D-dimers in advanced liver cirrhosis: Useful biomarker or not?

In clinical practice, the d-dimer levels rule out venous thromboembolism and diagnose disseminated intravascular coagulation. d-dimers increase in both physiological and pathological conditions. Liver cirrhosis, especially in the final stages, is characterized by complex coagulation and fibrinolysis factor disorders. Multiple mechanisms tried to explain the increased d-dimer levels in patients with liver cirrhosis and ascites. The d-dimer cut-off level used to rule out venous thromboembolism in cirrhosis is higher than that used to confirm the diagnosis of VTE or DIC in noncirrhotic patients. The cut-off d-dimer level used for the prognosis of thrombotic events is not standardized in advanced liver cirrhosis. Thus, it is necessary to update the clinical guidelines regarding the usefulness of d-dimer testing in advanced liver cirrhosis and the cut-off d-dimer levels, which should vary based on the detection method.

Management of Postpartum Extensive Venous Thrombosis after Second Pregnancy.

Background: Pregnancy induces a physiological prothrombotic state. The highest risk period for venous thromboembolism and pulmonary embolism in pregnant women is during the postpartum period. Materials and Methods: We present the case of a young woman who gave birth 2 weeks before admission and was transferred to our clinic for edema. She had an increased temperature in her right limb, and a venous Doppler of the limb confirmed thrombosis of the right femoral vein. From the paraclinical examination, we obtained a CBC with leukocytosis, neutrophilia, and thrombocytosis, and a positive D-dimer test. Thrombophilic tests were negative for AT III, lupus anticoagulant negative, and protein S and C, but were positive for heterozygous PAI-1, heterozygous MTHFR A1298C, and EPCR with A1/A2 alleles. After 2 days of UFH with therapeutic APTT, the patient had pain in her left thigh. We performed a venous Doppler, which revealed bilateral femoral and iliac venous thrombosis. During the computed tomography examination, we assessed the venous thrombosis extension on the inferior cava, common iliac, and bilateral common femoral veins. Thrombolysis was initiated with 100 mg of Alteplase given at a rate of 2 mg/h; however, this did not lead to a considerable reduction in the thrombus. Additionally, the treatment with UFH was continued under therapeutic APTT. After 7 days of UFH and triple antibiotic therapy for genital sepsis, the patient had a favorable evolution with remission of venous thrombosis. Results: Alteplase is a thrombolytic agent that is created with recombinant DNA technology, and it was successfully used to treat thrombosis that occurred in the postpartum period. Conclusions: Thrombophilias are associated with a high VTE risk but also with adverse pregnancy outcomes, including recurrent miscarriages and gestational vascular complications. In addition, the postpartum period is associated with a higher VTE risk. A thrombophilic status with heterozygous PAI-1, heterozygous MTHFR A1298C, and EPCR with A1/A2 positive alleles is associated with a high risk of thrombosis and cardiovascular events. Thrombolysis can be successfully used postpartum to treat VTEs. Thrombolysis can be used successfully in VTE developed in the postpartum period.

Surgery for Inflammatory Bowel Disease in the Era of Biologic Therapy: A Multicenter Experience from Romania.

Background and Objectives: Biologic therapy has fundamentally changed the opportunity of medical treatment to induce and maintain remission in inflammatory bowel disease (IBD). Nevertheless, the rate of surgery is still at a very high rate, profoundly affecting the quality of life. We aimed to analyze surgical cases at three major IBD units in order to identify the main risk factors and the impact of biologic therapy on pre- and postsurgical outcomes. Material and Methods: This was a multicenter retrospective cohort study that included 56 patients with IBD-related surgical interventions from 3 tertiary care hospitals in Bucharest, Romania. The study was conducted between January 2017 and June 2021. All data were retrospectively collected from the medical records of the patients and included the age at diagnosis, age at the time of surgery, IBD type and phenotype, biologic therapy before or/and after surgery, timing of biologic therapy initiation, extraintestinal manifestations, type of surgery (elective/emergency), early and long-term postoperative complications and a history of smoking. Results: A low rate of surgical interventions was noted in our cohort (10.3%), but half of these occurred in the first year after the IBD diagnosis. A total of 48% of the surgical interventions had been performed in an emergency setting, which seemed to be associated with a high rate of long-term postoperative complications. We found no statistically significant differences between IBD patients undergoing treatments with biologics before surgery and patients who did not receive biologics before the surgical intervention in terms of the IBD phenotype, type of surgery and postoperative complications. Conclusion: Our study showed that biologics initiated before the surgical intervention did not influence the postoperative complications. Moreover, we demonstrated that patients with Crohn's disease and no biologics were the most susceptible to having to undergo surgery. Conclusion: In conclusion, the management of patients with IBD requires a multidisciplinary approach that considers an unpredictable evolution.

Low-Cost Predictors for Liver Function and Clinical Outcomes after Sustained Virological Response in Patients with HCV-Related Cirrhosis and Thrombocytopenia.

Background and Objectives: To find low-cost markers that can identify the hepatitis C virus cirrhotic patients that are at risk for long-term severe adverse liver effects (ascites, ascites or upper gastrointestinal bleeding, hepatocellular carcinoma), after treatment. There is established evidence for the benefits of treating hepatitis C virus cirrhotic patients, but there is still some need for clarification concerning the real impact on the long-term evolution after achieving sustained virological response; there is no general consensus in the literature about identifying the patients that do not improve post-treatment. Materials and Methods: Our retrospective analysis investigated the long-term (2 years) evolution of 46 patients with cirrhosis with thrombocytopenia, previously infected with VHC, treated and who obtained an SVR after DAA treatment. Results: Despite the overall improvement, 8.7% patients developed hepatocellular carcinoma and 6.5% patients ascites/upper GI bleeding. We found that FIB-4, MELD and AFP changes at 1 year were the most significant predictors for these outcomes. Additionally, a drop in leukocyte count after 1 year seemed to indicate a risk for hepatocellular carcinoma, but this was not consistent. Conclusions: It might be beneficial to intensify the surveillance for post-treatment adverse liver effects for the patients with these marker changes at 1 year.

Epithelioid hemangioendothelioma - an unexpected diagnosis of a mediastinal tumor with extensive local thrombosis.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor and the mediastinal localization is amongst the most infrequent. We present the case of a 37-year-old woman with a history of resected left thyroid tumor that presented to our department for evaluation of a left supraclavicular palpable mass in close contact with local vascular structures, and with heterogeneous contrast enhancement as described by computed tomography (CT) and magnetic resonance imaging (MRI). Considering the history of the patient, the presumptive diagnosis of thyroid tumor recurrence was established, and the patient was referred to surgical department. During procedure, we encountered important bleeding from a ruptured jugular vein branch, which we assumed to be a newly formed tumor blood vessel. After surgery (48 hours postoperatively), the patient developed important local thrombosis that encompassed the left internal jugular vein, left subclavian vein and the left brachiocephalic trunk that partially subsided after anticoagulant therapy. The histological examination revealed the presence of a vascular tumor proliferation of epithelioid endothelial cells that was characteristic of an EHE confirmed later on the immunohistochemical studies as Yes-associated protein 1-transcription factor E3 (YAP1-TFE3) subtype. In addition to the case report, some relevant information from the scarce literature data about mediastinal EHE were reviewed here.

Hyposplenism, Hashimoto's Autoimmune Thyroiditis and Overlap Syndrome (Celiac Disease and Autoimmune Hepatitis Type 1).

Hyposplenism is associated with autoimmune diseases, inflammatory bowel disease, severe celiac disease, autoimmune thyroiditis, untreated HIV infection and chronic graft-versus-host disease. The aim of this study was to review the existing data on hyposplenism associated with celiac disease and Hashimoto's autoimmune thyroiditis. Our research was based on a clinical case concerning a 41-year-old female who presented with asthenia, fatigue, dyspepsia and chronic diarrhea. The medical history revealed autoimmune Hashimoto's thyroiditis, type 2 diabetes, fatty liver disease, chronic gastritis and thrombocytosis. Multiple investigations showed hyposplenism and complex autoimmune dysfunction with positive serum markers for celiac disease and type 1 autoimmune hepatitis along with minor symptomatology. The intestinal symptomatology of celiac disease is often hid by hypothyroidism-associated autoimmune thyroiditis. Asymptomatic or minimally symptomatic celiac disease associated with Hashimoto's autoimmune thyroiditis is diagnosed by biomarkers. Hyposplenism in celiac disease can occur regardless of the disease stage, latent or symptomatic.

Incidental case of primary renal lymphoma (PRL) in a patient with chronic hepatitis C infection. Report of a rare case.

Chronic viral hepatitis C (CHC) is a global health problem, being responsible for about 399 000 deaths worldwide, mostly from cirrhosis and hepatocellular carcinoma. Virus C infection has well known hepatic manifestations - cirrhosis and liver cancer - but the extrahepatic ones are responsible for up to 75% of morbidity in these patients. The well-known hepatitis C virus (HCV) lymphotropism is probably linked with the most frequent extrahepatic manifestations, mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma (BCNHL). We report a very rare entity, the case of an 82-year-old female with Child-Pugh class A viral C cirrhosis associated with a primary renal lymphoma (PRL). PRL is a non-Hodgkin's lymphoma (NHL) localized in the kidney, without any involvement of extrarenal lymphatic tissue. In addition to the case report, some relevant data from the literature were reviewed here.

Cecal Malakoplakia - an Unusual Cause of Anemia in Liver Cirrhosis.

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A randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy, safety, and tolerability of prucalopride in men with chronic constipation.

OBJECTIVES: Prucalopride is effective at alleviating symptoms of chronic constipation in women. The aim of this study was to assess the efficacy of 12 weeks of prucalopride treatment compared with placebo in men with chronic constipation. METHODS: This was a multicenter, stratified, randomized, parallel-group, double-blind, placebo-controlled, phase 3 study (ClinicalTrials.gov identifier: NCT01147926). The primary end point was the proportion of patients with a mean of three or more spontaneous complete bowel movements (SCBMs) per week across the treatment period. Efficacy end points were assessed using daily electronic diaries, global assessment of the severity of constipation and efficacy of treatment, and Patient Assessment of Constipation-Symptoms (PAC-SYM) and Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaires. RESULTS: In total, 374 patients were enrolled in the study. Significantly more patients achieved a mean of three or more SCBMs per week in the prucalopride group (37.9%) than in the placebo group (17.7%, P<0.0001). The proportion of patients rating their constipation treatment as "quite a bit" to "extremely" effective at the final on-treatment visit was 46.7 and 30.4% in the prucalopride and placebo groups, respectively. The difference between treatment groups was statistically significant (P<0.0001). The proportion of patients with an improvement of at least 1 point in PAC-QOL satisfaction subscale score was 52.7 and 38.8% in the prucalopride and placebo groups, respectively (P=0.0035). Prucalopride had a good safety profile and was well tolerated. CONCLUSIONS: Prucalopride is effective, has a good safety profile, and is well tolerated for the treatment of men with chronic constipation.

Idiopathic colonic varices: case report and review of literature.

INTRODUCTION: Colonic varices represent a very rare entity, either an incidental finding at colonoscopy or discovered due to its complication, the lower gastrointestinal bleeding. The most common cause of colonic varices is portal hypertension associated with liver disease or secondary to pancreatic conditions, like chronic pancreatitis or malignancies. The incidence of colonic varices is very low, even in liver cirrhosis where the patients frequently develop varices in the upper gastrointestinal tract, but surprisingly uncommon present with varices localized in the colon. CASE PRESENTATION: We report a case of idiopathic colonic varices, diagnosed at a routine colonoscopy performed for nespecific abdominal disturbances in a female patient without liver disease or pancreatic conditions responsible for portal hypertension development. CONCLUSIONS: The development of colonic varices in the absence of a certain trigger represents a major issue for practitioners due to its major complication, lower gastrointestinal bleeding.

Partial splenic embolization for hypersplenism in cirrhotic patients. A case series.

The prognosis of liver cirrhosis depends on the presence of its major complications as well as on other factors such as hypersplenism with thrombocytopenia. Partial splenic embolization is an effective interventional procedure performed in liver cirrhosis complicated with portal hypertension to improve the low platelet count. This technique represents an efficient alternative to splenectomy, which has major drawbacks and is associated with a high morbidity. We report a series of patients with liver cirrhosis and portal hypertension who presented with severe thrombocytopenia and were treated with partial splenic embolization eventually having a favourable outcome.

First multicenter study of modified release phosphatidylcholine "LT-02" in ulcerative colitis: a randomized, placebo-controlled trial in mesalazine-refractory courses.

OBJECTIVES: Phosphatidylcholine is a key component of the mucosal barrier. Treatment with modified release phosphatidylcholine aims to improve the impaired barrier function. The primary objective is to evaluate the efficacy of LT-02, a newly designed modified release phosphatidylcholine formula, in a multicenter setting. METHODS: This is a double-blinded, randomized, placebo-controlled, superiority study conducted in 24 ambulatory referral centers in Germany, Lithuania, and Romania. A total of 156 patients with an inadequate response to mesalazine, a disease activity score (Simple Clinical Colitis Activity Index (SCCAI)) of ≥ 5, and bloody diarrhea underwent treatment with 0, 0.8, 1.6, or 3.2 g LT-02. The primary end point was defined a priori as changes in SCCAI from baseline to the end of treatment. The primary statistical model was a general linear least-squares model. The study was funded by the sponsor Lipid Therapeutics, Heidelberg, Germany, and registered at http://clinicaltrials.gov/show/NCT01011322. RESULTS: Baseline characteristics and dropouts were well balanced between all groups. The primary analyses revealed an SCCAI drop of 33.3% in the placebo group (from 9.0 to 6.0 points) compared with 44.3% in the 0.8 g LT-02 (from 8.8 to 4.9, P>0.05) and 40.7% in the 1.6 g groups (from 8.6 to 5.1, P>0.05). The 3.2 g group improved 51.7% from 8.5 to 4.1 (P=0.030 in comparison with placebo). The remission rate was 15% (6/40) in the placebo group compared with 31.4% (11/35) in the highest LT-02 dose group (P=0.089). Mucosal healing was achieved in 32.5% of placebo patients compared with 47.4% of LT-02 patients (P=0.098); the rates for histologic remission were 20% compared with 40.5%, respectively (P=0.016). There were 17 (48.6%) treatment-emergent adverse events in the highest dose group (and 0 serious adverse events (SAEs)) compared with 22 (55%) in the placebo group (4 SAEs). CONCLUSIONS: The primary end point analysis showed a statistically significant improvement in disease activity during LT-02 treatment in comparison with placebo. The drug was found to be very safe.

Upper gastrointestinal bleeding in a young patient with Budd Chiari syndrome due to a mutation of factor V Leiden: a case report.

Budd Chiari syndrome or hepatic venous outflow obstruction is a complex entity with multiple etiologies and various clinical manifestations. It is often difficult to establish the diagnosis. The most common cause is a hypercoagulable state due to either genetic disorders of blood coagulation or several acquired conditions such as hematological diseases, tumors, infections, chronic inflammatory diseases, pregnancy. The most common clinical presentation is hepatomegaly, abdominal pain and ascites, but the onset can also be dramatical and life threatening with upper digestive bleeding due to portal hypertension through postsinusoidal blockage. We report the case of a young patient with a coagulation disorder secondary to a mutation of factor V Leiden, who presented with upper digestive bleeding as the first manifestation of Budd Chiari syndrome and who also was associated with myocardial infarction in his past medical history.

Noninvasive investigations for non alcoholic fatty liver disease and liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflammation and fibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several noninvasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. These markers are currently neither available in all centers nor validated in extensive studies. Examples include high-sensitivity C reactive protein and plasma pentraxin 3, which are associated with extensive liver fibrosis in NASH. Interleukin-6 correlates with inflammation, and cytokeratin-18 represents a marker of hepatocyte apoptosis (prominent in NASH and absent in simple steatosis). Tissue polypeptide specific antigen seems to have a clinical utility in the follow-up of obese patients with NASH.

Liver involvement in Langerhans' cell histiocytosis. Case report.

Langerhans'cell histiocytosis (Histiocytosis X) is a rare disease of unknown cause characterized by oligoclonal proliferation of Langerhans cells. It occurs mostly in children and young adults and involves one or more body systems such as bone, hypothalamus, posterior pituitary gland, lymph nodes, liver or various soft tissues. The diagnosis is always made by a histological approach. We report a case of Langerhans'cell histiocytosis in a young patient with clinical signs of diabetes insipidus and hepatic involvement in whom the immunohistochemical analysis of the liver tissue led to the definitive diagnosis.