Outcomes after curative treatment for cryptogenic cirrhosis-associated hepatocellular carcinoma satisfying the Milan criteria

Background and Aim: The prognosis of cryptogenic cirrhosis‐associated hepatocellular carcinoma (CC‐HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC‐HCC. Methods: Consecutive 36 curatively treated CC‐HCC patients satisfying the Milan Criteria were compared with corresponding 211 HCV‐associated HCC (HCV‐HCC) patients. The clinical background, tumor recurrence rate, overall survival rate, and prognostic values of the patients were assessed. Results: The size of CC‐HCCs was larger than that of HCV‐HCCs (P = 0.01). The respective tumor recurrence rates at 1, 3, and 5 years were 11%, 32%, and 46% in the CC‐HCC, and 21%, 59%, and 81% in the HCV‐HCC. The respective overall survival rates at 1, 3, and 5 years were 94%, 85%, and 80% in the CC‐HCC, and 98%, 81%, and 61% in the HCV‐HCC. CC‐HCC patients had a lower tumor recurrence rate and a higher survival rate compared to the HCV‐HCC patients (P = 0.001 and P = 0.02, respectively). Via multivariate analysis, significant factors for high recurrence rate were number of HCCs (P = 0.02) and serum alpha fetoprotein levels (P = 0.03) in CC‐HCC, whereas multiple tumors (P < 0.001), large tumor size (P = 0.01), and high alanine aminotransferase (P = 0.04) in HCV‐HCC. The factor for survival was albumin in both groups. Conclusion: The size of CC‐HCC was larger than that of HCV‐HCC even in patients who received curative treatment; however, the risk for recurrence and the mortality of the patients with CC‐HCC was lower than those with HCV‐HCC.     

Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection

Background and Aim: Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non‐cirrhotic and non‐diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance. Methods: Fifty‐six patients diagnosed with HCV‐related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)‐α and HCV‐RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA‐IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA‐IR, and the clinical factors responsible for the increase in HOMA‐IR in non‐diabetic patients was investigated. Results: Homeostasis model assessment of insulin resistance and IRI levels increased parallel with the progression of fibrosis. Among the non‐diabetic patients with mild to moderate liver fibrosis, BMI, serum levels of AST and TNF‐α were related with HOMA‐IR (BMI: r = 0.395, P = 0.041; AST: r = 0.465, P = 0.014; TNF‐α: r = 0.396, P = 0.040). In contrast, HOMA‐IR related to TNF‐α (r = 0.526, P = 0.013) in non‐diabetic patients with advanced liver fibrosis. Conclusion: Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.     

Negative hepatitis B envelope antigen predicts intrahepatic recurrence in hepatitis B virus-related hepatocellular carcinoma after ablation therapy

Background and Aim: Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV‐related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation. Methods: Patients with HBV‐related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan–Meier method and Cox regression model to identify risk factors for intrahepatic recurrence. Results: A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥ 2000 IU/mL. The median follow‐up duration was 28.9 months (range, 12.0–57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P = 0.026) and late (≥ 1 year) recurrence (HR, 0.288; P = 0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P = 0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence. Conclusions: These findings show that HBeAg‐negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg‐negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV‐related HCC.     

Highly sensitive AFP-L3% assay is useful for predicting recurrence of hepatocellular carcinoma after curative treatment pre- and postoperatively

Aim: The micro‐total analysis system (µTAS), a fully automated immunoassay system using microchip capillary electrophoresis, is highly sensitive and able to quickly assay the AFP‐L3%. The clinical usefulness of this system was studied. Methods: We retrospectively enrolled 250 patients who underwent curative treatment for primary hepatocellular carcinoma (HCC) (93 patients underwent hepatic resection and 157, radiofrequency ablation [RFA]). Results: The sensitivity for µTAS AFP‐L3% was 40.3% at the cutoff value of 5% in a range of AFP less than 20 ng/mL where the conventional method was unable to determine AFP‐L3%. The sensitivity for AFP‐L3% remained high even at stage I and at tumor size less than 2 cm (42.5% and 46.0%, respectively). Recurrence rate of patients with AFP‐L3% greater than 5% was significantly higher than that of patients with less than 5% (P = 0.001). Furthermore, in resected patients, the postoperative AFP‐L3% remained elevated with value greater than 5% was related to HCC recurrence (P = 0.001). Multivariate analysis revealed that multiple tumors (P = 0.004), preoperative AFP‐L3% greater than 5% (P = 0.003), albumin less than 3.5 g/dL (P = 0.008), and RFA (P = 0.003) were significant prognostic factors of recurrence. Conclusions: The µTAS was found to be a highly sensitive assay for AFP‐L3% in patients with curative treatment of HCC. A cutoff value of 5% was useful for predicting recurrence after the curative treatment and detecting small tumors and early stage HCC. Additionally, postoperative AFP‐L3% was found to be a prognostic factor of HCC recurrence.     

Influence of anti‐HBc seropositivity on the risk of hepatocellular carcinoma in HCV‐infected patients after adjusting for confounding factors

Summary. It is controversial whether past hepatitis B virus infection constitutes an additional risk of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV). The incidence of HCC between 1994 and 2004 was analysed among 1262 patients who were only positive for HCV. The cumulative incidence of HCC was assessed by Kaplan–Meier analysis and the difference between two groups was assessed by the log‐rank test. The effect of anti‐HBc positivity on the risk of HCC was assessed with multivariate Cox proportional analysis. Anti‐HBc was positive in 522 (41.4%) patients. The proportion of male patients (56.7 vs 46.8%, P < 0.001) and mean age (60.8 vs 56.9 years, P < 0.001) were significantly higher in the anti‐HBc positive group. HCC developed in 339 patients (mean follow‐up 7.0 years), with cumulative incidence rates at 3, 5 and 10 years of 12.7, 24.5 and 41.9% in the anti‐HBc positive group and 10.6, 17.7 and 33.4% in the negative group, respectively (P = 0.005). However, anti‐HBc seropositivity did not reach statistical significance in multivariate analysis including age and gender (hazard ratio, 1.06; 95% CI, 0.85–1.31; P = 0.63). Anti‐HBc positivity and HCC incidence were confounded by male gender and older age.     

Metabolic disorders associated with chronic hepatitis C: impact of genotype and ethnicity

Background & aim: Patients with hepatitis C virus (HCV) infection, especially those with genotypes 1 and 4, have an increased risk of developing metabolic disorders. The aim of this study was to evaluate the associations among metabolic disorders, ethnicity and genotype in a large cohort of patients with chronic hepatitis C (CHC). Patients and Methods: All consecutive patients with CHC who were seen in our hepato‐gastroenterology unit between January 2002 and September 2008 were included. Demographical data and variables related to the metabolic syndrome were collected. Insulin resistance was assessed using the homeostasis model for the assessment of insulin resistance test (HOMA‐IR) test. Results: Among the 454 CHC patients, the prevalence of the metabolic syndrome was 12.4%. The HOMA‐IR test was performed in 140 patients, and 35.0% had insulin resistance. There were more Black Africans among the patients with genotypes 1/4 than among those with genotypes 2/3 (32.0 vs 1.2%, P<0.0001). Insulin resistance was more common in patients with genotypes 1/4 than in those with genotypes 2/3 (17 vs 1.7%, P=0.0001 and 43.3 vs 16.3%, P=0.001, respectively). Genotypes 1/4 were more frequently present in patients with insulin resistance than in those without insulin resistance (85.7 vs 60.5%, P=0.001). By logistic regression, genotypes 1/4 [odds ratio (OR)=2.79; 95% confidence interval (CI): 1.09–7.12, P=0.032] and older age (OR=1.03; 95% CI: 1.004–1.06, P=0.024) were independently associated with the presence of insulin resistance. Conclusions: In CHC, insulin resistance is independently associated with the presence of genotypes 1/4. Ethnicity is not independently associated with metabolic disorders in patients with CHC.     

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

Aim: To evaluate changes in liver function parameters and risk factors 1 year after percutaneous radiofrequency ablation (RFA) therapy in patients with hepatocellular carcinoma (HCC). Methods: Subjects in this retrospective study comprised 45 patients with HCC who underwent RFA therapy (RFA alone, n = 25; transcatheter arterial embolization therapy before RFA, n = 20) and showed no recurrence of HCC 1 year after RFA. Serial changes in serum total bilirubin, albumin, prothrombin time and Child–Pugh score (CPs) were evaluated before and after RFA. In addition, Cox proportional hazards regression analysis was used to clarify risk factors for aggravation of liver function after RFA therapy. Results: Serum albumin levels showed a significant decrease from before (3.6 ± 0.4 g/dL) to 12 months after RFA therapy (3.2 ± 0.4 g/dL; P ≤ 0.05). CPs was significantly increased from before (6.4 ± 1.4) to both 6 months (6.8 ± 1.9; P ≤ 0.05) and 12 months after RFA (6.9 ± 2.0; P ≤ 0.05). Based on stepwise multivariate analysis, CPs of 9 or more before RFA was selected as a significant risk factor for long‐term aggravation of liver function after RFA. Conclusion: Liver function parameters, particularly serum albumin level, gradually and dominantly decreased in HCC patients with grade B and C according to the CPs classification over the course of 1 year after RFA therapy. A CPs of 9 or more represents a major risk factor for the aggravation of liver function after RFA therapy.     

Virologic control and severity of liver disease determine survival after radiofrequency ablation of hepatocellular carcinoma on cirrhosis

Background

We aimed to identify the main determinants of long-term overall survival (OS), including virologic control, and recurrence after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) on cirrhosis.

Hepatitis C virus antibody-positive patients with HIV infection have a high risk of insulin resistance: a cross-sectional study

Objective

The aim of the study was to characterize and compare insulin resistance (IR) in hepatitis C virus (HCV)‐antibody (Ab)‐positive and HCV‐Ab‐negative patients with HIV infection.

Methods

This was a single‐centre cross‐sectional study of 1041 HIV‐infected patients (373 HCV‐Ab‐positive; 167 with detectable plasma HCV RNA). Metabolic and anthropometric assessments were performed, including measurement of IR using the homeostasis model for assessment of insulin resistance (HOMA‐IR).

Results

The prevalence of IR (i.e. a HOMA‐IR score ≥3.8) was significantly higher in HCV‐Ab‐positive than in HCV‐Ab‐negative patients (47.7 vs. 32.7%; P<0.0001). On multivariable linear regression analysis, the following variables were associated with HOMA‐IR score, expressed as an estimate of the percentage variation (Est.): high‐density lipoprotein cholesterol (per 0.3 mmol/L increase: Est.–4.1; P=0.01), triglycerides (per 0.1 mmol/L increase: Est. 0.6; P<0.001), alcohol intake (Est. ?12.4; P=0.002), sedentary lifestyle (Est. 14.7; P<0.001), CD4 T‐cell count in the highest quartile, i.e. ≥690 cells/μL (Est. 20.7; P=0.002), body mass index in the highest quartiles, i.e. ≥22.54 kg/m² (Est. 30.5–44.7; P<0.001), waist‐to‐hip ratio in the highest quartile, i.e. >1 (Est. 30.2; P<0.001) and HCV‐Ab positivity (Est. 24.4; P<0.001).

Conclusions

Our data confirm that HCV‐Ab positivity is an independent risk factor for IR. Management aimed at correcting known risk factors for IR should be implemented.     

Percutaneous radiofrequency ablation as first‐line treatment for small hepatocellular carcinoma: Results and prognostic factors on long‐term follow up

Background and Aims: We evaluated the prognosis and associated factors in patients with small hepatocellular carcinoma (HCC; up to 3 nodules, each up to 3cm in diameter) treated with percutaneous radiofrequency ablation (RFA) as first‐line treatment. Methods: Eighty‐eight consecutive patients who underwent percutaneous RFA as first‐line treatment were enrolled, among whom 70 who had hypervascular HCC nodules which were treated by a combination of transcatheter arterial chemoembolization and RFA. RFA was repeated until an ablative margin was obtained. Results: The rate of local tumor progression at 1 and 3 years was 4.8% and 4.8%, respectively. The rate of overall survival at 3 and 5 years was 83.0% and 70.0%, and the rate of disease‐free survival at 3 and 5 years was 34.0% and 24.0%, respectively. On multivariate analysis, age (< 70 years; hazard ratio [HR] = 2.341, 95% confidence interval [CI] = 1.101–4.977, P = 0.027) and indocyanine green retention rate at 15 min (< 15%; HR = 3.621, 95% CI = 1.086–12.079, P = 0.036) were statistically significant determinants of overall survival, while tumor number (solitary, HR = 2.465, 95% CI = 1.170–5.191, P = 0.018) was identified for disease‐free survival. Overall survival of patients with early recurrence after RFA was significantly worse than that of patients with late recurrence. Tumor size was the only independent risk factor of early recurrence after RFA of HCC (tumor size > 2 cm; risk ratio [RR] = 4.629, 95% CI = 1.241–17.241, P = 0.023). Conclusion: Percutaneous RFA under the protocol reported here has the potential to provide local tumor control for small HCC. In addition to host factors, time interval from RFA to recurrence was an important determinant of prognosis.     

Hyperinsulinaemia reduces the 24‐h virological response to PEG‐interferon therapy in patients with chronic hepatitis C and insulin resistance

Summary. Insulin resistance (IR) reduces response to pegylated‐interferon (PEG‐IFN)/ribavirin in chronic hepatitis C (CHC), but the mechanisms are still undefined. We examined the relationship between baseline insulin levels, the main component affecting homeostasis model of assessment – insulin resistance (HOMA‐IR) for assessment of IR in non‐diabetic patients, and the ‘acute’ virological response to PEG‐IFN measured 24 h after the first injection and taken as correlate of intracellular interferon signalling. In 62 patients treated with PEG‐IFN/Ribavirin, serum insulin and HOMA‐IR were assessed at baseline, while hepatitis C virus (HCV)‐RNA was measured at baseline and 24 h, 1, 2, 4 and 12 weeks after treatment initiation. Sustained virological response was examined 24 weeks after therapy discontinuation. Mean baseline insulin was 11.52 ± 8.51 U/L and mean HOMA‐IR was 2.65 ± 2.01 both being significantly higher with advanced liver fibrosis. Hepatitis C virus‐RNA decay observed 24 h after the first injection of PEG‐IFN was significantly lower (0.7 ± 0.8 log) in patients with HOMA ≥3 compared with those with HOMA <3 (1.7 ± 0.8, P = 0.001). A highly significant (r = ?0.42) inverse correlation was observed between baseline insulin levels and the 24‐h HCV‐RNA decay. The difference in early viral kinetics between patients with HOMA ≥3 or <3 resulted in a significant difference in the percentage of patients achieving rapid (week 4) and sustained virological response. Multivariate analysis, inclusive of patient age, HCV genotype and fibrosis stage, identified baseline insulin levels as the main independent variable affecting the 24‐h response to PEG‐IFN. Hyperinsulinaemia reduces the cellular response to Pegylated‐interferon in CHC with IR. Strategies to reduce insulin levels before initiation of treatment should be pursued to improve efficacy of anti‐viral treatment.     

Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation

Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). We studied whether peripheral blood neutrophil‐to‐lymphocyte ratio (NLR), a marker of systemic inflammatory response, would be a useful predictor for outcome in patients with early HCC undergoing radiofrequency ablation (RFA). Methods: A total of 158 patients with early HCC underwent RFA. Potential prognostic factors such as age, gender, tumoral characteristics, Child‐Turcotte‐Pugh (CTP) class and NLR were analyzed. The study endpoints were overall survival (OS) and new recurrence. Results: We modeled NLR as a continuous explanatory variable in regression analyses. Multivariate analysis revealed that tumor size (P = 0.005) and high baseline NLR (P = 0.001) were independent explanatory variables associated with unfavorable OS. Regarding new recurrence, multivariate analysis showed that CTP class B (P = 0.002), α‐fetoprotein > 400 ng/mL (P = 0.030), tumor size (P = 0.002) and tumor multiplicity (P = 0.013) were found to be worse prognosticators, but not baseline NLR. In a subset analysis of 140 patients whose post‐RFA NLR data at first follow‐up visit were available, multivariate analysis revealed that high post‐RFA NLR was identified as an independent covariate, not only for OS (P = 0.006), but for new recurrence (P = 0.010) as well. Conclusions: High baseline NLR was associated with worse OS for patients with early HCC; post‐RFA NLR predicted not only OS, but also tumor recurrence.     

Transarterial chemoembolization in combination with percutaneous ablation therapy in unresectable hepatocellular carcinoma: a meta‐analysis

Background: Recent evidence suggests that transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) or a percutaneous ethanol injection (PEI) may have a synergistic effect in treating hepatocellular carcinoma (HCC). The aim of the current meta‐analysis was to identify the survival benefits of TACE combined with percutaneous ablation (PA) therapy (RFA or PEI) for unresectable HCC compared with those of TACE or PA alone. Methods: Randomized‐controlled trials (RCTs) published as full papers or abstracts were searched to assess the survival benefit or tumour recurrence for patients with unresectable HCC on electronic databases. The primary outcome was survival. The secondary outcomes were response to therapy and tumour recurrence. Results: Ten RCTs met the criteria to perform a meta‐analysis including 595 participants. TACE combined with PA therapy, respectively improved, 1‐, 2‐, and 3‐year overall survival compared with that of monotherapy [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.14–4.57; P=0.020], (OR=4.53, 95% CI 2.62–7.82, P<0.00001) and (OR=3.50, 95% CI 1.75–7.02, P=0.0004). Sensitivity analysis demonstrated a significant benefit in 1‐, 2‐ and 3‐year overall survival of TACE plus PEI compared with that of TACE alone for patients with large HCC lesions, but not in TACE plus RFA vs RFA for patients with small HCCs. The pooled result of five RCTs showed that combination therapy decreased tumour recurrence compared with that of monotherapy (OR=0.45, 95% CI 0.26–0.78, P=0.004). Conclusion: TACE combined with PA therapy especially PEI improved the overall survival status for large HCCs.     

Effects of hepatitis B e‐antigen on recurrence of hepatitis B‐related hepatocellular carcinoma after curative resection: A meta‐analysis

Aim: The impact of hepatitis B e‐antigen (HBeAg) on recurrence of hepatocellular carcinoma (HCC) after curative resection remains controversial. This meta‐analysis aimed to determine whether the presence of HBeAg influenced the recurrence of HCC after curative resection. Methods: We performed a meta‐analysis including six studies (a total of 865 patients) to assess the effect of HBeAg on recurrence of HCC after curative resection. The pooled odds ratios (OR) were calculated using a random or fixed effects model. PUBMED, MEDLINE, EMBASE and the Cochrane Database were searched for articles published from 1990 to March 2012. Sensitivity analysis and publication bias estimate were also performed to evaluate the potential risk bias in the overall results of pooled analysis. Results: Our results showed that the presence of HBeAg significantly increased the overall HCC recurrence risk after curative resection (OR = 1.63, 95% confidence interval (CI) = 1.11–2.40; P = 0.01). Pooled data from three studies on the risk of early recurrence among HBeAg positive patients compared with HBeAg negative patients showed an increased risk of early recurrence (OR = 1.50, 95% CI = 1.02–2.19; P = 0.04). However, there was no significant difference in late HCC recurrence between HBeAg positive and negative patients (OR = 1.17, 95% CI = 0.62–2.19; P = 0.62). Conclusion: The present study suggested that HBeAg positive patients had a significantly higher risk of early recurrence after curative resection of HCC.     

Meta‐analysis: interferon‐alpha prevents the recurrence after curative treatment of hepatitis C virus‐related hepatocellular carcinoma

Summary. Various clinical studies have indicated that interferon (IFN)‐alpha treatment prevents the development of hepatocellular carcinoma (HCC) in people chronically infected with hepatitis C virus. However, it has been controversial whether IFN‐alpha treatment prevents HCC recurrence. The aim of this study was to identify the preventive effect of IFN‐alpha treatment after curative therapy of primary tumours within the Milan criteria (three or fewer nodules 3 cm or less in diameter or a single nodule of 5 cm or less) on HCC recurrence. We conducted a meta‐analysis of five trials including 355 patients (167 patients received IFN‐alpha treatment after curative therapy of primary tumours) and estimated relative risks (RRs) and 95% confidence intervals (CIs) for the effect of IFN‐alpha on HCC recurrence according to the DerSimonian and Laird method. IFN‐alpha treatment after curative therapy of primary tumours significantly prevented HCC recurrence (RR 0.33; 95%CI 0.19–0.58, P < 0.0001) without a significant heterogeneity (Q = 4.52, P = 0.34). An evaluation using the Begg method suggested no evidence of publication bias. Sub‐group analyses revealed that IFN‐alpha treatment reduced HCC recurrence in two studies achieving sustained virologic response (SVR) rates >30% (RR 0.20; 95%CI 0.05–0.81, P = 0.02) and in three studies achieving SVR rates ≤30% (RR 0.44; 95%CI 0.23–0.84, P = 0.01). In conclusion, IFN‐alpha treatment after curative treatment of primary tumour within Milan criteria may be effective for the prevention of HCC recurrence, and higher SVR rate may be associated with better preventive effect of IFN‐alpha treatment on HCC recurrence.     

Insulin resistance is an independent correlate of increased urine albumin excretion: a cross‐sectional study in Iranian Type 2 diabetic patients

Aims To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients. Methods Three hundred and sixty‐one men and 472 women with Type 2 diabetes were enrolled from three different outpatient clinics (Tehran, Iran) during the period 2005–2008. Patients with obstructive uropathy, severe heart failure, liver disease, cancer, autoimmune disease and macroalbuminuria were not included. Microalbuminuria (MA; defined as UAE ≥ 30 mg/day) was found in 242 (29.1%) patients; 591 (70.9%) subjects had normoalbuminuria (UAE < 30 mg/day). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA‐IR). Results HOMA‐IR index values were higher in subjects with MA than those with normoalbuminuria (P < 0.00001). Adjusted values (for age, sex and duration of diabetes) of UAE and HOMA‐IR were 11.81 ± 7.51 (mg/day) and 3.30 ± 2.21 in normoalbuminuric and 75.36 ± 55.57 (mg/day) and 4.98 ± 3.22 in the MA group, respectively (P < 0.00001 for all). Multiple regression analysis showed that UAE was predicted by HOMA‐IR, independently of age, duration of diagnosed diabetes, triglycerides, waist circumference, metabolic control, blood pressure and related treatments (P < 0.00001). When patients were categorized into quartiles of HOMA‐IR, those of the fourth quartile (i.e. the most insulin resistant) were at a higher risk of increased UAE than other quartiles [odds ratio (OR) 3.7 (95% confidence intervals 2.7–6.2)]. Conclusions In Iranian Type 2 diabetic patients, albuminuria was strongly associated with insulin resistance. HOMA‐IR is an independent predictor of UAE.     

Insulin resistance increases loss of antibody to hepatitis B surface antigen in nondiabetic healthy adults

The aim of this study was to evaluate the impact of insulin resistance on the persistence of a protective level of anti‐HBs (hepatitis B surface antigen) in a nondiabetic general population. A cohort study was designed comprising of 38 473 Korean men and women with anti‐HBs at concentrations ≥10 mIU/mL, who underwent a health examination. Insulin resistance was assessed with a homoeostasis model assessment of insulin resistance (HOMA‐IR). A decline in anti‐HBs to <10 mIU/L during the follow‐up was considered to be a loss of protective anti‐HBs. Cox‐proportional hazard models were used to estimate the adjusted hazard ratios and 95% confidence intervals for anti‐HBs loss across quintiles of HOMA‐IR and insulin. We identified 20 826 incidents of loss of anti‐HBs antibody during 180 522 person‐years of follow‐up (incident rate 11.5 per 100 person‐years). Increasing HOMA‐IR was positively associated with incident loss of anti‐HBs. The multivariable‐adjusted hazard ratios (95% confidence intervals) for incident loss of anti‐HBs comparing quintiles 2–5 vs quintile 1 of HOMA‐IR were 1.09 (1.04–1.14), 1.14 (1.09–1.19), 1.14 (1.09–1.19) and 1.21 (1.16–1.27), respectively. These associations were stronger in younger individuals under the age of 35 than in people 35 years of age or older (P for interaction = 0.004). The association was also more evident in subjects with higher titres (≥100 mIU/mL) of anti‐HBs than in those with low titres (P for interaction < 0.001). Insulin resistance was associated with an increased risk for loss of vaccine‐acquired anti‐HBs in a large sample of a nondiabetic, general population, indicating a possible role of insulin resistance in vaccine‐induced immunity.     

Early prediction of sustained virological response at day 3 of treatment with albinterferon‐α‐2b in patients with genotype 2/3 chronic hepatitis C

Background: Albinterferon‐α‐2b (albIFN) is a long‐acting fusion polypeptide composed of albumin and IFN‐α‐2b. In a phase 2 study of albIFN 1500 μg q2wk or q4wk in patients with genotype 2/3 chronic hepatitis C, albIFN demonstrated sustained virological response (SVR) rates of 62–77% (intent‐to‐treat population). Aims: To assess the association of initial viral kinetics during albIFN therapy with baseline factors and SVR prediction. Methods: In all, 43 patients were treated with albIFN 1500 μg (q2wk/q4wk) plus ribavirin (RBV) 800 mg/day for 24 weeks. Hepatitis C virus (HCV)‐RNA levels were measured by real‐time polymerase chain reaction, insulin resistance by homeostasis model assessment of insulin resistance (HOMA‐IR) and serum albIFN levels by enyzme‐linked immunosorbent assay. Prediction analysis was performed in a per protocol 28‐patient subset who were ≥80% adherent to albIFN/RBV and had HCV‐RNA levels measured at treatment day 3. Results: Day‐3 HCV‐RNA level and first‐phase viral decline as well as second‐phase slope of viral decline were significantly associated with SVR. In adherent patients, 82.1% had a day‐3 viral load <4.2 log₁₀ IU/ml or first‐phase decline >1.25 log₁₀ IU/ml, which was predictive of SVR, both positively (95.7%; sensitivity: 100%) and negatively (100%; specificity: 83.3%). As low first‐phase decline was associated with a high pretreatment HOMA‐IR index (P=0.004) and a low day‐3 serum albIFN level (P=0.01). Conclusions: First‐phase viral decline with albIFN/RBV was predictive of SVR in this study and may be modulated in part by IR.