Combining the age-male-albumin-bilirubin-platelets score and shear wave elastography stratifies carcinogenic risk in hepatitis C patients after viral clearance.

BACKGROUND: The treatment of hepatitis C with direct-acting antiviral agents (DAAs) produces a high rate of sustained virological response (SVR) with fewer adverse events than interferon (IFN) therapy with a similar effect in inhibiting carcinogenesis as IFN therapy. The age-male-albumin-bilirubin-platelets (aMAP) score is useful for stratifying the risk of hepatocellular carcinoma in chronic hepatitis patients, and the velocity of shear waves (Vs) measured by shear wave elastography has also been shown to be useful for diagnosing the level of fibrotic progression in hepatitis C and predicting carcinogenic risk. Combining these two may improve the prediction of carcinogenic risk. AIM: To determine whether combining the aMAP score with Vs improves carcinogenic risk stratification in medium-to-high-risk hepatitis C patients. METHODS: This retrospective, observational study involved hepatitis C patients treated with DAAs who achieved SVR. Vs was measured before treatment (baseline), at the end of treatment (EOT), and 12 wk (follow-up 12) and 24 wk (follow-up 24) after treatment. The patients were followed for at least six months after EOT to determine whether cancer developed. Multiple regression analysis was used to identify factors contributing to hepatic carcinogenesis. The diagnostic performances of clinical parameters for predicting the presence of hepatocellular carcinoma were evaluated using receiver-operating characteristic (ROC) curve analyses. RESULTS: A total of 279 patients (mean age 65.9 years, 118 males, 161 females) were included in the analysis. Multiple regression analysis was performed with carcinogenesis as the target variable and alanine aminotransferase, platelets, α-fetoprotein, Vs, and the Fib-4 index as explanatory variables; only Vs was found to be significant (P = 0.0296). The cut-off value for Vs for liver carcinogenesis calculated using the ROC curve was 1.53 m/s. Carcinoma developed in 2.0% (3/151) of those with Vs < 1.53 m/s and in 10.5% (9/86) of those with Vs ≥ 1.53 m/s. CONCLUSION: In hepatitis C patients after SVR, combining the aMAP score and Vs to stratify the risk of carcinogenesis is more efficient than uniform surveillance of all patients.

Novel multi-parametric diagnosis of non-alcoholic fatty liver disease using ultrasonography, body mass index, and Fib-4 index.

BACKGROUND: Shear wave speed (SWS), shear wave dispersion (SWD), and attenuation imaging (ATI) are new diagnostic parameters for non-alcoholic fatty liver disease. To differentiate between non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver (NAFL), we developed a clinical index we refer to as the "NASH pentagon" consisting of the 3 abovementioned parameters, body mass index (BMI), and Fib-4 index. AIM: To investigate whether the area of the NASH pentagon we propose is useful in discriminating between NASH and NAFL. METHODS: This non-invasive, prospective, observational study included patients diagnosed with fatty liver by abdominal ultrasound between September 2021 and August 2022 in whom shear wave elastography, SWD, and ATI were measured. Histological diagnosis based on liver biopsy was performed in 31 patients. The large pentagon group (LP group) and the small pentagon group (SP group), using an area of 100 as the cutoff, were compared; the NASH diagnosis rate was also investigated. In patients with a histologically confirmed diagnosis, receiver-operating characteristic (ROC) curve analyses were performed. RESULTS: One hundred-seven patients (61 men, 46 women; mean age 55.1 years; mean BMI 26.8 kg/m2) were assessed. The LP group was significantly older (mean age: 60.8 ± 15.2 years vs 46.4 ± 13.2 years; P < 0.0001). Twenty-five patients who underwent liver biopsies were diagnosed with NASH, and 6 were diagnosed with NAFL. On ROC curve analyses, the areas under the ROC curves for SWS, dispersion slope, ATI value, BMI, Fib-4 index, and the area of the NASH pentagon were 0.88000, 0.82000, 0.58730, 0.63000, 0.59333, and 0.93651, respectively; the largest was that for the area of the NASH pentagon. CONCLUSION: The NASH pentagon area appears useful for discriminating between patients with NASH and those with NAFL.

Role of liver stiffness measurements in patients who develop hepatocellular carcinoma after clearance of the hepatitis C virus.

PURPOSE: To measure changes in liver stiffness over time due to direct-acting antiviral (DAA) therapy in hepatitis C patients using shear wave elastography (SWE). METHODS: Patients with hepatitis C treated with DAA therapy in a university medical center between July 2015 and April 2020 were evaluated. Shear wave velocity (Vs) of the liver was measured using SWE. Alanine aminotransferase (ALT), platelet count, and α-fetoprotein (AFP) were measured at the same time, and the FIB-4 index was estimated. Absence of hepatocellular carcinoma was confirmed at baseline and end of therapy. Imaging was then performed every 6 months. Patient characteristics were compared between patients who did and did not develop carcinoma. RESULTS: The mean age of the 229 patients (93 men) was 65.6 years. Eight patients developed carcinoma during follow-up (mean 32.6 ± 19.5 months). Significant differences were found between the groups in terms of AFP, platelet count, and Fib-4 index at baseline; the pre-treatment data had the best relationship with hepatocarcinogenesis. Mean Vs decreased significantly during DAA therapy, and then decreased further. Liver stiffness 6 months after treatment ended had the best relationship with hepatocarcinogenesis. CONCLUSION: In patients with a sustained virological response, risk of developing cancer can be predicted by measuring Vs approximately 6 months after treatment.

Hypozincemia in Chronic Hepatitis C Is Improved with Viral Clearance by Direct-acting Antiviral Agents.

Objective Hypozincemia is a decrease in the serum zinc level of patients with hepatitis C and often requires zinc supplementation to improve the hepatic function. Our previous study showed the efficacy of direct-acting antiviral agent (DAA) treatment on serum zinc levels in patients with hepatitis C without zinc supplementation. In this study, we aimed to prospectively examine factors related to the improvement of serum zinc levels of patents with hepatitis C with DAA treatment. Methods Fifty-three patients with hepatitis C treated with DAAs between March 2018 and February 2019 at a university medical center were divided into two groups based on their initial serum level: the zinc deficiency group (n=43, <80 µg/dL) and the normal zinc group (n=10, ≥80 µg/dL). Their serum zinc levels and clinical parameters were measured before DAA treatment, at the end of treatment and 12 weeks post-treatment. Results All 53 patients achieved a sustained viral response to DAAs at the end of treatment and at follow-up. There was a significant increase in the serum zinc level from baseline to follow-up in the zinc deficiency group but not in the normal zinc group. The change in serum albumin was the only factor contributing to the observed increase in serum zinc levels by a multiple regression analysis. Conclusion DAA treatment in patients with hepatitis C improved hypozincemia due to the restored function of serum albumin, which binds to about 60% of serum zinc, upon the amelioration of the hepatitis C infection.

Changes in serum zinc levels in hepatitis C patients before and after treatment with direct-acting antiviral agents.

AIM: Zinc supplementation therapy has been shown to improve the prognosis of patients with hepatitis C virus (HCV) infection. However, little is known about the changes in serum zinc levels with treatment using direct-acting antiviral agents (DAAs). This prospective study investigated the changes in serum zinc levels before and after treatment with DAAs in hepatitis C patients. METHODS: Thirty-one patients with chronic hepatitis C or HCV-related compensated cirrhosis who were treated with DAAs (glecaprevir/pibrentasvir or elbasvir/grazoprevir) were included in the study. Serum zinc and serum albumin levels were measured before DAA treatment (Baseline), at the end of treatment (EOT), and at 12 weeks after EOT (Follow-up 12). The changes over time in the serum zinc and serum albumin levels were investigated. RESULTS: The mean age of the patients was 68.5 ± 12.1 (range, 40-86) years, and 17 (55%) were women. Based on the Japanese Society of Clinical Nutrition diagnostic criteria, 6 patients had zinc deficiency (<60 µg/dL), and 21 patients had subclinical zinc deficiency (60-80 µg/dL). Significant differences in serum zinc levels were seen between Baseline and EOT (P = 0.01) and between EOT and Follow-up 12 (P = 0.0003). There was no significant difference in serum albumin levels between Baseline and EOT (P = 0.76), but a significant increase was seen between EOT and Follow-up 12 (P = 0.01). CONCLUSIONS: Increases in serum zinc are directly related to DAA treatment and are not a result of increases in albumin. Inhibition of the non-structural protein (NS)3 and NS5A by DAAs could be associated with the improvement of serum zinc levels in hepatitis C patients.