Real-world efficacy and safety of Ledipasvir plus Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir +/- Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience

Background/Aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population.Material and Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)+/- ribavirin (RBV) ombitasvir/paritaprevir/ritonavir +/- dasabuvir (PrOD)+/- RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed.Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90 +/- 54.60 U/L to 17.00 +/- 14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51 +/- 4.54 to 7.32 +/- 3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0 +/- 16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%).Conclusion: LDV/SOF or PrOD +/- RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.Turkish Association for the Study of The Liver (TASL

Recurrence of hepatocellular carcinoma following deceased donor liver transplantation: case series.

AbstractAim: We aimed to study the clinical and pathological characteristics of liver transplant recipients with hepatocellularcarcinoma recurrence.Methods: We reviewed the data for 26 patients who had tumor recurrence after deceased donor liver transplant forhepatocellular carcinoma at the Johns Hopkins Hospital from January 2005 to December 2015.Results: In total, 88% of recipients were males. The mean age was 59 years. On explant, poor differentiation wasdetected in 43%, while 73% had microvascular invasion. Overall, 62% were diagnosed to be outside of Milan criteria.Out of these, 15% met the criteria for downstaging. Twenty (77%) patients had pre-transplant alpha fetoprotein levels≥ 20 ng/mL. In 54% of patients, the location of hepatocellular carcinoma (HCC) recurrence was extrahepatic, followedby intrahepatic in 31% and both intra- and extrahepatic in 15%. The post-transplant tumor recurrence was diagnosedat a mean of 427 days (range 34-1502). Fifty percent of HCC recurrences were diagnosed within one year followingliver transplant. Twenty (77%) patients received treatment for their recurrent HCC: external radiation (n = 10), surgicalresections (n = 8; brain 4, spine 2, bone 1, and Whipple surgery 1), sorafenib (n = 7), locoregional therapy (n = 5).Overall, 24 out of 26 (92%) recipients died within four years after the transplant.Conclusion: HCC recurrence after liver transplant is infrequent. More than fifty percent of HCC recurrences followingliver transplant are extrahepatic. Despite better recipient selection for liver transplant, the curative options are limited inrecurrent cases and associated with extremely poor outcomes.</p

Psychometric tests, critical flicker frequency, and inflammatory indicators in covert hepatic encephalopathy diagnosis

Background and Aim:&nbsp;Hepatic encephalopathy (HE) is a frequent complication of liver diseases. Systemic inflammation is key for HE pathogenesis. The main goal of the study was to investigate the role of psychometric tests, critical flicker frequency (CFF), and comparative evaluation of inflammatory indicators for the diagnosis of covert HE (CHE).Material and&nbsp;Methods:&nbsp;The study was a prospective, nonrandomized, case–control study with a total of 76 cirrhotic patients and 30 healthy volunteers. The West Haven criteria were used to determine the occurrence of CHE in cirrhotic patients. Psychometric tests were applied to healthy and cirrhotic groups. CFF, venous ammonia, serum endotoxin, IL-6, IL-18, tumor necrosis factor alpha (TNF-α) levels, and hemogram parameters were evaluated for cirrhotic patients.Results:&nbsp;CFF values and psychometric tests were found to accurately discriminate CHE positives from CHE negatives (p&lt;0.05). When the control group was excluded, the digit symbol test and the number connection A test failed, unlike CFF and other psychometric tests. Using CFF, a 45 Hz cutoff value had 74% specificity and 75% sensitivity. Basal albumin levels (p=0.063), lymphocyte-to-monocyte ratio (LMR) (p=0.086), and neutrophil-to-lymphocyte ratio (p 0.052) were significant, albeit slightly, among CHE groups. Basal albumin levels had 50% sensitivity and 71% specificity when 2.8 g/dL was used as a cutoff value to determine CHE.Conclusion:&nbsp;Both psychometric tests and CFF can be useful in diagnosing CHE. Using cytokine and endotoxin levels seems to be inadequate to diagnose CHE. Using LMR and albumin levels instead of psychometric tests for diagnosing CHE can be promising.</p

Ekstramedüller Hematopoez Odağı İçeren Karaciğer: Olgu Sunumu

GİRİŞ: Ekstramedüller hematopoez; kemik iliği ve periferik kan dışında hematopoetik doku üretimi ile karakterize bir hastalıktır. Özellikle hemoliz ile seyreden hemoglobinopatiler ve kemik iliğinde üretimin yetersiz olduğu myelofibrozis gibi Hematolojik hastalıklarda kompansatuar bir mekanizma olarak görülebilir. Karaciğer, dalak, toraksın paraspinal bölgesi gibi alanlarda saptanır. Çalışmamızda Esansiyel Trombositoz (ET) ve Myelofibrozis (MF) nedeni ile Hematoloji kliniğinde takipli olan ve tarafımıza karaciğer fonksiyon testi bozukluğu ile yönlendirilen, tetkik sonuçları karaciğerde ekstramedüller hematopoez lehine sonuçlanan 76 yaşındaki olgu sunulmaktadır. OLGU: Bilinen KOAH ve Hipertansiyon komorbiditeleri olan olgu, 1996 yılında yapılan sağlık kontrollerinde saptanan trombositoz nedeni ile ileri tetkik edilerek ET tanısı alıp Hematoloji tarafından izleme alınmış. Takiplerinde 2013 yılında alınan kemik iliği biyopsisi ile MF olarak değerlendirilmiş. Uzun bir süre hidroksiüre ve tromboredüktin ile izlendikten sonra Nisan 2021'de tedavisi ruksolitinib olarak revize edilmiş. Şubat 2022'de ise tedavisine danazol eklenmiş. Mart 2022'de ALT: 124, AST: 58, ALP: 67 ve GGT: 143 olarak sonuçlanmış, bu nedenle Gastroenteroloji konsültasyonu istenerek yönlendirilmiş. KCFT bozukluğu açısından ileri tetkik edilmiş. Abdomen US'de hepatosplenomegali saptanan hastanın parankim ekojenitesi normal değerlendirilmiş, Portal Doppler US'de patolik bulgu saptanmamış. Viral, metabolik ve immunolojik diğer etyolojik faktörler ekarte edildikten sonra hastanın mevcut durumu ön planda Hematoloji tarafından tedavide kullanılan hepatotoksik ajanlara bağlanmış. İlaç dozları Hematoloji tarafından revize edilmiş. Bu süreçte yeni gelişen kaşıntı yakınması dışında herhangi bir yakınması olmayan hastanın izleminde Şubat 2023'te AST: 51, ALT: 86, GGT: 201 ve ALP: 104 sonuçlandığı için süreci aydınlatmak adına karaciğer biyopsi planı yapılmış. Biyopsi sonucu Ekstramedüller Hematopoez olarak sonuçlanmış. TARTIŞMA: Özellikle hemoliz ile seyreden hemoglobinopatiler ve kemik iliğinde üretimin yetersiz olduğu myelofibrozis gibi Hematolojik hastalıkların varlığında KCFT bozukluğu, hepatomegali ve hepatosplenomegali gibi durumların saptanması halinde eskstramedüller hematopoez ayırıcı tanıda akılda bulundurulmalıdır.Anahtar Kelimeler: karaciğer, hepatomegali, ekstramedüller hematopoez, hepatosplenomegali</p

Ileal Dieulafoy Lesion in a Patient with Glanzmann Thrombasthenia Presented with Hematochezia

Dieulafoy lesion (DL) is an important cause of acute gastrointestinal hemorrhage (GIH) because endoscopic diagnosis is very difficult. We report an ileal DL in a patient with Glanzmann Thrombasthenia (GT). A forty-year old female presented with bloody stool. Records showed that she was diagnosed with GT at 3 years of age. Physical examination on admission, she was clinically stable, except for tachycardia (110 bpm). Rectal examination revealed bright red blood. Her haemoglobin level was 8.7 g/dl. Colonoscopy revealed a DL at the terminal ileum. It was treated with combined endoscopic therapy of epinephrine injection followed by two clips application. Haemoglobin values were stable in the post-procedural period. DL in the terminal ileum is very rare. There have been fewer than 20 cases reported in the literature to date. Also GT is a rare congenital bleeding disorder. This case report revealed the coincidence of two rare disorders