Sarcopenia in patients with non-alcoholic fatty liver disease: is it a clinically significant entity?

Sarcopenia, described as the loss of muscle mass and/or strength, is gaining importance as it can be increasingly related to many chronic diseases. It is also associated with chronic liver disease, and recently it has been more frequently linked to non-alcoholic fatty liver disease (NAFLD) in particular. Both sarcopenia and NAFLD are subject to complex and intermingled pathophysiological processes, of which some are in common. Furthermore, it is presently unclear if sarcopenia directly contributes to NAFLD or vice versa. The mechanisms that are involved may include obesity, insulin resistance, vitamin D deficiency, aging, physical inactivity and certain cytokines. Current clinical evidence is subject to an important heterogeneity in methods and definitions, with additionally also a relative overrepresentation of evidence in Asian ethnicities. Nonetheless, all studies so far point towards the same association between sarcopenia and NAFLD, including an association with NAFLD-severity and NAFLD-related fibrosis. Since the field is in its infancy, clear definitions and further research are needed to aid to improve understanding of the association between NAFLD and sarcopenia. This can eventually lead to additional potential therapeutic interventions. This review attempts to give an overview of the current published literature that links sarcopenia to NAFLD, followed by a discussion of the presumably involved pathophysiological factors, and ends by discussing current unmet needs.

The potential role of vascular alterations and subsequent impaired liver blood flow and hepatic hypoxia in the pathophysiology of non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disease ranging from steatosis to steatohepatitis (NASH) and fibrosis, but the underlying pathophysiological mechanisms remain largely unknown. As there is currently no approved pharmacological therapy and the prevalence of NAFLD keeps increasing, understanding of its pathophysiology is crucial. We hypothesise that vascular alterations in early NAFLD play a role in the progression of the disease by inducing an increased intrahepatic vascular resistance and consequently relative hypoxia in the liver. Evidence of the detrimental effects of hypoxia in NAFLD has already been observed in liver surgery, where the outcomes of steatotic livers after ischaemia-reperfusion are worse than in healthy livers, and in obstructive sleep apnoea, which is an independent risk factor of NAFLD. Moreover, early histological damage in NAFLD is situated in the pericentral zone, which is also the first zone to be affected by a decreased oxygen tension because of the unique hepatic vacsular anatomy that causes the pericentral oxygen tension to be the lowest. Angiogenesis is also a characteristic of NAFLD, driven by hypoxia-induced mechanisms, as demonstrated in both animal models and in humans with NAFLD. Relative hypoxia is most probably induced by impaired blood flow to the liver, caused by increased intrahepatic vascular resistance. An increased intrahepatic vascular resistance early in the development of disease has been convincingly demonstrated in several animal models of NAFLD, whereas an increased portal pressure, a consequence of increased intrahepatic vascular resistance, has been proven in patients with NAFLD. Animal studies demonstrated a decreased intrahepatic effect of vasodilators and an increased reactivity to vasoconstrictors that results in an increased intrahepatic vascular resistance, thus the presence of a functional component. Pharmacological products that target vasoregulation can hence improve the intrahepatic vascular resistance and this might prevent or reverse progression of NAFLD, representing an important therapeutic option to study. Some of the drugs currently under evaluation in clinical trials for NASH have interesting properties related to the hepatic vasculature. Some other interesting drugs have been tested in animal models but further study in patients with NAFLD is warranted. In summary, in this paper we summarise the evidence that leads to the hypothesis that an increased intrahepatic vascular resistance and subsequent parenchymal hypoxia in early NAFLD is an important pathophysiological driving mechanism for the progression of the disease.

Mechanisms contributing to visceral hypersensitivity: focus on splanchnic afferent nerve signaling.

BACKGROUND: Visceral hypersensitivity is a main characteristic of functional bowel disorders and is mediated by both peripheral and central factors. We investigated whether enhanced splanchnic afferent signaling in vitro is associated with visceral hypersensitivity in vivo in an acute and postinflammatory rat model of colitis. METHODS: Trinitrobenzene sulfonic acid (TNBS)-colitis was monitored individually by colonoscopy to confirm colitis and follow convalescence and endoscopic healing in each rat. Experiments were performed in controls, rats with acute colitis and in postcolitis rats. Colonic afferent mechanosensitivity was assessed in vivo by quantifying visceromotor responses (VMRs), and by making extracellular afferent recordings from splanchnic nerve bundles in vitro. Multiunit afferent activity was classified into single units identified as low threshold (LT), wide dynamic range (WDR), high threshold (HT), and mechanically insensitive afferents (MIA). KEY RESULTS: During acute TNBS-colitis, VMRs were significantly increased and splanchnic nerve recordings showed proportionally less MIA and increased WDR and HT afferents. Acute colitis gave rise to an enhanced spontaneous activity of both LT and MIA and augmented afferent mechanosensitivity in LT, WDR and HT afferents. Postcolitis, VMRs remained significantly increased, whereas splanchnic nerve recordings showed that the proportion of LT, WDR, HT and MIA had normalized to control values. However, LT and MIA continued to show increased spontaneous activity and WDR and HT remained sensitized to colorectal distension. CONCLUSIONS & INFERENCES: Visceral hypersensitivity in vivo is associated with sensitized splanchnic afferent responses both during acute colitis and in the postinflammatory phase. However, splanchnic afferent subpopulations are affected differentially at both time points.

Rapidly evolving liver decompensation with some remarkable features 14 years after biliopancreatic derivation: a case report and literature review.

Because of the rising incidence of obesity the use of bariatric surgery is also increasing. For the obese it is the only treatment with a proven long-term benefit on weight, comorbidities including non alcoholic steatohepatitis, and long-term mortality. There are, however, several reports on hepatic complications after bariatric surgery leading to malabsorption. The risk of liver decompensation or cirrhosis is one of the reasons jejunoileal bypass has been abandoned. Hepatic complications following Roux-en-Y gastric bypass and biliopancreatic derivation (BPD) are also reported but never beyond 2 years of follow-up. There is only one confirmed case of development of cirrhosis following BPD which presented 10 months after surgery. We present a case of a 39-year-old patient who developed rapidly evolving, and ultimately fatal, liver decompensation in previously unknown cirrhosis, 14 years after BPD. This is the first report of a severe hepatic complication such a long time after a BPD. Existing literature on hepatic complications after bariatric surgery is discussed as are 2 coincidental findings of pronounced ductular reaction on histology and autoimmune haemolytic anaemia.

Biopsy of focal liver lesions: guidelines, comparison of techniques and cost-analysis.

When a focal liver lesion is discovered, differentiation between a benign and malignant nature and further characterization are mandatory to guide further treatment. Histology remains the golden standard. Improving imaging techniques such as contrast enhanced Doppler ultrasonography, spiral CT and new MRI procedures are promising, but not 100% accurate. When there is any doubt, biopsy should be performed. Fine Needle Aspiration Biopsy (FNAB) has a high sensitivity and specificity (90-95%) in experienced hands, but has a high insufficient sampling rate (up to 15%). In a series of 245 Fine Needle Tru-cut Biopsies (FNTCB) of focal solid liver lesions performed at our institution, sensitivity and specificity for the diagnosis of malignancy were 86% and 100% respectively, with an overall accuracy of 88%. Positive predictive value was 100%, but negative predictive value was rather low (56%). Insufficient sampling rate was low (2.5%), and a more accurate histological characterization was possible compared to FNAB. Finally, the cost-analysis of different biopsy techniques is presented for the Belgian situation according to used materials, pathology procedures and hospitalization.

Perforating oesophageal carcinoma presenting as necrotizing fasciitis of the neck.

A patient with a history of schizophrenia was admitted to our hospital in an already severe stage of necrotizing fasciitis of the neck, complicated with mediastinitis and gangrene. Later on, he also developed a vena cava superior syndrome and sepsis. In the few cases and small series described in the literature, necrotizing fasciitis of the neck is usually associated with surgery or trauma. Less frequently, an orodental or pharyngeal infection, often innocuous, is the underlying cause. None of these causes could be identified in our patient. Initially, on computer-assisted tomography (CT) scan, a tracheal rupture was suspected, but this diagnosis could not be confirmed on bronchoscopic examination. On gastroscopy, a stenotic oesophageal segment was discovered. Biopsy of this segment showed a poorly differentiated squamous cell carcinoma. The patient died in sepsis. Autopsy confirmed the presence of a large proximal oesophageal tumour with perforation. As far as we know, no case of a necrotizing fasciitis of the neck caused by perforation of a formerly unknown oesophageal carcinoma has been reported. Even mediastinitis, with or without gangrene, is rarely associated with oesophageal cancer, and in the few cases reported it is always due to fistulization after surgery.

Ultrasonically guided fine needle puncture of focal liver lesions. Review and personal experience.

Despite recent advances in diagnostic imaging of the liver, the management of a patient with focal liver lesions often depends on obtaining tissue for histological diagnosis. Ultrasound guided fine needle biopsy is recommended as a safe and reliable method for cyto-histological confirmation of suspected hepatic malignancy. A fine needle is conventionally defined as having an outer diameter < or = 0.9 mm or > or = 19 G. Ultrasound guided fine needle aspiration cytology is found reliable for diagnosing malignancy. Limitations of this method are inadequate sampling and limited value in diagnosis of well-differentiated malignant tumours and benign tumours. Ultrasound guided fine needle cutting biopsy allows to obtain tissue for histological examination according to the Menghini technique. Both methods have high sensitivity, specificity and accuracy in detecting malignancy. In a personal series of 50 fine needle aspiration cytologies, a sensitivity for malignancy of 87% was obtained, with a specificity of 100%. The insufficient sampling rate, however, was 10%. Ultrasound guided fine needle trucut biopsy combines the advantages of a fine needle and a better sampling quality; a lower insufficient sampling rate can be expected without increase in complication rate. Despite the availability of numerous manually operated or (semi-) automated devices, little data have been published up to now on liver lesions. In our hands, it has proven to be a safe and reliable method, with low insufficient sampling rate, allowing correct identification of primary liver malignancies, correct suggestion of the primary source of the majority of metastases and correct identification of most benign liver lesions. Therefore it is considered as the method of choice when focal noncystic liver lesions are to be biopsied.