Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies with hepatitis B and hepatitis C infection: Review.

BACKGROUND: Viruses are common and are involved in the etiology of idiopathic rheumatological diseases. Hepatitis B virus (HBV), a member of the family Hepadnaviridae and hepatitis C virus (HCV), play an important role in the undetermined etiology of arthritis. The clinical manifestations of hepatitis B and C show similarities with various diseases, such as rheumatic diseases. Anti-cyclic citrullinated peptide (anti-CCP) is a specific serological marker for rheumatoid arthritis. OBJECTIVES: The aim of this study was to analyze anti-CCP and rheumatoid factor (RF) levels in patients with a hepatitis B and C infection. MATERIAL AND METHODS: Forty-four patients with hepatitis B, 43 patients with hepatitis C, 25 patients with rheumatoid arthritis, and 46 healthy control serums and their RF and anti-CCP levels were compared. RF was measured by the nephelometer, which detects IgM-RF. Anti-CCP was measured using enzymelinked immunosorbent assay (ELISA) that is included in the second-generation anti-CCP antibody assays (anti-CCP2). RESULTS: The anti-CCP positivity levels were 20.5%, 32.5%, 72.4% and 10.9% for HBV, HCV and RA groups and healthy control group, respectively. When the groups were compared based on their RF positivity and anti-CCP positivity while the values for HBV and HCV group and healthy control group were the same, in RA group there is a significant difference to the rest of the groups (p < 0.01). CONCLUSIONS: Anti-CCP may be positive for HBV and HCV as well, but it is a sensitive and specific immunological marker for RA diagnosis, especially in high-titres.

Relationship between liver injury and serum cytokeratin 18 levels in asymptomatic hepatitis B virus carriers and in patients with chronic hepatitis B infection.

BACKGROUND AND STUDY AIMS: Apoptosis represents a well-known mechanism of cell death involved in most chronic liver injuries. Our aim was to investigate the serum fragment level of cytokeratin 18 (CK18), M30, in asymptomatic hepatitis B virus (HBV) carriers and patients with chronic hepatitis B (CHB) and to evaluate the relationship between serum M30 levels and the severity of hepatic injury. PATIENTS AND METHODS: Asymptomatic HBV carriers (n=169), patients with CHB (n=100), and healthy control subjects (n=43) were enrolled in the study. Serum CK18 (M30) levels were analysed in all subjects. Liver biopsy for histopathological assessment was performed in asymptomatic HBV carriers and in patients with CHB infection. RESULTS: Serum CK18 (M30) levels were significantly higher in asymptomatic HBV carriers (198.77±77.62U/L) than in healthy control subjects (146.92±40.18U/L). Patients with CHB (283.02±147.45U/L) had significantly higher CK18 (M30) levels than asymptomatic HBV carriers (p=0.001). The diagnostic efficacy of CK18 (M30) levels in distinguishing patients with HBeAg-negative CHB from asymptomatic HBV carriers was found to be moderate (c-statistics: 0.695), and the diagnostic cut-off value of CK18 (M30) was 262U/L (specificity: 85%, sensitivity: 48%, positive likelihood ratio: 3.35, and negative likelihood ratio: 0.60). There was a positive correlation between serum CK18 (M30) levels and histological activity index scores in asymptomatic HBV carriers and patients with CHB. CONCLUSIONS: Serum CK18 (M30) levels may be a valuable indicator in distinguishing asymptomatic HBV carriers from patients with HBeAg-negative CHB when considered together with ALT and HBV-DNA levels.

Drug- and herb-induced liver injury: a case series from a single center.

BACKGROUND/AIMS: Drug-induced liver injury (DILI) is common worldwide and has a potentially fatal outcome. It accounts for more than half of the cases of acute liver failure in the United States. Herb-induced liver injury (HILI) is a less documented condition but a growing problem. We present here the clinical characteristics and outcome of patients with drug- and herb-induced liver injury from our center. MATERIALS AND METHODS: In this 4-year retrospective study, 82 patients in whom there was a causal or highly probable relationship between herbal medicine or drug use and liver disease are presented. RESULTS: The mean age of patients was 43.1±14.8 years; sexual distribution was 53 females and 29 males. The major cause of hepatotoxicity was drugs (87.8%), with herbal medicine accounting for 12.2%. The leading causative agents were nonsteroidal anti-inflammatory drugs (NSAIDs) (23.1%), followed by antibiotics (19.5%). The pattern of hepatotoxicity was hepatocellular in 35 patients (42.6%), mixed in 28 (34.1%), and cholestatic in 19 patients (23.1%). Teucrium polium (known popularly as felty germander), which is a traditionally used herbal medicine of the Labiatae family in our region, was the most common cause of herb-induced liver injury and responsible in 7 of 10 herbal hepatotoxic cases. Acute liver failure developed in 3 patients (two patients related with flurbiprofen and diclofenac and one patient due to an isoniazid-rifampicin combination). CONCLUSION: Antibiotics and NSAIDs were the most common etiologic agents for drug-induced liver injury. Surprisingly, herbs follow these groups of drugs and must be questioned more carefully.

Anti-cyclic citrullinated peptide (anti-CCP) antibodies with brucellosis.

Anti-cyclic citrullinated peptide (anti-CCP) was positive in 11.5 % and rheumatoid factor was positive in 8.8 % of the patients with Brucella. After a comparative evaluation, we have found out that there was not a statistical significance concerning the anti-CCP levels between the patients with brucellosis and healthy control.

NADPH oxidase p22phox gene expression in ulcerative colitis.

BACKGROUND/AIMS: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which catalyzes the formation of reactive oxygen species (ROS) in phagocytic cells, has five subunits: p67phox ("phox"refers to "phagocyte oxidase"), p47phox, p40phox, p22phox, and gp91phox (catalytic subunit). Oxidative stress resulting from the accumulation of ROS and/or defective removal of ROS by antioxidants has detrimental effects on cellular functions and may contribute to chronic inflammation. Disruption of the colonic mucosa due to the dysregulation of antioxidants or transformation enzymes may play a role in the pathogenesis of ulcerative colitis (UC) and influence the clinical features of this disease. In this study, we examined the expression of the gene encoding NADPH oxidase subunit p22phox cytochrome b-245, alphapolypeptidein the colonic mucosa to test its possible contribution in the pathogenesis of UC. MATERIALS AND METHODS: Expression levels of mRNA in the inflamed and non-inflamed colonic mucosa (determined using colonoscopy)of 22 patients with UC and in the normal mucosa of 22 healthy controls were analyzed using real-time polymerase chain reaction. RESULTS: Expression levels of mRNA were not significantly different between patients with inflamed and non-inflamed colonic mucosa (p>0.05) and betweenpatients with inflamed colonicmucosa and healthy controls (p>0.05). CONCLUSION: Although our data suggest that expression of the gene encoding p22phox is not associated with chronic inflammation in patients with UC, other mechanisms can affect oxidative stress in these patients.

Ultrathin endoscopy for gastrointestinal strictures.

BACKGROUND AND AIM: The assessment and treatment of advanced gastrointestinal (GI) strictures, which are defined as the inability to pass through the strictured segment with standard endoscopes, might require radiological work-up, repeated endoscopies and surgery. The aim of the present study was to assess the role of ultrathin endoscopy (UTE) for the evaluation and treatment of advanced GI strictures. METHODS: Patients in whom an initial diagnostic upper or lower endoscopy attempt was incomplete because of a tight stricture underwent a second procedure with a UTE (5.9 mm diameter) in the same session. An interventional endoscopic therapy was also carried out according to the etiology and nature of the stricture using the same UTE. Diagnostic and therapeutic outcomes were recorded and followed up prospectively. The study was conducted in a tertiary endoscopy center. RESULTS: During a one and half year study period, 62 patients (51 at upper and 11 at lower endoscopy) were detected with advanced GI stricture among 8456 diagnostic upper and 3815 lower endoscopy patients. A complete endoscopic examination was successful with UTE in 40 (78%) patients with upper and in nine patients (82%) with lower GI strictures. An interventional procedure was also carried out in 16 patients with the assistance of UTE. CONCLUSION: UTE is a useful tool for the evaluation of patients with advanced GI strictures. It provides a complete diagnostic endoscopy in most patients and gives an opportunity for therapeutic endoscopic procedures.

The relation between serum cytokeratin 18 and acute pancreatitis: can it be a serological predictive marker?

BACKGROUND/AIMS: Acute pancreatitis is well defined as pancreatic inflammation due to the activation of pancreatic enzymes secondary to several etiological factors. In the majority of patients, the clinical symptoms are self-limited, but it can also cause tissue necrosis and severe organ failures. In experimental animal models, it has been shown that wide apoptotic cell death is related to a clinically mild presentation of acute pancreatitis. Cytokeratin 18, a cytoskeletal protein, is shown to be related with apoptosis. In this study, we aimed to show the relation between serum cytokeratin 18 and the clinical presentation of acute pancreatitis in humans. MATERIALS AND METHODS: A total of 54 acute pancreatitis patients were enrolled into the study. Patients were classified as mild or severe pancreatitis according to Ranson's criteria. There were 36 (66.7%) patients in the mild pancreatitis group (score < 6), and 18 (33.3%) patients in the severe pancreatitis group (score ≥ 6). During the first admission, blood samples were obtained for serum cytokeratin 18 levels. RESULTS: Cytokeratin 18 levels in the mild pancreatitis group were significantly higher than in the severe pancreatitis group (271.2 ± 45.5 vs. 152.6 ± 38.2 IU/L; p < 0.001). There was a negative correlation between the disease activity score (Ranson score) and the serum cytokeratin 18 levels (p < 0.001; r = -0.724). CONCLUSIONS: This first human study suggests that cytokeratin 18 (marker of apoptosis) might be a serological predictive marker for acute pancreatitis for disease activity.

Unilobar tapering cirrhosis in a patient with Caroli syndrome associated with an abnormal common bile duct.

Caroli syndrome is a rare condition and is composed of congenital cystic dilatation of the biliary system and congenital hepatic fibrosis. Although many associated conditions are defined and hypothesized to occur concomitantly, due to the rarity of this syndrome, none has proven to be an essential component of this syndrome. In order to investigate a patient presenting with a cholestatic clinical picture, ultrasound, endoscopic retrograde cholangiopancreatography, abdominal computed tomography, liver biopsy, splenoportal venous angiography, and all available liver tests were performed. Upon typical findings, a diagnosis of Caroli syndrome was made and an orthotopic liver transplantation was performed. Investigation of the patient demonstrated multiple intracystic stones mimicking hemangiomatosis in the ultrasound; severe irregularity and narrowing in the main bile duct mimicking sclerosing cholangitis in the endoscopic retrograde cholangiopancreatography; partial portal vein thrombosis with irregularity in the portography; and a unilobar cirrhosis of the left liver lobe while the right lobe demonstrated only congenital hepatic fibrosis in the explanted liver. Caroli syndrome may be associated with main bile duct and portal vein abnormalities. Although the syndrome can be monolobar in nature, a cirrhotic left lobe sparing the right lobe, partially affected by the cirrhotic process, has never been defined. Here, we report a case of Caroli syndrome who had liver transplantation, with very rare and interesting findings of the explanted liver, such as tapering cirrhosis from the left lobe to the right lobe and countless stones in biliary cysts mimicking hemangiomas.

What are the clinical implications of nodular gastritis? Clues from histopathology.

There is no widely accepted histopathological definition for nodular gastritis. In this study we aim to uncover the pathologic entity responsible for the nodular appearance and to find clues about the clinical implications of nodular gastritis. Antral biopsy specimens of 160 patients with nodular gastritis and 133 patients without nodular gastritis were examined by an experienced pathologist for dysplasia, foveolar hyperplasia, inflammatory activity, intraepithelial lymphocytosis, intestinal metaplasia, and lymphoid follicle/aggregate formation, and comparative analysis was performed between the two groups of patients. The presence of intraepithelial lymphocytosis was more frequent in patients with nodular gastritis (P < 0.05). There was no difference between the two groups regarding the other pathological features such as presence of dysplasia, inflammatory activity, intestinal metaplasia, lymphoid hyperplasia, and Helicobacter pylori (H. pylori) infection. Increase of intraepithelial lymphocytes may contribute to formation of macroscopical nodules in this peculiar type of gastritis. Nodular gastritis would not indicate a new therapeutic approach in addition to the current measures for Helicobacter pylori infection.

Capability of capsule endoscopy in detecting small bowel ulcers.

Capsule endoscopy (CE) has proved to be the preferred modality for mucosal pathologies of the small bowel. We evaluated the capability of CE for detecting small bowel ulcers and the contribution of CE in establishing the diagnosis. From a total of 66 patients who had undergone normal upper and lower endoscopy and small bowel follow-through, CE revealed previously undiagnosed ulcer(s) in the small intestines of 22 patients. Final diagnoses of the ulcers of these 22 patients were Crohn's disease (n = 9), Behçet's disease (n = 2), nonspecific jejunoileitis (n = 2), vasculitis (n = 1), gastrointestinal stromal tumor (n = 1), adenocarcinoma (n = 1), lymphoma (n = 1), multiple myeloma (n = 1), Meckel's diverticulum (n = 1) and unknown (n = 3). Capsule endoscopy was extremely useful in establishing the diagnosis. In this study, proximal, distal and diffuse small bowel ulcers were determined at rates of 27.3, 59.0 and 13.7%, respectively. Capsule endoscopy facilitated the detection and assessment of ulcerated mucosal lesions located in the small bowel.

Hepatic granuloma in Turkish adults: a report of 13 cases.

BACKGROUND: Hepatic granuloma (HG) is a well defined histopathological finding with an heterogenous clinical presentation. Diagnosis of a specific clinical entity is not possible every time. Descriptive studies may shed light on the various etiologies also common and distinctive findings among these patients. METHODS: We reviewed the results of the liver biopsies of 592 patients. Characteristics of the patients with HG were extracted from the hospital charts. Laboratory studies included biochemical tests, hepatitis C virus (HCV) antibody, Brucella agglutination tests, tuberculin skin test. According to the diagnostic clues further tests (thoracic computed tomography (CT), ultrasonography, organ biopsy in addition to liver, antimitochondrial antibody, hepatitis B surface (HBs) antigen, venereal disease research laboratory (VDRL)) were performed. RESULTS: HG was found in 13 of the 592 patients (2.2%). Primary biliary cirrhosis (three cases) was the most frequent cause followed by sarcoidosis, miliary tuberculosis and BCGitis (Bacillus Calmette Guerin) (two cases each). Two patients with HG could not be diagnosed. Only three patients had remarkable physical examination findings. Alkaline phosphatase and gamma-glutamyl transpeptidase were the most frequently elevated enzymes. Abdominal ultrasonography provided no specific diagnostic clue in any patient. Localization of the HGs was portal in 6 patients, parenchymal in 5 patients and both portal and parenchymal in 2 patients. Three exitus were due to BCGitis, miliary tuberculosis and fungal infection. CONCLUSIONS: Tuberculosis is still among the most common etiologic factors. BCGitis has a fulminant rather than an indolent course. Abdominal ultrasonography could be used to rule out obstructive jaundice rather than to reach a specific diagnosis. Involvement of portal area by HG in most of the cases might cause obstruction of the biliary canaliculi and elevation of the cholestatic enzymes. Follow up of the difficult cases may be the best approach since the presence of HG was not proved as a bad prognostic factor for any disease.

"Portal double ductopathy sign" in patients with portal vein cavernous transformation.

BACKGROUND/AIMS: The aim of this study was to determine to what extent portal vein cavernous transformation affects the biliary tract and pancreatic duct system concurrently. METHODOLOGY: Patients who had liver cirrhosis, liver malignancy, history of chronic alcohol use, chronic pancreatitis, pancreatic cancer, or surgery of upper abdomen were excluded. Endoscopic retrograde cholangiopancreatography was performed on all patients. The radiographic images from the biliary and pancreatic systems obtained at the same session were evaluated. RESULTS: In 36 patients, both systems were evaluated. In 2 out of 36 patients, the biliary system was normal, while in 5 patients (13.9%) the pancreatic duct was found to be normal. Thus, 31 patients (12 men, 19 women) had successful visualization. Additionally, 31 out of 36 patients had luminal narrowing throughout the pancreatic duct, local atrophy at head of the pancreas with moderate dilatation behind the narrowed segment. These findings were not found in control patients. In 4 patients who underwent splenectomy for severe hypersplenism, radiological findings were consistent with surgical findings. CONCLUSIONS: The above mentioned morphological findings which are demonstrated in biliary and pancreatic duct are novel findings which the authors propose to call "portal double ductopathy sign" when both ducts are affected concurrently.

A case of patent ductus venosus complicated with tumor-like lesions of the liver.

Patent ductus venosus (PDV) is a very rare congenital vascular anomaly of the liver. We report a 17-year-old male patient presenting with elevated liver enzymes and multiple liver masses. Physical examination was normal except for pectus excavatum deformity. Ultrasonography revealed multiple tumor-like lesions of the liver and a dilated portal vein with mild splenomegaly. Liver biopsy obtained from liver parenchyma revealed minimal hepatocellular damage. PDV was diagnosed by CT (computed tomography) portography. The radiologic findings of chronic liver disease and multiple liver masses were attributed to presence of PDV. Although it is very rare, PDV might be a diagnostic possibility in patients with mass lesions in the liver.

Budd-Chiari syndrome: etiology, pathogenesis and diagnosis.

Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more than one etiologic factor may play a role in 25% of the patients. Primary myeloproliferative diseases are the leading cause of the disease. Two of the hepatic veins must be blocked for clinically evident disease. Liver congestion and hypoxic damage of hepatocytes eventually result in predominantly centrilobular fibrosis. Doppler ultrasonography of the liver should be the initial diagnostic procedure. Hepatic venography is the reference procedure if required. Additionally liver biopsy may be helpful for differential diagnosis. The prognosis of the chronic form is acceptable compared to other chronic liver diseases.