Progress of ulcerative colitis patients during the COVID-19 pandemic.

BACKGROUND: We have previously demonstrated that the first wave of the coronavirus disease 2019 (COVID-19) pandemic caused exacerbations in ulcerative colitis (UC) patients, probably through psychological and physical stress. However, successive waves of the COVID-19 pandemic continuously followed the first. The effects of this chronic stress on the disease condition in UC patients are of interest. AIM: To clarify the effect of chronic stress from COVID-19 on disease condition in patients aggravated after the first wave. METHODS: Our previous study investigated 289 consecutive UC outpatients treated in one center during March and April 2020, the period of the first wave of the COVID-19 pandemic. In this study, an identical group of 289 UC patients was evaluated using UC-disease activity index (UC-DAI), endoscopic mucosal appearance score, and Matts pathological grade scoring. RESULTS: Of the 289 UC patients included in the study in 2020, 10 patients dropped out as of 2021 and another 11 patients dropped out as of 2022, making three groups for 2020, 2021 and 2022. No significant differences in characteristics were found among the three groups. UC-DAI scores had aggravated during the period of the first wave of the COVID-19 pandemic, but significantly recovered in 2021 and remained stable in 2022. Matts grade scores significantly recovered in 2021 from those in 2020 and remained stable in 2022. CONCLUSION: Disease activity of UC patients recovered in 2021 and remained stable in 2022, aggravated by the stress of the first wave of COVID-19 in 2020 despite persistence of the pandemic.

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.

COVID-19 pandemic and exacerbation of ulcerative colitis.

BACKGROUND: In 2020, the world faced the unprecedented crisis of coronavirus disease 2019 (COVID-19). Besides the infection and its consequences, COVID-19 also resulted in anxiety and stress resulting from severe restrictions on economic and social activities, including for patients with ulcerative colitis (UC). Fresh acute stress exerts stronger influences than continuous stress on UC patients. We therefore hypothesized that the first wave of the COVID-19 pandemic would have serious effects on UC patients and performed this retrospective control study. AIM: To determine whether the first wave of the COVID-19 pandemic would have serious effects on UC patients included in a retrospective controlled study. METHODS: A total of 289 consecutive UC outpatients seen in March and April 2020 were included in this study. Modified UC disease activity index (UC-DAI) scores on the day of entry and at the previous visit were compared. An increase of ≥ 2 was considered to indicate exacerbation. The exacerbation rate was also compared with that in 256 consecutive control patients independently included in the study from the same period of the previous year in the same manner. RESULTS: No significant differences in patient characteristics or pharmacotherapies before entry were seen between the groups. Mean UC-DAI score was significantly higher in subjects during the first wave of COVID-19 (0.67 + 0.07) compared to the previous visit (0.26 + 0.04; P = 0.0000). The exacerbation rate was significantly increased during the first wave of COVID-19, as compared with the previous year (15.9% [46/289] vs 8.9% [23/256]; P = 0.0151). CONCLUSION: This study demonstrated that the COVID-19 pandemic caused exacerbations in UC patients, probably through psychological and physical stress.

Histopathologic Change of a Case of Gastric Oxyntic Neoplasm (Gastric Adenocarcinoma of Fundic Gland Mucosa Type) Through 5 Years With Concurrent Other Oxyntic Gland Lesions.

Some gastric epithelial neoplasms show predominant chief cell differentiation (oxyntic gland neoplasms), in which the entity of "gastric adenocarcinoma of fundic gland type" was firstly designated, whereas a possible more aggressive subgroup "gastric adenocarcinoma of fundic gland mucosa type" (GA-FGM) was subsequently proposed. However, the histopathologic progression mode of these neoplasms has not been sufficiently reported. In this article, we describe a case of GA-FGM in which we could observe its progression during 5 years. The tumor was removed by endoscopic submucosal dissection 5 years after the first biopsy, which had already shown a feature of oxyntic gland neoplasm. During the follow-up period, the endoscopy revealed little change in the tumor appearance. However, the histology of endoscopic submucosal dissection showed submucosal extension with its histological progression. Besides, other oxyntic gland neoplasms of the stomach were observed metachronously or synchronously, giving an implication about a common pathogenetic basis of these lesions.

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.

Shear wave elastography in hepatitis C patients before and after antiviral therapy.

AIM: To investigate shear wave (SW) propagation velocity in patients with untreated hepatitis C and patients with sustained virological response (SVR). METHODS: A total of 136 hepatitis C patients [85 patients who had not received antiviral therapy (naïve group) and 51 patients who had received antiviral therapy and subsequently achieved SVR of at least 24 wk (SVR group)] and 58 healthy volunteers and outpatients without liver disease (control group) underwent evaluation of liver stiffness by SW elastography (SWE). Various parameters were evaluated in the chronic hepatitis C patients at the time of SWE. RESULTS: SW propagation velocity (Vs) was 1.23 ± 0.14 m/s in the control group, 1.56 ± 0.32 m/s in the SVR group, and 1.69 ± 0.31 m/s in the naïve group. Significant differences were seen between the control group and the SVR group (P = 0.0000) and between the SVR group and the naïve group (P = 0.01417). All four fibrosis markers were higher in the naïve group than in the SVR group. In the naïve group, Vs was positively correlated with alanine aminotransferase (ALT) (r = 0.5372), α feto protein (AFP) (r = 0.4389), type IV collagen (r = 0.5883), procollagen III peptide (P-III-P) (r = 0.4140), hyaluronic acid (r = 0.4551), and Mac-2 binding protein glycosylation isomer (M2BPGi) (r = 0.6092) and negatively correlated with albumin (r = -0.4289), platelets (r = -0.5372), and prothrombin activity (r = -0.5235). On multiple regression analysis, Vs was the most strongly correlated with ALT (standard partial regression std ß = 0.4039, P = 0.00000). In the SVR group, Vs was positively correlated with AFP (r = 0.6977), type IV collagen (r = 0.5228), P-III-P (r = 0.5812), hyaluronic acid (r = 0.5189), and M2BPGi (r = 0.6251) and negatively correlated with albumin (r = -0.4283), platelets (r = -0.4842), and prothrombin activity (r = -0.4771). On multiple regression analysis, Vs was strongly correlated with AFP (standard partial regression std ß = 0.5953, P = 0.00000) and M2BPGi (standard partial regression std ß= 0.2969, P = 0.03363). CONCLUSION: In hepatitis C patients, liver stiffness is higher in treatment-naïve patients than in those showing SVR. SWE may be a predictor of hepatocarcinogenesis in SVR patients.

Two cases of immunoglobulin G4-related sclerosing cholangitis in which transabdominal ultrasonography was useful in diagnosis and follow-up observation.

Immunoglobulin G4-related disease (IgG4-RD) represents a group of disorders that share features of inflammation, plasma cell infiltrates, and fibrosis. Sclerosing cholangitis is a disorder involving inflammation, scarring, and destruction of the bile ducts. IgG4-related sclerosing cholangitis (IgG4-SC) has been proposed as a bile duct lesion associated with IgG4-RD. This disease entity can be distinguished from other types of sclerosing cholangitis and classified into four types based upon the region of strictures revealed by cholangiography. Here, we present two cases in which the finding of bile duct wall thickening visualized with transabdominal ultrasonography was useful in the diagnosis of patients with IgG4-SC. At present, transabdominal ultrasonography is not included in the diagnostic algorithm for IgG4-SC. We are certain that detailed observation of the bile duct wall with transabdominal ultrasonography can make a significant contribution to the diagnosis of IgG4-SC. Furthermore, we propose that transabdominal ultrasonography may be useful in following clinical improvement in cases where a steroid trial is the best option for treatment. Both cases emphasize the practicality of transabdominal ultrasonography in the diagnosis and follow-up observation of IgG4-SC.

Abdominal ultrasound examination training using an ultrasound phantom and volume navigation system.

PURPOSE: The purpose of this study was to examine the effects of using an ultrasound phantom (ECHOZY) and a volume navigation system (Vnavi) in abdominal ultrasonography training for young residents. METHODS: Nine third-year residents underwent abdominal ultrasonography training: controls, comprising five residents; and the ECHOZY + Vnavi group, comprising four residents. Residents were trained in abdominal ultrasound examinations using both educational videos and hands-on clinical training. The ECHOZY + Vnavi group also received training using an ultrasound phantom and volume navigation system. The time needed for abdominal ultrasound examination was calculated at 4 months (early), 8 months (middle), and 12 months (late) after starting training. The ability of each resident to visualize 20 abdominal structures on normal patients was also evaluated retrospectively. RESULTS: In the early period, the ECHOZY + Vnavi group needed significantly longer to complete examinations than controls (545 ± 125 s versus 392 ± 81 s, p < 0.01), but showed significantly better ability scores (17.5 ± 0.6 versus 13.4 ± 1.1, p < 0.05). Both these differences disappeared by the middle period (338 ± 107 s versus 259 ± 130 s and 17.8 ± 0.5 versus 16.0 ± 0.7). CONCLUSION: In spite of longer examination times, training residents in abdominal ultrasonography using an ultrasound phantom and volume navigation system may be useful in the early period.