scholarly journals Metabolomic Signatures of Autoimmune Hepatitis in the Development of Cirrhosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Shan-shan Li ◽  
Ming Niu ◽  
Jing Jing ◽  
Ying Huang ◽  
Zi-teng Zhang ◽  
...  
Keyword(s):  
Autoimmune Hepatitis ◽  
Energy Supply ◽  
Decompensated Cirrhosis ◽  
Liver Inflammation ◽  
Compensated Cirrhosis ◽  
Persistent Inflammation ◽  
Underlying Mechanisms ◽  
Metabolic Biomarkers ◽  
Sera Samples ◽  
Metabolomics Analysis

Objectives: Autoimmune hepatitis (AIH) can progress into severe outcomes, i.e., decompensated cirrhosis, from remarkable and persistent inflammation in the liver. Considering the energy-expending nature of inflammation, we tried to define the metabolomics signatures of AIH to uncover the underlying mechanisms of cirrhosis development and its metabolic biomarkers.Methods: Untargeted metabolomics analysis was performed on sera samples from 79 AIH patients at the stages (phenotypes) of non-cirrhosis (n = 27), compensated cirrhosis (n = 22), and decompensated cirrhosis (n = 30). Pattern recognition was used to find unique metabolite fingerprints of cirrhosis with or without decompensation.Results: Out of the 294 annotated metabolites identified, 2 metabolic fingerprints were found associated with the development of cirrhosis (independent of the decompensated state, 42 metabolites) and the evolution of decompensated cirrhosis (out of 47 metabolites), respectively. The cirrhosis-associated fingerprints (eigenmetabolite) showed better capability to differentiate cirrhosis from non-cirrhosis patients than the aminotransferase-to-platelet ratio index. From the metabolic fingerprints, we found two pairs of metabolites (Mesobilirubinogen/6-Hydroxynicotinic acid and LysoPA(8:0/0:0)/7alpha-Hydroxycholesterol) calculated as ratio of intensities, which revealed robust abilities to identify cirrhosis or predict decompensated patients, respectively. These phenotype-related fingerprint metabolites featured fundamental energy supply disturbance along with the development of AIH cirrhosis and progression to decompensation, which was characterized as increased lipolysis, enhanced proteolysis, and increased glycolysis.Conclusions: Remodeling of metabolism to meet the liver inflammation-related energy supply is one of the key signatures of AIH in the development of cirrhosis and decompensation. Therefore, drug regulation metabolism has great potential in the treatment of AIH.

scholarly journals Maternal and Fetal Outcomes of Pregnant Women with Hepatic Cirrhosis

2020 ◽  
Vol 2020 ◽  
pp. 1-4 ◽  
Author(s):  
Harun Egemen Tolunay ◽  
Mesut Aydın ◽  
Numan Cim ◽  
Barış Boza ◽  
Ahmet Cumhur Dulger ◽  
...  
Keyword(s):  
Cesarean Section ◽  
Pregnant Women ◽  
Esophageal Varices ◽  
Hepatic Cirrhosis ◽  
Morbidity And Mortality ◽  
Decompensated Cirrhosis ◽  
Band Ligation ◽  
Compensated Cirrhosis ◽  
The Mean ◽  
Upper Gastrointestinal

Aim. The reproductive hormone levels and systemic physiology of women with hepatic cirrhosis are altered. Existing data have indicated the adverse effects of cirrhosis on both the mother and the fetus. Pregnancy is successful in most of the patients with chronic liver disease. But maternal and fetal complication rates are still high for decompensated hepatic cirrhosis. In this study, we aimed to evaluate the clinical features, etiological factors, medications, morbidity, mortality, and obstetric outcomes of pregnant women with hepatic cirrhosis. Methods. Pregnant women, who were diagnosed with maternal hepatic cirrhosis and followed up in our clinic between 2014 and 2017, were retrospectively evaluated. The pregnant women that had been followed up for hepatic cirrhosis were classified as compensated disease and decompensated disease. Eleven cases were included in this period. Results. The mean age of cases was 33.5±5.5 years. The mean gravida number was 3.2±1.1, and the mean parity number was 1.7±1. Six cases were in the compensated cirrhosis stage, and 5 cases were in the decompensated cirrhosis stage. A pregnancy with decompensated cirrhosis was terminated after the fetal heart sound was negative in the 9th week of pregnancy. Spontaneous abortus occurred in one case (<20 weeks). The mean gestational week of the 9 cases was 33.3±6.2. Two of the 9 cases delivered birth vaginally. Seven cases delivered by cesarean section. The mean first- and fifth-minute APGAR scores were 6.6±1.41 and 8.2±1.56, respectively. The mean birth weight was 2303±981 g. Among 9 cases with live birth, 6 had compensated cirrhosis and 3 had decompensated cirrhosis. In the second trimester, upper gastrointestinal endoscopy was performed to all patients in terms of esophageal varices. Endoscopic band ligation was performed in 3 cases with upper gastrointestinal bleeding. The postpartum mortality did not occur. Discussion. Pregnancy is not recommended for patients with hepatic cirrhosis due to high maternal and fetal morbidity and mortality. The pregnancy course of cases with cirrhosis changes according to the stage of liver injury and severity of disease. Although the delivery method is controversial, delivery by cesarean section is recommended for patients with esophageal varices by the reason of bleeding from varices after pushing during labor. The bleeding risk must be kept in mind as coagulopathy is common in hepatic diseases. The maternal-fetal morbidity and mortality rates have been decreased by the current developments in hepatology, prevention of bleeding from varices with drugs and/or band ligation, improvement in liver transplantation, and increasing experience in this issue.

scholarly journals Safety of ERCP in patients with liver cirrhosis: a national database study

2017 ◽  
Vol 05 (04) ◽  
pp. E303-E314 ◽  
Author(s):  
Udayakumar Navaneethan ◽  
Basile Njei ◽  
Xiang Zhu ◽  
Kiran Kommaraju ◽  
Mansour Parsi ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Multivariable Analysis ◽  
National Database ◽  
Decompensated Cirrhosis ◽  
Compensated Cirrhosis ◽  
Post Procedure ◽  
Biliary Sphincterotomy ◽  
Increased Risk ◽  
Cirrhotic Patients ◽  
Matched Case

Abstract Background and aims Given the limited data on the safety of endoscopic retrograde cholangiopancreatography (ERCP) in patients with liver cirrhosis, we attempted to evaluate this question using a large national database. Methods We conducted a matched case – control study using the 2010 National Inpatient Sample database in which four non-cirrhotic controls were matched randomly for every cirrhotic patient from the same 10-year age group. We compared adverse events and safety of inpatient ERCP between patients with (n = 3228) and without liver cirrhosis (controls, n = 12 912). Results Of the 3228 cirrhotic patients, 2603 (80.6 %) had decompensated and 625 (19.4 %) had compensated disease. Post-procedure bleeding (2.1 % vs. 1.2 %, P < 0.01) was higher in patients compared to controls. On multivariable analysis, decompensated cirrhosis (adjusted odds ratio [aOR], 2.7; 95 % confidence interval [CI], 2.2 – 3.2), compensated cirrhosis (aOR 2.2; 95 %CI 1.2 – 3.9), therapeutic ERCPs (aOR 1.4; 95 % CI 1.2 – 2.1), and biliary sphincterotomy (aOR 1.6; 95 %CI 1.1 – 2.1) were independently associated with increased risk of post-procedure bleeding. Performing ERCPs in large (aOR 0.5; 95 %CI 0.4 – 0.6) and medium (aOR 0.7; 95 %CI 0.6 – 0.9) sized hospitals was associated with a decreased risk of post-procedure bleeding. Biliary sphincterotomy (aOR 1.7; 95 %CI 1.2 – 2.3) and therapeutic ERCPs (aOR 1.1; 95 %CI 1.1 – 1.3) increased the risk of post-ERCP pancreatitis, and pancreatic stent placement was associated with a decreased risk of post-ERCP pancreatitis (aOR 0.8; 95 %CI 0.7 – 0.9). Conclusions Cirrhosis (both compensated and decompensated), performing therapeutic ERCPs and biliary sphincterotomy increase the risk of post-procedure bleeding. Performing ERCPs in large and medium sized hospitals may improve outcomes.

scholarly journals Defining refractory rheumatoid arthritis

2018 ◽  
Vol 77 (7) ◽  
pp. 966-969 ◽  
Author(s):  
Maya H Buch
Keyword(s):  
Rheumatoid Arthritis ◽  
Controlled Trial ◽  
Real Life ◽  
Outcome Data ◽  
Refractory Disease ◽  
Persistent Inflammation ◽  
Antidrug Antibody ◽  
Underlying Mechanisms ◽  
Randomised Controlled ◽  
Future Evaluation

While biologic disease-modifying antirheumatic drugs (bDMARDs) have transformed outcomes of people with rheumatoid arthritis (RA), a proportion of patients are refractory to multiple bDMARDs. Definitions of refractory RA thus far have been arbitrary, and outcome data and impact of such cohorts remain limited. Extrapolation from randomised controlled trial and some real-life data suggest approximately 20% progress onto a third bDMARD with a more modest proportion failing additional bDMARDs. This viewpoint discusses an opinion of refractory RA disease and proposes key principles to accurately identify refractory cohorts. These include demonstrating presence of persistent inflammation despite multiple therapies and acknowledging development of antidrug antibody. Potential basis of refractory disease is summarised, and suggestions for an initial approach in the future evaluation of refractory disease are offered. Specific investigation of refractory RA disease is necessary to inform the clinical need and provide a basis for robust investigation of underlying mechanisms.

Caffeine clearance and biotransformation in patients with chronic liver disease

1988 ◽  
Vol 74 (4) ◽  
pp. 377-384 ◽  
Author(s):  
Nigel R. Scott ◽  
Drago Stambuk ◽  
J. Chakraborty ◽  
Vincent Marks ◽  
Marsha Y. Morgan
Keyword(s):  
Liver Disease ◽  
Decompensated Cirrhosis ◽  
Control Group ◽  
Total Recovery ◽  
Control Subjects ◽  
Compensated Cirrhosis ◽  
Elimination Half ◽  
The Mean ◽  
Caffeine Metabolism ◽  
Caffeine Clearance

1. The clearance and biotransformation of caffeine (1,3,7-trimethylxanthine) were investigated in eight healthy control subjects and 16 patients with cirrhosis, by measuring serial serum caffeine concentrations and recoveries of methylxanthine metabolites in urine for 48 h after a 400 mg oral caffeine load. 2. In the control group, the mean (± sd) serum caffeine clearance was 1.3 ± 0.4 ml min−1 kg−1 and a mean of 56.4 ± 16.5% of the administered caffeine was recovered from the urine over 48 h as methyluric acids and methylxanthines. The majority of the metabolites were excreted in the first 24 h period and only 2.0 ± 1.4% of the administered caffeine was excreted unchanged. 3. Patients with compensated cirrhosis (n = 10) metabolized caffeine similarly to the control subjects. Thus the mean serum caffeine clearance was 1.4 ± 1.2 ml min−1 kg−1 and a mean of 57.2 ± 11.7% of the administered caffeine was recovered from the urine over 48 h. The majority of the metabolites were excreted in the first 24 h; the pattern of metabolic excretion was unaltered and only 2.2 ± 0.9% of the administered caffeine was excreted unchanged. 4. In the patients with decompensated cirrhosis (n = 6), significant changes were observed in caffeine metabolism. The mean serum caffeine clearance (0.4 ± 0.2 ml min−1 kg−1) was significantly impaired compared with controls (P < 0.01) and a significant delay was observed in metabolite excretion in the urine. Thus the mean recovery of metabolites in the urine during the first 24 h (25.0 ± 11.2%) was significantly reduced compared with controls (44.1 ± 12.4%, P = 0.03), whereas the mean urinary metabolite recovery in the second 24 h (20.9 ± 10.5%) was insignificantly increased compared with controls (12.3 ± 7.8%). Overall, the mean recovery of metabolites in the urine in 48 h (45.9 ± 15.4%) was similar to that in the control group. The overall recovery of unchanged caffeine was significantly greater than in controls (5.0 ± 2.8% vs 2.0 ± 1.4%, P = 0.04), but the pattern of metabolite excretion was otherwise unchanged. 5. In the patients with liver disease there were significant linear correlations between the degree of hepatocellular dysfunction and the serum caffeine elimination half-life (r = 0.774; P < 0.01) and the total recovery of methylxanthine metabolites in the urine, in the 0–24 h (r = 0.702; P = 0.002) and 0–48 h (r = 0.581; P = 0.018) periods. 6. Caffeine clearance is impaired in patients with decompensated cirrhosis either because of a reduction in hepatic caffeine uptake or else because of a reduction in ‘functioning hepatocyte mass’. However, the biotransformation of caffeine is unaltered in the presence of hepatic dysfunction.

scholarly journals Health State Utilities and Quality of Life in Patients with Hepatitis B

2012 ◽  
Vol 26 (7) ◽  
pp. 445-451 ◽  
Author(s):  
Gloria Woo ◽  
George Tomlinson ◽  
Colina Yim ◽  
Les Lilly ◽  
George Therapondos ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Hepatocellular Carcinoma ◽  
Standard Gamble ◽  
Antiviral Treatment ◽  
Decompensated Cirrhosis ◽  
Health State ◽  
Disease States ◽  
Compensated Cirrhosis ◽  
Health State Utilities

BACKGROUND: The effect of chronic hepatitis B (CHB) infection on health-related quality of life (HRQoL) and health state utilities has not been well characterized.OBJECTIVE: To measure utility scores and HRQoL across disease states associated with CHB infection.METHODS: Patients attending four tertiary care clinics for CHB were approached between July 2007 and March 2009. Respondents completed version 2 of the Short-Form 36 Health Survey, the EQ5D, a visual analogue scale, the Health Utilities Index Mark 3, standard gamble, and demographics and risk factor surveys in English, Cantonese or Mandarin. Charts were reviewed to determine disease stage and comorbidities.RESULTS: A total of 433 patients were studied: 294 had no cirrhosis; 79 had compensated cirrhosis; seven had decompensated cirrhosis; 23 had hepatocellular carcinoma; and 30 had received a liver transplant. The mean standard gamble utilities for these disease states were 0.89, 0.87, 0.82, 0.84 and 0.86, respectively. HRQoL scores in noncirrhotic patients were similar to those of the general population. Scores of patients with compensated cirrhosis were not significantly lower; however, patients with decompensated cirrhosis and hepatocellular carcinoma had significantly lower HRQoL scores compared with noncirrhotic patients (P<0.05). Similar scores were observed among patients on and off oral antiviral treatment. Post-liver transplant patients had a higher HRQoL than patients with decompensated cirrhosis. Age, number of comorbidities and relationship status were significantly associated with HRQoL scores.CONCLUSIONS: HRQoL in CHB patients is only impaired in the later stages of liver disease. Neither CHB infection nor antiviral treatment is associated with a lower quality of life.

scholarly journals A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation

Hepatology ◽  
2015 ◽  
Vol 62 (5) ◽  
pp. 1536-1550 ◽  
Author(s):  
Muhammed Yuksel ◽  
Yipeng Wang ◽  
Ningwen Tai ◽  
Jian Peng ◽  
Junhua Guo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiota ◽  
Autoimmune Hepatitis ◽  
Liver Inflammation ◽  
Humanized Mouse ◽  
Humanized Mouse Model

scholarly journals Finally... Real Utility Scores for Hepatitis C Patients!

2004 ◽  
Vol 18 (6) ◽  
pp. 411-412
Author(s):  
Kevork M Peltekian
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
The United States ◽  
Hcv Infection ◽  
Health State Utility ◽  
Decompensated Cirrhosis ◽  
Health State ◽  
Compensated Cirrhosis ◽  
Progression Of Disease ◽  
Utility Scores

Chong and colleagues (1) used gold-standard methods to assess health-state utilities in 193 outpatients at various stages of liver disease due to chronic hepatitis C (HCV) infection. They showed worsening of health-state utility scores with progression of disease from mild to moderate chronic hepatitis, to compensated cirrhosis, to decompensated cirrhosis and to hepatocellular carcinoma. They also confirmed improvement in health-state utility scores after liver transplantation and with sustained virological response (SVR) to treatment of HCV infection. Patients with HCV infection had lower health-state utility scores than the general Canadian population (PÃ0.001) and significantly poorer quality of life compared with population norms in the United States (PÃ0.005).

scholarly journals The frequency of occurrence of Hepatocellular Carcinoma after direct antiviral therapy in Hepatitis C virus patients

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Bilal Aziz ◽  
Tazeen Nazar ◽  
Suhair Akhlaq
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Sampling Technique ◽  
Decompensated Cirrhosis ◽  
Frequency Of Occurrence ◽  
Genotype 3 ◽  
Cross Sectional ◽  
Compensated Cirrhosis

Objective: To study the frequency of occurrence of hepatocellular carcinoma (HCC) in hepatitis C virus patients treated with direct acting antiviral (DAA) agents. Methods: This hospital based cross-sectional study was conducted in Mayo Hospital, Lahore from June, 2016 to January, 2018. Total 300 patients with HCV genotype 3, selected via Non-Probability Purposive Sampling technique, without prior or concurrent history of HCC, were given DAA agents and were followed up for 6 months after completion of therapy. Results were based on Quantitative PCR to assess Sustained Virological Response (SVR) and Ultrasound Abdomen to look for the appearance of any new lesion. Data was presented as mean±SD, frequency and percentages and was analyzed using SPSS Version 24.0. Results: Out of 300 patients, 179 (59.7%) were males and 121(40.3%) were females. Mean age of the patients was 55.08 ± 5.602 years. 214(71.3%) patients had compensated cirrhosis at the start of treatment and 86(28.7%) had decompensated cirrhosis. SVR was achieved in 200(93.4%) out of 214 patients with compensated cirrhosis and in 76(88.3%) out of 86 patients with decompensated cirrhosis. At six months post- treatment, 10(3.33%) patients developed HCC,2(0.7%) in the compensated group and 8(2.7%) in the decompensated group, out of which 5(6.6%) patients had achieved SVR. Conclusion: The frequency of HCC following DAA agents is significant (3.3%) even after achieving SVR. Caution must be exercised in prescribing DAA agents to HCV patients keeping this complication of HCC in mind. How to cite this:Aziz B, Nazar T, Akhlaq S. The frequency of occurrence of Hepatocellular Carcinoma after direct antiviral therapy in Hepatitis C virus patients. Pak J Med Sci. 2019;35(1):---------. doi: https://doi.org/10.12669/pjms.35.1.109 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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