Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients.

Background and Aims: Chronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies. Methods: We screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients' baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and ß-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment. Results: High IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in ß-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039). Conclusions: There were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience.

Direct-acting antiviral therapy of chronic hepatitis C improves liver fibrosis, assessed by histological examination and laboratory markers.

BACKGROUND/PURPOSE: Direct-acting antiviral agents achieve sustained virological response in most chronic hepatitis C patients. However, histological responses are not consistent among all patients. We conducted an observational study to analyze the histological changes after direct-acting antiviral agent therapy. METHODS: We recruited 220 patients who achieved sustained virological response after direct-acting antiviral agent. Histology was assessed by liver biopsy and laboratory indices including fibrosis-4 and aspartate aminotransferase to platelet ratio index. Primary outcomes were change in the dynamic laboratory results. Secondary outcomes were histological changes on liver biopsy. We analyzed the factors predictive of histological regression. RESULTS: The mean fibrosis-4 index decreased from 4.78 at baseline to 3.30, 3.31, 3.65, and 3.66 at week 4, 8, end of treatment, and 12 weeks after treatment, respectively (all p < 0.01). Mean aspartate aminotransferase to platelet ratio index decreased from 1.62 at baseline to 0.61, 0.66, 0.64, and 0.82 at week 4, 8, end of treatment, and 12 weeks after treatment, respectively (all p < 0.01). Mean Histological Activity Index at baseline and post-treatment was 6.9 ± 1.9 and 5.0 ± 2.3. The METAVIR fibrosis scores improved in 61.9% of the patients. We compared patients who achieved fibrosis-regression with the non-regression group. There was no significant difference in the baseline host/virological factors between the groups. CONCLUSION: Reversal of liver inflammation and fibrosis was achieved in a significant number of patients who received direct-acting antiviral agent. No baseline host or virological factor was predictive of histological regression after antiviral treatment.

Subgroup analysis of the predictive ability of aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) for assessing hepatic fibrosis among patients with chronic hepatitis C.

BACKGROUND: There are many laboratory indices to assess liver fibrosis. Aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index have been used as well-known serum markers of liver fibrosis. With the increasing use of non-invasive fibrosis assessment, it is important to recognize the limitations of these tests. The factors influencing the diagnostic accuracy to evaluate liver fibrosis are not well-established. This study aimed to perform a subgroup analysis of the predictive ability of laboratory indices. METHODS: Overall, 113 patients with chronic hepatitis C infection who underwent liver biopsy were retrospectively examined. The histological assessment of liver fibrosis was performed using the METAVIR scoring system, and the values of several laboratory tests were also evaluated on the same day. We categorized our study population by treatment status, body mass index (BMI), and age. RESULTS: The two laboratory indices APRI and FIB-4 index could predict advanced (F3-4) liver fibrosis and cirrhosis (F4), with the area under the receiver operating characteristic curve (AUROC) > 0.8 and accuracy >70%. The AUROCs and accuracies were higher among patients with sustained virological response (SVR) than among those without SVR. A higher predictive ability was also observed among patients with BMI <25 kg/m2. Age did not appear to affect liver fibrosis predictability. CONCLUSIONS: The laboratory indices APRI and FIB-4 index exhibit good diagnostic performance for determining advanced fibrosis and cirrhosis among patients with hepatitis C infection. The diagnostic accuracy appears better among patients with SVR and those with BMI <25 kg/m2.

Long-term histological change in chronic hepatitis C patients who had received peginterferon plus ribavirin therapy with sustained virological response.

BACKGROUND: The improvement in liver histology is an important aim in the management of hepatitis C virus (HCV) infection. Previous studies suggest that antiviral treatment could reduce the progression of hepatic fibrosis, especially in patients with sustained virological response (SVR). However, most studies were limited by short-term evaluations and the liver stiffness was assessed by non-invasive methods. In our study, we performed a paired liver biopsy study aimed at analyzing the long-term histological changes in patients with SVR. METHODS: We included 31 patients who had been previously treated with peginterferon plus ribavirin. All patients achieved SVR and had received pre- and post-treatment liver biopsies. The histological appearance of fibrosis and inflammation were assessed with METAVIR scoring system and Histological Activity Index (HAI) criteria. We analyzed several factors associated with the histological response. RESULTS: The median interval between two biopsies was 93.0 months. The percentage of patients with fibrosis regression, stable, and progression were 19%, 45%, and 36%. A total of 71% of patients achieved inflammation improvement, whereas 6% and 23% of patients had stable disease and disease-progression, respectively. We showed that the patients without baseline advanced fibrosis and those having a lower baseline HAI score had higher risk of fibrosis worsening. Baseline fibrosis and necroinflammation status did not influence HAI change significantly. CONCLUSION: The progression of hepatic fibrosis and inflammation can be reversed in some patients who had long-term virological suppression. Patients with advanced baseline fibrosis and higher inflammatory stages seemed to receive more histologic benefit from successful antiviral treatments.

Genotype distribution and treatment response among incarcerated drug-dependent patients with chronic hepatitis C infection.

The prevalence of hepatitis C virus (HCV) infection is disproportionately high among prisoners, especially among those who are drug-dependent. However, current screening and treatment recommendations are inconsistent for this population, and appropriate care is not reliably provided. To address these problems, the present study aimed to identify unique characteristics and clinical manifestations of incarcerated patients with HCV infection. We included incarcerated patients who received treatment with pegylated-interferon combined with ribavirin at Mackay Memorial Hospital in Taitung and were serving sentences at either the Taiyuan Skill Training Institute or the Yanwan Training Institute. HCV genotypes 1 (41.4%), 3 (25.9%), and 6 (24.1%) were the most prevalent in the incarcerated patients. During the study period, we analyzed treatment response among 58 incarcerated patients and compared obtained results with treatment response among 52 patients who were living in the community. Higher sustained virological response rate was observed among patients with incarceration and HCV genotype other than 1. The odds ratios (corresponding 95% confidence intervals) for incarceration and genotype 1 were 2.75 (1.06-7.11) and 0.37 (0.14-0.99), respectively. Better treatment compliance among incarcerated patients might partially explain these results. The results of this study suggest that treatment of prisoners with HCV infection is feasible and effective. More appropriate and timely methods are needed to prevent HCV transmission among injection drug users inside prisons.

High frequencies of a favorable IL-28B rs8099917 polymorphism and the clinical implications in patients with HCV in one multiracial area of Taiwan.

There is a strong association between hepatitis C virus (HCV) treatment efficacy and the interleukin (IL)-28B gene. However, the IL-28B variant's distribution and potential role in the therapeutic response are not well established in Taitung, a racially diverse county in Taiwan. Here, we investigated the distribution pattern of IL-28B rs8099917 and its influence on treatment efficacy. In this retrospective study, we enrolled 180 patients who had been treated with pegylated-interferon plus ribavirin. Patients' general information, virological characteristics, IL-28B status, laboratory results, treatment course, and outcome were analyzed. Of the patients enrolled, 56.7% were male, with a mean age of 54.11 years. A total of 24.4% of the population were indigenous people. The majority of patients had the favorable IL-28B polymorphism (rs8099917 TT/TG/GG: 94.4%/5.6%/0%). The proportion of patients with the TT genotype seemed to be higher in indigenous patients. The rate of sustained virological response (SVR) among included patients was 73.0%. Univariate analysis showed that genotype non-1, patients achieved rapid virological response (RVR), lower body mass index (BMI), and lower baseline HCV viral load were significantly associated with SVR. Multivariate analysis revealed that BMI <25 and RVR are the independent predictor of success treatment. In conclusion, the favorable IL-28B rs8099917 polymorphism occurs in high frequency in this multiracial area, which might be important to help guide physicians and patients in their future clinical decisions.

Application of chronic liver failure-sequential organ failure assessment score for the predication of mortality after esophageal variceal hemorrhage post endoscopic ligation.

BACKGROUND: Esophageal variceal hemorrhage (EVH) is one of the high mortality complications in cirrhotic patients. Endoscopic variceal ligation (EVL) is currently the standard therapy for EVH. However, some patients have expired during hospitalization or survived shortly after management. AIM: To evaluate hospital and 6-week mortality by receiver operating characteristic (ROC) curve of chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score compared to a model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) class. METHODS: We retrospectively collected 714 cirrhotic patients with EVH post EVL between July 2010 and June 2016 at Taitung MacKay Memorial Hospital, Taiwan. CLIF-SOFA score, MELD score, and CTP class were calculated for all patients admitted. RESULTS: Among the 714 patients, the overall hospital and 6-week mortality rates were 6.9% (49/715) and 13.1% (94/715) respectively. For predicting hospital death, area under receiver operating characteristic curve (AUROC) values of CLIF-SOFA score, MELD score, and CTP class were 0.964, 0.876, and 0.846. For predicting 6-week death, AUROC values of CLIF-SOFA score, MELD score, and CTP class were 0.943, 0.817, and 0.834. CLIF-SOFA score had higher AUROC value with statistical significance under pairwise comparison than did MELD score and CTP class in prediction of not only hospital but also 6-week mortality. The history of hepatocellular carcinoma was the risk factor for 6-week mortality. For patients with hepatocellular carcinoma the cut-point of CLIF-SOFA score was 5.5 for 6-week mortality and 6.5 for hospital mortality on admission. For patients without hepatocellular carcinoma, the cut-point of CLIF-SOFA score was 6.5 for both 6-week and hospital mortality. CONCLUSION: CLIF-SOFA score predicted post-EVL prognosis well. For patients without hepatocellular carcinoma, CLIF-SOFA score ≥6 suggests higher 6-week mortality and CLIF-SOFA score ≥7 suggests higher hospital mortality. For patients with hepatocellular carcinoma, CLIF-SOFA score ≥7 suggests higher 6-week and hospital mortality.

The genotype distribution of hepatitis C in southeastern Taiwan: Clinical characteristics, racial difference, and therapeutic response.

The genotypes of hepatitis C virus (HCV) are associated with the therapeutic response. The racial diversity of Taitung, Taiwan is heterogeneous and a distinguishing feature; how such racial differences influence the genotype distribution and treatment outcome has not been well studied. The objective of this study is to elucidate the HCV genotype distribution in southeastern Taiwan and to analyze the racial differences influencing genotypes and clinical implications. In this retrospective cohort study, we included 343 patients who had been treated with peginterferon-alpha plus ribavirin. The predominant HCV genotype in the southeastern area was type 1 (43.7%), followed by type 2 (37.0%). The proportion of patients mixed with genotype 1 was lower in indigenous vis-à-vis nonindigenous groups (46.1% and 60.2%, p = 0.02). The prevalence of genotype 6 (5.2%) seems higher than in the general population of Taiwan and showed no difference between indigenous and nonindigenous people. The sustained virological response rate was higher in patients without genotype 1, low baseline HCV RNA (≤ 400,000 IU/mL), and in patients who achieved rapid virological response. Racial differences did not influence the therapeutic response. In this retrospective study, the proportion of HCV genotype 6 appeared slightly higher in southeastern areas than in the general population in Taiwan. The prevalence of genotype 1 in indigenous people was statistically lower than in nonindigenous people. Sustained virological response rate did not show any significant difference between indigenous and nonindigenous people in the current study.

Hepatitis C treatment outcome in relation to alcohol consumption and racial differences in southeastern Taiwan.

BACKGROUND/PURPOSE: Alcohol use may have negative impacts on hepatitis C virus (HCV) treatment due to low adherence, and racial differences can influence HCV sustained virological response (SVR) rate between East Asian and European ancestry. The objective of this study is to confirm the influence of alcohol consumption and racial differences on HCV treatment outcome in aboriginal and nonaboriginal people of southeastern Taiwan. METHODS: In this retrospective cohort study, a total of 195 patients were treated with peginterferon-alpha once weekly plus ribavirin for 24 weeks. The efficacy analysis was performed based on the SVR rate for patients who received at least one dose of the study medication or who completed treatment. The endpoints were denoted by virological response rate including the influences of alcohol use, HCV genotype, serum level of HCV virological load, and racial differences. RESULTS: No differences were observed in the baseline clinical characteristics between drinkers and nondrinkers, but a significant difference was noted in the body mass index between aboriginal and nonaboriginal populations (28.3 vs. 25.8; p < 0.01). With respect to the SVR rate, no difference was found between drinkers and nondrinkers, and between aboriginal and nonaboriginal people. The treatment efficacy of SVR in the whole group was significantly different between patients with HCV genotype 1 and nongenotype 1 (73.5% vs. 91.2%; p < 0.01). An analysis of the SVR rate in the aboriginal group showed no significant difference between patients with genotype 1 and nongenotype 1 (80.0% vs. 91.3%; p = 0.31). CONCLUSION: In southeastern Taiwan, alcohol consumption did not influence the HCV treatment outcome, and the SVR rates were similar between patients with HCV genotype 1 and nongenotype 1 infections in the aboriginal group.

Refeeding syndrome in Southeastern Taiwan: our experience with 11 cases.

AIM: To present our experience with refeeding syndrome in southeastern Taiwan. METHODS: We conducted a retrospective study during a 2-year period at the Mackay Memorial Hospital, Taitung Branch. We enrolled patients with very little or no nutrition intake for more than 10 d, a high risk group of refeeding syndrome, including those suffering from alcohol abuse, cancerous cachexia, chronic malnutrition, and prolonged starvation. RESULTS: A total of 11 patients (7 males, 4 females) with nasogastric feeding were included as having refeeding syndrome. Most of them had the symptoms of diarrhea, lethargy, and leg edema. The initial nutritional supplement was found to be relatively high in calories (1355.1 ± 296.2 kcal/d), high in protein (47.3 ± 10.4 gm/d), low in vitamin B1 (2.0 ± 0.5 mg/d), low in potassium (1260.4 ± 297.7 mg/d), and low in phosphorus (660.1 ± 151.8 mg/d). Furthermore, hypophosphatemia (2.4 ± 0.9 mg/dL) was noted during follow-up. Based on the suggestions of a dietician and a gastroenterologist, the clinical disorders of diarrhea, malaise and leg edema were significantly improved. The level of phosphate was also increased (3.3 ± 0.6 mg/dL). CONCLUSION: Refeeding syndrome is an overlooked and risky disorder that has some potentially fatal complications. Nasogastric feeding in nursing homes is an important risk factor for patients and deserves greater attention based on the initial results of this study.

Peginterferon alpha-2b plus ribavirin for chronic hepatitis C virus mixed genotype infection.

BACKGROUND AND AIM: The treatment efficacy of peginterferon plus ribavirin for patients with HCV genotype 1 is inferior to that in patients with HCV genotype 2, but the efficacy among patients with mixed HCV genotype 1 + 2 is less clear. We compared the treatment outcome of peginterferon alpha-2b plus ribavirin among naïve chronic hepatitis C patients in Taiwan with HCV genotype 1 and 2, and mixed genotype 1 + 2. MATERIAL AND METHODS: In this retrospective cohort study, 150 patients were treated with peginterferon alpha-2b once weekly, plus ribavirin, for 24 weeks. The endpoint was sustained virological response after receiving at least one dose of the study medication. RESULTS: There were no differences in clinical characteristics among the 3 groups. There were significant differences in rapid virological response rate between patients with genotype 1 and genotype 2 (64.7 vs. 85.5%, respectively; p < 0.05) and a sustained virological response rate (55.9 vs. 83.6%, respectively; p = 0.001). The rapid virological response rate differed between the genotype 1 and mixed genotype 1 + 2 groups (64.7 vs. 85.2%, respectively; p < 0.05), but the sustained virological response rate was similar (55.9 vs. 74.1%; p = 0.101). CONCLUSIONS: Using peginterferon alpha-2b plus ribavirin for 24 weeks to treat patients with HCV genotype 1 + 2 achieved a 74.1% sustained virological response rate; the treatment efficacy was not inferior to patients with HCV genotype 1, but the percentage of liver cirrhosis in mixed genotype 1 + 2 group was higher to 22%, it is worth to be appropriately valued and studied.

Socioeconomic status, personal habits, and prevalence of Helicobacter pylori infection in the inhabitants of Lanyu.

BACKGROUND/PURPOSE: Lanyu Island is a closed environment inhabited by the Yami people, Taiwan's smallest and most primitive tribe. This study assessed the prevalence and risk factors of Helicobacter pylori infection among Lanyu Island residents. METHODS: A cross-sectional study was conducted among the inhabitants of Lanyu Island, using the (13)C urea breath test to determine the prevalence of H. pylori. All study participants completed a form requesting demographic data and anthropometric measurements and a questionnaire evaluating socioeconomic characteristics and personal habits. Multiple logistic regression analyses were used to identify independent factors of H. pylori infections, and a two-sided p < 0.05 was considered significant. RESULTS: Among 796 participants, the mean age was 45 ± 13.2 years, with a range of 12-89 years. The overall prevalence of H. pylori infection was 72.1%, and there was no significant difference between genders. The H. pylori-infected group contained higher proportions of Yami people, married individuals, as well as higher rates of alcohol consumption and betel chewing, but lower family incomes and education levels. Multiple logistic models found that Yami ethnicity [odds ratio (OR) = 2.567, 95% confidence interval (CI): 1.344-4.905], alcohol consumption (OR = 1.641, 95% CI: 1.151-2.341), and marital status (OR = 1.779, 95% CI: 1.043-3.032] were associated with H. pylori infection. CONCLUSION: This cross-sectional study identified a high prevalence of H. pylori infection on Lanyu Island. When investigating H. pylori infection status in a closed environment, such as Lanyu Island, it is important to consider all factors relating to the host population, including environment and lifestyle.

Clinical manifestations and risk factors of amebic liver abscess in Southeast Taiwan compared with other regions of Taiwan.

Amebic liver abscess (ALA) had previously been endemic in Taiwan, particularly in the southern region, although its occurrence in the southeastern area was unknown. Thus, we conducted a retrospective study for southeastern Taiwan. We identified 14 patients who were diagnosed with ALA between July of 1995 and July of 2008. These patients were predominantly male and older in age. Most patients lived in rural areas (85.7%). Alcoholism (78.6%) and diabetes (35.7%) were risk factors for ALA. No human immunodeficiency virus (HIV) infections were detected. The most common clinical symptoms were fever (100%) and abdominal pain (100%). Short mean durations of symptoms, high bilirubin levels, and low albumin levels were also noted. Most patients (92.86%) had a single lesion, particularly in the right liver lobe (71.4%). Six patients also had secondary Klebsiella pneumoniae bacterial infections. Clinicians should be aware of the different risk factors in different regions when diagnosing amebic liver abscess in Taiwan.