The 2019
suggested that patients with nonalcoholic fatty liver disease (NAFLD) should be evaluated for liver fibrosis. However, the performance of noninvasive clinical models/scores and plasma ...biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and advanced fibrosis has not been carefully assessed in patients with type 2 diabetes mellitus (T2DM).
In this cross-sectional study, patients (
= 213) had a liver MRS, and those with a diagnosis of NAFLD underwent a percutaneous liver biopsy. Several noninvasive clinical models/scores and plasma biomarkers were measured to identify NASH and advanced fibrosis (NASH: ALT, cytokeratin-18, NashTest 2, HAIR, BARD, and OWLiver; advanced fibrosis: AST, fragments of propeptide of type III procollagen PRO-C3, FIB-4, APRI, NAFLD fibrosis score, and FibroTest).
None of the noninvasive tools assessed for the diagnosis of NASH in patients with T2DM had an optimum performance (all areas under the curve AUCs <0.80). Of note, none of the panels or biomarkers was able to outperform plasma ALT (AUC 0.78 95% CI 0.71-0.84). Performance was better to diagnose advanced fibrosis, in which plasma PRO-C3, AST, and APRI showed better results than the other approaches (AUC 0.90 0.85-0.95, 0.85 0.80-0.91, and 0.86 0.80-0.91, respectively). Again, none of the approaches did significantly better than plasma AST. Sequential use of plasma AST and other noninvasive tests may help in limiting the number of liver biopsies required to identify patients with advanced fibrosis.
Performance of noninvasive clinical models/scores and plasma biomarkers for the diagnosis of NASH or advanced fibrosis was suboptimal in patients with T2DM. Combination of multiple tests may provide an alternative to minimize the need for liver biopsies to detect fibrosis in these patients.
Fibromax is a diagnostic tool composed of the combination of 4 non-invasive biomarker panels for the diagnosis of steatosis (SteatoTest), necrosis and inflammation (ActiTest and NashTest-2) and ...fibrosis (FibroTest). The purpose of this study was to assess the performance of these biomarker panels in patients with type 2 diabetes mellitus (T2DM). All patients underwent routine labs, a 75 g oral glucose tolerance test, a liver proton magnetic resonance spectroscopy (1H-MRS) to measure intrahepatic triglyceride content, and a percutaneous liver biopsy to establish the diagnosis of non-alcoholic steatohepatitis (NASH) and to grade and stage the disease in those patients with non-alcoholic fatty liver disease (NAFLD) by 1H-MRS. For determination of the scores, plasma samples were blindly provided to establish the SteatoTest, ActiTest, NashTest-2 and FibroTest scores. A total of 220 patients with T2DM were included in this study. When the ability of the SteatoTest to identify patients with T2DM with NAFLD by 1H-MRS was assessed, the overall performance expressed as the area under the receiver operating characteristic curve was 0.73 (95% CI 0.65 to 0.81). The performance of the ActiTest and NashTest-2 to diagnose definite NASH among patients with T2DM was 0.70 (95% CI 0.63 to 0.77) and 0.69 (95% CI 0.62 to 0.76), respectively. Regarding the FibroTest score, its performance to identify patients with moderate or advanced fibrosis was 0.67 (95% CI 0.58 to 0.76) and 0.72 (95% CI 0.61 to 0.83), respectively. Non-invasive panels for the diagnosis of steatosis, NASH and/or fibrosis, which were developed and validated in non-diabetic cohorts, underperformed when applied to a large cohort of patients with T2DM. Results from non-diabetic populations should not be extrapolated to patients with T2DM.
Chronic hepatitis C infection is the leading cause of chronic liver disease, cirrhosis, hepatocellular carcinoma as well as the primary indication for liver transplantation in the United States. ...Despite recent advances in drugs for the treatment of hepatitis C, predictive models estimate the incidence of cirrhosis due to hepatitis C infection will to continue to rise for the next two decades. There is currently an immense interest in the treatment of patients with fibrosis and early-stage cirrhosis as treatment can lead to decrease in the rates of decompensated cirrhosis, hepatocellular carcinoma and need for liver transplantation in these patients. The goal of this paper is to provide clinicians and health care professionals further information about the treatment of patients with hepatitis C infection and cirrhosis. Additionally, the paper focuses on the disease burden, epidemiology, diagnosis and the disease course from infection to treatment. We provide an overview of multiple studies for the treatment of chronic hepatitis C infection that have included patients with cirrhosis. We also discuss the advantages and disadvantages of treatment in cirrhotic patients and focus on the most up to date guidelines available for treatment.
The aim of the present study was to determine the treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC). A retrospective chart review ...was performed for patients diagnosed with ICC between 2000 and 2009 at a single institution. We identified a total of 105 patients with ICC. Among them, 63.8% were older than 60 years of age, 50.5% were male and 88.6% were Caucasian. By preoperative imaging approximately half of the patients (50.5%) were surgical candidates and underwent resection. The other half of the patients (49.5%) were unresectable. The unresectable group received chemoradiotherapy (53%) and transarterial chemoembolization (7.7%) as palliative treatments while 23.0% of the patients (12/52) received best supportive care alone. The median survival rates were 16.1 months (13.1-19.2) for the entire cohort, 27.6 months (17.7-37.6) for curative resection, 12.9 months (6.5-19.2) for palliative chemoradiotherapy and 4.9 months (0.4-9.6) for best supportive care (P<0.001). Independent predictors on multivariate analysis were advanced stage at diagnosis and treatment received. In those patients who underwent resection, advanced AJCC stage and presence of microvascular invasion were also independent predictors of poor survival. We concluded that surgery offers the most beneficial curative option and outcome, emphasizing the importance of resectability as a major prognostic factor. The present study also revealed that use of chemoradiotherapy in the adjuvant setting failed to improve survival but its palliative use in those patients with unresectable ICC offered a modest survival advantage over best supportive care. The overriding factors influencing outcome were stage and the presence of microvascular invasion on pathology.
Nonalcoholic fatty liver disease (NAFLD) is typically associated with obesity. Little is known about the prevalence of cirrhosis in patients with NAFLD and a normal body mass index (BMI).
We ...determined prevalence of cirrhosis, cardiovascular disease (CVD), and metabolic abnormalities among participants in all BMI categories in the TARGET-NASH study. A total of 3386 patients with NAFLD were enrolled from August 2016 through March 2019. The odds ratios of cirrhosis, CVD, and metabolic abnormalities were estimated by age and race, adjusting for sex and center type.
Based on standard BMI cutoff values, 12.8% of study subjects were lean, 27.1% were overweight, 26.5% had class 1 obesity, and 33.7% had class 2 or 3 obesity. Asians accounted for 48.7% of lean participants, and proportions decreased as BMI categories increased (P < .0001). Lower proportions of lean participants had cirrhosis (22.6% vs 40.2% of non-lean participants), CVD history (9.0% vs 14.8% of nonlean participants), diabetes (32.6% vs 53.5% of non-lean participants), hypertension (47.8% vs 67.4% of non-lean participants), or dyslipidemia (54.0% vs 64.1% of non-lean participants). Asian participants had a lower prevalence of cirrhosis, history of CVD, cardiovascular events, and diabetes compared with non-Asians, independent of BMI category. After we adjusted for age, sex, and center type and site, the odds of NAFLD-associated cirrhosis in Asians who were lean was almost half the odds of NAFLD-associated cirrhosis in non-Asians who were lean (odds ratio, 0.47; 95% CI, 0.29-0.77).
More than 10% participants in a cohort of persons with NAFLD in the United States are lean; Asians account for almost half of the lean persons with NAFLD. Lean participants had a lower prevalence of cirrhosis, CVD, and metabolic abnormalities than non-lean persons with NAFLD. Asian participants had a significantly lower prevalence of cirrhosis, CVD, and metabolic abnormalities than non-Asians in all BMI categories. ClinicalTrials.gov, Number: NCT02815891.
The CD4+CD25+ regulatory T lymphocytes have been implicated in suppressing T cell immune responses. Our aim was to characterize the frequency, phenotype, function, and specificity of CD4+CD25+ T ...cells in hepatitis C virus (HCV) infection. Peripheral CD4+CD25+ cells from recovered (n = 15), chronic infected (n = 30), and normal control (n = 15) subjects were analyzed ex vivo for quantitation, phenotype, and effect on HCV‐specific interferon gamma production and proliferation. CD4+CD25+ specificity was determined by intracellular cytokine staining for interleukin 10 (IL‐10). A higher proportion of CD4+CD25+ were found in chronic infection (mean, 3.02%) when compared with recovered (1.64%, P = .001) and normal controls (2.27%, P = .02). CD4+CD25+ cells display CD45ROhigh, CD45RAlow, CD28high, CD62Lhigh, and CD95high phenotype. HCV‐specific interferon gamma activity was enhanced in peripheral blood mononuclear cells depleted of CD4+CD25+ and suppressed in peripheral blood mononuclear cells enriched with CD4+CD25+. Depletion of CD4+CD25+ cells also enhanced HCV‐specific CD4+ and CD8+ T cell proliferation. Cytokine analysis suggested CD4+CD25+ cells secrete transforming growth factor beta (TGF‐β1) and IL‐10. The inhibitory role for TGF‐β1 was confirmed by anti–TGF‐β1. Transwell studies showed CD4+CD25+ mediated suppression to be dose dependent and requiring cell contact. CD4+CD25+ cells showed HCV‐specificity through IL‐10 production, with a frequency ranging from 1.9% to 5.3%. A positive correlation was detected between CD4+CD25+ T cell frequency and HCV RNA titer, whereas an inverse relation was found with liver inflammatory activity. In conclusion, CD4+CD25+ T lymphocytes constitute a highly differentiated population and appear to play a role in viral persistence by suppressing HCV‐specific T cell responses in a cell–cell contact manner. (HEPATOLOGY 2004;40:1062–1071.)
Cirrhosis secondary to hepatitis C virus(HCV)is a very common indication for liver transplant.Unfortunately recurrence of HCV is almost universal in patients who are viremic at the time of ...transplant.The progression of fibrosis has been shown to be more rapid in the post-transplant patients than in the transplant na?ve,hence treatment of recurrent HCV needs to be considered for all patients with documented recurrent HCV.Management of recurrent HCV is a challenging situation both for patients and physicians due to multiple reasons as discussed in this review.The standard HCV treatment with pegylated interferon and Ribavarin can be considered in these patients but it leads to a lower rate of sustained virologic clearance than in the nontransplanted population.Some of the main challenges associated with treating recurrent HCV in post-transplant patients include the presence of cytopenias;need to monitor drug-drug interactions and the increased incidence of renal compromise.In spite of these obstacles all patients with recurrent HCV should be considered for treatment since it is associated with improve-ment in survival and a delay in fibrosis progression.With the arrival of direct acting antiviral drugs there is renewed hope for better outcomes in the treatment of post-transplant HCV recurrence.This review evaluates current literature on this topic and identifies challenges associated with the management of post-transplant HCV recurrence.
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