The liver-kidney axis: Is serum leptin a potential link in non-alcoholic fatty liver disease-associated chronic kidney disease?

BACKGROUND AND STUDY AIMS: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for chronic kidney disease (CKD). Previous studies argued that leptin levels increase significantly with the progression of CKD. But the association between leptin and CKD has not been investigated in patients with NAFLD. Therefore, we conducted this study to establish whether increased leptin level is associated with CKD in NAFLD patients. PATIENTS AND METHODS: In our prospective study with a follow up period of six months thirty-five teetotaller biopsy-proven NAFLD patients were divided as groups with mild, versus advanced, fibrosis. Liver fibrosis was also assessed with Fibroscan. Serum leptin levels were measured by radioimmunoassay. For insulin resistance we used the homeostasis model assessment method (HOMA-IR). For the kidney function, we used the abbreviated formula Modification of Diet in Renal Disease (MDRD) formula, which estimates GFR. For statistical analysis, Student's-t test, Mann-Whitney test, linear regression-binary logistic regression analyses and the ROC curve analysis were used. RESULTS: Advanced fibrosis and increased HOMA-IR were risk factors for decreased eGFR. Leptin correlated inversely with advanced fibrosis (p: 0.03) and low leptin was a risk factor for CKD (p: 0.02). In ROC curve analysis, advanced fibrosis and low leptin were risk factors for decreased eGFR (p: 0.007 and 0.004, respectively). Low leptin level was dependently associated with decreased eGFR. CONCLUSION: Advanced fibrosis in NAFLD patients is a risk factor for CKD. Leptin correlated inversely with advanced fibrosis. Unlike the previous studies, which were not performed in NAFLD patients, we found decreased leptin in NAFLD patients with decreased eGFR. Low leptin level was found to be a dependent predictor for differentiating NAFLD patients with high risk for CKD.

Clinical Contribution of Standardized Terminology for Pancreatic Lesions' Cytopathology.

INTRODUCTION: Demonstration of diagnostic contribution of Papanicolaou Society of Cytopathology-standardized nomenclature for pancreaticobiliary cytology (PSC-PC) in endoscopic ultrasonography (EUS) fine-needle biopsy (FNA) biopsies is important for widespread use and further development. METHODS: 179 EUS-FNA biopsies (89: solid, 90: cystic) and PSC-PC categories were compared with surgical definite histopathology and definite clinical diagnosis. Overall risk of malignancy (oROM) was calculated for each PSC-PC category. Diagnostic accuracy was evaluated. RESULTS: The cytopathology of lesions was nondiagnostic in 27%. Ductal dilatation, lymphadenopathy, and solid characteristic (independently) were associated with diagnostic result, while lesion size was not. PSC-PC categories had 89% diagnostic consistency with surgical definite histopathology. Category mismatch was detected in 3 patients (11%), of which 2 had adenocarcinoma. oROM was 14.3% for nondiagnostic group, 46% for cat. III (atypia), and 12% for cat. IVB (neoplastic - other). In terms of malignancy, the PSC-PC system had 100% specificity; PPV, 92% sensitivity, and 81% NPV; and the diagnostic accuracy was 94%. CONCLUSION: Using PSC-PC in EUS-FNA biopsies, pancreatic malignancy can be diagnosed with high diagnostic accuracy. In mucinous cystic lesions, some malignancies may be missed. To predict the malignancy risk of cat. IVB, assessment of dysplasia seems important. Although PSC-PC is not the only parameter in terms of diagnosing malignancy, its contribution to the clinical decision is quite high.

SARS-CoV-2 vaccination and risk of severe COVID-19 outcomes in patients with autoimmune hepatitis.

BACKGROUND: Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. PATIENTS AND METHODS: We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. RESULTS: We included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10-0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11-0.35). CONCLUSIONS: SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

Frequency, Predisposing Factors, and Clinical Outcome of Azathioprine-Induced Pancreatitis Among Patients With Inflammatory Bowel Disease: Results From a Tertiary Referral Center.

OBJECTIVE: The aim of the study was to identify the frequency of azathioprine-induced acute pancreatitis (AZA-AP) and related factors. METHODS: Seven hundred eighty-seven inflammatory bowel disease (IBD) patients on AZA therapy were retrospectively analyzed. Azathioprine-induced AP was diagnosed with positive imaging and/or an at least 3-fold increased amylase level, in presence of typical abdominal pain. The AZA-AP group was compared with patients on AZA therapy with no history of pancreatitis and 4 numerical adjacent cases with the same diagnosis were selected (group B). RESULTS: Fifty-four patients developed gastrointestinal symptoms (6.9%); however, only half of them (26 of 54) had pancreatitis, except 1, all within the first 2 months under AZA. When the AZA-AP group was compared with group B, only budesonide usage and active smoking were significantly more common in group A (46.2% vs 25%, P = 0.034, and 77% vs 51%, P = 0.017, respectively). Active smoking was the only independent risk factor for AZA-AP development (odds ratio, 3.208 [95% confidence interval, 1.192-8.632]). CONCLUSIONS: All IBD patients developed AZA-AP nearly all within the first 2 months. Azathioprine intolerance may be a hidden diagnosis in at least half of the patients with AZA-AP symptoms. All smoker IBD patients should be monitored closely for AZA-AP development.

Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study.

BACKGROUND AND AIMS: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. APPROACH AND RESULTS: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score-matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. CONCLUSIONS: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.

Evaluation of Ocular Parameters in Adult Patients with Celiac Disease.

PURPOSE: To evaluate ophthalmic parameters in adult celiac patients. METHODS: This cross-sectional study included 31 celiac patients (58 eyes) and 25 healthy controls (50 eyes). Tear break up time (TBUT), schirmer test were measured; corneal thickness, anterior chamber parameters were obtained using scheimpflug camera; retinal nerve fiber layer thickness (RNFL) evaluated by using spectral domain optical cohorence tomography. RESULTS: There were no statistically significant differences between the groups in terms of gender, age, and intraocular pressure (p > .05). Schirmer's test results and TBUT were significantly lower in celiac patients (p < .001, p < .001). Additionally, the superior RNFL was significantly thinner (p = .017), nasal RNFL thicker (p = .007), and anterior chamber depth larger (p = .037) in celiac patients. The tissue transglutaminase 2 IgA antibody and superior RNFL were negatively correlated (r = -0.394, p = .012). The anterior chamber volume and anti-gliadin IgA antibody were positively correlated (r = 0.369 p = .027). CONCLUSION: Celiac disease affects Schirmer's test results, TBUT, segmental RNFL thickness, and anterior chamber parameters. Ocular parameters might be affected in celiac disease especially in the presence of high antibody titer.

The effect of concomitant ankylosing spondylitis on long-term outcome of patients with inflammatory bowel disease.

BACKGROUND/AIMS: The aim of the present study was to compare the demographic features and long-term outcomes of patients with inflammatory bowel disease (IBD) with or without ankylosing spondylitis (AS). MATERIALS AND METHODS: Among 1640 IBD (Crohn's disease and ulcerative colitis), 76 patients with IBD+AS were identified. The study group consisted of 76 patients with IBD with synchronous AS. The control group consisted of patients with only IBD, and those were selected according to their registry sequence number being the previous and next case to the diseased case with IBD+AS. The primary endpoint was to compare the rate of intestinal resections between both groups (IBD vs. IBD+AS). RESULTS: Among 76 patients with IBD+AS, 52 (68%) first presented with IBD, 11 (15%) with AS, and the remaining 13 (17%) had both diagnoses at the same time. The mean follow-up time was significantly longer in patients with IBD+AS (43.4 vs. 27.8 months; p=0.01). Twenty-two percent of patients with IBD and 14% of those with IBD+AS had an intestinal resection (p=NS). Biologic and systemic corticosteroid treatments were significantly more common among patients with IBD+AS (32% vs. 7% for biologics, p<0.0001 and 44% vs. 28% for corticosteroids, p=0.042). Age-sex-adjusted regression analysis for both groups disclosed IBD duration as the only independent predictor for resection (R2=0.178; p=0.016). CONCLUSION: The present study shows that up to 5% of patients with IBD may have AS. Patients with IBD+AS do not have a worse disease outcome than solo patients with IBD.

Coexistence of Hermansky-Pudlak syndrome and JAK2V617F-positive essential thrombocythemia.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder consisting of oculocutaneous albinism, platelet storage pool deficiency, and lysosomal accumulation of ceroid lipofuscin. The storage pool deficiency of HPS is associated with the lack of dense bodies in the platelets, resulting in impaired response in the secondary phase of aggregation. Patients with HPS have normal coagulation tests; however, their bleeding time is usually prolonged despite normal or increased platelet counts. Essential thrombocythemia (ET) is an uncommon condition, with an incidence of approximately 1.1 per 100,000/year, and it is the most common cause of primary thrombocytosis. JAK2V617F positivity can be observed in approximately half of the patients with ET. Bleeding events in ET have usually been associated with acquired von Willebrand syndrome paradoxically occurring when the platelet counts are extremely high. We, herein, present a case with bleeding diathesis diagnosed as having both HPS and JAK2V617F-positive ET.

Which Type of Temporary Hemodialysis Catheter Should Be Used for the Right Internal Jugular Vein? Prospective Observational Study of Straight vs. Precurved Catheters.

Weak evidence is present for choosing amongst different temporary hemodialysis catheter (THC) designs with regards to the risk of venous thrombosis, therefore two THC designs for the right internal jugular vein (RIJV) were compared. Patients aged ≥18 years who needed THC insertion into the RIJV for acute hemodialysis due to either acute or chronic renal failure were included. The type of THC (precurved/straight) was dependent on the date of hospital admission. Clinical and ultrasonographic surveillance was conducted prospectively. Thrombosis of the RIJV was the primary objective. Precurved and straight catheters were inserted into 32 and 23 patients (mean age 63 ± 15 years, females 28), respectively. The baseline characteristics and catheter dwell-times were similar in both groups. Partial and total thrombosis of the RIJV during catheter dwell-time developed at a higher rate in the straight group (52% vs. 9.3%, P = 0.000; 47.8% vs. 9.3%, P = 0.001, respectively). At least 2 weeks after catheter removal, total thrombosis was found in 43.4% vs. 9.6% (P = 0.004) of patients with straight and precurved THCs, respectively. The hazard ratios for total thrombosis was 0.161 (P = 0.006) during catheter dwell-time and 0.190 (P = 0.012) after catheter removal. Catheter dysfunction did not occur and only one catheter-related bloodstream infection (CRBI) was seen. Thrombosis rates of the RIJV were higher with straight vs. precurved THCs, both during catheter dwell-time and after catheter removal. Catheter dysfunction was not noted in any group and the rate of CRBI was extremely low.

Prevalence of fecal incontinence and associated risk factors in elderly outpatients: a cross-sectional study.

BACKGROUND: Data on the prevalence of fecal incontinence in elderly patients admitted to outpatient clinics in Turkey are scarce. AIMS: The aim of this study was to assess the prevalence of fecal incontinence and the associated risk factors in the elderly outpatients. METHODS: Patients 60 years and older admitted to a geriatrics outpatient clinic between October 2013 and March 2014 were included. Demographic characteristics, anthropometric measurements, marital status, educational status, parity (for females), fecal incontinence (FI), urinary incontinence (UI), constipation, comorbid conditions, and medications were recorded. FI assessment was based on the Fecal Incontinence Severity Index (FISI). RESULTS: A total of 364 patients (64.8% female, n = 236) with a mean age of 73.2 ± 8.1 years were enrolled in the study. The prevalence of FI was 9.9% (10.2% female, 9.4% male). UI was 42.6%. Co-occurrence of FI and UI was 7.4%. According to the FISI, the most frequent type of defecation was liquid stool (61.1%). While the predictive factors for FI were polypharmacy (standardized coefficient, [r] = 0.203, 95% confidence interval [CI] = 0.009-0.040, p = 0.002), UI (r = 0.134, 95% CI = 0.006-0.156, p = 0.035), and being married (r = 0.200, 95% CI = -0.088 to -0.020, p = 0.002) in females, those were UI (r = 0.306, 95% CI = 0.093-0.309, p < 0.001) and polypharmacy (r = 0.251, 95% CI = 0.009-0.043, p = 0.003) in males. CONCLUSIONS: In both genders, urinary incontinence and polypharmacy seem to be the most important risk factors for fecal incontinence. Fecal incontinence should be questioned in detail and evaluated using FISI in elderly outpatients.

Apoptosis and Disease Severity is Associated with Insulin Resistance in Non-alcoholic Fatty Liver Disease.

BACKGROUNDS AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). We evaluated whether IR contributes to hepatocyte apoptosis, inflammation, and fibrosis in NAFLD. METHODS: Forty-four teetotaller patients with biopsy-proven diagnosis of NAFLD were enrolled. Twenty-eight NAFLD patients with IR were compared with 16 subjects without IR. For apoptotic activity caspase 3 and 8, transcription nuclear factor kB (NF-kB), and anti-apoptotic Bcl-2 protein were determined through immunohistochemical methods. RESULTS: HOMA-IR index was significantly correlated with the stage and caspase 3- and 8 levels (p= 0.001, 0.02, and 0.01, respectively). HOMA-IR index was independently associated with the severity of fibrosis ( = 5.9, p = 0.001), caspase-3 ( = 0.16, p = 0.001), and caspase-8 (b =0.032, p = 0.018) levels. TNF-sRp55 level was positively correlated with HOMA-IR index (p = 0.024). Patients with IR had significantly higher necroinflammatory grade, stage, caspase-3, and caspase-8 levels than those without IR (p = 0.022, 0.007, 0.031, and p = 0.011, respectively). HOMA-IR index had statistically significant values for distinguishing of severe necroinflammatory grade, stage and for differentiating NASH from simple fatty liver (AUC = 0.78, 0.76, and 0.82, respectively). CONCLUSION: This study demonstrates that IR in NAFLD is associated with enhanced hepatocyte apoptosis and histopathologic disease severity. These data indicate that NAFLD patients with IR may have increased risk for disease progression.

Role of oxidative stress and insulin resistance in disease severity of non-alcoholic fatty liver disease.

BACKGROUND/AIMS: Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to find the relation between oxidative stress parameters and histopathological findings in NAFLD patients with and without insulin resistance (IR). MATERIALS AND METHODS: Thirty-two patients with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied (M/F: 17/15; mean age 46.5±11.4 years). Twenty-one NAFLD patients with IR were compared with 11 patients without IR. The fasting insulin level was measured, and the insulin resistance index was calculated using the homeostasis model assessment (HOMA) method. Malondialdehyde (MDA) and superoxide dismutase (SOD) activities were measured in tissue and serum specimens. Glutathione (GH) was measured in tissue homogenates. Nitric oxide (NO), vitamin E and C levels were measured in serum. RESULTS: Patients with IR had significantly higher tissue MDA levels (p=0.001) and significantly decreased tissue SOD and GH levels (p=0.001 and 0.002, respectively) than those without IR. The steatosis grade, necroinflammatory grade and stage were significantly higher in patients with IR (p=0.035, 0.003 and 0.001, respectively). HOMA IR significantly correlated with the necroinflammatory grade, stage, tissue MDA, SOD and GH (p=0.013, 0.001, 0.008, 0.001 and 0.001, respectively). Serum MDA (ß=1.88, p=0.002), serum SOD (ß=0.57, p=0.006), tissue MDA (ß=0.22, p=0.006), tissue SOD (ß=1.48, p=0.071) and stage (ß=2.81, p=0.003) were independently associated with increased HOMA IR. Increased MDA [OR: 1.51; 95% CI: (1.03-2.22); p=0.034] was a risk factor for non-alcoholic steatohepatitis (NASH), and increased SOD activity had a preventive effect against NASH [OR: 0.008; 95% CI: (0.001-0.98); p=0.04]. CONCLUSION: This study shows that insulin resistance in NAFLD correlates with enhanced oxidative stress. Histopathological disease severity significantly correlated with oxidative stress parameters. These data show that NAFLD patients with IR may have increased risk for disease progression.

Five-year results of oral antiviral therapy in HBeAg-negative chronic Hepatitis B.

BACKGROUND/AIMS: Several guidelines recommend the use of tenofovir or entecavir as the first-line treatment for hepatitis B due to the lower resistance rates of these drugs than lamivudine, although lamivudine may still be preferred because of its low adverse effect profile and cost. It is important to know which patients might benefit from lamivudine as the first-line treatment. We aimed to assess the success rates of lamivudine, entecavir, and tenofovir, as well as the resistance rates, frequencies of HBsAg clearance, and risk factors for lamivudine resistance. MATERIALS AND METHODS: A total of 191 patients with chronic HBeAg-negative hepatitis who were treated with lamivudine, entecavir, or tenofovir were included. Predictors of resistance to lamivudine were analyzed. RESULTS: The cumulative first-, second-, third-, fourth-, and fifth-year rates of virologic breakthrough during extended lamivudine therapy were 24%, 30%, 38%, 46%, and 54%, respectively. The rate of undetectable DNA at the 60th month of those who took lamivudine was 51%. Cox regression analysis revealed that positive HBV DNA at the sixth month (HR=15; 95% CI: [7.1-33], p=0.001), being aged 41 years or more (HR=3.4; 95% CI: [1.8-6.4], p=0.001), and baseline HBV DNA of 170,500 IU/mL or higher (HR=2.1; 95% CI: [1.2-3.7], p=0.01) were independently associated with the development of resistance to lamivudine. CONCLUSION: In HBeAg-negative chronic hepatitis B, baseline serum hepatitis B virus DNA levels exceeding 170,500 IU/mL, partial virologic response in the sixth month, and age of 41 years or more were independent predictors for virologic breakthrough. Moreover, 2% of these patients cleared HBsAg.

Low lipase levels as an independent marker of pancreatic cancer: a frequently neglected condition in clinical setting.

BACKGROUND/AIMS: Low lipase levels, which may be an indication of low production due to organ failure, are frequently encountered in a clinical setting, but are usually overlooked. This study examined the values of low serum lipase levels and other clinical parameters in the diagnosis of several clinical conditions, such as in pancreatic cancer. MATERIALS AND METHODS: Patients with low lipase levels (≤8 U/L) were included in this retrospective study. Clinical data, including diagnostic category, demographic properties, and biochemical and hematological measurements, including serum lipase levels, were extracted. A multivariate analysis was used to identify the independent predictors of certain diagnostic categories. RESULTS: A total of 198 patients with low lipase levels were included. Among these patients with low lipase levels, 45 (22.7%) were diagnosed with pancreas cancer. Multivariate analysis identified low lipase level as a significant predictor of pancreas cancer (OR 0.70 [%95 CI, 0.52-0.93], p=0.02). For predicting pancreatic cancer, an optimal cut-off value of ≤5.5 U/L for lipase was utilized, which had a sensitivity and specificity of 76% and 37%, respectively. CONCLUSION: Low lipase levels close to zero may be an indication of pancreatic cancer and should not be underestimated in the clinical setting. However, large studies are warranted to delineate the exact diagnostic significance of such low lipase levels.