Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma

AIM: To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma.METHODS: The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA (HBV DNA) level and hepatitis B e antigen (HBeAg) were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS: During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio: 95.74 (12.13-891.31); P < 0.0001], male sex [odds ratio: 7.61 (2.20-47.95); P = 0.006], and higher log10 HBV DNA [odds ratio: 4.69 (1.16-20.43); P < 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio: 26.51 (2.36-381.47); P = 0.007], presence of precore mutants [odds ratio: 4.23 (1.53-19.58); P = 0.02] and presence of basal core promoter mutants [odds ratio: 2.93 (1.24-7.57); P = 0.02] were independent predictors for progression to hepatocellular carcinoma.CONCLUSION: Our results show that high levels of baseline serum HBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, how ever, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.

Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c

AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustained virologic response(SVR).METHODS We performed a retrospective analysis of all hepatitis C virus(HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1 c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment(SVR12).RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2 DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2 DM. Within that cohort,patients who achieved SVR12 had lower mean HbA1 c pre treatment(7.35 vs 8.60,P = 0.02),and lower mean HbA1 c post-treatment compared to non-responders(6.55 vs 8.61,P = 0.01). The mean reduction in HbA1 c after treatment was greater for those who achieved SVR12 than for non-responders(0.79 vs 0.01,P = 0.03). In adjusted models,patients that achieved SVR12 were more likely to have a HbA1 c decrease of ≥ 0.5 than those that did not achieve SVR12(adjusted OR = 7.24,95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2 DM,successful treatment with DAA was associated with a significant reduction in HbA1 c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore,the presence of T2 DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA.

Tumor growth rates and recurrence-free survival in chronic viral hepatitis patients with hepatocellular carcinoma

Aim:Survival in patients with hepatocellular carcinoma(HCC)is impacted by stage of liver disease,tumor characteristics,and HCC surveillance in high-risk individuals.Factors associated with HCC tumor growth rate(TGR)and its influence on recurrence-free survival after treatment was investigated.Methods:TGR was calculated in 164 HCC patients with chronic viral hepatitis who had two consecutive magnetic resonance imaging or computed tomography scans≥30 days apart prior to treatment and who were followed prospectively to determine the rates of recurrence-free survival.Results:The median TGR in 164 patients was 17.8%per month(mean 33.3%per month).Regression tree analysis indicated that the top three predictors of TGR were alpha-fetoprotein(AFP)levels(≥16.7 ng/mL),platelet counts(≥140,000 mm3),and serum albumin level(<3.55 g/dL).The regression tree identified patient groups with TGRs ranging from 0.65%to 39.4%per month.At a median follow-up of 22 months,the overall recurrence-free survival was 53.8%.The Cox model with backwards AIC search identified TGR(HR=1.34,P=0.029),age>56 years(HR=1.08,P=0.072),hepatitis C virus(HR=1.44,P=0.091),macrovascular invasion(HR=1.94,P=0.092),and the most definitive treatments(orthotopic liver transplantation,HR 0.14,P<0.001;surgical resection,HR=0.54,P=0.072;radiofrequency ablation,HR=0.58,P=0.060)as independent predictors of recurrence-free survival.For all treatment modalities,slow ;TGR was significant for prolonged survival(P=0.029).The poorest survival rates were observed in patients with fast TGRs treated by transarterial chemoembolization.Conclusion:The TGR correlated with AFP,platelet count,and albumin level.Patients with fast TGRs had shorter recurrence-free survival after HCC treatments.TGR is a potential imaging biomarker to predict clinical outcomes in HCC.