A combination of non-invasive tests for the detection of significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease is not superior to magnetic resonance elastography alone.

OBJECTIVES: The aims of the present study were to investigate a combination of magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE) or MRE and fibrosis score 4 (FIB-4) in the detection of significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: Between November 5, 2021, and March 4, 2022, a total of 119 consecutive patients with MASLD were included. Liver stiffness was measured using liver biopsy, MRE, VCTE, and FIB-4. Data were collected from outpatient visit charts. Significant fibrosis was defined as ≥ stage 2 fibrosis. RESULTS: All 119 MASLD patients were Caucasian, and their median age was 55 years. MRE, VCTE, and FIB-4 demonstrated significant accuracy in the detection of significant fibrosis with an area under the ROC curve (AUC) of 0.848 ± 0.036 (p < 0.001), 0.632 ± 0.052 (p = 0.012), and 0.664 ± 0.051 (p = 0.001), respectively. However, the diagnostic performance of MRE was superior compared to that of VCTE (AUC difference: 0.216 ± 0.053, p < 0.001) and FIB-4 (AUC difference: 0.184 ± 0.058, p = 0.001). With logistic regression analysis, it was determined that when compared to MRE alone, a combination of MRE and TE (p = 0.880) or MRE and FIB-4 (p = 0.455) were not superior for detecting significant fibrosis. CONCLUSIONS: MRE alone is an accurate and non-invasive method for the identification of MASLD patients with significant fibrosis. CLINICAL RELEVANCE STATEMENT: Magnetic resonance elastography alone accurately detects significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. KEY POINTS: • In routine clinical practice, several non-invasive biochemical-based biomarkers and imaging methods are widely used to assess liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. • Magnetic resonance elastography (MRE) is more accurate than vibration-controlled transient elastography (VCTE) or fibrosis score 4 (FIB-4) for assessing liver fibrosis and identifying significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. • The combination of MRE and VCTE or MRE and FIB-4 was not superior to MRE alone.

Role of hepatosteatosis in HBsAg seroconversion in HBeAg-negative chronic hepatitis B patients.

BACKGROUND: In chronic Hepatitis B virus (HBV) infection, certain individual and viral characteristics such as advanced age, presence of hepatic steatosis (HS), normal ALT levels, initially negative HBeAg and HBV DNA, and genotype of the virus are associated with HBsAg seroclearance and seroconversion. Herein, we report the results of our study evaluating the association between hepatosteatosis and HbsAg seroconversion. METHODS: The clinical and biochemical data of patients with CHB and hepatosteatosis (HS) (HBsAg seroconversion, n:52, and non-HbsAg seroconversion, n:352), and the rate of development of HBsAg seroconversion were evaluated. RESULTS: We collected data from 404 patients with HBeAg negative CBH (mean age ± SD: 36.2 ± 11 years; 223 [55.2%] men, 181 [44.8%] women). The mean age at diagnosis of disease was 36.2 ± 11 years. The mean duration of the disease was 10.6 ± 7 years. Seroconversion developed in 52 patients (12.8%) with serum HBsAg positive (mean ± SD: 12.7 ± 5.8). Elderly age and the duration of disease time were significantly associated with seroconversion (P < .001). The presence of serum HBsAg seroconversion was significantly associated with hepatosteatosis (OR: 3.06, 95% CI 1.64-5.71, P < .01). Serum HBsAg seroconversion was more frequent in patients with mild HS than patients with moderate-severe HS (P = .04). In multivariate regression analysis, the presence of HS was found to be an independent factor predicting the development of HBsAg seroconversion (OR: 2.07 95% GA:1.07-4.0 P = .03). CONCLUSION: The presence of mild HS in HBeAg negative chronic hepatitis B patients contributes to HBsAg seroconversion. Further studies are required to better understand the relationship between steatosis and HBsAg seroconversion.

Pregabalin: A New Adjunct in Calcineurin Inhibitor Pain Syndrome Treatment.

Tacrolimus and cyclosporin are calcineurin inhibitors (CIs) commonly used in organ transplants. These agents rarely cause a severe, debilitating pain syndrome of especially lower extremities, known as CI pain syndrome (CIPS). Although the pathogenesis is not well understood, neuropathic pain mechanisms have started to be discussed in the recent literature. Here, presenting a 48-year-old male with CIPS who recovered after pregabalin 150 mg twice daily, we aimed to emphasize the importance of this syndrome and offer a new approach for the treatment. This is the first report in the literature where pregabalin is demonstrated to be effective in CIPS.

Assessing hepatic steatosis by magnetic resonance in potential living liver donors.

PURPOSE: To determine the accuracy of magnetic resonance imaging-proton density fat fraction (MRI-PDFF) measurements for detecting liver fat content in potential living liver donors and to compare these results using liver biopsy findings. METHODS: A total of 139 living liver donors (men/women: 83/56) who underwent MRI between January 2017 and September 2021 were included in this analysis retrospectively. The PDFFs were measured using both MR spectroscopy (MRS) and chemical shift-based MRI (CS-MRI) for each donor in a blinded manner. RESULTS: Significant positive correlations were found between liver biopsy and MRS-PDFF and CS-MRI PDFF in terms of hepatic steatosis detection [r = 0.701, 95% confidence interval (CI): 0.604-0.798, r = 0.654, 95% CI: 0.544-0.765, P < 0.001, respectively). A weak level correlation was observed between liver biopsy, MRI methods, and vibration-controlled transient elastography attenuation parameters in 42 available donors. Based on receiver operating characteristic (ROC) analysis, MRS-PDFF and CS-MRI PDFF significantly distinguished >5% of histopathologically detected hepatic steatosis with an area under the ROC curve (AUC) of 0.837 ± 0.036 (P < 0.001, 95% CI: 0.766-0.907) and 0.810 ± 0.036 (P < 0.001, 95% CI: 0.739-0.881), respectively. The negative predictive values (NPVs) of MRS-PDFF and CS-MRI PDFF were 88.3% and 81.3%, respectively. In terms of distinguishing between clinically significant hepatic steatosis (≥10% on histopathology), the AUC of MRS-PDFF and CS-MRI were 0.871 ± 0.034 (P < 0.001 95% CI: 0.804-0.937) and 0.855 ± 0.036 (P < 0.001, 95% CI: 0.784-0.925), respectively. The NPVs of MRS-PDFF and CS-MRI were 99% and 92%, respectively. CONCLUSION: The methods of MRS-PDFF and CS-MRI PDFF provide a non-invasive and accurate approach for assessing hepatic steatosis in potential living liver donor candidates. These MRI PDFF techniques present a promising clinical advantage in the preoperative evaluation of living liver donors by eliminating the requirement for invasive procedures like liver biopsy.

Changing trends in the etiology of liver transplantation in Turkiye: A multicenter study.

Background and Aim: This study aimed to identify the indications for liver transplantation (LT) based on underlying etiology and to characterize the patients who underwent LT. Materials and Methods: We conducted a multicenter cross-sectional observational study across 11 tertiary centers in Turkiye from 2010 to 2020. The study included 5,080 adult patients. Results: The mean age of patients was 50.3±15.2 years, with a predominance of female patients (70%). Chronic viral hepatitis (46%) was the leading etiological factor, with Hepatitis B virus infection at 35%, followed by cryptogenic cirrhosis (24%), Hepatitis C virus infection (8%), and alcohol-related liver disease (ALD) (6%). Post-2015, there was a significant increase in both the number of liver transplants and the proportion of living donor liver transplants (p<0.001). A comparative analysis of patient characteristics before and after 2015 showed a significant decline in viral hepatitis-related LT (p<0.001), whereas fatty liver disease-related LT significantly increased (p<0.001). Conclusion: Chronic viral hepatitis continues to be the primary indication for LT in Turkiye. However, the proportions of non-alcoholic fatty liver disease (NAFLD) and ALD-related LT have seen an upward trend over the years.

Complete Recovery After Immunosuppressive Treatment Change in a Patient With Posttransplant Lymphoproliferative Disorder.

Posttransplant lymphoproliferative diseases are a rare but important cause of morbidity and mortality secondary to immunosuppression after solid-organ or bone marrow transplant. Generally, posttransplant lymphoproliferative diseases develop in the first 2 years after transplant, when immunosuppressive therapy is the most intense. Change or reduction in immunosup - pressive treatment is an option for treatment of posttransplant lymphoproliferative diseases. We evaluated the treatment of a patient with posttransplant lymphoproliferative disease after liver transplant. A 64-year-old man underwent liver transplant from a living donor (the patient's son) in 2011 to treat hepatocellular cancer secondary to chronic hepatitis B. Tacrolimus and mycophenolate mofetil were used for immunosuppression through 9 years after liver transplant. In the abdominal computed tomography performed in response to abdominal pain during follow-up in March 2019, multiple solid lesions were observed. A liver biopsy revealed posttransplant lymphoproliferative disease with diffuse large B-cell lymphoma. Fluorine-18 positron emission tomography/computed tomography imaging of the patient showed no pathology in favor of primary lymphoproliferative disease. Mycophenolate mofetil and tacrolimus treatment was changed to everolimus. In the follow-up dynamic magnetic resonance imaging examination that was performed at 3 months after treatment change, we observed that the lesion at liver segment 6 had regressed to 30 mm and several lesions with similar features were observed in the right lobe of the liver. Additional liver biopsy results were compatible with complete remission. The patient's clinical symptoms had fully regressed at 18 months after the diagnosis of PTLD, at the time of this writing. Ongoing radiological and clinical follow-up has shown complete remission. Change from calcineurin treatment to treatment with an inhibitor of the mechanistic target of rapamycin may be an essential and new option for treatment of posttransplant lymphoproliferative disease after liver transplant.

Rare hepatocellular carcinoma presentation: Hepatoportal sclerosis.

Hepatoportal sclerosis (HPS) is an idiopathic non-cirrhotic portal hypertension (INCPH) characterized by hypersplenism, portal hypertension, and splenomegaly. Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Non-cirrhotic portal hypertension is an extremely rare cause of HCC. A 36-year-old woman was referred to our hospital with esophageal varices. All serologic tests for etiology were negative. Serum ceruloplasmin and serum Ig A-M-G were normal. In the follow-up, two liver lesions were identified on a triple-phase computer. The lesions had arterial enhancement but no washout in the venous phase. In the magnetic resonance imaging examination, differentiation in favor of HCC was considered at one of the lessions. Radiofrequency ablation therapy was first applied to a patient who had no signs of metastasis. Within 2 months, the patient underwent a living donor liver transplant. In explant pathology, well-differentiated HCC and HPS were considered the cause of non-cirrhotic portal hypertension. The patient has been followed without relapse for 3 years. The development of HCC in INCPH patients is still debatable. Despite the presence of liver cell atypia and pleomorphism in nodular regenerative hyperplasia liver specimens, a causal link between HCC and INCPH is yet to be established.

Effect of Pretransplant Sarcopenia on Mortality in Liver Transplant Recipients.

OBJECTIVES: Sarcopenia is an important metabolic disorder associated with end-stage liver disease and is an independent predictor of mortality in liver transplant candidates. We evaluated effects of pretransplant muscle mass, muscle quality, and visceral adipose tissue on mortality after liver transplant. MATERIALS AND METHODS: For 2015-2020, we included 65 liver transplant recipients whose records contained pretransplant liver computed tomography images. We calculated skeletal muscle mass index (muscle tissue area in centimeters squared divided by height in meters squared), visceral-to-subcutaneous fat ratio (visceral adiposity indicator), and intramuscular adipose tissue content ratio (muscle quality indicator). RESULTS: Median age was 55 years (IQR, 45-63 years), and 48 (73.8%) patients were men. During follow-up, 53 (81.5%) study group patients survived; mean survival time was 71.73 ± 3.81 months. The deceased patient group had a statistically higher pretransplant visceral-to-subcutaneous fat ratio than the survival group (P = .046). Survival was 100% for 1 positive indicator, 86.2% for 2 positive indicators, and 70.4% for 3 positive indicators (P = .096). Positive correlation was confirmed between pretransplant skeletal muscle mass index and age (P = .043) and pretransplant body mass index (weight in kilograms divided by height in meters squared) (P < .001). There was a moderate positive correlation between pretransplant intramuscular adipose tissue content ratio and age (R = 0.529, P ≤ .001) and a weak positive correlation with pretransplant body mass index (R = 0.361, P = .003). Furthermore, pretransplant visceral- tosubcutaneous fat ratio showed a weak positive correlation with age (R = 0.306, P = .013) and a weak negative correlation with the Model for End-Stage Liver Disease score (R = -0.301, P = .016). CONCLUSIONS: Pretransplant sarcopenia is an important indicator to predict mortality and morbidity in posttransplant follow-up. Visceral-to-subcutaneous fat ratio is an important parameter to evaluate sarcopenia in liver transplant patients.

Multidrug-Resistant Infections After Liver Transplantation, Etiology and Risk Factors: A Single-Center Experience.

OBJECTIVES: Patients undergoing liver transplant are at an increased risk of morbidity and mortality due to the development of infections. We aimed to evaluate the risk factors affecting the incidence of infectious diseases after liver transplant and to present the epidemiological data. MATERIALS AND METHODS: We investigated patients aged ≥18 years who underwent liver transplant between 2012 and 2020 at our center. We collected infections, causative microorganisms, and antibacterial resistance patterns seen during the first 6 months posttransplant. Risk factors affecting the development of infectious diseases were also analyzed and evaluated. RESULTS: Of 112 patients included in our study, 76 (67.9%) were men, and the median age was 50 years (range, 20-66 years). Within month 1 and month 6 after transplant, at least 1 episode of infection occurred in 67 (59.8%) and 80 (71.4%) patients, respectively. Bacterial infections were the most common type (n = 78, 95.1%), followed by fungal (n = 2, 2.4%) and viral (n = 2, 2.4%) infections. The rate of multidrug resistance in bacterial infections was high (n = 38, 52.7%) and was also a risk factor for mortality in the first 6 months after transplant (P < .001). Pretransplant values of international normalized ratio, creatinine, bilirubin, and posttransplant intensive care unit stay, as well as the presence of encephalopathy, were shown to increase the risk of infection after transplant. CONCLUSIONS: Multidrug-resistant bacterial infections are a significant risk factor for mortality in liver transplant patients. Many risk factors that contribute to the development of infections aftertransplant have been included in prognostic scoring systems of liver failure. Consequently, the severity of end-stage liver failure is directly related to the risk of posttransplant infections.

Management of Biliary Complications in Liver Transplant Recipients with Duct-To-Duct Anastomosis: A Single-Center Experience.

BACKGROUND: The aims of this study were to investigate biliary complications in liver transplant recipients with choledochocholedocho stomy anastomosis, to identify the risk factors for the development of such complications, and to evaluate the success of endoscopic approaches in liver transplant recipients. METHODS: Between January 2013 and May 2021, a total of 238 patients with liver diseases underwent liver transplantation: 174 recipients undergoing choledochocholedochostomy anastomosis were included in the analysis. RESULTS: Their median age was 54.0 years. The median posttransplant follow-up period was 29 months. Hepatitis B virus infection (33%) was the most common indication for liver transplantation. Most patients (87%) received living donor liver transplantation. The overall prevalence of posttransplant biliary complications was 31%. Anastomotic biliary strictures were the most common biliary complications (72%), followed by biliary leakage (13%). The median time between endoscopic retrograde cholangiography and liver transplantation was 4 months, with a mean of 3 ± 1.6 sessions. Endoscopic retrograde cholangiography-guided drainage and balloon dilation with or without stent placement was the most common treatment modalities for recipients with biliary strictures. The overall success rate of endoscopic treatment modalities was 83.3%, with 65% of the recipients exhibiting complete biochemical and endoscopic responses. The response did not differ significantly between living donor liver transplantation and cadaveric donor liver transplant recipients (P > .05). Three recipients required revision surgery for biliary complication repair. Six patients died due to biliary sepsis. CONCLUSION: Biliary stricture and leakages were the most common biliary complications after liver transplantation. Endoscopic treatment was successful in most recipients.

The efficacy and tolerability of glecaprevir/pibrentasvir treatment in a real-world chronic hepatitis C patients cohort.

Background and Aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC). Materials and Methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study. Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed. Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC.

TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.

Factors associated with the development of extrahepatic malignancy in patients with nonalcoholic fatty liver disease: a single-center longitudinal study.

BACKGROUND AND AIMS: The aim of the present study was to determine incident cases of extrahepatic malignancy in patients with nonalcoholic fatty liver disease (NAFLD) and to identify whether the factors are associated with cancer development. METHODS: Between 15 January 2001 and 14 March 2021, a total of 1365 patients had been diagnosed with NAFLD were enrolled in the study. RESULTS: The median follow-up period was 59.5 months. The mean age was 50.9 ± 10.9 years. The female gender was predominant (57%). During the follow-up period, 62 extrahepatic malignancies and 11 hepatocellular carcinomas were identified. Of all extrahepatic malignancies, 51 were solid organ malignancies and 11 were hematological malignancies. Female breast cancer was the most frequent (25.8%), followed by thyroid cancer (19.4%), lymphoma (12.9%), and lung cancer (9.7%). In univariate and multivariable analyses, after adjusting for age and sex, the presence of diabetes and high initial baseline gamma glutamyl transpeptidase (GGT) levels were significantly associated with the development of extrahepatic malignancies [hazard ratio (HR) = 1.82, 95% confidence interval (CI): 1.04-3.20, P = 0.036] and HR = 1.96, 95% CI: 1.14-3.38, P = 0.015, respectively). In 424 biopsy-proven NAFLD patients, the development of extrahepatic cancer was significantly associated with the severity of hepatic fibrosis (HR = 3.31, 95% CI: 1.36-8.07; P = 0.008). CONCLUSION: Extrahepatic malignancies are frequently seen in patients with NAFLD. Diabetes mellitus, high baseline GGT levels, and significant hepatic fibrosis are associated with the development of extrahepatic cancer in patients with NAFLD.

The prevalence of metabolic-associated fatty liver disease in the Turkish population: A multicenter study.

Background and Aim: The objective of the present study was to investigate the prevalence of metabolic-associated fatty liver disease (MAFLD) in patients with dyspepsia. Materials and Methods: A total of 909 consecutive patients who presented with dyspepsia at 8 tertiary care centers in Turkey between March 2019 and December 2019 were included. Results: The median age was 47 years. Among them, 30.3% of the patients were obese, 18.8% had type 2 diabetes mellitus (T2DM), 35.1% had metabolic syndrome, 84.8% had dyslipidemia, and 23.9% had hypertension. The prevalence of MAFLD was 45.5%. Among the patients with MAFLD, the prevalence of obesity, T2DM, metabolic syndrome, dyslipidemia, and hypertension was 43.3%, 24.9%, 52.5%, 92.3%, and 31.9%, respectively. MAFLD was significantly associated with all of the metabolic comorbidities (p<0.001). The median Fibrosis-4 Index score of the MAFLD patients was 0.88 (range: 0.1-9.5). Of note, 53 patients with hepatic steatosis did not meet the MAFLD criteria. Conclusion: The results of the present study indicated that there was a significantly high prevalence of MAFLD observed in daily clinical practice in Turkey. Early diagnosis and prevention efforts should be implemented to reduce disease progression, and a region-based strategy is recommended.

Recommendations for Hepatitis B Immunoglobulin and Antiviral Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

Prevalence and characteristics of bone disease in cirrhotic patients.

Background and Aim: Chronic liver disease is a risk factor for osteoporosis, osteopenia and bone fractures. In this study, prevalence and risk factors of osteoporosis and vitamin D deficiency and also their effects on survival were investigated in 218 patients with chronic liver disease. Materials and Methods: Prevalence of osteoporosis and vitamin D levels was calculated. Risk factors for osteoporosis (gender, age, body mass index, etiology), serum bilirubin, albumin, 25-hydroxy (OH) vitamin D, parathyroid hormone levels, bone mineral density (BMD) with DEXA, bone formation (osteocalcin) and bone resorption (type 1 collagen) levels, Model for End-Stage Liver Disease (MELD) Na and Child-Pugh (CP) score were recorded. The effects of vitamin D levels and BMD on survival were evaluated. Results: One hundred forty-seven (67.4%) patients were female (mean age, 50.4±11.7). Patients were Child A by 40.8%, Child B by 47.1%, and Child C by 12.1%. Mean MELD Na score was 8.4±2.8. Data of the BMD were established in 218 patients and 25-OH D levels in 122 patients. Mean serum 25-OH D level was 14.26±9.44 ng/mL. Osteoporosis was identified in 42 (19.3%) and osteopenia in 115 (52.8%) patients, according to BMD. Osteocalcin levels and collagen type 1 levels were high in 25.6% and 12.5% of patients, respectively. No statistically difference was found, including gender (p=0.69), age (p=0.38), etiology (p=0.16), BMI (p=0.32), CP score (p=0.42), MELD (0.14), albumin (p=0.11), total bilirubin (p=0.99), Ca (0.67), PTH (0.88), osteocalcin (0.92), collagen type 1(p=0.25) between osteoporotic and non-osteoporotic patients. Patients were followed-up for a median of 30.07±11.83 months after BMD measurement. Fifty-four (24.8%) patients died during the follow-up period, none of them are related to bone fracture. There was no statistically difference on survival between osteoporosis group (32.2±2.3 months) and non-osteoporosis group (37.2±1.7 months; p=0.26) or when patients with 25-OH D3 ≤10 ng/mL were compared to patients with 25-OH D3 >20 ng/mL (34.4±2.0 months vs. 39.1±1.6 months, p=0.308). Conclusion: In conclusion, the prevalence of bone disease was found to be higher in cirrhotic patients. Although osteoporosis and vitamin D deficiency were found to decrease survival, this effect was not statistically significant. We suggest designing multi-institutional and/or multinational studies with larger and more heterogenous patient groups would enable better testing of this phenomenon.

Dipeptidyl peptidase IV (DDP IV) in NASH patients.

OBJECTIVE(S): Non-alcoholic steatohepatitis (NASH) is a chronic liver disease with unknown etiology. The insulin resistance, immune mechanisms and oxidative stress are the main factors in its pathogenesis. Dipeptidyl peptidase IV (DPPIV) or CD26 is a protein with endocrine and immune functions. This study aimed to elicudate the changes related to DPPIV in NASH patients. METHODS: Serum and urinary DPPIV activities were measured in 31 NASH patients and 17 healthy controls. The liver biopsies of 29 patients were immunolabeled for CD26. RESULTS: The mean age of patients were 46 +/- 11 years and 14 (45%) of them were female. The serum DPPIV activity was higher in patients (57.3 +/- 7.8 U/L) than controls (43.6 +/- 10.6 U/L) (p < 0.0001), and correlated with the histopathological grade (p = 0.038, r = 0.373) and hepatosteatosis (p = 0.018, r = 0.423) but not with stage (p = 0.286), class (p = 0.286) or CD26 staining (p = 0.743). The urinary DPPIV activity was similar in patients (1.52 +/- 0.94 U/mmol creatinine) and controls (1.37 +/- 0.68 U/mmol creatinine) (p = 0.861). Three acinar zones of liver had equal CD26 expression (p = 0.076). The intensity of CD26 immunostaining was correlated with histopathological grade (p = 0.001) and hepatosteatosis (p = 0.003) but no correlation with stage or class could be detected (p = 0.610 and 0.956, respectively). In CONCLUSIONS: The serum DPPIV activity and the staining intensity of CD26 in liver are correlated with histopathologic grade of NASH and hepatosteatosis. DPPIV can be proposed as a novel candidate with several potential functions in NASH pathogenesis.