Taylan Kav

Factors Associated With Response to Therapy and Outcome of Patients With Primary Biliary Cirrhosis With Features of Autoimmune Hepatitis

BACKGROUND & AIMS For patients with primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid (UDCA) alone or in combination with immunosuppression is controversial. Little is known about the factors associated with initial response to therapy or outcome. We performed a retrospective analysis of treatment strategies and factors associated with outcomes of patients with PBC-AIH. METHODS We analyzed data from 88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7 centers in 5 countries. First-line therapies included UDCA alone (n = 30) or a combination of UDCA and immunosuppression (n = 58). RESULTS Of patients who received UDCA alone as the first-line therapy, 37% did not respond to treatment. Severe interface hepatitis was independently associated with lack of response to treatment (P = .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The combination of UDCA and immunosuppression was effective in 73% of patients who had not been previously treated or had not responded to UDCA. The presence of advanced fibrosis was associated with lack of response to the combination of UDCA and immunosuppression (P = .003; odds ratio, 0.13; 95% confidence interval, 0.03-0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and mycophenolate mofetil) led to biochemical remission in 54% of patients who did not respond to initial immunosuppression. Liver transplants were given to 4 patients with PBC-AIH. Five patients died during follow-up (3 from liver-related causes). CONCLUSIONS In a retrospective study of a large cohort of patients with PBC-AIH, UDCA alone did not produce a biochemical response in most patients with severe interface hepatitis; these patients require additional therapy with immunosuppression. Second-line immunosuppressive agents are effective in controlling disease activity in patients who do not respond to conventional immunosuppression.

Use of Complementary and Alternative Medicine: A survey in Turkish Gastroenterology Patients

BackgroundThe study examined complementary and alternative medicine (CAM) usage by patients attending a Turkish gastroenterology outpatient clinic.MethodsThe survey was conducted on 216 patients presenting with gastrointestinal problems during their first visit to the clinic using a 31 item, self-report questionnaire between May and October 2005. Data included information on patient demographics and their gastrointestinal symptoms, as well as items to identify CAM use and patient satisfaction with these therapies.ResultsSeventy-nine patients (36.6%) reported using one or more forms of CAM. The most commonly used therapy was herbal therapy, usually taken as a tea or infusion. These were used by 27 people (29%) in this subgroup. Common indicators for their use were epigastric pain, constipation, bloating and dyspepsia or indigestion. CAM use among upper GI patients was marginally higher than lower GI patients (41.8% versus 41.2%), but the highest usage was amongst patients with liver disease where 53.8% reported using one or more CAM therapy. About half of the patients learned about CAM from their relatives or friends, with more women than men using the therapies (p < 0.05). Clinical characteristics such as diagnosis, duration of symptoms and prior surgical intervention did not differ between users and non-users of CAM therapies. Multivariate analysis showed that being female and higher educational status were positively associated with CAM usage (p < 0.05).ConclusionCAM usage in our sample of gastrointestinal patients was lower than that described in other countries and other chronic disease groups. This could be due to their low perceived efficacy, or the relatively transient duration of symptoms experienced by the sample. Healthcare professionals need however, to be aware of CAM usage in order to educate patients appropriately about possible adverse effects or drug-interactions.

Pregnancy in women with primary biliary cirrhosis

BACKGROUND & AIMS Primary biliary cirrhosis (PBC) may present in all decades of life, also in childbearing age. Data on maternal and fetal outcome is limited. We aimed to investigate the impact of pregnancy and childbirth on the disease course and possible effects of PBC on fetal outcome. METHODS Retrospective study of local cases and a compact review of published reports between 1950 and 2014. RESULTS Our cases along with literature review provided 98 pregnancies in 72 PBC patients. PBC was diagnosed during pregnancy in 26 (36%) patients and 46 (64%) had the diagnosis before conception. Twenty-four (30%) of the pregnancies were associated with biochemical flares and 55 (70%) with clinical improvement or stabilization. De novo onset or worsening of pruritus was seen in 49% (45/92). No maternal deaths were reported. Post-partum disease activation was observed in 60% (53/88). One patient was referred for liver transplantation after delivery. A miscarriage rate of 24% and three stillbirths were reported. Most patients were treated with ursodeoxycholic acid (UDCA) during breastfeeding and 12 patients also received UDCA during the first trimester without any identified side effects. CONCLUSION Most women with PBC maintain a stable disease during pregnancy, but post-partum biochemical flares are common. Symptomatic pruritus may be challenging in pregnant PBC patients. UDCA appears to be safe during pregnancy and breastfeeding. A successful pregnancy outcome is a realistic expectation for women with PBC.

Effect of Connective Tissue Manipulation on Symptoms and Quality of Life in Patients With Chronic Constipation: A Randomized Controlled Trial

OBJECTIVE The purpose of this study was to examine the effects of connective tissue manipulation (CTM) on the severity of constipation and health-related quality of life in individuals diagnosed with chronic constipation. METHODS Fifty patients with a diagnosis of chronic constipation according to Rome III criteria were recruited and randomized to an intervention (n = 25) or control group (n = 25). The intervention group received CTM in addition to the lifestyle advice, whereas the control group was given only lifestyle advice for constipation. All assessments were performed at baseline and at the end of 4 weeks. The primary outcome measure was the Constipation Severity Instrument. Secondary outcomes included Patient Assessment of Constipation Quality of Life Questionnaire, Bristol Stool Scale, and 7-day bowel diary. Differences between groups were analyzed with t tests, Mann-Whitney U test and χ(2) test. RESULTS Compared with the control group, subjects in the intervention group reported significantly greater improvement in total and subscale scores of the Constipation Severity Instrument and Patient Assessment of Constipation Quality of Life Questionnaire (P < .05). Based on the results from bowel diaries, the improvements in the number of bowel movements, duration of defecation, stool consistency, and the feeling of incomplete evacuation in the intervention group were also significantly more than the control group (P < .05). CONCLUSION This study showed that CTM and lifestyle advice were superior to reducing symptoms of constipation and quality of life compared with lifestyle advice alone for patients with chronic constipation.

Long-term follow-up study in Budd-Chiari syndrome: single-center experience in 22 years.

Goals: We aimed to present our long-term surveillance experience in patients with Budd-Chiari syndrome (BCS), and we retrospectively evaluated the natural history, results of thrombophilia studies, and the factors related to mortality. Background: Primary BCS is a rare form of vascular disease, secondary to underlying thrombophilia. Because of its rarity and heterogeneous nature, there is a scarcity of knowledge about the natural history of the disease. Study and Results: In 22 years, a total of 62 patients with primary BCS were followed in our tertiary hospital. We identified an acquired cause of BCS in 40 out of 62 patients (64.5%), whereas in 6 patients (9.7%), we found no identifiable cause. One or more thrombophilia causes were identified in 56 patients (90.3%). In 19 patients with myeloproliferative disease, 15 had Janus tyrosine kinase 2 mutation analysis and Janus tyrosine kinase 2 positivity was found in 10 patients. In regression analysis, portal vein thrombosis was found to be the only indicator of mortality, with an estimated instantaneous risk of 8.4. Conclusions: In this study, we present one of the largest series of BCS in the English literature. We have shown that the multifactorial nature of underlying thrombophilia should be thoroughly investigated. In a patient with BCS, a clinician should be alert for the development or coexistence of portal vein thrombosis due to its deleterious effect on mortality.

Sequential presentation of primary biliary cirrhosis and autoimmune hepatitis.

Background Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is used to describe the coexistence of both diseases, with either a sequential or a simultaneous presentation in the same patient. Available studies have focused on the simultaneous form, whereas there is limited information on sequential PBC-AIH. We carried out a retrospective study of patients who sequentially developed PBC-AIH overlap syndrome. Methods The medical data of 1065 patients diagnosed with PBC (n=483) and AIH (n=582) were retrospectively analyzed. Results A sequential development of PBC-AIH was observed in 19 (1.8%) patients after a mean of 6.5 (1–14) years of follow-up. AIH developed in 12 (2.5%) PBC patients, whereas PBC occurred in seven (1.2%) patients with AIH. The baseline serologic and histological findings of patients who developed PBC-AIH were similar to those of patients with typical PBC or AIH. Eighteen patients were treated with a combination of ursodeoxycholic acid (UDCA) and immunosuppression after the diagnosis of PBC-AIH was established. One patient showed a spontaneous resolution of hepatitic flare under UDCA therapy. Biochemical remission was achieved in 16 patients, whereas three progressed to decompensated cirrhosis and required liver transplantation. Conclusion The sequential overlap of PBC-AIH can occur during the follow-up of patients with pure PBC or AIH. In our cohort, we could not identify any factors that predicted the development of this rare condition. The combination of UDCA and immunosuppression seems to be an appropriate therapy in the setting of PBC-AIH.

Red cell distribution width can predict intestinal atrophy in selected patients with celiac disease.

Red cell distribution width (RDW) has been shown as a distinctive marker of mortality and morbidity in a wide spectrum of conditions related to systemic inflammation or deficiency of antioxidant nutrients.

Angiotensin-converting enzyme for noninvasive assessment of liver fibrosis in autoimmune hepatitis.

Background and aim There are no validated noninvasive markers of liver fibrosis in autoimmune hepatitis (AIH). An activated renin–angiotensin system (RAS) and its key element angiotensin-converting enzyme (ACE) have been implicated in the pathogenesis of hepatic fibrogenesis. We aimed to study the assumed role of activated RAS in the fibrogenic process and whether the serum concentration of ACE can predict different fibrosis stages in AIH. Patients and methods Serum samples of 73 consecutive patients who were diagnosed with AIH were analysed for ACE concentration. All patients underwent a liver biopsy. Results Serum ACE levels increased significantly for each fibrosis score. The median ACE was 45 U/l in patients with fibrosis score I, 54 U/l in patients with fibrosis score II, 68 U/l in patients with fibrosis score III and 87 U/l in patients with fibrosis score IV. For significant fibrosis (⩽F2), a 56 U/l cut-off value of ACE had 95.5% sensitivity and 74.5% specificity, and receiver-operating characteristic curves showed an area under the curve (AUC) of 0.89. For advanced fibrosis (⩽F3), a 64 U/l cut-off level of ACE had 85.2% sensitivity and 94.8% specificity, and AUC was 0.91. For cirrhosis, a 68 U/l cut-off level of ACE had 100% sensitivity and 84.4% specificity, and AUC was 0.95. Conclusion Our results suggest that activated RAS may sustain hepatic fibrogenesis in AIH. Measurement of serum ACE offers an easy, accurate and inexpensive noninvasive method that differentiates significant from nonsignificant liver fibrosis in AIH. Blockade of RAS may exert beneficial effects on fibrosis progression in AIH.

Is enteroscopy necessary for diagnosis of celiac disease

Celiac disease (CD) is an autoimmune inflammatory disease of the small intestine as a result of reaction to wheat protein, gluten. Exclusion of dietary gluten is the mainstay of the treatment that necessitates a precise diagnosis of the disease. Serological screening may aid in identifying patients with suspected CD, which should be confirmed by intestinal biopsy. It has been shown that duodenal biopsies are good for detection of the disease in most patients. However, there is a group of patients with positive serology and inconclusive pathology. As a result of the widespread use of serology, many patients with equivocal findings grow quickly. Unfortunately current endoscopic methods can only diagnose villous atrophy, which can be present in the later grades of disease (i.e., Marsh III). To diagnose CD correctly, going deeper in the intestine may be necessary. Enteroscopy can reveal changes in CD in the intestinal mucosa in 10%-17% of cases that have negative histology at initial workup. Invasiveness of the method limits its use. Capsule endoscopy may be a good substitute for enteroscopy. However, both techniques should be reserved for patients with suspected diagnosis of complications. This paper reviews the current literature in terms of the value of enteroscopy for diagnosis of CD.

Gastrointestinal: An unexpected cause of refractory iron deficiency anemia; Taenia SPP. on capsule endoscopy

A 20 year-old man presented to our clinic for evaluation of iron deficiency anemia (IDA). He complained of fatigue, weight loss, intermittent abdominal pain and diarrhea. Upper and lower gastrointestinal endoscopic examinations were normal whereas serological markers for Celiac disease were also negative. Evaluation with capsule endoscopy revealed the presence of a tapeworm identified as belonging to the genus Taenia in the proximal third of the small bowel (Figure 1) and healing ulcers (Figure 2) which were also attributed to the parasite. No other lesion that could explain the anemia were found in this patient and he was started on iron replacement therapy with a course of niclosamide. During the follow up, his symptoms were resolved and hemoglobin turned normal levels. Although anemia is not considered a classical finding of infestation with Taenia spp., there are two reports of patients with unexplained refractory IDA in whom treatment of the infestation resulted in resolution of symptoms. The absence of any other lesion to which the anemia could be attributed led us to conclude that the tapeworm was responsible for the IDA in our patient in more ways than one (loss of appetite, interference with nutrient absorption and mucosal ulceration). The patient will of course be followed-up closely with regard to clinical response to treatment. According to international guidelines for the management of obscure gastrointestinal bleeding (including unexplained iron deficiency anemia), capsule endoscopy is indicated after negative upper and lower endoscopic studies. On the other hand, helminths are a recognized cause of anemia, particularly in developing countries where infestation is endemic. Unless patients confess to passing active or passive proglottids in the stool, arriving at a diagnosis may be challenging. In the event of unexplained IDA, empirical anti-helminthic treatment may be warranted for patients living in endemic areas before endeavoring on expensive and perhaps unnecessary investigations.