scholarly journals Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis

2021 ◽  
Vol 22 (22) ◽  
pp. 12545
Author(s):  
Peter M. Abuja ◽  
Kurt Zatloukal ◽  
Helmut Denk

Understanding the pathomechanism of steatohepatitis (SH) is hampered by the difficulty of distinguishing between causes and consequences, by the broad spectrum of aetiologies that can produce the phenotype, and by the long time-span during which SH develops, often without clinical symptoms. We propose that SH develops in four phases with transitions: (i) priming lowers stress defence; (ii) triggering leads to acute damage; (iii) adaptation, possibly associated with cellular senescence, mitigates tissue damage, leads to the phenotype, and preserves liver function at a lower level; (iv) finally, senescence prevents neoplastic transformation but favours fibrosis (cirrhosis) and inflammation and further reduction in liver function. Escape from senescence eventually leads to hepatocellular carcinoma. This hypothesis for a pathomechanism of SH is supported by clinical and experimental observations. It allows organizing the various findings to uncover remaining gaps in our knowledge and, finally, to provide possible diagnostic and intervention strategies for each stage of SH development.

2016 ◽  
Vol 34 (5) ◽  
pp. 404-408 ◽  
Author(s):  
Aisling Barry ◽  
Jennifer J. Knox ◽  
Alice C. Wei ◽  
Laura A. Dawson

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 78-year-old woman with a past medical history of hepatitis C virus (HCV) presented on routine examination to her family doctor with abnormal liver function tests. She was referred for liver ultrasound, which detected a liver mass. Multiphasic magnetic resonance imaging (MRI) diagnosed liver cirrhosis and a segment 7/8 lesion measuring 4 cm, suspicious for a hepatocellular carcinoma (HCC), without evidence of portal hypertension. Child-Pugh (CP) score (ranging from 5 to 15) is a clinically relevant measure of synthetic liver function, based on international normalized ratio and albumin and bilirubin levels, as well as presence or absence of ascites and encephalopathy. A score of A5 or 6 is associated with better postoperative survival compared with CP B7 to 9 or CP C10 to 15, in which surgery is contraindicated. Her CP score was A6, based on a low albumin of 34 g/L. Platelets were slightly depressed at 121,000 μL, and alpha-fetoprotein level was 89 μg/L. She had not received treatment of her HCV because of her age and low viral load. She does not drink alcohol. Clinically the patient had an Eastern Cooperative Oncology Group performance status (PS) of 1, no stigmata of chronic liver disease, and no ascites or encephalopathy or other associated clinical symptoms. An HCC multidisciplinary cancer conference recommended surgical resection. The patient was taken to the operating room for a planned liver nonanatomic wedge resection. At the time of laparotomy, extensive cirrhosis was found and resection was abandoned because of the high risk of liver failure. A biopsy was not obtained, as the tumor had classic arterial enhancement and washout on venous and delayed-phase computed tomography (CT) imaging, which is diagnostic for HCC. After laparotomy, the patient developed liver insufficiency manifested by new ascites and peripheral edema, treated with diuretics, a low-salt diet, and fluid restriction. She was discharged home after a week and referred for a radiation oncology opinion. Three months after laparotomy, her liver function had recovered, with resolution of her ascites and PS of 2. It was decided to proceed with nonsurgical local therapy to the liver mass with curative intent.


ALQALAM ◽  
2015 ◽  
Vol 32 (1) ◽  
pp. 83
Author(s):  
Maftuh Maftuh

For many observers, Banten is well known as an area where the population has a strict religious understanding onislamic law. Colonial officials and experts in Islamic studies such as Snouck Hurgronje and GF Pijper, testified that compared to other Muslims across Java , Muslim in Banten and Cirebon were stricter in practicing Islam . The phenomenon of the social life of the religious community in Banten is necessarily formed within a very long time span. This paper traces the root of the formation of public religious understanding ojMuslim in Banten. Using a socio-historical approach, this paper then leads to the conclusion that the sultan of Banten issued policies that had a greater emphasis to the adherence to the Shari'a rather than Sufism. Religious orientation on the fiqh-oriented can explain the Islamic militancy Banten community, as witnessed by the colonial officials, and even still can be seen up to this present moment.Key words: Jslamization, Sultanate, Banten


2020 ◽  
Vol 1 (19) ◽  
pp. 39-46
Author(s):  
T. V. Pinchuk ◽  
N. V. Orlova ◽  
T. G. Suranova ◽  
T. I. Bonkalo

At the end of 2019, a new coronavirus (SARS-CoV-2) was discovered in China, causing the coronavirus infection COVID-19. The ongoing COVID-19 pandemic poses a major challenge to health systems around the world. There is still little information on how infection affects liver function and the significance of pre-existing liver disease as a risk factor for infection and severe COVID-19. In addition, some drugs used to treat the new coronavirus infection are hepatotoxic. In this article, we analyze data on the impact of COVID-19 on liver function, as well as on the course and outcome of COVID-19 in patients with liver disease, including hepatocellular carcinoma, or those on immunosuppressive therapy after liver transplantation.


Liver Cancer ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 734-743
Author(s):  
Kazuya Kariyama ◽  
Kazuhiro Nouso ◽  
Atsushi Hiraoka ◽  
Akiko Wakuta ◽  
Ayano Oonishi ◽  
...  

<b><i>Introduction:</i></b> The ALBI score is acknowledged as the gold standard for the assessment of liver function in patients with hepatocellular carcinoma (HCC). Unlike the Child-Pugh score, the ALBI score uses only objective parameters, albumin (Alb) and total bilirubin (T.Bil), enabling a better evaluation. However, the complex calculation of the ALBI score limits its applicability. Therefore, we developed a simplified ALBI score, based on data from a large-scale HCC database.We used the data of 5,249 naïve HCC cases registered in eight collaborating hospitals. <b><i>Methods:</i></b> We developed a new score, the EZ (Easy)-ALBI score, based on regression coefficients of Alb and T.Bil for survival risk in a multivariate Cox proportional hazard model. We also developed the EZ-ALBI grade and EZ-ALBI-T grade as alternative options for the ALBI grade and ALBI-T grade and evaluated their stratifying ability. <b><i>Results:</i></b> The equation used to calculate the EZ-ALBI score was simple {[T.Bil (mg/dL)] – [9 × Alb (g/dL)]}; this value highly correlated with the ALBI score (correlation coefficient, 0.981; <i>p</i> &#x3c; 0.0001). The correlation was preserved across different Barcelona clinic liver cancer grade scores (regression coefficient, 0.93–0.98) and across different hospitals (regression coefficient, 0.98–0.99), indicating good generalizability. Although a good agreement was observed between ALBI and EZ-ALBI, discrepancies were observed in patients with poor liver function (T.Bil, ≥3 mg/dL; regression coefficient, 0.877). The stratifying ability of EZ-ALBI grade and EZ-ALBI-T grade were good and their Akaike’s information criterion values (35,897 and 34,812, respectively) were comparable with those of ALBI grade and ALBI-T grade (35,914 and 34,816, respectively). <b><i>Conclusions:</i></b> The EZ-ALBI score, EZ-ALBI grade, and EZ-ALBI-T grade are useful, simple scores, which might replace the conventional ALBI score in the future.


HPB Surgery ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Antonio Siniscalchi ◽  
Giorgio Ercolani ◽  
Giulia Tarozzi ◽  
Lorenzo Gamberini ◽  
Lucia Cipolat ◽  
...  

Introduction. Laparoscopic liver resection is considered risky in cirrhotic patients, even if minor surgical trauma of laparoscopy could be useful to prevent deterioration of a compromised liver function. This study aimed to identify the differences in terms of perioperative complications and early outcome in cirrhotic patients undergoing minor hepatic resection for hepatocellular carcinoma with open or laparoscopic technique. Methods. In this retrospective study, 156 cirrhotic patients undergoing liver resection for hepatocellular carcinoma were divided into two groups according to type of surgical approach: laparoscopy (LS group: 23 patients) or laparotomy (LT group: 133 patients). Perioperative data, mortality, and length of hospital stay were recorded. Results. Groups were matched for type of resection, median number of nodules, and median diameter of largest lesions. Groups were also homogeneous for preoperative liver and renal function tests. Intraoperative haemoglobin decrease and transfusions of red blood cells and fresh frozen plasma were significantly lower in LS group. MELD score lasted stable after laparoscopic resection, while it increased in laparotomic group. Postoperative liver and renal failure and mortality were all lower in LS group. Conclusions. Lower morbidity and mortality, maintenance of liver function, and shorter hospital stay suggest the safety and benefit of laparoscopic approach.


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