[A case of liver abscess with meningitis and endophthalmitis: invasive liver abscess syndrome].

A woman in her 70s was hospitalized and was diagnosed with liver abscess and managed with antibiotics in a previous hospital. However, she experienced altered consciousness and neck stiffness during treatment. She was then referred to our hospital. On investigation, we found that she had meningitis and right endophthalmitis concurrent with a liver abscess. Klebsiella pneumoniae was detected from both cultures of the liver abscess and effusion from the cornea. A string test showed a positive result. Therefore, she was diagnosed with invasive liver abscess syndrome. Although she recovered from the liver abscess and meningitis through empiric antibiotic treatment, her right eye required ophthalmectomy. In cases where a liver abscess presents with extrahepatic complications, such as meningitis and endophthalmitis, the possibility of invasive liver abscess syndrome should be considered, which is caused by a hypervirulent K. pneumoniae.

Machine learning-based model for prediction and feature analysis of recurrence in pancreatic neuroendocrine tumors G1/G2.

BACKGROUND: Pancreatic neuroendocrine neoplasms (PanNENs) are a heterogeneous group of tumors. Although the prognosis of resected PanNENs is generally considered to be good, a relatively high recurrence rate has been reported. Given the scarcity of large-scale reports about PanNEN recurrence due to their rarity, we aimed to identify the predictors for recurrence in patients with resected PanNENs to improve prognosis. METHODS: We established a multicenter database of 573 patients with PanNENs, who underwent resection between January 1987 and July 2020 at 22 Japanese centers, mainly in the Kyushu region. We evaluated the clinical characteristics of 371 patients with localized non-functioning pancreatic neuroendocrine tumors (G1/G2). We also constructed a machine learning-based prediction model to analyze the important features to determine recurrence. RESULTS: Fifty-two patients experienced recurrence (14.0%) during the follow-up period, with the median time of recurrence being 33.7 months. The random survival forest (RSF) model showed better predictive performance than the Cox proportional hazards regression model in terms of the Harrell's C-index (0.841 vs. 0.820). The Ki-67 index, residual tumor, WHO grade, tumor size, and lymph node metastasis were the top five predictors in the RSF model; tumor size above 20 mm was the watershed with increased recurrence probability, whereas the 5-year disease-free survival rate decreased linearly as the Ki-67 index increased. CONCLUSIONS: Our study revealed the characteristics of resected PanNENs in real-world clinical practice. Machine learning techniques can be powerful analytical tools that provide new insights into the relationship between the Ki-67 index or tumor size and recurrence.

Development of performance indicators for hepatitis countermeasures as a tool for the assessment and promotion of liver cancer prevention in Japan.

BACKGROUND: Hepatitis countermeasures are being promoted by governments in Japan. We aimed to develop performance indicators (PIs) to assess the process and outcome of such countermeasures implemented for the prevention of viral hepatitis-related liver cancer at the national and prefectural government levels. METHODS: We developed 19 PIs for hepatitis countermeasures implemented by local governments, covering the morbidity and mortality of liver cancer, hepatitis testing, subsidy programs for examinations and antiviral treatment, and education on hepatitis patient care to healthcare workers. We analyzed the PIs for each prefecture from Fiscal Year (FY) 2018-2020. RESULTS: The morbidity and mortality of liver cancer significantly decreased in the study period. The percentage of municipalities conducting hepatitis screening was already high at 95% in FY2017. The usage rate of government-subsidized screenings did not change. The subsidy usage rate for periodic viral hepatitis examination significantly increased. Meanwhile, the subsidy usage rate for antiviral treatment of hepatitis B increased, whereas that for hepatitis C decreased. The number of certified healthcare workers providing care for hepatitis patients increased significantly, and these workers were efficiently placed at regional core centers, institutions specialized in liver diseases, health care centers, and municipal governments. Liver cancer mortality was positively correlated with hepatitis screening, subsidies for periodic examinations, and the number of hepatitis medical care coordinators but was negatively correlated with subsidies for anti-HCV therapy, suggesting that rigorous countermeasures were implemented in prefectures with high liver cancer mortality. CONCLUSIONS: The developed PIs could be a useful tool for monitoring government efforts and achievements, thereby providing basic data for setting practical goals in liver cancer prevention.

Gemcitabine plus nab-paclitaxel in older patients with metastatic pancreatic cancer: A post-hoc analysis of the real-world data of a multicenter study (the NAPOLEON study).

OBJECTIVES: This study aimed to examine the efficacy and safety of gemcitabine plus nab-paclitaxel (GnP) in older patients with metastatic pancreatic cancer (MPC), especially those ≥75 years old. MATERIALS AND METHODS: This study retrospectively enrolled 153 patients with MPC who received GnP as first-line chemotherapy. Patients ≥75 years old were allocated to the older group, and those <75 years old were assigned to the non-older group. We compared safety, antitumor efficacy, and survival between the two groups. In the older group, prognostic indicators of survival were also assessed. RESULTS: The pretreatment characteristics of the two groups were not significantly different excluding age, history of malignancy, and C-reactive protein levels. The initial dose and relative dose intensities of GnP were significantly lower in the older group. There were no significant differences in the adverse event and antitumor response rates between the two groups. Median progression-free survival and overall survival were 5.5 and 12.0 months, respectively, in the older group, versus 6.0 and 11.1 months, respectively, in the non-older group. In the older group, a Geriatric Nutrition Risk Index (GNRI) of less than 86 was associated with poor prognosis. CONCLUSION: GnP exhibited acceptable efficacy and safety in patients ≥75 years old with MPC. GNRI might be helpful for identifying older individuals at higher risk of unfavorable outcomes.

Applicability of APRI and FIB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis.

BACKGROUND AND AIMS: The usefulness of APRI or FIB-4 is well established as a non-invasive liver fibrosis marker at a point of diagnosis in patients with chronic liver disease. However, their applicability for the monitoring of progression of liver fibrosis over time is yet to be determined. We aimed to clarify the feasibility of APRI and FIB-4 for the longitudinal evaluation of liver fibrosis in patients with chronic hepatitis B and C. METHODS: This is a multi-center retrospective and prospective cohort study, enrolling 1029 patients with HCV and 384 patients with HBV who were histologically diagnosed by liver biopsy. The observation period of retrospective and prospective study was 14 and 12 years, respectively. The APRI and FIB-4 were traced back in cases of histologically diagnosed cirrhosis, and those were prospectively analyzed after biopsy in cases diagnosed as F3 of METAVIR score, respectively. RESULTS: The averaged APRI and FIB-4 exhibited time-dependent increase in the retrospective study of hepatitis C patients (increase by 0.09/year in APRI and 0.29/year in FIB-4). In the prospective study of untreated hepatitis C patients, such increases were 0.14/year in APRI and 0.40/year in FIB-4, respectively. Neither the average of APRI nor FIB-4 showed a specific tendency with hepatitis B patients and treatment-experienced hepatitis C patients. CONCLUSION: The APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naïve patients with chronic hepatitis C.

Prediction of Nonalcoholic Fatty Liver Disease Using Noninvasive and Non-Imaging Procedures in Japanese Health Checkup Examinees.

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index (p < 0.001) and FLI (p = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis.

Nationwide survey on activities of regional core centers for the management of liver disease in Japan: Cumulative analyses by the Hepatitis Information Center 2009-2017.

AIM: Regional core centers for the management of liver disease, which are located in every prefecture in Japan, not only take the lead in hepatitis care in their respective regions, but also serve a wide range of other functions, such as education, promotion of hepatitis testing, treatment, and research. METHOD: Since fiscal year 2010, the Hepatitis Information Center has conducted surveys of regional core centers throughout Japan regarding information about their facilities, programs for patient support, training, and education of medical personnel. RESULTS: By compiling and analyzing the results of these surveys, we have elucidated the status of regional core centers and the issues they currently have. We found that regional core centers have come to play widely varied roles in hepatitis treatment and have expanded their programs. These surveys also suggest that uniform accessibility of hepatitis treatment has been implemented throughout Japan. CONCLUSION: To continue serving their diverse roles, regional core centers require further development of hepatitis care networks that include specialized institutions, primary care physicians, and local and central governments; as well as collaboration with other professions and groups.

Epidemiological survey of hemoglobin A1c and liver fibrosis in a general population with non-alcoholic fatty liver disease.

AIM: The association between glycemia and liver fibrosis was analyzed using hemoglobin A1c (HbA1c) and the Fibrosis-4 (FIB-4) index in a large general population cohort that underwent a health checkup. METHODS: A total of 6927 subjects without hepatitis B or C virus infection or habitual alcohol intake were enrolled. Non-alcoholic fatty liver disease (NAFLD) was diagnosed by ultrasonography and potential liver fibrosis (FIB-4 index ≥1.3) in NAFLD was analyzed in relation to HbA1c level. Factors associated with potential liver fibrosis of NAFLD were also analyzed. RESULTS: The overall frequency of NAFLD was 27.9% (1935 subjects) and the frequency of NAFLD by HbA1c level (<4.9%, 5.0-5.9%, 6.0-6.9%, 7.0-7.9%, ≥8.0%) was 16%, 27%, 54%, 53%, and 54%, respectively. Among the 1935 NAFLD cases, the frequency of potential liver fibrosis was 25.2% (487 subjects) overall and 19%, 22%, 30%, 52%, and 31%, respectively, by HbA1c category. From multivariate analysis, an HbA1c level ≥6.5% was significantly associated with potential liver fibrosis (P = 0.017, hazard ratio = 1.7). CONCLUSIONS: The prevalence of NAFLD and liver fibrosis of NAFLD increased according to glycemia, up to 8.0% HbA1c. Measuring HbA1c and calculating the FIB-4 index in health checkups could help to identify potential cases of liver fibrosis of NAFLD, which should then be further evaluated using other techniques to confirm liver fibrosis.

Current activities and future directions of comprehensive hepatitis control measures in Japan: The supportive role of the Hepatitis Information Center in building a solid foundation.

In Japan, hepatitis B or C virus infection has been a major health issue. For the prevention of liver-related deaths, multifaceted strategies have been taken against hepatitis virus. In fiscal year (FY) 2002, nationwide screening for hepatitis was started as a part of health examinations provided by municipal governments. From FY2007, the hepatitis treatment network has been strengthened by the nationwide establishment of regional government-based hepatitis treatment systems, comprising linked regional core centers, specialized institutions for hepatitis treatment, primary care physicians, and regional governments. Special subsidy program for patients with viral hepatitis was started at FY2008. The range of coverage has been expanding from patients treated with interferon to those on nucleotide analogs or interferon-free therapies, including drug prices and examination expenses. The Basic Act on Hepatitis Measures was established in 2009. The Basic Guidelines for Promotion of Control Measures for hepatitis was issued in 2011, comprising nine principles in order to promote measures for hepatitis B and C. The Hepatitis Information Center was established in 2008. Its mission is to provide up-to-date hepatitis-related information, supporting collaboration between regional core centers, and training medical personnel. The revision of the above-mentioned Basic Guidelines in 2016 set the target as the reduction of patients progressing to cirrhosis and/or liver cancer. Achieving this goal definitely requires active collaboration among the national and local governments, regional core centers, and the Hepatitis Information Center, and participation by medical personnel, patients, and people with awareness.

Impact of Body Weight Reduction via Diet and Exercise on the Anti-Viral Effects of Pegylated Interferon Plus Ribavirin in Chronic Hepatitis C Patients with Insulin Resistance: A Randomized Controlled Pilot Trial.

OBJECTIVE: Insulin resistance (IR) modifies the anti-viral effects of interferon (IFN) therapy in patients with chronic hepatitis C (CHC). This prospective study evaluated whether lifestyle interventions improve the anti-viral response to treatment with pegylated (PEG)-IFN plus ribavirin (RBV) in patients with CHC. METHODS: The study cohort consisted of 60 patients chronically infected with a high viral load of hepatitis C virus genotype 1b and a homeostasis model assessment of IR (HOMA-IR) value above 2. The patients were divided into two groups, an intervention group (n=26) and a control group (n=34). The patients in the intervention group were prescribed diet and exercise treatment for 3-6 months to reduce their body weight by ≥5% before starting treatment with PEG-IFN plus RBV. RESULTS: Diet and exercise significantly reduced the HOMA-IR values in the intervention group, from 3.4 to 2.5 (p=0.0009), especially among the 15 patients who achieved a body weight reduction of ≥5%. The viral disappearance rate at 12 weeks was significantly higher in the intervention group among the patients with a ≥5% weight reduction than in the control group (53.3% vs. 23.5%, p=0.01). However, the sustained viral response (SVR) rates were similar. CONCLUSION: Improvements in IR achieved through weight reduction via lifestyle interventions may enhance the early viral response to PEG-IFN plus RBV in patients with CHC. However, this intervention program has no effect on the SVR rate.

Efficacy of ezetimibe for reducing serum low-density lipoprotein cholesterol levels resistant to lifestyle intervention in patients with non-alcoholic fatty liver disease.

AIM: To investigate the efficacy of ezetimibe and lifestyle intervention for treating patients with non-alcoholic fatty liver disease (NAFLD) and residual dyslipidemia via a combination of ezetimibe and lifestyle intervention. METHODS: Patients with NAFLD with residual dyslipidemia after a 6-month lifestyle intervention program were included. After completion of the 6-month program, the patients received p.o. administration of ezetimibe at 10 mg/day, in addition to lifestyle intervention, for 6 months. RESULTS: Of the 59 patients with NAFLD who had participated in the 6-month lifestyle intervention program between 2007 and 2012, 21 with residual dyslipidemia (10 males and 11 females) were enrolled. Median age was 58 years (range, 27-75), median bodyweight was 63.0 kg (range, 39.4-109.0), median body mass index was 25.4 kg/m2 (range, 18.2-37.1), median alanine aminotransferase was 23 IU/L (14-73), median high-density lipoprotein (HDL) was 58 mg/dL (range, 37-93), median triglycerides (TG) was 105 mg/dL (range, 42-216) and median low-density lipoprotein (LDL) was 153 (66-209) mg/dL. After 6 months of treatment with ezetimibe, serum LDL levels were improved in 15 of 20 (75%) patients (P = 0.0015), while no improvements were observed in the remaining five patient (25%). Ezetimibe was discontinued in one patient who developed skin rash. CONCLUSION: Ezetimibe is effective for treating residual dyslipidemia after lifestyle intervention in patients with NAFLD.

Impairment of health-related quality of life in patients with chronic hepatitis C is associated with insulin resistance.

BACKGROUND: Although it has been reported that hepatitis C virus (HCV) infection is associated with a significant decline in health-related quality of life (HRQOL), the underlying causes and mechanisms are still unknown. Insulin resistance (IR) is recognized as a distinct aspect of chronic HCV infection. Therefore, we attempted to identify the factors including IR indices that are related to the HRQOL of patients with chronic hepatitis C (CHC). METHODS: One hundred and seventy-five CHC patients (91 female, 84 male, mean age, 56.4 years) not using antidiabetic agents were included and underwent a 75-g oral glucose tolerance test (OGTT) and completed a self-administered HRQOL questionnaire, the Short Form 36 (SF-36), which is a well-validated questionnaire for assessing general QOL. Scale scores were standardized and summarized into physical and mental component summary (PCS and MCS). We investigated which clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), were associated with decline in PCS and MCS scores in CHC patients. RESULTS: There were no significant differences in clinical parameters between high and low MCS, but there were significant differences in age, sex, hemoglobin, liver fibrosis, OGTT pattern, and HOMA-IR between high and low PCS. Multivariate analysis showed that HOMA-IR >2 was independently associated with lower PCS (OR 2.92, p < 0.01). CONCLUSIONS: Our results suggest that impairment of HRQOL, especially physical domains, in CHC patients is associated with IR.

Efficacy of pegylated interferon plus ribavirin in combination with corticosteroid for two cases of combined hepatitis C and autoimmune hepatitis.

The treatment strategy for cases of combined autoimmune hepatitis (AIH) and chronic hepatitis C (CHC) has not yet been established. A 47-year-old woman and a 53-year-old-woman were hospitalized for treatment of CHC. Ultrasonography and histological findings revealed that their liver was not cirrhotic but did have chronic damage. The histological findings of both patients were suggestive of AIH. The patients were systematically treated with pegylated interferon-alpha 2b plus ribavirin which was preceded by and combined with corticosteroid (CS), and showed sustained virological responses and normal liver function. Although these two patients with combined AIH and CHC were successfully treated with this regimen, careful attention to exacerbation of hepatic inflammation is needed because hepatitis C viral load was increased due to immunosuppression during CS treatment.

Post-challenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C.

BACKGROUND: Several epidemiological studies have reported that diabetes mellitus is a risk factor for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients. However, it is unclear whether or not post-challenge hyperglycemia is a risk factor. The purpose of this study was to determine the association between post-challenge hyperglycemia and hepatocarcinogenesis in HCV-positive patients. METHODS: A total of 203 HCV-RNA-positive subjects (108 males, mean age 54.3 ± 10.8 years; 95 females, mean age 56.6 ± 10.3 years; genotype 1b/2a/2b/3a: 152/38/12/1) who underwent liver biopsy and a 75-g oral glucose tolerance test, and who were treated with interferon (IFN) were enrolled in this study. None of the subjects had been treated with antidiabetic drugs. The subjects underwent ultrasonography and/or computed tomography every 6 months after the end of the IFN therapy. RESULTS: Thirteen patients, including one patient who achieved a sustained viral response (SVR) with IFN, developed HCC. On multivariate analysis, male sex, age >65 years, excessive alcohol consumption, non-SVR, liver steatosis area >5% in liver specimens, and 120-min post-challenge hyperglycemia were risk factors for the development of HCC. After matching subjects for sex, age, alcohol intake, and response to the IFN therapy, advanced fibrosis stages [hazard ratio (HR) 2.8], liver steatosis (HR 5.4), and 120-min post-challenge hyperglycemia (HR 4.9) were significant risk factors for the development of HCC. Furthermore, after matching for the fibrosis stage, liver steatosis (HR 5.7) and 120-min post-challenge hyperglycemia (HR 6.9) remained as significant factors for HCC development. CONCLUSION: Post-challenge hyperglycemia is an independent risk factor for HCC in HCV-positive patients.

Metabolic factors are associated with serum alanine aminotransferase levels in patients with chronic hepatitis C.

BACKGROUND: Although serum alanine aminotransferase (ALT) activity is an important marker for the management of chronic hepatitis C (CHC), the factors associated with serum ALT levels remain to be fully understood. This study aimed to clarify the association between serum ALT levels and clinical, histological, and virological factors in patients with CHC. METHODS: We retrospectively analyzed 256 patients with CHC who underwent liver biopsy, and classified them into three groups according to serum ALT levels: normal to minimal (<40 IU/L), mild (40-80 IU/L), and moderate to severe elevation (≥80 IU/L). All demographic and laboratory data were collected at the time of liver biopsy. All biopsies were evaluated for fibrosis, inflammation, and steatosis. Glucose metabolism was assessed by various indices derived from oral glucose tolerance tests, including the homeostasis model assessment for insulin resistance (HOMA-IR). In 180 patients, visceral fat area was measured at the umbilical level by abdominal computed tomography. RESULTS: Ordered logistic regression analysis showed that higher serum ALT levels were significantly associated with male sex, lower high-density lipoprotein cholesterol (HDL-C), higher HOMA-IR, and higher grades of histological inflammation and steatosis. HOMA-IR, HDL-C, and hepatic steatosis were associated with visceral fat accumulation. CONCLUSIONS: Metabolic factors, as well as sex and hepatic inflammation, are independent risk factors for serum ALT elevation in hepatitis C virus (HCV)-infected patients. Metabolic factors may offer targets to decrease serum ALT levels.

Presence of esophageal varices is a risk factor for non-hemorrhagic death of hepatocellular carcinoma patients treated with radiofrequency ablation.

BACKGROUND/AIMS: The presence of esophageal varices (EVs) is believed to be a factor that affects the prognosis of patients with hepatocellular carcinoma (HCC). We examined whether the presence and severity of EVs affected either survival prognosis or the cause of death in HCC patients treated with radiofrequency ablation (RFA). METHODOLOGY: The study included 89 HCC patients treated with RFA who were endoscopically evaluated for EVs before treatment. To determine factors associated with survival, we performed univariate and multivariate analyses of variables including demographics, tumor stage, Child-Pugh class and status of EVs. Furthermore, we investigated the association between the presence of EVs and causes of death. RESULTS: Multivariate analyses showed both Child-Pugh class B (odds ratio: 2.654; p = 0.017) and EVs (odds ratio: 3.18; p = 0.004) to be independent factors of poor prognosis. Of 34 patients who died during the period of observation, one died because of an EV rupture. CONCLUSIONS: The existence of EVs may affect survival prognosis of HCC patients treated with RFA independently of Child-Pugh status, but is not associated with hemorrhagic death.

Whole-body insulin sensitivity index is a highly specific predictive marker for virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients with genotype 1b and high viral load.

Insulin resistance is a candidate predictive factor for virological response to peginterferon plus ribavirin (PEG/RBV) therapy in chronic hepatitis C patients. We examined whether indices of insulin resistance could serve as a predictor of sustained virological response (SVR). Fifty-one patients with genotype 1b and high viral load who received PEG/RBV therapy for 48 weeks were included. Homeostasis model assessment of insulin resistance (HOMA-IR) and whole-body insulin sensitivity index (WBISI) calculated from the 75-g oral glucose tolerance test and serum levels of soluble tumor necrosis factor receptor 2 (sTFNR2) were evaluated before therapy. Patients who achieved SVR had significantly lower HOMA-IR and sTNFR2 levels and a higher WBISI compared with non-SVR patients. The positive predictive value for SVR was 0.653 for a HOMA-IR of <2 and 0.846 for a WBISI of 6 or higher. WBISI may serve as a highly specific predictor for SVR in PEG/RBV therapy.

A pilot trial of body weight reduction for nonalcoholic fatty liver disease with a home-based lifestyle modification intervention delivered in collaboration with interdisciplinary medical staff.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of the metabolic syndrome. The aim of this study was to evaluate a 6-month home-based lifestyle modification intervention delivered in collaboration with physicians, hygienists, registered dietitians, and nurses. METHODS: Outpatients with NAFLD diagnosed by abdominal ultrasonography were eligible for this study. Abdominal computed tomography (CT) scan evaluated liver fat deposition by the liver-spleen ratio (L/S ratio) and visceral fat accumulation as the visceral fat area (VFA; cm(2)). During the 6-month home-based lifestyle modification intervention, each patient was examined by physicians, nurses, hygienists, and registered dietitians, who provided individualized advice to the patients. Patients recorded their daily weight for self-control of weight with recommended diet and exercise regimens. RESULTS: Sixty-seven NAFLD patients were enrolled in this study and 22 patients (32.8%) completed the 6-month intervention. Nineteen of the 22 patients achieved significant improvements in body weight, body mass index (BMI), waist circumference, VFA, L/S ratio, and systolic blood pressure, with improved laboratory data. Overall, 39 patients withdrew from the intervention. The mean age of the patients who withdrew was 50.0 +/- 11.0 years, which was significantly younger than that of the patients who were followed up (60.1 +/- 10.1 years; P < 0.01). CONCLUSIONS: The reduction in body weight achieved by NAFLD patients during the 6-month intervention was associated with improved fat deposition and liver function. This intervention offers a practical approach for treating a large number of NAFLD patients with lifestyle modification therapy.

Eradication of hepatitis C virus by interferon improves whole-body insulin resistance and hyperinsulinaemia in patients with chronic hepatitis C.

BACKGROUND/AIMS: To investigate whether eradication of hepatitis C virus (HCV) by interferon (IFN) therapy influences systemic glucose metabolism. METHODS: Seventy-two patients with chronic hepatitis C were enrolled in this study. Patients received IFN therapy and were classified into two groups: sustained responders (n=48) and nonsustained responders (n=24). We analysed systemic glucose metabolism in terms of the following indices: homeostasis model assessment for insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta), insulinogenic index (II), composite insulin sensitivity index (ISI composite) and the area under the curve of plasma glucose (PG-AUC) and serum insulin (SI-AUC) in oral glucose tolerance tests. In 28 sustained responders and 16 nonsustained responders, serum levels of soluble tumour necrosis factor receptor 2 (sTNFR2) were measured. Indices were determined before and 6 months after therapy. RESULTS: In the sustained responders, HOMA-beta (P=0.0004) and SI-AUC (P=0.002) were significantly decreased and the ISI composite was increased (P=0.009), although there were no significant changes in HOMA-IR, II or PG-AUC. Serum sTNFR2 levels decreased significantly after therapy in sustained responders (P=0.001). In the nonsustained responders, there were no changes in any index. CONCLUSIONS: Eradication of HCV by IFN therapy could improve whole-body insulin resistance and insulin hypersecretion with reduced serum TNF-alpha levels.