Target Therapies for NASH/NAFLD: From the Molecular Aspect to the Pharmacological and Surgical Alternatives.

Non-alcoholic fatty liver disease represents an increasing cause of chronic hepatic disease in recent years. This condition usually arises in patients with multiple comorbidities, the so-called metabolic syndrome. The therapeutic options are multiple, ranging from lifestyle modifications, pharmacological options, to liver transplantation in selected cases. The choice of the most beneficial one and their interactions can be challenging. It is mandatory to stratify the patients according to the severity of their disease to tailor the available treatments. In our contribution, we review the most recent pharmacological target therapies, the role of bariatric surgery, and the impact of liver transplantation on the NAFLD outcome.

Liver transplantation for rare liver diseases and rare indications for liver transplant.

Liver transplantation (LT) is currently considered the gold standard treatment for end-stage liver failure. Compared to the first decades of its use, LT is associated with lower comorbidity and mortality, with a 5-year survival over 70%. Worldwide, liver cirrhosis and hepatocellular carcinoma represent the major indications to LT. However, almost 1% of LT is performed for rare diseases or rare indications, which include non-hepatocellular malignancy, vascular disorders, metabolic and congenital liver disorders. These diseases can lead to hepatocellular necrosis, biliary tree abnormality and/or hepatomegaly. Most of these diseases are not associated with liver failure but in highly selected patients, LT represent an effective therapy improving the overall survival and quality of life. Rare indications for LT often overlap with rare diseases. However, rare LT indications for non-rare diseases are rising in the last decades, especially for benign primary liver tumor, colon rectal liver metastasis, neuroendocrine liver metastasis, and cholangiocarcinoma (CCA). Non-rare diseases with rare indication for LT and rare adult disease with an indication for LT are categorized and discussed in detail, focusing on some disorders for which the literature provides a more definitive evidence base. Early referral to a transplant center is encouraged to provide an effective therapeutic option in these non-standard indications for LT.

Foodborne botulism presenting as small bowel obstruction: a case report.

BACKGROUND: Small bowel obstruction is one of the leading reasons for accessing to the Emergency Department. Food poisoning from Clostridium botulinum has emerged as a very rare potential cause of small bowel obstruction. The relevance of this case report regards the subtle onset of pathognomonic neurological symptoms, which can delay diagnosis and subsequent life-saving treatment. CASE PRESENTATION: A 24-year-old man came to our Emergency Department complaining of abdominal pain, fever and sporadic self-limiting episodes of diplopia, starting 4 days earlier. Clinical presentation and radiological imaging suggested a case of small bowel obstruction. Non-operative management was adopted, which was followed by worsening of neurological signs. On specifically questioning the patient, we discovered that his parents had experienced similar, but milder symptoms. The patient also recalled eating home-made preserves some days earlier. A clinical diagnosis of foodborne botulism was established and antitoxin was promptly administered with rapid clinical resolution. CONCLUSIONS: Though very rare, botulism can mimic small bowel obstruction, and could be associated with a rapid clinical deterioration if misdiagnosed. An accurate family history, frequent clinical reassessments and involvement of different specialists can guide to identify this unexpected diagnosis.

A Translational Approach to Standardization of Machine Perfusion Adoption in Ex Vivo Liver Resection.

BACKGROUND: Hepatic resection represents the best treatment for primary and metastatic liver tumors but is not always feasible. In early 1980, Piclmayr described a complex liver resection technique, termed "ex vivo liver resection," for the treatment of locally advanced tumors not conventionally resectable. The authors approached this technique with translational research in a preclinical setting and then similarly reproduced it in human patients. METHODS: In the swine median xyphopubic laparotomy, the liver was mobilized to expose the vena cava. A temporary porto-caval shunt was previously prepared on the back table using a segment of thoracic aorta, and a vascular anastomosis between the supra-hepatic vena cava and a caval graft was quickly performed. The liver was placed in a machine perfusion system and continuously perfused for 2 h for its final implantation orthotopically in the same animal. The anastomoses were performed as usual. Based on this experience, the intervention was reproduced in the human model of a 39-year-old woman affected by large intrahepatic cholangiocarcinoma considered unresectable.' RESULTS: All animals survived the procedure. The peak aspartate aminotransferase level (460 ± 87 U/L) was recorded 60 min after reperfusion. Lactate levels flared up for 120 min (3.6 ± 0.2 mmol/L). In the clinical case, the postoperative period was uneventful, and the patient was discharged on day 22. CONCLUSIONS: The described procedure is feasible only for surgeons with a transplantation background. The study showed that this translational approach enhances the surgeon's ability to perform the intervention systematically in a shorter time and with a good outcome.