Takamasa Ohki

Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography

Liver stiffness, noninvasively measured by transient elastography, correlates well with liver fibrosis stage. The aim of this prospective study was to evaluate the liver stiffness measurement (LSM) as a predictor of hepatocellular carcinoma (HCC) development among patients with chronic hepatitis C. Between December 2004 and June 2005, a total of 984 HCV‐RNA positive patients, without HCC or a past history of it, visited the University of Tokyo Hospital. LSM was performed successfully in 866 patients, who gave informed consent. During the follow‐up period (mean, 3.0 years), HCC developed in 77 patients (2.9% per 1 person‐year). The cumulative incidence rates of HCC at 1, 2, and 3 years were 2.4%, 6.0%, and 8.9%, respectively. Adjusting for other significant factors for HCC development, patients with higher LSM were revealed to be at a significantly higher risk, with a hazard ratio, as compared to LSM ≤10 kPa, of 16.7 (95% confidence interval [CI], 3.71‐75.2; P < 0.001) when LSM 10.1‐15 kPa, 20.9 (95% CI, 4.43‐98.8; P < 0.001) when LSM 15.1‐20 kPa, 25.6 (95%CI, 5.21‐126.1; P < 0.001) when LSM 20.1‐25 kPa, and 45.5 (95% CI, 9.75‐212.3; P < 0.001) when LSM >25 kPa. Conclusions: This prospective study has shown the association between LSM and the risk of HCC development in patients with hepatitis C. The utility of LSM is not limited to a surrogate for liver biopsy but can be applied as an indicator of the wide range of the risk of HCC development. (HEPATOLOGY 2009.)

Obesity Is an Independent Risk Factor for Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients

BACKGROUND & AIMS It is not fully elucidated whether obesity enhances hepatocarcinogenesis in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between body weight and risk of hepatocarcinogenesis in chronic hepatitis C patients. METHODS We enrolled 1431 patients with chronic hepatitis C who visited our liver clinic between 1994 and 2004, excluding those with hepatocellular carcinoma (HCC) at their visit or with a previous history of HCC. They were divided into 4 groups according to body mass index (BMI): underweight (< or =18.5 kg/m(2), N = 112); normal (18.5 to less than 25 kg/m(2), N = 1023); overweight (25 to less than 30 kg/m(2), N = 265); and obese (>30 kg/m(2), N = 31). We assessed the impact of obesity on the hepatocarcinogenesis adjusted by multivariate Cox proportional hazard regression with other risk factors found significant in univariate analysis. RESULTS During the follow-up period (mean, 6.1 y), HCC developed in 340 patients, showing cumulative incidence rates of 10.5%, 19.7%, and 36.8% at 3, 5, and 10 years, respectively. The incidence differed significantly among the BMI groups (P = .007). Adjusting for other significant factors, overweight and obesity were shown to be an independent risk factor of HCC, with a hazard ratio of 1.86 (95% confidence interval, 1.09-3.16; P = .022) and 3.10 (95% confidence interval, 1.41-6.81; P = .005) as compared with the underweight patients. CONCLUSIONS The risk of HCC in patients with chronic hepatitis C increases in proportion to BMI in a wide range of its values, from underweight to obese.

Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences

Interleukin‐6 (IL‐6) may play a role in the pathogenesis of hepatocellular carcinoma (HCC). Recently, it was reported in mouse models that estrogen‐mediated inhibition of IL‐6 production explains the gender disparity in HCC. We conducted a retrospective cohort study to examine whether this hypothesis is applicable to human HCC. We enrolled 330 patients with chronic hepatitis C whose serum samples were collected between January 1994 and December 2002. Serum IL‐6 concentrations were measured and patients were divided into three groups according to IL‐6 levels: low, middle, and high. We evaluated the association between serum IL‐6 levels and the risk of subsequent HCC development, including subgroup analysis on each gender. During the follow‐up period (mean 9.0 yr), HCC developed in 126 patients. The incidence rates differed significantly among the three groups (p = 0.015), increasing in accordance with serum IL‐6 levels. However, unexpectedly, this tendency was significant only in female patients. In a multivariate analysis, higher serum IL‐6 level was an independent risk factor for HCC development in female patients, with a hazard ratio of 1.61. Although female patients showed a weak negative correlation between serum IL‐6 levels and estradiol levels, the lower risk of HCC in female patients cannot be fully explained by estrogen‐mediated inhibition of IL‐6 production. In conclusion, higher serum IL‐6 level was an independent risk factor for HCC development in female but not male chronic hepatitis C patients. Measurement of serum IL‐6 levels may provide useful information for predicting future HCC development in female chronic hepatitis C patients.

Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH

Background and Aim: Visceral fat accumulation reportedly increases the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. However, it has not beeen fully elucidated whether visceral fat accumulation increases the risk of HCC recurrence after curative treatment in patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was investigated in the current study. Methods: 62 patients with naïve HCC with suspected NASH were enrolled. All were curatively treated with percutaneous radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was determined in each patient from CT images, taken at the time of HCC diagnosis. Patients were divided into two groups based on VFA: the high VFA group (>130 cm2 in males, >90 cm2 in females, n = 27) and the others (n = 35). The effects of VFA on HCC recurrence were analysed together with other factors including patients’ background, tumour-related factors and liver function-related factors. Results: The cumulative recurrence rates differed significantly between the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p = 0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio 1.08, per 10 cm2, p = 0.046) and older age (risk ratio 1.06 per 1 year, p = 0.04) as independent risk factors of HCC recurrence. Conclusions: Visceral fat accumulation is an independent risk factor of HCC recurrence after curative treatment in patients with suspected NASH.

Neoplastic seeding after radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND:Neoplastic seeding reportedly occurs in up to 12.5% of patients treated with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study is to assess the incidence, risk factors, and prognosis of neoplastic seeding after RFA among a large number of patients with a long-term follow-up.METHOD:From February 1999 to December 2004, 1,031 patients underwent a total of 1,845 treatments with RFA for a total of 3,837 HCC nodules. The following variables were assessed to elucidate the risk factors of neoplastic seeding: age, sex, positivity for viral markers, tumor size, number of tumor nodules, number of RFA sessions, tumor location, percutaneous biopsy prior to RFA, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP) and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) levels, and the degree of tumor differentiation.RESULTS:Neoplastic seeding was detected in 33 patients (3.2% per patient) at intervals of 4.8–63.8 (median, 15.2) months after RFA. On multivariate logistic regression analysis, only the poor differentiation degree was associated with the risk of neoplastic seeding (P = 0.012). Of tumor factors, tumor size, and AFP, DCP, and AFP-L3 levels were significantly associated with the poor differentiation degree. The cumulative survival rates 1 and 2 yr after the detection of neoplastic seeding were 86% and 47%, respectively.CONCLUSION:Poor differentiation degree was the risk factor of neoplastic seeding after RFA for HCC. The surrogate markers for poor differentiation degree were larger tumor size and elevated tumor marker levels. Indication for RFA should be carefully considered for HCC patients under these conditions.

Extrahepatic metastasis of hepatocellular carcinoma: incidence and risk factors

Background: Extrahepatic metastasis of hepatocellular carcinoma (HCC) is of growing importance as the survival of patients has been improved owing to advances in treatments to intrahepatic lesions.

Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update

There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.

The effectiveness of liraglutide in nonalcoholic fatty liver disease patients with type 2 diabetes mellitus compared to sitagliptin and pioglitazone.

Background. Liraglutide leading to improve not only glycaemic control but also liver inflammation in non-alcoholic fatty liver disease (NAFLD) patients. Aims. The aim of this study is to elucidate the effectiveness of liraglutide in NAFLD patients with type 2 diabetes mellitus (T2DM) compared to sitagliptin and pioglitazone. Methods. We retrospectively enrolled 82 Japanese NAFLD patients with T2DM and divided into three groups (liraglutide: N = 26, sitagliptin; N = 36, pioglitazone; N = 20). We compared the baseline characteristics, changes of laboratory data and body weight. Results. At the end of follow-up, ALT, fast blood glucose, and HbA1c level significantly improved among the three groups. AST to platelet ratio significantly decreased in liraglutide group and pioglitazone group. The body weight significantly decreased in liraglutide group (81.8 kg to 78.0 kg, P < 0.01). On the other hands, the body weight significantly increased in pioglitazone group and did not change in sitagliptin group. Multivariate regression analysis indicated that administration of liraglutide as an independent factor of body weight reduction for more than 5% (OR 9.04; 95% CI 1.12–73.1, P = 0.04). Conclusions. Administration of liraglutide improved T2DM but also improvement of liver inflammation, alteration of liver fibrosis, and reduction of body weight.

Hemorrhagic complications of percutaneous radiofrequency ablation for liver tumors.

Background Although radiofrequency ablation (RFA) is widely accepted as a percutaneous treatment for liver tumors; serious complications may occur resulting in 0.1% to 0.5% mortality. This study analyzed the risk factors and management of hemorrhagic complications, such as hemoperitoneum, hemothorax, and hemobilia. Methods We performed 4133 RFA treatments in 2154 patients with primary and metastatic liver tumors from February 1999 to December 2007. Of these, we enrolled patients with hemorrhagic complications and reviewed their medical records thoroughly. The risk factors for each hemorrhagic complication were analyzed using unconditional logistic regression. Results Hemorrhagic complications occurred in 63 out of 4133 treatments (1.5%), including hemoperitoneum in 29 (0.7%), hemothorax in 14 (0.3%), and hemobilia in 20 (0.5%). Eleven, 8, and 4 of these patients, respectively, were categorized as major complications requiring blood transfusion or drainage. Two patients died after hemoperitoneum. Logistic regression analysis revealed large tumor size [odds ratio (OR) 1.06 per 1 mm increase in diameter] and low platelet count (OR 0.88 per 10,000/μL increase) were significant risk factors for hemoperitoneum. The location of tumor nodules was a significant risk factor for hemothorax (segment 7, OR 2.31) and hemobilia (segment 1, OR 3.30). Other factors, including the number of needle insertions or the duration of ablation, were not significant. Conclusions Although hemorrhagic complications were relatively rare with percutaneous RFA, specific treatments, such as blood transfusion and drainage, were required in some cases. Care must be taken, especially in high-risk patients.

Noninvasive estimation of hepatic steatosis in living liver donors: usefulness of visceral fat area measurement.

Background. Hepatic steatosis in the donor liver is associated with an increased risk of complications after liver transplantation. Mandatory liver biopsy for all potential donors, however, remains controversial. To define clinico-pathological correlation, we reviewed our criteria for liver biopsy and examined the use of visceral fat area (VFA) estimation by computed tomography image. Methods. Our criteria for biopsy are as follows: an aspartate aminotransferase/alanine aminotransferase ratio of less than 1, a body mass index more than or equal to 25 kg/m2, and a suspected fatty liver on ultrasonography. Dietary intervention is indicated for overweight donor candidates and for those with more than 10% hepatic steatosis. Clinical data of consecutive 78 potential donors who underwent percutaneous liver biopsy (biopsy group) and 70 donors whose biopsy were omitted (control group) were reviewed. Results. Donors in biopsy group were male dominant with a median age of 35 (20–63) years. Hepatic steatosis more than or equal to 10% was seen in nine of 78 donors; older age (P=0.012), ultrasonographic findings (P=0.002), VFA (P=0.008), and percent VFA (VFA/[VFA+subcutaneous fat area]; P=0.009) were associated with more than 10% hepatic steatosis. The area under the receiver operating characteristics curve of VFA and percent VFA for detecting hepatic steatosis more than or equal to 10% were 0.803 and 0.778, respectively. Hepatic steatosis was successfully reduced to less than 10% through dietary intervention in six of the nine donor candidates. Conclusions. Our current biopsy criteria are acceptable to select donor candidates at risk for hepatic steatosis. Visceral fat measurement can be used as an additional factor to narrow donors at risk and to monitor visceral fat reduction during dietary intervention.