Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial.

BACKGROUND: Olipudase alfa is a recombinant human acid sphingomyelinase enzyme replacement therapy for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). The ASCEND randomized placebo-controlled trial in adults with ASMD demonstrated reductions in sphingomyelin storage, organomegaly, interstitial lung disease and impaired diffusion capacity of the lung (DLCO), during the first year of olipudase alfa treatment. In an ongoing open-label extension of the ASCEND trial, individuals in the placebo group crossed over to olipudase alfa, and those in the olipudase alfa group continued treatment. RESULTS: Thirty-five of 36 participants continued in the extension trial, and 33 completed year 2. Change-from-baseline results are presented as least-square mean percent change ± SEM. Improvements in the cross-over group after 1 year of treatment paralleled those of the olipudase alfa group from the primary analysis, while clinical improvement continued for those receiving olipudase alfa for 2 years. In the cross-over group, percent-predicted DLCO increased by 28.0 ± 6.2%, spleen volume decreased by 36.0 ± 3.0% and liver volume decreased by 30.7 ± 2.5%. For those with 2 years of olipudase alfa treatment, the percent predicted DLCO increased by 28.5 ± 6.2%, spleen volume decreased by 47.0 ± 2.7%, and liver volume decreased by 33.4 ± 2.2%. Lipid profiles and elevated liver transaminase levels improved or normalized by 1 year and remained stable through 2 years of treatment. Overall, 99% of treatment-emergent adverse events were mild or moderate, with one treatment-related serious adverse event (extrasystoles; previously documented cardiomyopathy). No individual discontinued due to an adverse event. CONCLUSION: Treatment with olipudase alfa is well tolerated and reduces manifestations of chronic ASMD with sustained efficacy. Trial registration NCT02004691 registered 9 December 2013, https://clinicaltrials.gov/ct2/show/NCT02004691.

In a Real-Life Setting, Direct-Acting Antivirals to People Who Inject Drugs with Chronic Hepatitis C in Turkey.

BACKGROUND: People who inject drugs (PWID) should be treated in order to eliminate hepatitis C virus in the world. The aim of this study was to compare direct-acting antivirals treatment of hepatitis C virus for PWID and non-PWID in a real-life setting. METHODS: We performed a prospective, non-randomized, observational multicenter cohort study in 37 centers. All patients treated with direct-acting antivirals between April 1, 2017, and February 28, 2019, were included. In total, 2713 patients were included in the study among which 250 were PWID and 2463 were non-PWID. Besides patient characteristics, treatment response, follow-up, and side effects of treatment were also analyzed. RESULTS: Genotype 1a and 3 were more prevalent in PWID-infected patients (20.4% vs 9.9% and 46.8% vs 5.3%). The number of naïve patients was higher in PWID (90.7% vs 60.0%), while the number of patients with cirrhosis was higher in non-PWID (14.1% vs 3.7%). The loss of follow-up was higher in PWID (29.6% vs 13.6%). There was no difference in the sustained virologic response at 12 weeks after treatment (98.3% vs 98.4%), but the end of treatment response was lower in PWID (96.2% vs 99.0%). In addition, the rate of treatment completion was lower in PWID (74% vs 94.4%). CONCLUSION: Direct-acting antivirals were safe and effective in PWID. Primary measures should be taken to prevent the loss of follow-up and poor adherence in PWID patients in order to achieve World Health Organization's objective of eliminating viral hepatitis.

Efficacy and Safety of Direct-Acting Antivirals in Elderly Patients with Chronic Hepatitis C: A Nationwide Real-Life, Observational, Multicenter Study from Turkey.

BACKGROUND: The number and proportion of elderly patients living with chronic hepatitis C are expected to increase in the coming years. We aimed to compare the real-world efficacy and safety of direct-acting antiviral treatment in elderly and younger Turkish adults infected with chronic hepatitis C. METHODS: In this multicenter prospective study, 2629 eligible chronic hepatitis C patients treated with direct-acting antivirals between April 2017 and December 2019 from 37 Turkish referral centers were divided into 2 age groups: elderly (≥65 years) and younger adults (<65 years) and their safety was compared between 2 groups in evaluable population. Then, by matching the 2 age groups for demographics and pretreatment risk factors for a non-sustained virological response, a total of 1516 patients (758 in each group) and 1244 patients (622 in each group) from the modified evaluable population and per-protocol population were included in the efficacy analysis and the efficacy was compared between age groups. RESULTS: The sustained virological response in the chronic hepatitis C patients was not affected by the age and the presence of cirrhosis both in the modified evaluable population and per-protocol population (P = .879, P = .508 for modified evaluable population and P = .058, P = .788 for per-protocol population, respectively). The results of the per-protocol analysis revealed that male gender, patients who had a prior history of hepatocellular carcinoma, patients infected with non-genotype 1 hepatitis C virus, and patients treated with sofosbuvir+ribavirin had a significantly lower sustained virological response 12 rates (P < .001, P = .047, P = .013, and P = .025, respectively). CONCLUSION: Direct-acting antivirals can be safely used to treat Turkish elderly chronic hepatitis C patients with similar favorable efficacy and safety as that in younger adults.

Vitamin D deficiency in patients with chronic hepatitis D viral infection.

AIM OF THE STUDY: Vitamin D deficiency is known to be associated with disease severity, unresponsiveness to treatment, and morbidity among patients with chronic viral hepatitis B and C, autoimmune hepatitis, and alcoholic hepatitis. This study aims to research vitamin D levels in patients suffering from cirrhotic and non-cirrhotic phases of hepatitis D. MATERIAL AND METHODS: 170 individuals in total were included in the study in the form of two groups: the first group of 100 patients with chronic hepatitis D (CHD), 30 of whom had cirrhosis, and the second control group of 70 individuals with similar characteristics to those of the first group in terms of age, type, and seasonal sampling. Levels of 25-hydroxy vitamin D [25(OH)D] were measured in the serum collected from patients and the control group. RESULTS: The lowest 25(OH)D levels were identified in patients with cirrhotic CHD. When these levels were compared with those of the control group, they were found to be significant (15.30 ±6.92 and 18.90 ±8.30 ng/ml, respectively, p = 0.04). 25(OH)D deficiency (< 10 ng/ml) was detected at significantly higher rates in patients with both cirrhotic and non-cirrhotic CHD compared to the healthy controls (30%, 25%, and 8.5%, respectively, p = 0.01). A significant correlation was established between 25(OH)D levels and bilirubin in patients with CHD (r = 0.252, p = 0.012). Multivariate analysis showed that chronic hepatitis D (odds ratio [OR] = 3.608, 95% confidence interval [CI]: 1.31-9.89, p = 0.013) and age (OR = 1.04, 95% CI: 1.00-1.08, p = 0.033) were associated with vitamin D deficiency. CONCLUSIONS: Frequency of 25(OH)D vitamin deficiency is higher in patients with CHD. The identification of vitamin D levels and the replacement of any deficiency may create a positive effect on disease progression, morbidity, and mortality levels.

Are There Differences in the Management of Acute Pancreatitis Cases Due to Severe Hypertriglyceridemia in Pregnant Women?

BACKGROUND The aim of this study was to determine the prognosis of severe disease and treatment approaches of both normal and pregnant, especially in patients with severe pancreatitis due to hypertriglyceridemia. MATERIAL AND METHODS We included 30 patients (20 females and 10 males) in this study whose follow-ups and treatments were performed after a diagnosis of hypertriglyceridemia-induced acute pancreatitis between January 2011 and May 2017. Patient personal information, such as age, sex, pre-treatment and post-treatment triglyceride levels, receipt of anti-hyperlipidemic treatments or plasmapheresis, and family history, were collected from hospital records and patient files. Patients with severe pancreatitis history, score, and prognosis were included to increase the value of our study. Mild and moderate cases were excluded. RESULTS The mean age of the patients was 35±6 years. Twenty-four patients (80%) received an anti-hyperlipidemic treatment before their pancreatitis attacks. Plasmapheresis was performed on 8 patients before their pancreatitis attacks. Eighteen patients (60%) had a family history suggesting familial hypertriglyceridemia. Twelve patients (40%) were pregnant. CONCLUSIONS The treatment of hypertriglyceridemia-induced acute pancreatitis was mostly confined to supportive, palliative treatments. However, plasmapheresis is a possible treatment option and should be used in the early stages of this disease. The response to medical treatment and support treatment was better in pregnant patients than in the other patient group, and pregnant patients did not require plasmapheresis.

Acute pancreatitis after coronary artery bypass surgery treated by plasmapheresis.

Acute pancreatitis (AP) is a common disorder and an important cause of morbidity and mortality. There are different causes of AP, including gallstones and excessive alcohol consumption. AP after coronary artery bypass grafting (CABG) surgery is seen less frequently but it is associated with a high mortality rate due to its atypical and misleading symptoms. Supportive treatment, pain management, and treatment of complications are used in the treatment of AP. The treatment of hypertriglyceridemia-induced pancreatitis is plasmapheresis, which is an extracorporeal separation of blood components to assist in the removal of inflammatory mediators. Here we present the case of a 60-year-old male patient who developed severe AP (Ranson Score: 6) without hypertriglyceridemia after CABG. The patient received supportive treatment, but the response to conventional therapy was not predictable. Thus, plasmapheresis was started, and the patient was treated with plasmapheresis successfully. The use of plasmapheresis in patients with this condition is a new treatment modality as far as we know. This case illustrates the efficient and safe use of the plasmapheresis treatment modality in a patient with AP without hypertriglyceridemia.

Prophylactic Administration of Silybin Ameliorates L-Arginine-Induced Acute Pancreatitis.

BACKGROUND Oxidative stress have been shown to play a role in the pathogenesis of acute pancreatitis. The aim of this study was to investigate the potential effect of silybin, a potent antioxidant, on L-arginine-induced acute pancreatitis in an experimental rat model. MATERIAL AND METHODS Forty female Wistar Albino rats were divided into 5 groups as follows: Group 1 (C): control group (n=8), Group 2 (SL): silybin group (n=8), Group 3 (LA): acute pancreatitis group (n=8), Group 4 (SLLA): prophylaxis group (n=8), and Group 5 (LASL): treatment group (n=8). Group C (control) received 2 intraperitoneal (i.p.) injections of physiological saline at an interval of 1 h. Group SL received only a single i.p. injection of silybin. The SLLA group received a single i.p. injection of silybin before the induction of acute pancreatitis with L-arginine, whereas the LASL group received the same injection after the induction of acute pancreatitis with L-arginine. Pancreatic tissues were histopathologically examined. Levels of amylase and oxidative stress markers (total oxidant status and total anti-oxidant status) were determined in the blood samples. Oxidative stress index was calculated. RESULTS In comparison to the LA, the prophylaxis and treatment groups showed significant improvements in serum oxidative stress parameters (p=0.001 and p=0.005, respectively). Histopathological analysis showed that the treatment group had significant improvements in edema scores only (p=0.006), whereas the prophylaxis group had the same improvements in inflammation and necrosis scores as well as in total scores (p=0.004, 0.006, and 0.004, respectively). CONCLUSIONS When used for prophylactic rather than therapeutic purposes, silybin ameliorates serum oxidative stress parameters and improves histopathological results via its antioxidant and anti-inflammatory properties.

Changes in HIV demographic patterns in a low prevalence population: no evidence of a shift towards men who have sex with men.

OBJECTIVES: This study aimed to examine the changes in HIV demographics over time in an exceptionally low prevalence population, with particular emphasis on men who have sex with men (MSM). METHODS: A total of 1292 newly diagnosed HIV-positive patients registered in the ACTHIV-IST Study Group database between 2000 and 2014 were included. The changes occurring over time in the characteristics of patients at the time of initial admission were examined retrospectively. RESULTS: A gradual increase in the total number of newly diagnosed patients was evident during the study period; however, it was not possible to show an increase in the proportion of MSM within the study population (p=0.63). There was a male predominance throughout the study (85% vs. 15%), with further increases in the proportion of males in recent years. The mean age was lower at the end of the study (p<0.05) and there was an increase in the number of unmarried patients (p<0.05). CONCLUSIONS: Sexual preference patterns of HIV patients in extremely low prevalence populations may be different, possibly due to an early phase of the epidemic. Nevertheless, MSM still represent a target subgroup for interventions, since they account for a substantial proportion of cases and a resurgent epidemic may be expected among this group in later phases of the epidemic.

Impaired Gallbladder Motility and Increased Gallbladder Wall Thickness in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Along with the increase in the incidence of NAFLD and associated obesity, an increase in gallbladder disease (GD) has been noted. This has led to the identification of a new disease entity called fatty GD. There is a gap in the literature on the dynamics of gallbladder function in patients with NAFLD. METHODS: An observational case-control study, a total of 50 patients with biopsy proven NAFLD without gallbladder stone/sludge and 38 healthy comparison subjects were enrolled. Fasting, postprandial gallbladder volumes (PGV), gallbladder ejection fraction (GEF), and fasting gallbladder wall thickness (FGWT) were measured by real-time 2-dimensional ultrasonography. RESULTS: Fasting gallbladder wall thickness, fasting gallbladder volumes and PGV were significantly higher in patients with NAFLD than control subjects (P < 0.001, P = 0.006, and P < 0.001, respectively). Gallbladder ejection fraction was significantly lower in the NAFLD group than the controls (P = 0.008). The presence of NAFLD was an independent predictor for GEF, PGV, and FGWT. Also, steatosis grade was an independent predictor for GEF, and GEF was significantly lower in the nonalcoholic steatohepatitis (NASH) subgroup than the controls. CONCLUSIONS: Gallbladder dysfunction and increase in gallbladder wall thickness exists in asymptomatic (without stone/sludge and related symptoms) patients with NAFLD and are useful in identifying fatty GD. Measurement of these variables in NAFLD patients may be useful in identifying those at higher risk for GD.

Increased serum soluble lectin-like oxidized low-density lipoprotein receptor-1 levels in patients with biopsy-proven nonalcoholic fatty liver disease.

AIM: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Fifty-three consecutive, biopsy-proven NAFLD patients (31 males and 22 females, mean age 42.5 ± 9.6 years) and 26 age- and gender-matched, healthy controls (14 males and 12 females, mean age 39 ± 10.7 years) were included. The patients with NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy. The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses. The histological evaluation was conducted according to the NAFLD activity scoring system recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. The serum LOX-1 levels were measured using an ELISA kit (Life Science Inc. USCN. Wuhan, Catalog No. E1859Hu) in both patients and healthy controls. A receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis (NASH) and healthy controls. A P-value < 0.05 was considered statistically significant. RESULTS: NAFLD and healthy control groups were similar in terms of age and sex. NAFLD patients consisted of 8 patients with simple steatosis (15%), 27 with borderline NASH (51%) and 18 with definitive NASH (34%). Metabolic syndrome was found in 62.2% of the patients with NAFLD. The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/mL compared to 4.08 ± 4.32 ng/mL in healthy controls (P = 0.001). The LOX-1 levels were significantly different between controls, simple steatosis and NASH (borderline+definite) cases (4.08 ± 4.32 ng/mL, 6.1 ± 6.16 ng/mL, 8.92 ± 6.45 ng/mL, respectively, P = 0.004). When the cut-off value for the serum LOX-1 level was set at 5.35 ng/mL, and a ROC curve analysis was performed to distinguish between steatohepatitis patients and controls; the sensitivity and specificity of the serum LOX-1 level were 69.8% and 69.2%, respectively. CONCLUSION: The serum LOX-1 levels were significantly higher in NAFLD patients than in healthy controls. Additionally, the serum LOX-1 levels could differentiate between steatohepatitis patients and healthy controls.

Comparison of a 4-Day versus 2-Day Low Fiber Diet Regimen in Barium Tagging CT Colonography in Incomplete Colonoscopy Patients.

Our aim was to compare the amount of residual feces, residual fluid, the tagging quality, and patient compliance using 4-day versus 2-day low fiber diet regimen in barium tagging CT colonography in incomplete colonoscopy patients. Methods. A total of 101 patients who underwent CT colonography were assigned to 2-day diet group (n = 56) and 4-day diet group (n = 45). Fecal tagging was achieved with barium sulphate while bisacodyl and sennoside B were used for bowel preparation. Residual solid stool was divided into two groups measuring <6 mm and ≥6 mm. We graded the residual fluid, tagging quality for solid stool, and fluid per bowel segment. We performed a questionnaire to assess patient compliance. Results. 604 bowel segments were evaluated. There was no significant difference between 2-day and 4-day diet groups with respect to residual solid stool, residual fluid, tagging quality for stool, and fluid observed in fecal tag CT colonography (P > 0.05). The prevalence of moderate discomfort was significantly higher in 4-day group (P < 0.001). Conclusion. Our study shows that 2-day limited bowel preparation regimen for fecal tag CT colonography is a safe and reasonable technique to evaluate the entire colon, particularly in incomplete conventional colonoscopy patients.

A potential treatment of non-alcoholic fatty liver disease with SIRT1 activators.

Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its anti-inflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there is no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed.

HLA DQB1 alleles are related with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is a complex disease and inflammation is a crucial component in the disease pathogenesis. Recent genome wide association studies in hepatology area highlighted significant relations with human leukocyte antigen (HLA) DQ region and certain liver diseases. The previous animal models also emphasized the involvement of adaptive immune system in the liver damage pathways. To investigate possible polymorphisms in the HLA region that can contribute to the immune response affecting the NAFLD, we enrolled 93 consecutive biopsy proven NAFLD patients and a control group consisted of 101 healthy people and genotyped HLA DQB1 alleles at high resolution by sequence specific primers-polymerase chain reaction. The mean NAFLD activity score (NAS) was 5.2 ± 1.2, fibrosis score was 0.9 ± 0.9, ALT was 77 ± 47.4 U/L, AST was 49.4 ± 26.3 U/L. Among 13 HLA DQB1 alleles analyzed in this study, DQB1*06:04 was observed significantly at a more frequent rate among the NAFLD patients compared to that of healthy controls (12.9 vs. 2 % χ(2) = 8.6, P = 0.003, P c = 0.039, OR: 7.3 95 % CI 1.6-33.7). In addition, the frequency of DQB1*03:02 was significantly higher in the healthy control group than the NAFLD patients (24.8 vs. 7.5 %, χ(2) = 10.4, P = 0.001, P c = 0.013, OR: 0.2, 95 % CI 0.1-0.6). NAFLD patients were grouped according to their fibrosis score and NAS. The distribution of DQB1 alleles over stratified NAFLD patients did not reveal any statistically significant relation. Taken together, immune repertoire of individuals may have an effect on NAFLD pathogenesis and therefore, in NAFLD, adaptive immunity pathways should be investigated.

First-line monotherapies of tenofovir and entecavir have comparable efficacies in hepatitis B treatment.

BACKGROUND: Hepatitis B virus (HBV) infection is a health problem worldwide. Current treatment options for chronic hepatitis B (CHB) are nucleoside or nucleotide analogues and pegylated interferons. Tenofovir and entecavir are much more commonly used as they have better efficacy, tolerability, and high genetic barriers to resistance. AIM: The aim of this study was to assess the efficacies of tenofovir and entecavir in previously untreated CHB patients in a treatment cohort. PATIENTS AND METHODS: We included CHB patients in a cohort including previously untreated HBeAg-positive and HBeAg-negative patients from 10 centers in Istanbul, Turkey. The patients were compared in terms of baseline characteristics, decrease in alanine transaminase (ALT), decrease in HBV-DNA to undetectable levels, HBeAg loss and anti-HBe development (among baseline HBeAg-positive patients), interventions to therapy because of lack of efficacy, side effects, severe side effects, and side effects that required change in treatment. RESULTS: The study included 121 patients who were administered tenofovir and 130 patients who were administered entecavir. The majority of patients were men, with mild to moderate histology in both treatment groups. The mean duration of follow-up was 18 and 20 months for tenofovir and entecavir, respectively. Patients receiving both drugs showed comparable rates of HBeAg loss, rates of undetectable HBV-DNA levels, rates of ALT normalization, ALT decrease, and decrease in HBV-DNA. Both drugs were well tolerated. CONCLUSION: This study shows that although the baseline characteristics did not match, tenofovir and entecavir sustained comparable virological efficacies. More patients discontinued entecavir during follow-up. Both drugs provided effective viral control, with few side effects.

Gallstone disease does not predict liver histology in nonalcoholic fatty liver disease.

BACKGROUND/AIMS: We sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score. METHODS: We included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy. RESULTS: Fifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84). CONCLUSIONS: The presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.

Not only type 2 diabetes but also prediabetes is associated with portal inflammation and fibrosis in patients with non-alcoholic fatty liver disease.

AIMS: Growing evidence suggests that not only type 2 diabetes (T2D) but also prediabetes (PD) is common in patients with non-alcoholic fatty liver disease (NAFLD). However, few data exist on how PD impacts the histological characteristics of NAFLD patients. In this exploratory study, we sought to investigate the associations of PD and T2D with the severity of the histological features in patients with NAFLD. METHODS: The population consisted of 280 patients with biopsy-proven NAFLD. The associations of PD and T2D with the severity of histological features of NAFLD were analyzed using multiple logistic (or ordinal logistic) regression models after adjustment for confounding factors. RESULTS: PD and T2D was noted in 102 (36.4%) and 92 (32.8%) of patients, respectively. Of the 92 patients with T2D, ten (10.9%) were diagnosed de novo after the OGTT. PD and T2D were significantly associated with more severe portal inflammation (P<0.01); the adjusted odds ratios (ORs) of PD and T2D for having a higher grade of portal inflammation were 1.8 [95% CI, 1.1, 3.2] and 2.6 [95% CI, 1.3, 5.8]), respectively. A similar relationship was observed for liver fibrosis (P<0.001); specifically, the adjusted ORs of PD and T2D for having a higher grade of hepatic fibrosis were 2.4 [95% CI, 1.3, 3.7] and 3.8 [95% CI, 1.9, 6.1]), respectively. CONCLUSION: Not only T2D but also PD is independently associated with portal inflammation and fibrosis in NAFLD patients. PD may be useful as a clinical indicator of patients who are likely to have already more severe histological findings.