Mesenteric Ischemia in a Patient with Essential Thrombocythemia: Does COVID-19 Play Any Role? A Case Report and Overview of the Literature.

INTRODUCTION: Chronic mesenteric ischemia is a rare entity with non-specific symptomatology; combined with rare etiologies, it could lead to unwarranted surgical indication. CASE REPORT: We report the case of an 85-year-old woman, with a history of hypertension, persistent thrombocytosis, atherosclerosis, and recent minor COVID-19 infection, presenting to the hospital with postprandial abdominal pain and nonspecific clinical examination findings; upon abdominal CT, superior mesenteric artery circumferential thrombosis was revealed. A bone marrow biopsy was performed due to suspected essential thrombocythemia, confirming the diagnosis. An endovascular approach was chosen as therapy option and a stent was placed in the occluded area. Dual antiplatelet and cytoreductive therapies were initiated after the intervention. Clinical course was excellent, with no residual stenosis 1 month after stenting. CONCLUSIONS: The therapeutic strategy in elderly patients with exacerbated chronic mesenteric ischemia requires an interdisciplinary approach in solving both the exacerbation and the underlying conditions in order to prevent further thrombotic events. Although the patient presented a thrombotic state, other specific risk factors such as COVID-19 related-coagulopathy and essential thrombocythemia should be considered.

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus Infection and Thyroid Disease with Follow-Up Thyroid Function and Autoantibody Testing.

BACKGROUND Thyroiditis is an important extrahepatic association in chronic hepatitis C virus (HCV) infection. There have been reports of an association between SARS-CoV-2 infection and the onset or re-activation of autoimmune hypothyroidism. Therefore, we performed this prospective observational study of 42 patients with COVID-19 infection and a history of hepatitis C virus infection and thyroid disease with follow-up thyroid function and autoantibody testing. MATERIAL AND METHODS From April 2020 to October 2020, we performed a prospective observational study of patients with cured hepatitis C virus (HCV) infection and documented thyroid disease who became infected with SARS-CoV-2 (confirmed by SARS-CoV-2 RNA detection via reverse-transcription polymerase chain reaction [RT-PCT] from the upper respiratory tract, both nasal and pharyngeal swabs). Evaluation at 1 and 3 months after SARS-CoV-2 infection included serum determination of antithyroid antibodies (anti-thyroglobulin [anti-Tg] and antithyroid peroxidase [ATPO]), thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and evaluation of thyroid medication, with dose adjustment if required. RESULTS One-month follow-up showed that both patients with autoimmune thyroiditis as well as patients without antibodies had increased ATPO levels. Also, levels of TSH, fT3, and fT4 were significantly decreased. At 3-month follow-up, levels of ATPO were decreased in all patient groups and the levels of thyroid hormones increased to normal values. CONCLUSIONS This study supports previous reports of an association between SARS-CoV-2 infection and thyroid dysfunction associated with thyroid autoantibodies. Thyroid function tests may be considered as part of the laboratory work-up in patients with COVID-19.

Safety and efficacy of direct-acting antivirals for chronic hepatitis C in patients with chronic kidney disease.

BACKGROUND: This is a real-world evidence study that aims to analyze the efficacy, tolerability and safety profile of paritaprevir/ombitasvir/ritonavir and dasabuvir, in patients with renal impairment. METHODS: We conducted an observational prospective study, on 232 patients with chronic kidney disease, undergoing treatment with paritaprevir/ombitasvir/ritonavir and dasabuvir, for chronic hepatitis C infection - genotype 1b. Renal and liver function were assessed at the beginning of therapy, monthly during treatment and three months after therapy completion. RESULTS: All patients achieved sustained virologic response. Common side effects were nausea, fatigue and headache. Close monitoring of tacrolimus blood levels and dose reduction was required in kidney transplant recipients. CONCLUSIONS: HCV therapy in the setting of renal dysfunction has always been a challenging topic. Direct-acting antivirals have shown promising effects, demonstrating good tolerance and efficacy in patients with HCV infection and renal impairment. Sustained virologic response within our study population was 100%.

Glycemic Control in Patients Undergoing Treatment With Paritaprevir/Ombitasvir/Ritonavir and Dasabuvir for Chronic Hepatitis C Infection.

BACKGROUND/AIM: Patients with hepatitis C virus (HCV)-associated cirrhosis are more prone to developing type 2 diabetes mellitus than patients with any other etiology of cirrhosis. The main objective of this study was to evaluate the impact of all oral antiviral treatment with ritonavir-boosted paritaprevir/ombitasvir and dasabuvir (OBV/PTV/r + DSV) in patients with chronic genotype 1b HCV infection. PATIENTS AND METHODS: We retrospectively evaluated 806 patients who underwent antiviral therapy between December 2015 and July 2019. The laboratory data analyzed were liver function tests, kidney function tests, HCV viremia, fasting glucose levels, and glycosylated hemoglobin. RESULTS: Patients with impaired glucose metabolism were predominantly male and of older age compared to patients with normal glucose tolerance, and also had higher levels of transaminases. Proteinuria and higher creatinine levels were found in patients with impaired glucose metabolism. Overall, we found a 98.01% rate of sustained virologic response (SVR), with a non-significant difference between patients with normal and abnormal glucose metabolism. A statistically significant difference in SVR rates in patients with low degrees of fibrosis (F0-F2) versus those with advanced degrees of fibrosis (F3-F4) was found in both groups. Antiviral treatment resulted in significant decreases in fasting glucose levels and glycosylated hemoglobin levels in all patients with impaired glucose metabolism at SVR. CONCLUSION: Patients with pre-diabetes, as well as diabetic patients, achieved a better glycemic control after SVR obtained by ritonavir-boosted paritaprevir/ombitasvir and dasabuvir.

Multimodal Treatment of Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antivirals.

BACKGROUND: Direct-acting antivirals (DAAs) opened a new era in the management of hepatitis C virus (HCV)-associated liver disease. However, hepatic cancer screening should not be stopped after obtaining a sustained virologic response (SVR). Current guidelines offer several treatment options for hepatocellular carcinoma (HCC), mainly depending on its stage and the extent of liver disease, including tumor resection, liver transplantation (LT), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and systemic agents. This article provides an overview of treatment modalities for hepatocellular carcinoma and associated survival rates based on the experience of the Internal Medicine Center at Fundeni Clinical Institute while bringing into light previous medical research. METHODS: We included 59 patients with a personal history of hepatitis C virus infection, diagnosed with hepatocellular carcinoma at least one year after achieving a sustained virologic response through direct-acting antivirals. The albumin-bilirubin (ALBI) score and Barcelona Clinic Liver Cancer (BCLC) classification were assessed in each case, and all patients were treated accordingly. The subjects were monitored by liver function tests, tumor markers, blood cell count, coagulation profile, and imaging explorations. We investigated the Eastern Cooperative Oncology Group (ECOG) performance status, the response to applied treatments, and survival. RESULTS: Cirrhotic patients and multinodular tumor patterns were predominant. Most patients only experienced one therapeutic procedure, while the rest of the study group went through multiple treatment modalities (2-4), with a better outcome in terms of survival parameters. A large proportion presented with disease progression despite the therapeutic measures applied. A total of two liver transplants were performed, resulting in a 12-month disease-free period among these patients. The presence of diabetes mellitus (DM), multinodular disease, alpha-fetoprotein (AFP) over 300 ng/mL, and tumor dimension over 6 cm indicate poor overall survival. Both overall survival and progression-free survival were better in subjects who presented complete responses (CR) to HCC treatment. In patients undergoing a single intervention, the best overall survival was associated with surgical resection and RFA. CONCLUSION: The multimodal treatment of hepatocellular carcinoma represents the best approach, in order to maintain patients on the waiting list for liver transplantation. In hepatitis C virus infection, viral clearance is important to obtain. At the same time, particular attention should be paid to liver cancer screening even after obtaining a sustained virologic response.

Calprotectin in viral systemic infections-COVID-19 versus hepatitis C virus.

This study aims to evaluate differences in serum and fecal calprotectin in patients with HCV chronic hepatitis and COVID-19 infection and compare them to a control group. This observational study was performed between April 2020 and October 2020 in a single Internal Medicine center. We determined serum and fecal calprotectin, as well as levels of transaminases, C-reactive protein, ferritin, in 25 patients with COVID-19 infection, 30 patients with active HCV chronic infection and 38 patients with cured HCV infection. Serum levels of ALT, AST, C-reactive protein and ferritin were significantly higher in patients with COVID-19 infection (mean values of 127 IU/mL, 135 IU/mL, 123 mg/L and 1034 ng/mL, respectively) than in patients with active HCV infection (mean values of 68 IU/mL, 51 IU/mL, 17 mg/L and 528 ng/mL, respectively) or in patients with cured HCV infection (37 IU/mL, 29 IU/mL, 3.4 mg/L and 274 ng/mL, respectively). Also, serum and fecal calprotectin had increased concentrations in patients with COVID-19 (7.3 µg/mL and 394 µg/mg) versus patients with active hepatitis (2.4 µg/mL and 217 µg/mg) and patients with cured hepatitis (1.2 µg/mL and 38 µg/mg). Values were significantly higher in patients with digestive symptoms related to COVID-19. Serum and fecal calprotectin can be used as inflammatory markers in patients with active viral infections. In COVID-19, calprotectin concentrations can be correlated to the severity of disease, particularly in patients with digestive symptoms.

Correlation Between Serum Alpha-Fetoprotein and Tumour Size in Patients With Hepatocellular Carcinoma Treated With Direct-Acting Antivirals.

OBJECTIVES: Since its first description, alpha-fetoprotein has become the most widely used marker for diagnosing and monitoring patients with hepatocellular carcinoma (HCC). This study aims to assess the correlation between serum levels of alpha-fetoprotein and tumour dimensions in patients diagnosed with HCC, that were previously treated with direct-acting antivirals for hepatitis C viral infection. MATERIALS AND METHODS: We conducted a retrospective cohort study on 47 patients with a personal history of hepatitis C virus infection, who were diagnosed with different forms of HCC more than one year after achieving sustained virologic response after 12 weeks post-treatment. Patients were monitored by liver function tests, tumoral markers, blood cell count and coagulation profile and underwent imagistic explorations such as abdominal ultrasonography and, in selected cases, computerised tomography/magnetic resonance imaging. Tumour burden was assessed by both tumour burden score and seven-eleven criteria. RESULTS: The study mostly included cirrhotic patients, multinodular HCC being the predominant pattern. All patients had alpha-fetoprotein levels over 100 ng/ml, with values largely varying, in accordance with the tumour dimensions. Most patients had medium-range Tumour Burden Score, a variable that also correlated with nodule size. CONCLUSIONS: The study found a significant correlation between serum alpha-fetoprotein and tumour size in patients with HCC. Alpha-fetoprotein also correlated well with Tumour Burden Score and remains a very important diagnostic and prognostic tool for patients with HCC.

Safety and Efficacy of Direct-acting Antiviral Therapies for Chronic HCV Infection in Hemodialysis Patients.

BACKGROUND/AIM: The aim of this study was to determine the safety and efficacy of a direct-acting antiviral treatment, ombitasvir/paritaprevir/ritonavir and dasabuvir, without ribavirin, in a real-life setting. PATIENTS AND METHODS: We performed a prospective observational study including 108 patients undergoing hemodialysis for end-stage kidney disease, referred to our clinic for antiviral therapy for chronic hepatitis C virus infection. Patients received treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, for 12 weeks. Sustained virologic response (SVR) was defined as undetectable viremia at 12 weeks after the end of therapy. For safety analysis, we monitored serum levels of hemoglobin, albumin, total bilirubin, alanine-aminotransferase and aspartate- aminotransferase at the beginning and end of therapy, as well as at SVR. Verbal Numeric Rating Scale was used to assess the presence of nausea, headaches and fatigue. RESULTS: We noted a high prevalence of diabetic and hypertensive nephropathy as the underlying cause of chronic kidney disease. Most of the patients had F2 and F3 liver fibrosis (32.40% and 34.25%, respectively). The SVR rate was 96.2% (103/107 patients). We recorded an unrelated death after the completion of antiviral therapy. We found increased levels of nausea, headaches and fatigue at the end of therapy compared to at initiation, The presence and degree of symptoms did not correlate with the underlying cause of renal disease (p=0.72) nor with the degree of fibrosis (p=0.08). Minimal increases in transaminases and bilirubin were recorded at the end of treatment, with no statistical significance. CONCLUSION: Oral antiviral therapy with ombitasvir/paritaprevir/ritonavir and dasabuvir can be safely used in hemodialysis patients, with similar response rates compared to the general population.

Management of Diagnosis and Treatment in a Case of Fibrolamellar Carcinoma.

Background/Aim: Fibrolamellar carcinoma is a rare primary hepatic malignancy that has recently been recognized as a distinct clinical entity, highly different from the well-known hepatocellular carcinoma. This report describes the clinical and paraclinical aspects of the fibrolamellar carcinoma, emphasizing its particularities. Case Report: A 30-year-old patient presented to the hospital with nonspecific symptoms and weight loss, with imaging findings showing abdominal and mediastinal masses. Multiple biopsies were performed, leading to a diagnosis of metastatic fibrolamellar carcinoma. Given the extent of the disease, systemic drug treatment was administered, although prognosis was poor with tumor growth, resulting in biliary duct invasion. Conclusion: Fibrolamellar carcinoma is a rare type of malignancy, with a difficult differential diagnosis in which imaging techniques are important but for which biopsy remains the gold standard. The prognosis depends on tumor extent and may include surgical methods or chemotherapy.

COVID-19 Mid-term Impact on Hepatocellular Carcinoma in Patients With Hepatitis C Chronic Infection.

BACKGROUND/AIM: Liver injury has been frequently reported in association with SARS-CoV-2 infection, but data are still lacking regarding the impact of pre-existing liver damage and neoplasia on SARS-CoV-2 infection outcome and vice-versa. This study aimed to assess the effects of SARS-CoV-2 infection on hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infected patients, both in therapeutic-naïve and patients treated with direct acting antivirals. PATIENTS AND METHODS: We conducted a retrospective cohort study on 21 patients with a personal history of HCV infection, that have been diagnosed with different forms of HCC and who were subsequently infected with SARS-CoV-2. Patients were monitored by liver function tests, tumoral markers, blood cell count, and coagulation profile periodically. RESULTS: Solitary HCC nodules were predominant among the subjects who achieved sustained virologic response, while multinodular and infiltrative patterns were mostly prevalent among the treatment-naïve group. Most patients had mild and moderate COVID-19 infections. CONCLUSION: Within the current global pandemic crisis, cancer patients are highly vulnerable and in need of constant monitoring. Among patients with HCC, the ones with cured HCV infection may be at a lower risk of fatality than those with active HCV infection, when diagnosed with SARS-CoV-2 infection.

Contrast-Enhanced Ultrasonography in the Diagnosis of Portal Vein Thrombosis: A Pictorial Review.

Portal vein thrombosis is a frequently encountered complication in hepatology and hematology. In patients with liver cirrhosis, it can occur in the natural history of the disease due to clotting disorders or associated with hepatocellular carcinoma. The development of a malignant thrombus is a contraindication to several therapeutic procedures in liver cancer, such as liver resection or transplantation or transarterial chemoembolization; therefore, patients need to be attentively evaluated. Contrast-enhanced ultrasonography is a relatively new noninvasive imagistic investigation with proven accuracy in focal liver lesions. Its use in differentiating malignant and nonmalignant portal vein thrombosis is still controversial. This article revises the characteristics of portal vein thrombosis on contrast-enhanced ultrasonography in order to determine its accuracy in the diagnosis of malignant portal vein thrombosis.

Budd-Chiari syndrome - various etiologies and imagistic findings. A pictorial review.

Budd Chiari syndrome defines an obstruction of the hepatic venous outflow. Primary causes include pro-coagulant states resulting in venous thrombosis, while secondary Budd Chiari syndrome appears in conditions associated with extrinsic compression of the hepatic veins or tumor invasion. Clinical presentation is greatly varied, from incidentally discovered asymptomatic thrombosis to fulminant liver failure due to hepatic congestion. Abdominal ultrasonography is the key diagnostic tool of Budd Chiari syndrome. This pictorial essay aims to show the ultrasonographic aspect of Budd-Chiari syndrome associated with other medical conditions (abdominal malignancy, hematologic disorders and abdominal surgery).

Hepatitis C-Associated B-cell Non-Hodgkin Lymphoma: A Pictorial Review.

BACKGROUND AND PURPOSE: Hepatitis C virus (HCV) can induce both hepatic and extrahepatic malignancies. A strong association between HCV and non-Hodgkin lymphomas (NHLs) has been demonstrated. The purpose of this article is to give emphasis on the clinical and imagistic particularities of the hepatitis C-associated NHL, revealing the importance of ultrasonography in discovering and characterizing splenic masses. METHODS: We present the cases of 3 women (aged 72, 61, and 56 years, respectively), all of which had a history of chronic hepatitis C and were subsequently diagnosed with different forms of lymphoma. In all 3 cases, conventional ultrasound exploration showed inhomogeneous splenomegaly. Contrast-enhanced ultrasound and computerized tomography were performed soon after admission, both clinical and imaging findings leading to the suspicion of lymphoma. The bone marrow biopsy was relevant for the diagnosis lymphoma in 2 patients, whereas the third woman only presented age-related changes in cellularity. Splenectomy was later performed in this case, for both diagnostic and therapeutic purposes; histopathological examination and immunohistochemistry revealed malignant non-Hodgkin diffuse large B-cell lymphoma. CONCLUSIONS: The cooccurrence of HCV infection and splenic lymphoma is a frequently encountered scenery. Ultrasonography, both conventional and contrast-enhanced, plays an important role in the exploration of the spleen, representing a first-line imagistic method and a valuable means of characterizing different types of splenic lesions. IMPLICATIONS FOR PRACTICE: This article states the importance of ultrasonographic evaluation regarding the splenic pathology, by revealing clinical and imagistic findings in 3 cases of hepatitis C-associated lymphoma.