Regression of steatohepatitis-related cirrhosis.

The authors document regression of cirrhosis in an obese 56-year-old man after significant weight loss by sequential liver biopsies. The patient had a known history of steatohepatitis. His initial laboratory workup 6 years earlier revealed elevated liver enzyme activities and blood triglyceride levels, and negative viral hepatitis serology screen. A liver biopsy at that time showed histological features consistent with precirrhotic stage of active steatohepatitis. A liver biopsy performed 4 years later revealed progression of the disease to cirrhosis. Following this diagnosis he went on a special strict diet and lost 49 kg. His body mass index decreased from 46 to 28 during a 2-year period and his liver enzyme activities returned to normal. A liver biopsy at this time demonstrated significant regression of the liver fibrosis and disappearance of the steatosis and necroinflammation. In conclusion, massive weight loss resulted in resolution of liver fibrosis in this obese patient with steatohepatitis-related cirrhosis.

Red blood cell distribution width as a non-invasive marker for the assessment of inflammation in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: The aim of this study was to assess the association between red cell distribution width and inflammation in biopsy proven non-alcoholic steatohepatitis. METHODOLOGY: Fifty four subjects with non-alcoholic steatohepatitis and thirty nine controls were enrolled for the study. Liver biopsy specimens were scored by using non-alcoholic fatty liver disease activity score by a single experienced liver pathologist. RESULTS: Red cell distribution width was higher in the severe inflammation group in non-alcoholic steatohepatitis (p < 0.05). The areas under the receiver operating characteristic curves for the predictive performance of aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and red cell distribution width in identifying inflammation in non-alcoholic steatohepatitis were 0.55 (0.41-0.68), 0.51 (0.37-0.64), 0.53 (0.39-0.67) and 0.73 (0.59-0.84) respectively and the differences of these values between red cell distribution width and other parameters were found to be statistically significant (p < 0.05). To determine the grading of inflammation, the specificity for using the red cell distribution width as an indicator in non-alcoholic steatohepatitis patients was calculated to be 73.3%, with 79.5% sen- sitivity. CONCLUSION: Red cell distribution width was a sensitive and specific method for the assessment of the inflammation in patients with non-alcoholic steatohepatitis.

The relationship between peritoneal membrane permeability and dyspepsia in peritoneal dialysis patients.

OBJECTIVE: The aim of this study is to determine whether there is a relationship between peritoneal membrane permeability and dyspepsia in peritoneal dialysis patients. PATIENTS AND METHODS: This study included 95 peritoneal dialysis patients aged 18 and older. The presence of dyspepsia in patients was recorded according to the 2016 ROME-IV Functional Dyspepsia Diagnostic Criteria. Subsequently, the Glasgow Dyspepsia Severity Score questionnaire was administered to assess the severity of dyspepsia. Endoscopy was performed for those who agreed to exclude organic pathology, or the results of endoscopy conducted within the last 2 years were recorded. Furthermore, stool samples were examined for H. pylori to exclude organic causes of dyspepsia. PET (peritoneal equilibration test) and Kt/V values of patients were calculated using the "PD Adequest" computer software. PET values were categorized as low and low-normal for low permeability and high and high-normal for high permeability. RESULTS: Dyspepsia was detected in 51.6% of all peritoneal dialysis patients. H. pylori was found positive in 11.6% of all patients and 12.2% of those with dyspeptic symptoms. There was no significant difference in the rate of H. pylori occurrence between low and high permeability groups. The Glasgow Dyspepsia Severity Score did not differ significantly between H. pylori-positive and -negative patients. Dyspepsia was more frequent and severe in the low permeability group. Dyspepsia in the low permeability group was mostly considered as functional dyspepsia due to the predominance of normal endoscopic findings. CONCLUSION: Dyspepsia is a common health problem in approximately half of peritoneal dialysis patients. Dyspepsia observed in those with low peritoneal membrane permeability is generally of functional origin. Furthermore, the frequency and severity of dyspepsia are higher in individuals with low permeability. When planning peritoneal dialysis for these patients, the current status should be taken into consideration, and patients should be informed about necessary precautions and recommendations.

Neutrophil-lymphocyte ratio as a predictor of disease severity in ulcerative colitis.

BACKGROUND: Blood neutrophil-to-lymphocyte (N/L) ratio is an indicator of the overall inflammatory status of the body, and an alteration in N/L ratio may be found in ulcerative colitis (UC) patients. The aims of this study were to investigate the utility of N/L ratio as a simple and readily available predictor for clinical disease activity in UC. METHODS: Twenty-six patients and 28 healthy controls were enrolled in the study. The neutrophil and lymphocyte counts were recorded, and the N/L ratio was calculated from these parameters. The extent of disease classified according to the Montreal classification, clinical disease activity was evaluated using a modified Truelove-Witts severity index, and endoscopic disease activities were classified according to Schroder et al. RESULTS: The serum N/L ratios of active patients were significantly higher than those of inactive UC and controls (P < 0.001). The optimum N/L ratio cut-off point for active UC was 2.47. There was no significant difference between inflammation parameters, disease extension, and disease activity. CONCLUSION: Our results demonstrate that N/L ratio is higher in patients with active UC compared with controls and UC patients in remission and a cut-off value of 2.47 can be used to identify patients with active ulcerative colitis.

Investigation of genome instability in exfoliated colonic epithelial cells and in mitogen-stimulated lymphocytes of patients with ulcerative colitis.

OBJECTIVE: The present study aimed to evaluate the micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in the mitogen-stimulated lymphocytes of patients with ulcerative colitis (UC). In addition, we assessed MN frequency in exfoliated colonic epithelial cells obtained from both the diseased and healthy colonic mucosa of patients. DESIGN: The study was conducted in 22 newly diagnosed patients with UC and in 22 healthy controls. MN, NPB and NBUD values scored in binucleated (BN) cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects. In addition, the MN values in exfoliated epithelial cells obtained from the diseased and healthy colonic mucosa of patients were evaluated. RESULTS: We found significantly higher MN, NPB and NBUD frequencies in the BN cells of patients with UC than in those of the control subjects (1.61 ± 0.75 vs. 0.89 ± 0.29, 3.93 ± 1.91 vs. 1.39 ± 1.10, and 1.55 ± 0.89 vs. 0.64 ± 0.48, p = 0.001). Also, a statistically significant difference was found between MN frequencies obtained from the diseased and healthy colonic mucosa of patients (1.07 ± 0.46 vs. 0.59 ± 0.21, p = 0.001). No significant relationship was found between age and MN frequency in patients with UC (r = 0.076, p = 0.735). CONCLUSION: Increased MN, NPB and NBUD frequencies observed in both the lymphocytes and exfoliated colonic epithelial cells obtained from patients with UC may reflect genomic instability.

Primary hepatic carcinosarcoma.

BACKGROUND: Primary hepatic carcinosarcoma is a rare malignant tumor containing an intimate mixture of carcinomatous and sarcomatous elements. Reports on risk factors, epidemiology, and pathogenesis of the tumor as well as the experience in its treatment are limited. METHOD: We present a case of primary carcinosarcoma of the liver in a 69-year-old man who complained of right hypochondrial pain and weight loss for two months. RESULTS: Magnetic resonance imaging revealed a 14 x 12 cm mass in segments 7-8 and 4 of the liver with vena hepatica invasion. An ultrasonography-guided biopsy showed osteoid tissue without osteoblastic rimming. Vascular structures accompanied the osteoid tissue. The patient underwent surgery after a diagnosis of hemangioma. Intraoperative frozen sections revealed a carcinosarcoma associated with an osteosarcoma and cholangiocellular carcinoma components. CONCLUSIONS: Preoperative diagnosis of this rare primary hepatic malignant tumor may be difficult by biopsy owing to intratumoral heterogeneity. Highly mature areas of the osteosarcomatous component may lead to misdiagnosis of metaplastic bone tissue. Clinicopathologic features of this rare entity are discussed.

Advanced oxidation protein products: a novel marker of oxidative stress in ulcerative colitis.

BACKGROUND/GOALS: The etiology and pathogenesis of chronic inflammatory bowel diseases are still poorly understood. Oxidative stress takes place in the pathogenesis of ulcerative colitis (UC) and advanced oxidation protein products (AOPP) are accepted as a novel marker of oxidative stress. There are no data concerning whether AOPP may be used as a simple serum marker to assess the disease activity, predict severity of the disease course in UC. STUDY: In this study, we determine the importance of neutrophil activation and the role of oxidative stress in the pathogenesis of UC, by quantification of AOPP and total thiol levels as markers of oxidative protein damage, malondialdehyde levels as a marker of lipid peroxidation, and myeloperoxidase activity as a marker of neutrophil activation in patients with UC. RESULTS: Serum levels of AOPP, thiol, myeloperoxidase activity, and malondialdehyde were found as increased in UC group compared with controls (P=0.004, 0.047, 0.001, and 0.001 respectively). CONCLUSIONS: Our finding of increased levels of plasma AOPP levels supports the presence of oxidative stress and protein oxidation in UC and this marker may be used as a simple serum marker to assess disease activity, predict the severity of disease course, and perhaps response to therapy.

Pyoderma gangrenosum and exacerbation of psoriasis resulting from pegylated interferon alpha and ribavirin treatment of chronic hepatitis C.

Interferon therapy is the cornerstone of chronic hepatitis C treatment. Side effects of interferon include possible triggering or exacerbation of immune diseases in consequence of immunomodulatory effects. We describe the unique case, in which pyoderma gangrenosum and exacerbation of psoriasis were developed 8 weeks after pegylated interferon alpha 2a and ribavirin therapy in a 45-year-old woman. The therapy had to be stopped on account of pyoderma gangrenosum and exacerbation of psoriasis in spite of a biochemical response to the therapy for hepatitis C. The evolution was favorable after stopping treatment. Therefore, we propose this would suggest a possible autoimmune mechanism for the development of pyoderma gangrenosum and exacerbation of psoriasis with pegylated interferon therapy. A susceptible patient, who has an autoimmune disease before interferon therapy, had to be informed that interferons may induce de novo or exacerbate existing immune diseases by immunomodulatory actions. To the best of our knowledge, this is the first case report of pyoderma gangrenosum and psoriasis that resulted from pegylated interferon alpha 2a and ribavirin treatment of chronic hepatitis C.

Clostridium difficile infection frequency in patients with nosocomial infections or using antibiotics.

BACKGROUND/AIMS: Clostridium difficile is the most common cause of nosocomial infectious diarrhea. The frequency of colonization in hospitalized patients varies between 10 and 43%. METHODOLOGY: Clostridium difficile common antigen was investigated in stool samples of 50 patients who developed nosocomial diarrhea (group 1), 65 outpatients who attended the clinic after development of diarrhea during antibiotic use (group 2), 18 patients with active chronic inflammatory bowel disease (group 3), and 30 control patients were studied. The Latex agglutination test and the toxin A was performed to investigate the presence of the Clostridium difficile common antigen in stool samples. The possible predisposing factors for nosocomial infection were analyzed. RESULTS: Clostridium difficile common antigen was found positive in 27.7% and 14% of group 2 and group 1, respectively while negative in stools of patients with inflammatory bowel disease. Asymptomatic fecal Clostridium difficile carriage in healthy volunteers was 3.3%. The antibiotic that induced diarrhea the most was clindamycin in group 1, and ampicillin-sulbactam in group 2. Enema was found to be the most important risk factor for C. difficile in hospitalized patients. CONCLUSIONS: The Clostridium difficile common antigen was detected more frequently in antibiotic-associated diarrhea patients than in nosocomial diarrhea patients. Clostridium difficile-associated diarrhea was also more frequent in immunosuppressive patients with uremia and diabetes mellitus.

Turkey 2017 Clinical Practice Guidelines on recommendations for screening diagnosing and managing hepatitis C virus.

The present guideline updates the Turkish recommendations for the screening, diagnosis and management of Hepatitis C virus (HCV) infection prepared by the Turkish Association for the Study of the Liver (TASL) and Viral Hepatitis Society (VHS). The aim of this guidance was to provide updates recommendations to physicians, who are interested in HCV care on the optimal screening, diagnosis and pre-treatment management for patients with HCV infection in Turkey. These recommendations, produced by panel experts, were aimed to addresses the management issues ranging from diagnosis and linkage to care, to the optimal treatment regimen in patients with HCV infection. Recommendations are based on evidence and opinions of more than 70% of the panelists. This guidance is supported by the memberships of two societies and not by pharmaceutical companies. This guidance will be updated frequently as new data become available.

Adrenal axis functions in patients with familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is a hereditary disease characterized by recurrent attacks of fever with peritonitis, arthritis, pleuritis or erysipelas-like rash. It is unclear what effects of FMF itself on endocrine system and hormones are. None of the FMF patients without amyloidosis have been reported to have any endocrine disorders, except those who developed colchicine-induced diabetes insipidus. There is a large body of evidence to show that cytokines (IL-1, IL-6 and TNF-alpha) activate the hypothalamic-pituitary-adrenal (HPA) axis. We have designated this study to investigate the HPA axis in FMF patients without amyloidosis. METHODS: Twenty-one patients with FMF were included. ACTH stimulation test was performed on the healthy subjects and during attack period in the patients. In the patient group, same test was repeated during remission period. RESULTS: Peak cortisol levels were significantly higher in the attack period than those in the remission period of patients (p<0.05). CONCLUSION: The cytokines play a role on the activation of the HPA axis; we thought the axis would be affected in this disease. The response of cortisol to 250 mug ACTH was significant in attack period when compared with remission period. This result reveals that HPA axis is more activated in an FMF attack. Previous studies suggest that the adrenal hormones increase in acute inflammatory events, and eventually, the changes on these hormones are related to TNF and IL-6 levels. During the FMF attack, HPA axis may be stimulated by cytokines. It seems that HPA axis is regulated normally in FMF patients.

Effects of balanced propofol sedation on QT, corrected QT, and P-wave dispersion on upper endoscopy.

OBJECTIVE: Combined sedation with propofol and benzodiazepines, known as balanced propofol sedation (BPS), was developed to increase patient comfort during endoscopy. However, the effects of BPS on P-wave dispersion (Pwd), QT interval, and corrected QT (QTc) interval after endoscopy have not been investigated. METHODS: The study population consisted of 40 patients with BPS and 42 without sedation who were scheduled to undergo upper endoscopy in this cross-sectional prospective study. Patients with hypertension, diabetes mellitus, renal failure, chronic obstructive pulmonary disease, coronary artery disease, or valvular heart disease and those on medications that interfere with cardiac conduction times were excluded. Electrocardiograms (ECGs) was recorded in all patients pre-endoscopy and 10 min post-endoscopy. QT, QT dispersion (QTd), and Pwd were defined from 12-lead ECG. The QTc interval was calculated using Bazett's formula. All analyses were performed using SPSS 15.0. RESULTS: Post-endoscopy P max duration and Pwd were prolonged compared with baseline values (86±13 ms vs. 92±10 ms and 29±12 ms vs. 33±12 ms, respectively; p<0.05). Post-endoscopy QTc and QTd were decreased compared with baseline values, but these decreases were not statistically significant (431±25 ms vs. 416±30 ms and 62±28 ms vs. 43±22 ms, respectively; p>0.05). CONCLUSION: The present study showed that P-wave duration and Pwd values increased after endoscopy with a combination of midazolam and propofol sedation. Physicians should be made aware of the potential effects of BPS in terms on P-wave duration and Pwd values.

Subclinical alveolar involvement in ulcerative colitis.

BACKGROUND: Although pulmonary dysfunction has been described in patients with ulcerative colitis (UC), the pathogenesis remains unclear. Our aim was to study alveolar epithelial damage using technetium-99m diethylene triamine penta acetic acid (Tc-99m DTPA) aerosol scintigraphy in patients with UC but without respiratory symptoms. METHODS: We enrolled 32 patients (18 women and 14 men; mean age, 36.4 +/- 11.6 yr) with active UC, 10 patients with inactive UC (6 women and 4 men; mean age, 43.4 +/- 11.8 yr), and 31 healthy controls (24 women and 7 men; mean age, 40 +/- 10 yr). Tc-99m DTPA aerosol scintigraphy was performed on all patients and controls. The relationship between alveolar epithelial permeability and the activity, localization, and duration of the disease was studied. RESULTS: There was a significant difference between alveolar epithelial permeability results in patients with active UC and those of the controls (P < 0.001). The same correlation was also found between the patients with inactive UC and the control group (P < 0.001). There was no correlation between Tc-99m DTPA alveolar scintigraphic test results and the stage of activity, localization, and duration of the disease. CONCLUSIONS: A latent pulmonary involvement may exist in patients with active and inactive UC. The alveolar involvement may be the earliest pulmonary damage, and a DTPA clearance test may show the early changes in pulmonary epithelial permeability that precedes clinical symptoms. Increased alveolar epithelial permeability is an extraintestinal manifestation in patients with UC and is not related to the activity of the colitis.

A new marker for lipid peroxidation: serum paraoxonase activity in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: Relationship between hepatic antioxidant paraoxonase 1 (PON1) activity, lipid peroxidation and liver injury was investigated in patients with non-alcoholic steatohepatitis. METHODS: A total of 23 patients with non-alcoholic steatohepatitis (15 males, 8 females; mean age: 40.30+/-7.67 yrs) and 23 healthy controls (14 males, 9 females; mean age: 39.70+/- 8.78 yrs) were enrolled in the study. Serum paraoxonase 1 activity and levels of a well-known lipid peroxidation marker, serum malondialdehyde, were determined. RESULTS: Serum paraoxonase 1 activity decreased significantly in non-alcoholic steatohepatitis compared to the control group (p<0.01). Serum malondialdehyde levels were significantly higher in patients with non-alcoholic steatohepatitis as compared with the control group (p<0.05). No statistically significant correlations were found between serum paraoxonase 1 activities and the grade-stage of non-alcoholic steatohepatitis, serum lipid levels or serum malondialdehyde levels (p>0.05). CONCLUSIONS: Increased lipid peroxidation may be either a cause or a result of liver injury in patients with non-alcoholic steatohepatitis. Although serum paraoxonase 1 activity does not reflect the degree of liver damage in non-alcoholic steatohepatitis, reduced paraoxonase 1 activity, especially in the presence of mild disease, could be interpreted as a biochemical marker of the lipid peroxidation.

An uncommon lesion: gastric xanthelasma.

Although the clinical significance of gastric xanthelasmas is unclear, they are important lesions because they may be confused with malignant lesions. The etiopathogenesis is also unclear, but chronic gastritis, Helicobacter pylori (H. pylori) infection, diabetes mellitus and hyperlipidemia have been implicated. Xanthelasma is more frequent in women and its incidence increases with age. The lesions are frequently located in the stomach, and less frequently in the esophagus, duodenum and the colon. The lesions have a yellowish-white appearance, are between 0.5 and 10 mm in size and can be single or multiple. Xanthelasmas were found to be associated with chronic gastritis, gastrointestinal anastomoses, intestinal metaplasia, and H. pylori infection. These lesions are predisposing conditions for gastric cancer. Therefore, endoscopic biopsy is mandatory and careful follow-up is required. In this paper, four patients who attended hospital with abdominal pain and dyspepsia and by chance were found to have xanthelasmas on endoscopic examination are presented, and gastric xanthelasmas are discussed.

Importance of anticoagulant proteins in chronic liver diseases.

BACKGROUND/AIMS: This study was conducted to elucidate the importance of anticoagulant proteins in chronic liver disease and their possible role as markers in determining the severity of the liver disease. METHODS: This study was conducted on 35 patients with cirrhosis, 15 patients with chronic active hepatitis and 10 healthy controls. Coagulation inhibitor proteins such as protein C, protein S and antithrombin, as well as D-dimer level and thrombin time, which reflect fibrin degradation products, were measured. Cirrhotic patients were categorized as Child A, B and C and chronic active hepatitis patients as mild or moderate activity according to the modified Knodell histopathologic classification. The parameters were compared between patient groups and healthy controls. RESULTS: In comparison with controls, the cirrhotics had significantly decreased protein C, protein S, antithrombin levels and increased D-dimer levels. The Child B and Child C patients differed significantly with respect to protein C and antithrombin levels only. In the chronic active hepatitis patients, protein S, protein C and fibrinogen were within normal limits, whereas antithrombin was low. CONCLUSIONS: In chronic active hepatitis, the antithrombin level may be used as an early marker of hepatocellular damage. In cirrhotics, protein C and antithrombin may be useful for assessment of hepatocellular damage, whereas D-dimer may be important for the transition to decompensation.

Hypothalamo-pituitary gonadal axis in men with chronic hepatitis.

BACKGROUND/AIMS: Hypothalamo-pituitary function of male patients with chronic active hepatitis was evaluated. The effects of interferon alpha therapy on hypothalamo-pituitary-gonadal axis were also investigated. METHODOLOGY: Twenty patients with chronic B and C hepatitis, and 10 healthy subjects were studied. Before and after treatment with IFN alpha, basal levels of FSH, and LH were obtained and all groups were evaluated with LH-RH stimulation test. RESULTS: Baseline hormone levels and FSH and LH responses to LH-RH stimulation test were similar in patients and controls. It was notable that the LH response was considerably greater than that of FSH and pretreatment FSH results in patients with HCV infection appeared earlier than those of patients with HBV infection. Following IFN alpha treatment, the results of LH-RH stimulation test were similar to those of controls but there were a delayed LH and FSH response to LH-RH stimulation test. CONCLUSIONS: Hypothalamic and/or gonadal hypogonadism is correlated with the degree of liver damage in cirrhosis. In patients with chronic hepatitis, which is characterized by lesser degree of liver damage than cirrhosis, HPG axis is not affected. IFN alpha, still in use for treatment of hepatitis, did not have any effect on HPG axis although it has many side effects.

Spontaneous bacterial peritonitis due to Brucella infection.

Brucella infection is a systemic disease, but the microorganism rarely causes infections in the gastrointestinal system such as hepatitis, cholecystitis, colitis and pancreatitis. Spontaneous bacterial peritonitis due to Brucella is extremely rare. Herein, we report a case of cirrhosis complicated with nongranulomatous hepatitis and peritonitis, both due to Brucella. A 63 year-old man with diabetes mellitus was admitted to hospital with complaints of weakness, backache, abdominal pain and abdominal swelling. On the basis of physical examination and laboratory findings, cryptogenic cirrhosis and spontaneous bacterial peritonitis were diagnosed. Due to persistent fever and backache, serum Brucella agglutination test was performed and found to be positive. Brucella melitensis was isolated from ascitic fluid culture. Liver biopsy findings revealed cirrhosis and a nongranulomatous hepatitis which was thought might be due to Brucella infection. Doxycycline and rifampicin, in addition to diuretics were administered for spontaneous ascites infection due to Brucella. A week later, the patient's condition improved and he became afebrile. After two months of therapy, the ascites had almost disappeared.

Peripartum genital tuberculosis presenting with ascites.

Extra-pulmonary tuberculosis may affect multiple sites within the body. The symptoms vary widely and diagnosis requires a high clinical suspicion. In rare cases, tuberculosis may be manifest in the genitalia, initially presenting as infertility. Here we report a clinical case of a 23-year-old female with peripartum genital tuberculosis who presented at 2 weeks after delivery with fever and increasing abdominal girth.