The relationship between resistin and ghrelin levels with fibrosis in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. It is generally accepted that insulin resistance is a pathophysiological factor in the development of NAFLD. In the present study, the aim was to determine the relationship between resistin and ghrelin levels, which were found to be closely related to insulin resistance and fibrosis scores in NAFLD. MATERIALS AND METHODS: A total of 40 (21 male, 19 female) NAFLD patients whose diagnosis was confirmed with biopsy and 40 (18 male, 22 female) healthy controls were included in the study. RESULTS: In the comparison of resistin and ghrelin levels, only resistin values were found to be significantly higher in NAFLD group while there was no significant difference in ghrelin values (respectively P < 0.05; P = 0.078). In according to the fibrosis groups there was no difference about fasting plasma glucose, insulin values, Homeostatic Measurement Assessment-Insulin Resistance measurements and also resistin and ghrelin levels. CONCLUSION: It has been understood that insulin resistance plays an important part in NAFLD. Larger studies are required that investigate the gene expression of hormones influencing insulin resistance, particularly resistin and ghrelin in order to determine their role in NAFLD.

Improvement of Work Productivity and Quality of Life with Anti-Tumor Necrosis Factor Treatment Used in Crohn's Disease in Routine Clinical Practice in Turkey.

BACKGROUND: Patients with Crohn's disease experience major deterioration in work productivity and quality of life. We aimed to provide the long-term effects of anti-tumor necrosis factor agents on work productivity and activity impairment and quality of life in patients with Crohn's disease using the Inflammatory Bowel Disease Questionnaire and the Short-Form Health Survey-36. METHODS: Patients with Crohn's disease and initiated an anti-tumor necrosis factor treatment were included and followed up for 12 months in this observational study. RESULTS: A total of 106 patients were included in this study, and 64.2% of the patients were males. Mean [± standard deviation] age was 36.8 [± 10.9] years. At baseline, mostly perianal fistulas [65.7%] were observed [n = 23]. Intestinal stenosis was detected in 34.9% of the patients [n = 37], and most of the stenosis was located in the ileum [70.6%] followed by the colon [20.6%]. Extraintestinal symp- toms were observed in 24 patients [22.6%]. Most frequent extraintestinal symptom was arthritis with 71.4% [n = 15]. Mean time from first symptom to initiation of anti-tumor necrosis factor treatment was 6.3 [± 5.0] years. Improvements in work productivity and activ- ity impairment scores throughout 12 months were -24.1% [P = .003] for work time missed, -18.0% [P = .006] for impairment at work, -8.5% [P = .160] for overall work impairment, and -17.0% [P < .001] for daily activity impairment. Similarly, significant improvements [P < .001] were detected in all components of the Inflammatory Bowel Disease Questionnaire when compared to baseline. Statistically sig- nificant improvements [P < .05] were detected for all components of Short-Form Health Survey-36 except for mental health [P = .095]. CONCLUSION: Our study indicates the significant improvement in work productivity and activity impairment and quality of life of patients with Crohn's disease who receive long-term anti-tumor necrosis factor treatment.

[Entecavir resistance in entecavir naive lamivudine treated chronic hepatitis B patients]. / Lamivudin tedavisi uygulanmis ve entekavir naif kronik hepatit B'li hastalarda entekavir ilaç direnci.

Approved hepatitis B virus (HBV) therapies include interferon-alpha and nucleos(t)ide analogues. Lamivudine (LVD) is a nucleoside analogue and following long term LVD therapy, resistance emerges in a significant number of patients. Entecavir (ETV) is a novel deoxyguanosine analogue with potent activity against HBV in chronically infected patients. ETV is highly efficacious in treating nucleoside naive and LVD refractory patients. The aim of the present study was to determine the prevalence of ETV drug resistance in LVD treated/ETV naive (study group) and in untreated naive (control group) patients with chronic B hepatitis. DNA sequencing was applied to 80.-250. amino acid positions on HBV polymerase gene to investigate the ETV resistance and also HBV genotype and HBV polymerase gene overlapped S-gene segment mutations. Primary LVD and ETV drug resistance were detected in 37 (42.6%) and 4 (4.5%) of 87 patients, respectively in the study group. rtT184A, rtT1841 and rtT1845 mutations were found related to primary ETV resistance. In these patients also rtL180M and rtQ215S mutations were detected as compensatory mutations and YVDD and YIDD variants were observed at the 204. amino acid codon position. None of the patients in the control group had LVD or ETV resistance. Two of the patients in the study group had mutations at the positions sG145R and sC137G in the overlapped S-gene segment. However, mutations at the overlapped S-gene segment were not affected by the mutations associated with ETV resistance. All of the patients in the study and the control group were of HBV genotype D. The results obtained from this study may guide the treatment choices with ETV in chronic HBV patients treated with LVD and developed resistance to LVD.

Differential diagnosis of Crohn's disease using antibodies to glycoprotein 2 and Saccharomyces cerevisiae.

BACKGROUND/AIMS: Glycoprotein 2 (GP2), the major autoantigen of Crohn's disease (CD)-specific pancreatic autoantibodies, is reportedly correlated with several characteristics of CD. We investigated this serological marker in Turkish patients with CD and assessed its utility in combination with anti-Saccharomyces cerevisiae antibodies (ASCAs) for differential diagnosis of CD. MATERIALS AND METHODS: A total of 60 patients with CD, 62 patients with ulcerative colitis (UC), and 46 healthy controls with a definite diagnosis who were similar in age and sex were enrolled in the study conducted from November 2011 to October 2012. ASCA and anti-GP2 levels were measured using commercially available kits. RESULTS: Anti-GP2 IgA and IgG levels were higher in patients with CD (25%) than in those with UC (5%) and controls (2%). The seroprevalence of anti-GP2 IgA was markedly higher than that of IgG in patients with CD in contrast to previous studies. The specificity and positive predictive value of seropositivity for both ASCA and anti-GP2 were 100%. ASCA IgA seropositivity was correlated with a complicated disease course and a history of surgery. There was no correlation between anti-GP2 seropositivity and disease location, disease behavior, or a history of surgery. CONCLUSION: The combination of ASCA and anti-GP2 may enable differentiation of CD from UC. As ASCA seropositivity is associated with a more complicated disease course, patients seropositive for ASCA at the initial diagnosis should undergo more intense therapy.

Methylenetetrahydrofolate reductase gene polymorphisms in patients with nonalcoholic steatohepatitis (NASH).

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of a history of alcohol use. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms result in hyperhomocysteinemia. To examine whether the C677T and A1298C polymorphisms of the MTHFR gene were associated with NASH, we analysed the allele and genotype distribution of the MTHFR C677T and A1298C polymorphisms in 57 well-diagnosed NASH patients, 324 healthy controls in a case-control study of Turkish subjects of Caucasian origin. The diagnosis of the NASH patients was based on liver biopsy. The method used in the analysis of genotypes was PCR-RFLP. The MTHFR A1298C polymorphism was significantly associated with NASH (chi(2) = 8.439; p = 0.015) in the total NASH patients compared with healthy controls. The MTHFR 1298C allele (odds ratio (OR) = 2.480; 95%CI = 1.286-4.782; chi(2) = 7.703; df = 1; p = 0.006) was significantly associated with NASH in the total NASH patients. The MTHFR C677C/A1298C compound genotype (OR = 2.218; 95%CI = 1.003-4.906; chi(2) = 3.998; df = 1; p = 0.046) in men patients was also significantly associated with NASH. Likewise the MTHFR C1298C genotype was significantly associated with NASH in women patients with NASH (OR = 2.979; 95%CI = 1.027-8.641; chi(2) = 4.343; df = 1; p = 0.037). In conclusion, the MTHFR 1298C allele in all NASH patients, C1298C genotype, C677C/C1298C compound genotype in women NASH patients and C677C/A1298C compound genotype in men NASH patients were genetic risk factors for NASH.

Clindamycin-induced acute cholestatic hepatitis.

We report a case of acute hepatotoxicity in a 42-year-old woman after administration of clindamycin for a dental infection. After 6 d of treatment, she had fatigue, nausea, vomiting, anorexia, pruritus and jaundice. Her laboratory analysis showed alanine aminotransferase (ALT), 1795 IU/L (normal range 0-40); aspartate aminotransferase (AST), 1337 IU/L (normal range 5-34); alkaline phosphatase (ALP), 339 IU/L (normal range 40-150); gamma-glutamyl transpeptidase (GGT), 148 IU/L (normal range 9-64 IU/L); total bilirubin, 4.1 mg/dL; direct bilirubin, 2.9 mg/dL and prothrombin time (PT), 13.5 s, with international normalized ratio (INR), 1.04. She was hospitalized, with immediate drug discontinuation. Her liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that clindamycin was the probable cause of the acute hepatitis. In susceptible individuals, clindamycin use may lead to acute mixed-type liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established.

Endothelial dysfunction in patients with ulcerative colitis.

BACKGROUND: Human intestinal microvessels from chronically inflamed ulcerative colitis (UC) show microvascular endothelial dysfunction. Whether generalized endothelial dysfunction could associate with UC has not been explored yet. Our aim was to assess the endothelial function in the patients with different UC activity and to hypothesize about the relationship of endothelial function to activity-related extraintestinal complications (AREC) of UC. METHODS: Twelve patients with mild UC, 14 patients with moderate UC, 16 patients with severe UC, and 24 healthy subjects were included in the study. The activity of UC is calculated according to the Seo Index. Endothelial functions of the brachial artery were evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation (EDD) was assessed by establishing reactive hyperemia and endothelial-independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. RESULTS: EDD was significantly worse in patients with severe UC as compared with patients with mild UC (8.7 +/- 1.6% versus 17.3 +/- 5.6%, P < 0.05) and even in patients with moderate UC as compared with patients with mild UC (13.1 +/- 3.2% versus 17.3 +/- 5.6%, P < 0.05). EDD was not significantly worse in patients with mild UC as compared with healthy subjects (17.3 +/- 5.6% versus 18.1 +/- 8.1%, P > 0.05). EID was significantly worse in patients with severe UC compared with patients with moderate UC (10.5 +/- 2.9% versus 13.4 +/- 3.7%, P < 0.05) and even in patients with mild UC compared with healthy subjects (20 +/- 6.7% versus 31.1 +/- 12.6%, P < 0.05). EDD and EID were significantly worse in patients with AREC compared with patients with no AREC (9.5 +/- 2.5% versus 14.9 +/- 5.1%, P < 0.05; 11.6 +/- 4.3% versus 16 +/- 6.1%, P < 0.05, respectively). CONCLUSIONS: Increased activity of UC is associated with significant endothelial dysfunction, which may relate to the pathophysiology of AREC of UC.

Serum levels of hepatoprotective peptide adiponectin in non-alcoholic fatty liver disease.

OBJECTIVE: Adiponectin is an adipose tissue-specific protein that has anti-inflammatory, antidiabetic and antiobesity effects. It has been suggested that adiponectin has a hepatoprotective role. Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent with increasingly adverse clinical outcomes. In this study, serum adiponectin levels were investigated in patients with NAFLD to determine its possible role on hepatic inflammation and injury. METHODS: Twenty-nine biopsy-proven NAFLD patients (14 women, 15 men) with elevated liver enzymes, 20 clinically diagnosed NAFLD patients (13 women, seven men) with normal liver enzymes, and 20 healthy adults (10 women, 10 men) were enrolled. From fasting blood samples, serum adiponectin levels were measured by enzyme-linked immunosorbent assay. The body mass index, serum glucose, insulin, cholesterol and triglyceride levels were determined. RESULTS: Serum adiponectin levels were 4.99+/-2.1, 9.49+/-3.91 and 7.74+/-4.41 micro/ml in the NAFLD with elevated liver enzymes, NAFLD with normal liver enzymes and healthy adult control groups, respectively. The mean serum adiponectin level in the NAFLD with elevated liver enzymes group was significantly lower than those of other groups tested (P<0.001). Insulin, cholesterol and triglyceride levels of NAFLD patients with elevated liver enzymes were significantly higher than control groups (P<0.05) but were not significantly different from the NAFLD group with normal liver enzymes (P>0.05). On histopathologic examination, the mean serum adiponectin levels of non-alcoholic steatohepatitis patients with grade 2 or more inflammatory activity was significantly lower than patients with grade 1 inflammatory activity (P=0.013). CONCLUSION: Serum adiponectin levels are significantly lower in NAFLD patients with elevated liver enzymes. Non-alcoholic steatohepatitis patients show lower levels of adiponectin with higher grades of inflammation.

Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastric pH in extensive metabolizer patients with gastroesophageal reflux disease.

BACKGROUND/AIMS: Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of these studies, comparison of only two PPIs have been made. There are few studies on the comparison of four or more PPIs. We aimed to compare the acid inhibitory effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on days 1 and 5 of treatment in patients with GERD, who were extensive metabolizers in regard to the CYP2C19 genotype. MATERIALS AND METHODS: Helicobacter pylori-negative with typical symptoms of GERD patients were randomly divided into four treatment groups. Efficacy analysis on days 1 and 5 were performed on the four groups which comprised 10 (esomeprazole), 11 (rabeprazole), 10 (lansoprazole), and 10 (pantoprazole) patients. RESULTS: On day 1 of PPI treatment, the mean percentage of time with intragastric Ph>4 were 54%, 58%, 60%, and 35% for the groups, respectively, and on day 5, these values were 67%, 60%, 68%, and 59%, respectively. Esomeprazole, rabeprazole, and lansoprazole were found to be superior to pantoprazole on the first day of treatment. CONCLUSION: Pantoprazole is a less potent proton pump inhibitor than the other PPIs tested on the first day of treatment. When the time needed to raise the intragatric pH to over 4 was evaluated, esomeprazole was found to have the most rapid action, followed by lansoprazole and rabeprazole.

Improvement of complete blood count in patients with iron deficiency anemia and Helicobacter pylori infection after the eradication of Helicobacter pylori.

BACKGROUND/AIMS: Recent reports support the possible association between Hp infection and iron deficiency anemia. In the present study, the effects of the eradication therapy on iron deficiency anemia were investigated. METHODOLOGY: Fourteen women with iron deficiency anemia were enrolled (mean age: 36.4 years; range: 20-52 years old). None of the patients received iron supplementation. Several examinations including upper and lower gastrointestinal endoscopy were performed to reveal any gastrointestinal bleeding sites in all patients. Gastric biopsies during endoscopy were taken from the subjects except one whose serum anti-Hp IgG was positive. After diagnosing the Hp infection by means of microbiology, histology and Gram stain, a combination therapy consisting of lansoprosol, clarithromycin and amoxicillin was administered to each patient. Hematologic examinations and the body iron status were evaluated periodically, following the eradication therapy. RESULTS: Endoscopic findings were as follows: Seven patients with antral gastritis, two patients with pangastritis, whereas five patients were found to be endoscopically normal. None of the subjects were found to have gastrointestinal bleeding of any type. Serum hemoglobin, iron and transferrin saturations of the patients were found to be increased at 20-24 weeks of follow-up after the eradication therapy. Serum ferritin levels were not found to be increased. CONCLUSIONS: Hp infection may be involved in cases of iron deficiency anemia of unknown origin, and the eradication of the infection may improve blood parameters other than serum ferritin levels.

Effects of losartan, somatostatin and losartan plus somatostatin on portal hemodynamics and renal functions in cirrhosis.

BACKGROUND/AIMS: Several drugs have been used to reduce portal hypertension. Losartan constitutes arteriolar and venous vasodilation by inhibiting the effects of the increased angiotensin II in cirrhotic patients. In this study, we analyzed the effects of losartan, when used alone and when combined with somatostatin, on portal and renal hemodynamics. METHODOLOGY: Seventeen patients with cirrhosis were enrolled. During the study, the patients were administered 250 micrograms of somatostatin i.v. bolus and subsequent infusion at a rate of 250 micrograms/hr for 2 hours on the second day; 25 mg losartan orally on the fourth day; and losartan and somatostatin together, in the same doses as the second and the fourth day, were given on the sixth day. RESULTS: The portal flow volume and the velocity that were measured after the administration of somatostatin, losartan and the combination of each drug, were found to be increased when compared with the initial values (P < 0.001). Additionally, the creatinine clearances were increased and statistically significant with somatostatin. CONCLUSIONS: Considering its low cost, easy usability, long lasting effect, we suggest that losartan can be used as an alternative treatment in the clinical conditions where portal pressure should be reduced and can be combined with somatostatin without any significant adverse effects.

Valsartan-induced acute pancreatitis.

Gastrointestinal toxicity is uncommon among patients treated with angiotensin II receptor antagonists. A 58-year-old man presented with nausea, vomiting and constant pain in the epigastrium that radiated to the flanks. He received treatment with valsartan (160 mg daily) for hypertension. The clinical, biochemical and radiological findings were compatible with a diagnosis of acute pancreatitis. After the patient achieved a clinical and biochemical recovery, the valsartan therapy was started again. Six weeks later, he returned to the hospital with an attack of pancreatitis. Subsequently, he returned with repeated attacks of pancreatitis twice, and the valsartan was discontinued. Ten months after the treatment, the patient had no complaints. When severe abdominal symptoms occur for no apparent reason during treatment with valsartan, a diagnosis of pancreatitis should be considered.

The relationship between fibrosis level and blood neutrophil to lymphocyte ratio in inactive hepatitis B carriers.

AIM: Neutrophil-lymphocyte ratio (NLR) has been used as a simple, affordable, and easily accessible marker to predict prognosis in a variety of inflammatory and neoplastic diseases. However, there are few studies investigating their role in patients with hepatitis B. The aim of this study was to investigate the relationship between NLR and liver fibrosis in patients who were being followed as inactive hepatitis B carriers. MATERIALS AND METHODS: The study included 78 patients who were followed for 1 year as inactive hepatitis B carriers. Liver biopsy was performed and the fibrosis scores of the histological activity index were assessed according to the Metavir scoring system. The patients were divided into two groups on the basis of the fibrosis scores: those with a score below 2 and those with a score above 2. In both groups, demographic data such as sex, age, and BMI were similar. The NLR of patients was calculated from blood samples taken at the same time as the biopsy. RESULTS: Histopathologic analysis of 78 patients showed that 41 (53%) had fibrosis grade 0-1 and 37 (47%) patients had fibrosis grade greater than 2. According to the biopsy results, there were no cirrhotic patients. NLR was found to be statistically significantly lower in the group with fibrosis grade of at least 2 (1.51±0.61 vs. 1.79±0.64, P=0.043). Other biochemical and hematological data were found to be similar in both groups. No correlation was found between laboratory values and NLR. In addition, there was no correlation between NLR with histologic activity. Spearman correlation analysis showed a negative correlation between the fibrosis score and NLR (r=-0.279, P=0.013). CONCLUSION: In inactive hepatitis B carriers, the histological activity index and NLR were found to be correlated negatively. NLR can be used as a predictor of fibrosis in combination with other noninvasive markers.

Endoscopic submucosal dissection for colorectal laterally spreading tumors.

BACKGROUND/AIMS: Colorectal laterally spreading tumors are superficial tumors classified into two groups as granular (G-laterally spreading tumor) and non-granular (non-granular-laterally spreading tumor) types. In this study, we aimed to investigate the efficacy and feasibility of endoscopic submucosal dissection in the treatment of laterally spreading tumors. MATERIALS AND METHODS: Forty-four laterally spreading tumors in 40 patients were treated with endoscopic submucosal dissection at a tertiary referral hospital. Patient data were collected retrospectively. In this study, we evaluated tumor size, macroscopic type, lesion location, histology, curative resection, and complications. RESULTS: Of the 44 laterally spreading tumors excised by endoscopic submucosal dissection, 29 (65.9%) were G-laterally spreading tumor and 15 (34.1%) were non-granular-laterally spreading tumor. Most of the non-granular-laterally spreading tumors were localized in the right colon, while most G-laterally spreading tumors were localized in the left colon (p<0.001). There was also no difference between G-laterally spreading tumors (6/29) and non-granular-laterally spreading tumors (2/15) with regard to exhibiting malignant features (p=0.69). Although median size (40 mm vs. 27.5 mm) and procedure time (115 minutes vs. 60 minutes) for G-laterally spreading tumors were bigger and longer respectively, procedure time per cm2 was not different (8.9 minutes vs. 8.2 minutes) between the two groups. Curative resection rates for laterally spreading tumors were quite high (95.5%), while en bloc resection rates were low (77.3%). The rates of endoscopic submucosal dissection-related complications such as perforation, major and minor bleeding were low (4.5%, 2.3%, 6.8%, respectively). CONCLUSION: Endoscopic submucosal dissection is an effective and safe therapeutic option with high curative rates for early-stage malignant and pre-malignant laterally spreading tumors not having an absolute indication for surgery, regardless of the lesion type and size.

Nonresponsive celiac disease due to Strongyloides stercoralis infestation.

Celiac disease (CD) is treated by eliminating all gluten from the diet. A 49-year-old man with CD was admitted to our clinic with complaints of recurrent diarrhea and abdominal pain despite strict adherence to a gluten-free diet. The duodenum was seen to be edematous on gastroduodenoscopic examination. Histological examination of the biopsy specimen taken from the duodenum showed multiple round shaped Strongyloides stercoralis (S. stercoralis) larvae within the crypts. He was successfully treated with albendazole. This case emphasizes the importance of duodenal biopsy in CD. To our knowledge, this is the first case in the literature showing CD and S. stercoralis together.

Frequency and mutation patterns of resistance in patients with chronic hepatitis B infection treated with nucleos(t)ide analogs in add-on and switch strategies.

BACKGROUND: Treatment for chronic hepatitis B (CHB) has improved over the last 10 years mainly due to the development of effective oral antiviral agents [nucleoside/nucleotide analogs (NUCs)]. OBJECTIVES: The aim of the present study is to identify the frequency and major patterns of resistance to the hepatitis B virus (HBV) in a Turkish population of CHB patients treated with NUCs using add-on and switch therapy strategies. PATIENTS AND METHODS: The investigation involved a total of 194 patients (88 were treated using add-on therapy, and 106 were treated using switch therapy). We analyzed the HBV polymerase gene by amplification and direct sequencing procedures. RESULTS: Primary drug-resistance mutations were detected in 84 patients (43%; 42 in add-on therapy, and 42 in switch therapy) taking lamivudine (LAM), 10 patients (5%; 6 in add-on therapy, and 4 in switch therapy) taking entecavir (ETV), and 16 patients (8%; 8 in add-on therapy, and 8 in switch therapy) taking adefovir (ADV). The most common LAM and ETV resistance mutations were rtM204I/V, rtL180M and rtT184A/I/S, respectively, while rtA181T/V and rtN236T substitutions were the most frequently observed ADV resistance mutations. CONCLUSIONS: Patients with CHB who developed NUC resistance were managed using 2 different rescue strategies. The frequency and mutation pattern of resistance were similar in patients treated with add-on and switch strategies. These findings may be helpful in the management of rescue strategies in LAM-resistant patients.

Severe jaundice due to coexistence of Dubin-Johnson syndrome and hereditary spherocytosis: a case report.

Dubin-Johnson syndrome is a chronic, benign, intermittent jaundice, mostly of conjugated hyperbilirubinemia. The level of bilirubin is not expected to be more than 20 mg/dl in this syndrome. In this article, we report a patient who was evaluated for hyperbilirubinemia and liver function test abnormalities and diagnosed with Dubin-Johnson syndrome coexisting with hereditary spherocytosis. We suggest that other diseases should be investigated if patients with Dubin-Johnson syndrome present with severe hyperbilirubinemia. Dubin-Johnson syndrome accompanied by hemolytic diseases might also have high coproporphyrin levels (as in Rotor's syndrome) than expected in pure Dubin-Johnson syndrome.