lobular cellular degeneration and focal necrosis, portal cellular inflammation (each 0-4) were estimated. In each case, the average HAI was calculated. The grade of malignancy of HCC was determined by World Health Organization (WHO) classification., Results: The average HAI score in the cirrhotic portion in 17 patients with poorly differentiated HCC (5.21 ± 1.15, mean ± standard deviation (SD)) was significantly larger than that in 14 patients without poorly differentiated HCC (4.05 ± 0.83, p<0.005). The occurrence rate of HCC containing poorly differentiated HCC component in the patients whose HAI was more than 5.0 was 80.0% (12 out of 15), and was significantly higher compared with those in patients whose HAI was less than 5.0 (5 out of 16, 31.3%, p<0.025). In univariate and multivariate analyses for contribution to poorly differentiated HCC development, HAI was the only significant contributor (p=0.011, p=0.012 respectively)., Conclusion: It is suggested that severe inflammation in the background cirrhosis accelerates the promotion in the HCC development from HCV-associated LC.

Colonic diverticulosis is now a common global disease, but the treatment has conventionally been directed towards its associated complications, such as infection and bleeding, and the treatment of diverticulosis itself has rarely been discussed. This is a case of complete resolution (disappearance) of multiple diverticula in the ascending colon of a Japanese 58-year-old male patient who undertook a frequent, long distance running program for a period of about 8 months. The disappearance was confirmed by barium enema. The patient continued the running program thereafter, and the third barium enema, which was performed 1 year and 3 months after the second, again revealed no diverticula in the ascending colon. He consumed more vegetables after the first barium enema examination (1.52-fold increase). The stools were solid and compact, and effort was needed to void before the running program, but after the running program began, they were loose and easy to void. This case suggests that frequent, vigorous physical exercise, such as long distance running, in conjunction with the consumption of more vegetables can resolve or reduce right-sided colonic diverticula. The decreased intracolonic luminal pressure after running was presumed to be effective.

Nowadays, patients with chronic hepatitis C in all countries are generally treated with interferon (IFN), and more than 50% of patients become HCV-RNA negative following PEG-IFN plus ribavirin therapy, but unfortunately, the IFN therapy is not effective in about 70% of patients with HCV-associated LC. In Japan, HCC actually develops in about 7% of those patients every year. A strategy for preventing HCC development other than IFN therapy is, therefore, urgently needed for those patients. We reported that the recurrence rate and the development of HCC was more rapid in the high serum ALT level (>80 IU) patients with HCV-associated LC. Sho-saiko-to, Juzen-taiho-to, and stronger-neo minophagen C are herbal medicines used in Japan to treat chronic viral liver diseases, and they work by reducing inflammatory processes and controlling ALT levels. Aggressive reduction therapy for ALT levels in HCV-LC patients could significantly prevent HCC development.

Abstract Objective. To assess retrospectively whether continuously high serum alanine aminotransferase (ALAT) levels (<80 IU) in the first three successive years after the diagnosis of liver cirrhosis (LC) are predictive of a subsequent high incidence of hepatocellular carcinoma (HCC) in patients with Child Stage A hepatitis C virus (HCV)-LC. Material and methods. The study comprised 132 HCV-LC (Child Stage A) patients who had not received interferon therapy but had been treated with anti-inflammatory agents. At the end of a 3-year follow-up after the diagnosis of LC, the patients were subdivided into three groups according to their serum ALAT levels and the subsequent incidence of HCC was assessed. Results. The cumulative incidence of HCC starting from 3 years after the diagnosis of LC in the continuously high ALAT group (annual average over 3 years always > or =80 IU; n=41; Group A) was markedly higher than that in the continuously low ALAT group (always <80 IU; n=48; Group B) (p<0.005) during an observation period of 7.9+/-3.7 years. The incidence of HCC in Group A was 11.8%/year. The odds ratios of developing HCC in Group A and Group C (mixed high and low ALAT levels; n=43) were 5.1-fold and 1.5-fold that of Group B, respectively. A multivariate analysis revealed that the ALAT group was independently associated with HCC development. Conclusions. Continuously high ALAT levels for three successive years following the diagnosis of LC can be predictive of a very high incidence of HCC in Child A HCV-LC patients. Prospective trials using therapeutic approaches aimed at decreasing ALAT levels are necessary in order to confirm a positive impact of ALAT reduction on the incidence of HCC in patients with HCV-LC.

Background: The probable role of cyclo-oxygenase-2 (COX-2) in the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases has been accepted to be relevant. The purpose of the present study was to determine whether overexpressed COX-2 in the background liver affects the clinical course of hepatitis C virus (HCV)-related cirrhosis patients after curative surgery for HCC., Methods: Twenty-nine clinical stage I HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in the present study (22 men and seven women, age range 53-73 years; follow-up period; range 22-159 months, median 61 months). The COX-2 expression in the cirrhotic liver was examined by immunohistochemistry using the avidin-biotin-peroxidase complex technique on paraffin-embedded formalin-fixed tissue. The COX-2 expression was scored, then correlated with monitored alanine aminotransferase (ALT) levels during the follow-up period after surgery, response to alternative therapy aiming to improve elevated ALT levels, and recurrence/survival after surgery., Results: The COX-2 expression scores were significantly higher in the high-ALT group than in the low-ALT group (Mann-Whitney, P = 0.010), and were significantly higher in non-responders to the alternative therapy than in responders (Mann-Whitney, P = 0.028). The higher COX-2 expression in the cirrhotic liver was the significant independent risk factor for residual liver recurrence (Cox multivariate analysis, P = 0.014), but not for survival., Conclusions: Overexpressed COX-2 in the background liver may play an important role in prolonged acceleration of necroinflammation, resistance to the alternative therapy, and recurrence/new development of HCC in HCV-related cirrhosis patients.