Tugrul Purnak

Mean platelet volume as an indicator of disease severity in patients with acute pancreatitis.

AIM Acute pancreatitis (AP) constitutes a systemic inflammatory process which is often accompanied by thrombosis and bleeding disorders. The role of platelets in the pathophysiology of the disease has not been elucidated yet. Mean platelet volume (MPV) is an index of platelet activation and reported to be influenced by inflammation. The objective of the present study is to assess whether platelet volume would be useful in predicting disease severity in AP. Additionally possible relationship of MPV with clinical and radiologic parameters in conjunction with other inflammatory markers during AP was also investigated. PATIENTS AND METHODS A total of 144 AP patients (male/female: 87/57), and 40 healthy subjects (male/female: 23/17) were enrolled in this study. Mean platelet volume and inflammatory parameters were measured for all study participants. Modified Glasgow Prognostic Score (mGPS) and the computerized tomography severity index (CTSI) were used as to predict the disease severity in AP patients. RESULTS A statistically significant decrease in MPV levels was observed in AP patients (8.06 ± 0.71 fL) compared with healthy controls (8.63 ± 0.62 fL) (P<0.001). According to the mGPS, overall accuracy of MPV in determining severe AP was 72.7% with a sensitivity, specificity, NPV and PPV of 70.6%, 73.9%, 81.9%, and 60 respectively (AUC: 0.762). Overall accuracy of MPV in predicting disease severity according to CTSI was not superior compared with other inflammation markers. CONCLUSION The present study demonstrated that MPV is decreased in AP. Assessment of MPV with other inflammatory markers may provide additional information about disease severity in AP.

Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome and associated extrahepatic autoimmune diseases.

Aim To assess the prevalence of concurrent extrahepatic autoimmune diseases in patients with autoimmune hepatitis (AIH)/primary biliary cirrhosis (PBC) overlap syndrome and applicability of the ‘mosaic of autoimmunity’ in these patients. Methods The medical data of 71 AIH/PBC overlap patients were evaluated for associated autoimmune diseases. Results In the study population, 31 (43.6%) patients had extrahepatic autoimmune diseases, including autoimmune thyroid diseases (13 patients, 18.3%), Sjögren syndrome (six patients, 8.4%), celiac disease (three patients, 4.2%), psoriasis (three patients, 4.2%), rheumatoid arthritis (three patients, 4.2%), vitiligo (two patients, 2.8%), and systemic lupus erythematosus (two patients, 2.8%). Autoimmune hemolytic anemia, antiphospholipid syndrome, multiple sclerosis, membranous glomerulonephritis, sarcoidosis, systemic sclerosis, and temporal arteritis were identified in one patient each (1.4%). A total of 181 autoimmune disease diagnoses were found in our patients. Among them, 40 patients (56.4%) had two, 23 (32.3%) had three, and eight (11.3%) had four diagnosed autoimmune diseases. Conclusion A large number of autoimmune diseases were associated with AIH/PBC overlap patients. Therefore, extended screening for existing autoimmune diseases during the routine assessment of these patients is recommended. Our study suggests that the concept of ‘mosaic of autoimmunity’ is a valid clinical entity that is applicable to patients with AIH/PBC overlap syndrome.

Long-term Efficacy and Safety of Lamivudine, Entecavir, and Tenofovir for Treatment of Hepatitis B Virus–Related Cirrhosis

BACKGROUND & AIMS Data are limited on the efficacy and safety of tenofovir and entecavir when given for more than 1 year to patients with hepatitis B-related cirrhosis. We investigated the long-term safety and efficacy of these antiviral drugs in patients with chronic hepatitis B virus (HBV) infection, with compensated or decompensated cirrhosis, and compared results with those from lamivudine. METHODS We performed a retrospective analysis of data from 227 adult patients with chronic HBV infection who were diagnosed with cirrhosis, beginning in 2005, at 18 centers throughout Turkey. There were 104 patients who had decompensated cirrhosis, and 197 patients were treatment naive before. Seventy-two patients received tenofovir (followed up for 21.4 ± 9.7 mo), 77 patients received entecavir (followed up for 24.0 ± 13.3 mo), and 74 patients received lamivudine (followed up for 36.5 ± 24.1 mo). We collected data on patient demographics and baseline characteristics. Laboratory test results, clinical outcomes, and drug-related adverse events were compared among groups. RESULTS Levels of HBV DNA less than 400 copies/mL were achieved in 91.5%, 92.5%, and 77% of patients receiving tenofovir, entecavir, or lamivudine, respectively. Levels of alanine aminotransferase normalized in 86.8%, 92.1%, and 71.8% of patients who received tenofovir, entecavir, and lamivudine, respectively. Child-Turcotte-Pugh scores increased among 8.5% of patients who received tenofovir, 15.6% who received entecavir, and 27.4% who received lamivudine. Frequencies of complications from cirrhosis, including hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma, and mortality, were similar among groups. Lamivudine had to be changed to another drug for 32.4% of the patients. CONCLUSIONS Tenofovir and entecavir are effective and safe for long-term use in patients with compensated or decompensated cirrhosis from HBV infection.

Mean platelet volume is increased in chronic hepatitis C patients with advanced fibrosis.

BACKGROUND AND AIMS Liver biopsy is the gold standard procedure for documenting liver damage in chronic hepatitis C (CHC), as for many other chronic liver diseases. Mean platelet volume (MPV) is a laboratory marker obtained from complete blood count (CBC) analysers in routine clinical practice. The goal of the present study was to evaluate whether MPV would be useful in predicting liver histologic severity in CHC. PATIENTS AND METHODS A total of 59 patients with CHC and 25 control subjects were recruited into the present study. There were 26 men and 33 women in the CHC group and 12 men and 13 women in the control group. MPV was recorded at the time of admission. The clinical characteristics of CHC patients, including demographics, laboratory and liver biopsy findings, were reviewed. RESULTS A statistically significant increase in MPV values was observed in CHC patients (8.54 ± 0.63 fL) compared to healthy controls (7.65 ± 0.42 fL) (P < 0.001). Moreover, MPV values were significantly higher among patients with advanced fibrosis as compared to those with mild fibrosis (8.99 ± 0.57 fL vs. 8.19 ± 0.50 fL P < 0.001). Receiver operator characteristic (ROC) curve analysis suggested that the optimum cut-off point for MPV value in advanced fibrosis was 8.75 fL. (Sensitivity: 80.8%, specificity: 81.8%, positive predictive value [PPV] 77.8%, negative predictive value [NPV] 84.4%, accuracy 81.3%, AUC: 0.98 P < 0.001) CONCLUSION The current study showed that MPV is increased in CHC with advanced fibrosis. Calculation of MPV along with the use of other markers may give further information about liver fibrosis severity in CHC.

The Development of Autoimmune Hepatitis and Primary Biliary Cirrhosis Overlap Syndrome During the Course of Connective Tissue Diseases: Report of Three Cases and Review of the Literature

The term hepatic overlap syndrome is used to describe variant forms of autoimmune hepatitis (AIH) that present characteristics of AIH and primary biliary cirrhosis (PBS) or primary sclerosing cholangitis (PSC). It is still unclear whether these overlap syndromes are different entities or they are only variants of major autoimmune hepatopathies, and they do not have codified definitions [1–3]. Patients with overlap syndrome present with both cholestatic and hepatitic profiles, either simultaneously or consecutively. AIH–PBC is the most common form, affecting almost 10% of patients with AIH or PBC [2–4]. Liver involvement in patients with connective tissue diseases (CTD) is an uncommon condition. Hepatotoxic drugs, coincident viral hepatitis and development of autoimmune hepatic diseases have been implicated as the main causes of liver diseases in patients with connective tissue diseases [5–7]. We present here the development of AIH–PBC overlap syndrome in three patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Sjögren’s syndrome (SS). Case Reports

Autoimmune liver disease in patients with systemic lupus erythematosus: A retrospective analysis of 147 cases

Abstract Objective. We aimed to investigate the characteristics of autoimmune liver disease (AILD) developed in patients with systemic lupus erythematosus (SLE), including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and the AIH/PBC overlap syndrome. We also evaluated the accuracy of diagnostic criteria and scoring systems for AILD in SLE. Methods. A retrospective analysis of patients attending the rheumatology and gastroenterology clinics in Ankara, Turkey, between 1999 and 2010. SLE patients with elevated liver enzymes were investigated for liver diseases. Results. A total of 147 SLE patients were identified and 36 of them had liver enzyme abnormalities. AILD was diagnosed in 4.7% of all SLE patients, in 19.4% of those with elevated liver enzymes. Of patients with liver enzyme abnormalities, 72.3% fulfilled the criteria for AIH proposed by the International Autoimmune Hepatitis Group (IAIHG), whereas 66.7% had AIH by using the simplified criteria. Yet, only 13.8% of these patients had liver biopsy findings consistent with AIH. Patients with AILD were treated with conventional therapy including ursodeoxycholic acid, prednisolone, azathioprine or combinations of these. Treatment failure and subsequent advanced liver disease developed in one patient. Conclusions. AILD may occur during the course of SLE. Due to biochemical similarities between AIH and SLE, AIH could be considered very probable by using both IAIHG scoring system and simplified criteria. For definitive diagnosis of AIH, liver biopsy should be performed in all SLE patients with chronic enzyme abnormalities. The response to therapy is favorable in these patients, and early diagnosis is important for preventing advanced liver disease.

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.

Mean platelet volume could be a promising biomarker to monitor dietary compliance in celiac disease

Abstract Background. Celiac disease (CD) is an autoimmune disease that develops in patients with a genetic predisposition, incurring a susceptibility to gluten-containing foods such as barley, wheat, and rye. The elimination of gluten from the diet is the main therapeutic approach and usually leads to clinical and laboratory improvement. There are no ideal markers that objectively assess dietary compliance in CD patients. Materials and methods. Sixty newly diagnosed CD patients (male/female: 43/17) and 40 healthy subjects (male/female: 23/17) were enrolled in this study. The diagnosis of CD was established by both histological findings of duodenum biopsy (total villous atrophy and lymphocytic infiltration) and positive antibodies against endomysium or gliadin. Results. A significantly higher mean platelet volume (MPV) was observed in the CD group compared with healthy subjects (8.45 ± 0.96 fL versus 7.93 ± 0.63 fL; p = 0.004). After introduction of a gluten-free diet, the MPV of CD patients in the dietary adherent group was significantly lower than that of the non-adherent group (8.09 ± 0.6 fL versus 8.9 ± 1.08 fL; p = 0.001). Overall dietary adherence rate was 71.6% (43/60 CD patients). In the dietary compliant group, initiation of gluten-free diet was associated with a significant decrease in MPV from base-line values (8.56 fL versus 8.25 fL; p = 0.008). In the non-adherent group, MPV on 3-month follow-up was higher than at base-line (8.05 fL versus 8.91 fL; p = 0.001). Conclusion. MPV could be a promising and easily available biomarker for monitoring of dietary adherence in CD patients at a low cost in comparison with other modalities.

Antibodies to soluble liver antigen in patients with various liver diseases: A multicentre study

Antibodies to soluble liver antigen (anti‐SLA) are specific serological markers of autoimmune hepatitis (AIH). The clinical significance and frequency of anti‐SLA have never been reported among AIH patients from Italy and Turkey.

The evaluation of bone mineral density in patients with nonalcoholic fatty liver disease

Background and aimNonalcoholic fatty liver diseases (NAFLD) are a clinical spectrum of disorders, of which nonalcoholic steatohepatitis (NASH) is the most strongly associated with inflammation. Inflammation is a known risk factor for low bone mass in the body. The primary goal of the present study was to evaluate the association between bone mineral density and liver function in patients with NASH.Materials and methodsConsenting patients with a diagnosis of NAFLD were included in the study. Extent of fatty change was graded based on ultrasonographic appearance (Grade 1, mild; Grade 2, moderate; Grade 3, severe). Bone mineral density was measured using the dual-energy x-ray absorptiometry method. ALT and hs-CRP were considered as noninvasive marker of NASH. According to ALT levels, patients were divided into two subgroups.ResultsA total of 102 patients with NAFLD and 54 healthy controls participated in the study. None of the patients with NAFLD had an abnormal bone mineral density. Furthermore, there was no difference between groups with regard to serum vitamin D levels. A subgroup analysis revealed that female patients with elevated serum ALT level had significantly lower bone mineral densities and higher hsCRP levels than female patients with normal ALT levels. The difference in vitamin D levels and body mass indices between the same subgroups was statistically insignificant.ConclusionsSimple steatosis of the liver does not affect bone mineral density. However, in a subgroup of patients with NAFLD, the presence of elevated serum ALT and hs-CRP levels, which are suggestive of NASH, was associated with lower bone mineral densities. Better understanding of the biological basis and the complex interactions between NAFLD and bone mass may help guide the clinical management of bone diseases associated with inflammation of the liver.ZusammenfassungHintergrund und ZielVom klinischen Spektrum der nicht-alkoholischen Fettlebererkrankungen (NAFLD) ist die nicht-alkoholische Steaotohepatitis (NASH) am meisten mit einer Entzündung assoziiert. Entzündung ist ein bekannter Risikofaktor für Abnahme der Knochenmasse des Körpers. Das primäre Ziel unserer Studie war es, bei Patienten mit NASH den Zusammenhang zwischen der Mineraldichte des Knochens und der Leberfunktion zu evaluieren.Material und MethodenNach Zustimmung zur Teilnahme wurden Patienten mit der Diagnose einer NAFLD in die Studie aufgenommen. Das Ausmass der Verfettung der Leber basierte auf dem sonographischen Befund (Grad 1: mild, Grad 2: mäßig, Grad 3: schwer). Die Knochendichte wurde mittels der Dualen-Energie Röntgen Absorptiomerie Methode erhoben. Die ALT und das hoch-sensitivive (hs) CRP dienten als nicht-invasive Marker der NASH: je nach ALT Werten wurden die Patienten in 2 Untergruppen eingeteilt.ErgebnisseInsgesamt nahmen 102 Patienten mit NAFLD und 54 Kontrollen an der Studie teil. Keiner der Patienten mit NAFLD hatte eine abnormale Knochendichte. Es bestand auch kein Unterschied bezüglich der Vitamin D Spiegel. Die Analyse der Subgruppen ergab, dass Frauen mit erhöhter ALT signifikant niedrigere Knochendichte und höhere hsCRP Spiegel im Vergleich zu weiblichen Patienten mit normalen ALT Spiegeln aufwiesen. Es bestand in diesen Untergruppen kein signifikanter Unterschied in den Vitamin D Spiegeln und den Body Mass Indices.SchlußfolgerungenDie Steatose der Leber allein hat keine Auswirkung auf die Mineraldichte des Knochens. In einer Untergruppe der Patienten mit NAFLD wurde jedoch bei jenen mit erhöhter ALT und hsCRP (was als Hinweis auf eine NASH gilt) eine relativ verminderte Knochendichte beobachtet. Ein besseres Verständnis der biologischen Grundlagen und der komplizierten Interaktionen zwischen den NAFLD und der Knochendichte könnten im klinischen Management von mit Entzündung der Leber assoziierten Knochenerkrankungen helfen.