M.L. Gabrieli

Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease

The role played by the gut in nonalcoholic fatty liver disease (NAFLD) is still a matter of debate, although animal and human studies suggest that gut‐derived endotoxin may be important. We investigated intestinal permeability in patients with NAFLD and evaluated the correlations between this phenomenon and the stage of the disease, the integrity of tight junctions within the small intestine, and prevalence of small intestinal bacterial overgrowth (SIBO). We examined 35 consecutive patients with biopsy‐proven NAFLD, 27 with untreated celiac disease (as a model of intestinal hyperpermeability) and 24 healthy volunteers. We assessed the presence of SIBO by glucose breath testing (GBT), intestinal permeability by means of urinary excretion of 51Cr‐ethylene diamine tetraacetate (51Cr‐EDTA) test, and the integrity of tight junctions within the gut by immunohistochemical analysis of zona occludens‐1 (ZO‐1) expression in duodenal biopsy specimens. Patients with NAFLD had significantly increased gut permeability (compared with healthy subjects; P < 0.001) and a higher prevalence of SIBO, although both were lower than in the untreated celiac patients. In patients with NAFLD, both gut permeability and the prevalence of SIBO correlated with the severity of steatosis but not with presence of NASH. Conclusions: Our results provide the first evidence that NAFLD in humans is associated with increased gut permeability and that this abnormality is related to the increased prevalence of SIBO in these patients. The increased permeability appears to be caused by disruption of intercellular tight junctions in the intestine, and it may play an important role in the pathogenesis of hepatic fat deposition. (HEPATOLOGY 2009.)

Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis

BACKGROUND/AIMS The association between NAFLD and psoriasis has never been explored in prospective epidemiological studies. The aim of this 2-phase study was to study the clinical features of NAFLD in patients with psoriasis. METHODS Phase 1: Investigation of prevalence and characteristics of NAFLD in an unselected cohort of 142 adult Italian outpatients with psoriasis vulgaris. Phase 2: Comparison of the psoriasis cohort subgroup with NAFLD and an age- and body mass index-matched retrospective cohort of 125 non-psoriasis patients with biopsy proven NAFLD. RESULTS Based on histories, laboratory tests, and ultrasound studies, 84 (59.2%) received clinical diagnosis of NAFLD; 30 had factors potentially associated with liver disease other than NAFLD (e.g., viral hepatitis, significant ethanol, methotrexate use); and 28 (19.7%) had normal livers. Comparison of the normal-liver and NAFLD subgroups revealed that NAFLD in psoriasis patients (Ps-NAFLD) was significantly correlated with metabolic syndrome (p<0.05); obesity (p=0.043); hypercholesterolemia (p=0.029); hypertriglyceridemia (p<0.001); AST/ALT ratio >1 (p=0.019), and psoriatic arthritis (PsA) (p=0.036). The association with PsA remained significant after logistic regression analysis (OR=3.94 [CI, 1.07-14.46]). Compared with the retrospective non-psoriatic NAFLD cohort (controls), Ps-NAFLD patients (cases) were likely to have severe NAFLD reflected by non-invasive NAFLD Fibrosis Scores and AST/ALT >1. CONCLUSIONS NAFLD is highly prevalent among psoriasis patients, where it is closely associated with obesity (overall and abdominal), metabolic syndrome, and PsA, and more likely to cause severe liver fibrosis (compared with nonPs-NAFLD). Routine work-up for NAFLD may be warranted in patients with psoriasis, especially when potentially hepatotoxic drug therapy is being considered.

Abdominal angina due to recurrence of cancer of the papilla of Vater: a case report

IntroductionAbdominal angina is usually caused by atherosclerotic disease, and other causes are considered uncommon. This is the first report of a case of abdominal angina secondary to neoplastic vascular stenosis caused by local recurrence of an adenocarcinoma of the papilla of Vater.Case presentationAn 80-year-old woman of Caucasian origin presented with abdominal pain and diarrhea. She had undergone a pancreaticoduodenectomy for adenocarcinoma of the papilla of Vater four years earlier. Computed tomography revealed a mass surrounding her celiac trunk and superior mesenteric artery. Her abdominal pain responded poorly to analgesic drugs, but disappeared when oral feedings were withheld. A duplex ultrasonography of the patients splanchnic vessels was consistent with vascular stenosis. Parenteral nutrition was started and the patient remained pain free until her death.ConclusionPain relief is an important therapeutic target in patients with cancer. In this case, abdominal pain was successfully managed only after the ischemic cause had been identified. The conventional analgesic therapy algorithm based on nonsteroidal anti-inflammatory drugs and opioids had been costly and pointless, whereas the simple withdrawal of oral feeding spared the patient of the discomfort of additional invasive procedures and allowed her to spend her remaining days in a completely pain-free state.

NON-INVASIVE ASSESSMENT OF HISTOLOGICAL INFLAMMATION IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)

Methods: We retrospectively reviewed all clinical records of patients with DILI admitted to our Unit from February 1996 to December 2006. A database was constructed, reporting data regarding age, sex, clinical features at onset, laboratory results, suspected drugs and follow-up. The diagnosis of DILI was based on the presence of at least three of the International Consensus Criteria (J Hepatol 1990). Liver damage was defined as hepatocellular, cholestatic or mixed, according to clinical and laboratory data, since histology was performed only in a minority of patients. All patients were negative for hepatitis A, B, C, EBV and CMV serology and non organ-specific autoantibody screening. Results: Forty six cases out of 6,134 patients received a discharge diagnose of DILI. There were 23 men and 23 women, mean age was 54.2 (range 11-88 yrs), 35 patient (74%) were older than 40 years. Five patients had an associated chronic liver disease (2 cirrhosis and 3 HCV-related chronic hepatitis). At clinical presentation all patients had abnormal liver function tests (LFTs), 22 patients were jaundiced and 3 patients was admitted for hepatic failure, manifest as hepatic encephalopathy. Liver damage was hepatocellular in 19 patients, cholestatic in 15 and mixed in 12. In 10 (22%) of cases, two or more drugs were involved. NSAIDs (n =17), psychotropic drugs (n =7) and antibiotics (n =10) were the most commonly involved drugs, followed by anti-platelet, anti-diabetic drugs and statins. NSAIDs were involved in three cases of acute liver failure and, among them, one was listed for liver transplantation but died while on the waiting list. All patients had regular follow-up visits every three months for at least one year after discharge. All patients, including those with pre-existing liver disease had a complete normalization of LFTs at the end of follow-up. Conclusions: Severe DILI requiring hospital admission is very rare and appears more common in patients over 40 years. NSAIDs, psychotropic drugs and antibiotics are the most common responsible drugs. Even in severe cases, recovery is almost the rule and only a few patients have an unfavourable course and eventually die