International Journal of Hepatology最新文献

Background and aims: Nonalcoholic fatty liver disease is the leading cause of chronic liver disease globally and can progress to cirrhosis, liver failure, and liver cancer. Current AASLD, AGA, and ADA guidelines recommend assessment for liver fibrosis in all patients with NAFLD. Serum biomarkers for fibrosis, while widely available, have notable limitations. Imaging-based noninvasive testing for liver fibrosis/cirrhosis is more accurate and is becoming more widespread.

Methods: We evaluated the feasibility of a novel shear wave absolute vibroelastography (S-WAVE) modality called Velacur® for assessing liver stiffness measurement (LSM) for fibrosis and attenuation coefficient estimation (ACE) in differentiating patients with chronic liver disease from normal healthy controls.

Results: Fifty-four healthy controls and 89 patients with NAFLD or cured HCV with a prior known LSM of >8 kPa were enrolled, and all subjects were evaluated with FibroScan® and Velacur®. Velacur® was able to discriminate patients with increased liver stiffness as determined by a FibroScan® score of >8 kPa from healthy controls with an AUC of 0.938 (0.88-0.96). For assessment of steatosis in NAFLD patients only, Velacur® could identify patients with steatosis from healthy controls with an AUC of 0.831 (0.777-0.880). The Velacur® scan quality assessment was superior in healthy controls, as compared to patients, and the scan quality, as assessed by the quality factor (QF) and interquartile range (IQR)/median, was affected by BMI. Velacur® was safe and well tolerated by patients, and there were no adverse events.

Conclusion: Velacur® assessment of liver stiffness measurement and liver attenuation is comparable to results obtained by FibroScan® and is an alternative technology for monitoring liver fibrosis progression in patients with chronic liver disease. This trial is registered with NCT03957070.

Background: The hTERT promoter mutation represents a common and early event in hepatocarcinogenesis, but its linkage to the morphological status of the underlying liver tissue is poorly understood. We analyzed the connection between the histopathological changes in tumor-bearing liver tissue and the occurrence of the hTERT promoter mutation in hepatocellular carcinoma (HCC), correlated with clinical data.

Methods: The study cohort comprised 160 histologically confirmed HCC in patients with or without cirrhosis that were investigated for the hTERT promoter mutation. We evaluated the frequency of the hTERT promoter mutation in patients with HCC with or without cirrhosis and correlated it with potential clinical and histopathological drivers. In particular, we examined tumor-bearing noncirrhotic liver tissue regarding inflammation; the modified histological activity index (mHAI), fibrosis, and steatosis; and its correlation with the frequency of the hTERT promoter mutation in HCC. We evaluated overall survival with multivariate Cox regression. Furthermore, we compared hTERT antibody immunohistochemistry and molecular hTERT promoter mutation analysis of both HCC and background liver tissue.

Results: The hTERT promoter mutation was especially related to HCC in cirrhotic compared with noncirrhotic liver (p < 0.001) and independently of cirrhosis in patients ≥ 60 years (p = 0.005). Furthermore, the hTERT promoter mutation was associated with cirrhosis caused by alcohol toxicity and hepatitis C virus infection. In noncirrhotic liver tissue, the frequency of hTERT-promoter-mutated HCC increased with the degree of inflammation and fibrosis. Nevertheless, 25% of the hTERT-promoter-mutated HCC developed in normal liver tissue without HCC risk factors. Multivariate Cox regression analysis did not reveal an influence of the hTERT promoter mutation in HCC on overall survival at 3, 5, and 16 years. Immunohistochemical analysis with the hTERT antibodies LS-B95 and 2D8 in hTERT-promoter-mutated HCC and hTERT-wildtype HCC showed a mildly stronger immunoreaction compared with the tumor-bearing liver tissue (LS-B95: p < 0.01, 2D8: p < 0.01).

Conclusions: Our study reveals a connection between pathological changes in tumor-bearing liver tissue and the hTERT promoter mutation in most HCC, even in noncirrhotic liver tissue. Immunohistochemical hTERT antibodies do not discriminate between hTERT-promoter-mutated and wildtype HCC.

Background: Chronic hepatitis B (CHB) is estimated to cause between 500,000 and 1.2 million deaths worldwide every year through cirrhosis and hepatocellular carcinoma (HCC). Liver cirrhosis and HCC are the commonest liver diseases causing death in Ghana. The most critical problem in the management of CHB in sub-Saharan Africa is the high cost of investigations and antiviral drugs. There is scanty information concerning newly diagnosed CHB patients and their management challenges in Ghana. This study sought to determine the clinical characteristics and management challenges of CHB patients in Ghana. Methodology. A prospective cohort study was conducted involving newly diagnosed CHB patients being managed at St. Dominic Hospital. Patient demographic and clinical features were abstracted using a standardized questionnaire. The proportion of patients able to undertake investigations and treatment were determined, and the limitations to standard management were recorded. The performance of APRI score in the diagnosis of cirrhosis was also investigated.

Results: Of the 334 patients with newly diagnosed CHB, the median age at diagnosis was 35 (IQR 28-44) years. Less than a quarter (22.2%) were able to undertake viral load testing and 23.4% were eligible for treatment. Of those who were eligible for treatment, only 42.3% were able to initiate treatment. Almost a third of cases (32.1%) reported late with liver-related complications. The sensitivity of APRI score with cut-off value of 2 in the diagnosis of liver cirrhosis was 70.2% and specificity was 97.9%.

Conclusion: A high proportion of newly diagnosed CHB patients presented late and with liver-related complications. Majority were not able to afford viral load testing and antiviral medication. Screening of hepatitis B among the general population and inclusion of CHB management in the National Health Insurance Scheme should be encouraged.

Background: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic disorder that results from defective mechanisms of bile secretion. We aim to describe different types of PFIC and their clinical features, treatment modalities, and outcomes in Saudi Arabia. Patients and Methods. This is a retrospective study of all patients diagnosed with PFIC at King Faisal Specialist Hospital and Research Center in Riyadh from January 1, 2002, to December 31, 2021. All relevant information was collected from patient charts and transferred into the REDcap® database for statistical analysis.

Results: A total of 79 patients were identified with PFIC, and PFIC type 3 was the most common (59.5%), followed by PFIC type 2 (34.2%), PFIC type 1 (5.1%), and PFIC type 4 (1.3%). Males and females were affected in 54.4% and 45.6%, respectively. Mutations in ATP8B1, ABCB11, and ABCB4 genes were observed in PFIC type 1, PFIC type 2, and PFIC type 3, and loss of function in a variant of TJP2 was detected in PFIC type 4, respectively. A total of 51 (64.6%) patients underwent liver transplantation: three patients (3/4) with PFIC type 1 (75%), twenty patients (20/27) with PFIC type 2 (74.1%), twenty-seven patients (27/47) with PFIC type 3 (57.4%), and one patient with PFIC type 4 (100%). The mean duration of disease before transplantation was 53.9 ± 67 months with a median of 30 months. Following liver transplantation, symptomatic control was achieved in 47 patients (92.2%). Recurrence after transplantation occurred in 4 patients (7.8%) within an average of 22.5 months and a median of 17 months.

Conclusion: PFIC is considered a rare disorder in Saudi Arabia; however, early recognition of the disease is important for appropriate management and early referral for liver transplantation evaluation. The overall rate of liver transplantation in our cohort was 64.6% with an excellent five-year survival rate.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer morbidity and mortality. Findings of microvascular invasion (MVI) in patients with HCC have emerged as an important prognostic factor for poor survival after tumor resection.

Aim: This study evaluated the relation between MVI and HCC within various anatomical Couinaud's segments of the liver.

Method: A multicenter retrospective review of HCC records was conducted from 2012 to 2017. HCC cases were identified using ICD-9 and 10 codes 155, C22.0, and C22.8. HCC patients who underwent liver transplants were included in this study. Liver segment of the location of HCC was obtained from radiographic records, and MVI information was obtained from pathology reports. Segmental distributions of HCC in MVI versus non-MVI groups were compared using Wilcoxon rank sum tests. p value was set at <0.05.

Results: We analyzed 120 HCC patients who underwent liver transplantation. The mean age of our cohort was 57 years, and the most common etiology of liver disease was hepatitis C at 58.3%. The median HCC size was 3.1 cm, and MVI was present in 23.3% of the explanted specimens. MVI was 2 to 3 times significantly higher in patients with HCC affecting segments 2 and 3 and segments 4b and 5 (p = 0.01). Moreover, median survival was significantly lower in patients with MVI versus those without MVI (50 vs. 137 months, p < 0.05).

Conclusion: MVI was significantly higher in HCC tumors located in liver segments 2 and 3 and 4b and 5, and survival was lower in patients with MVI compared with those without.

The alkaloid boldine occurs in the Chilean boldo tree (Peumus boldus). It acts as a free radical scavenger and controls glycemia in diabetic rats. Various mechanisms have been proposed for this effect, including inhibited glucose absorption, stimulated insulin secretion, and increased expression of genes involved in glycemic control. Direct effects on glucose synthesis and degradation were not yet measured. To fill this gap, the present study is aimed at ensuring several metabolic pathways linked to glucose metabolism (e.g., gluconeogenesis) in the isolated perfused rat liver. In order to address mechanistic issues, energy transduction in isolated mitochondria and activities of gluconeogenic key enzymes in tissue preparations were also measured. Boldine diminished mitochondrial ROS generation, with no effect on energy transduction in isolated mitochondria. It inhibited, however, at least three enzymes of the gluconeogenic pathway, namely, phosphoenolpyruvate carboxykinase, fructose-bisphosphatase-1, and glucose 6-phosphatase, starting at concentrations below 50 μM. Consistently, in the perfused liver, boldine decreased lactate-, alanine-, and fructose-driven gluconeogenesis with IC₅₀ values of 71.9, 85.2, and 83.6 μM, respectively. Conversely, the compound also increased glycolysis from glycogen-derived glucosyl units. The hepatic ATP content was not affected by boldine. It is proposed that the direct inhibition of hepatic gluconeogenesis by boldine, combined with the increase of glycolysis, could be an important event behind the diminished hyperglycemia observed in boldine-treated diabetic rats.

Introduction: The evaluation of the patterns of liver injury, derived from liver chemistry panels, often may narrow on probable causes of the liver insult especially when coupled with clinical history, examination, and other diagnostic tests.

Methods: Among people living with and without HIV and attending care, we used the R ratio to evaluate for liver injury patterns. Liver injury patterns were defined as cholestatic (R < 2), mixed (R = 2-5), and hepatocellular (R > 5).

Results: Overall, the proportions of participants with cholestatic liver injury, mixed liver injury, and hepatocellular liver injury were 55%, 34%, and 4%, respectively, with similar distribution when stratified by HIV status. Alcohol use among participants without HIV was associated with all patterns of liver injury (cholestatic liver injury (OR = 4.9 CI (1.0-24.2); p = 0.054), mixed liver injury (OR = 5.3 CI (1.1-27.3); p = 0.043), and hepatocellular liver injury (OR = 13.2 CI (1.0-167.3); p = 0.046)). Increasing age was associated with cholestatic liver injury among participants with HIV (OR = 2.3 CI (1.0-5.3); p = 0.038). Despite a high hepatitis B prevalence among participants with HIV, there was no association with liver injury.

Conclusions: Liver injury is prevalent among both people living with and without HIV in care, and cholestatic liver injury is the most common pattern. Alcohol is associated with all patterns of liver injury and increasing age associated with cholestatic liver injury among people living without HIV and people living with HIV, respectively.

Methods: We included 235 patients with chronic extrahepatic cholestasis due to pancreatic cancer, cholangiocarcinoma, or papillary carcinoma.

Results: GGT was significantly higher in patients without pruritus (median 967, IQR 587-1571) compared to patients with pruritus (median 561 IQR 266-1084 IU/l) (p < 0.01). In contrast, median alkaline phosphatase (AP) was 491 U/L (IQR; 353-684) in patients with pruritus and was not significantly different from 518 U/L (IQR; 353-726) in patients without pruritus (p = 0.524). Direct bilirubin was significantly higher in patients with pruritus compared to patients without pruritus (168 μmol/L (IQR; 95-256) vs. 120 μmol/L (IQR; 56.75-185.5)) (p < 0.01). After correcting for the extent of cholestasis via direct bilirubin, the negative association between GGT and pruritus remained significant and became stronger (p < 0.001).

Conclusion: Serum GGT activity is inversely associated with the presence of cholestatic itch in patients with chronic extrahepatic cholestasis.

Methods: An analytical cross-sectional study involving patients from 2 dialysis units (1 referral hospital and 1 private dialysis unit) in Denpasar, Bali, Indonesia, from January 2020 to December 2021. We evaluated age, gender, duration of hemodialysis, vascular access, history of transfusion, history of surgery, diabetes mellitus, hepatitis B, human immunodeficiency virus (HIV) infection, and type of dialyzer as possible risk factors of hepatitis C seroconversion among hemodialysis patients.

Results: A total of 338 hemodialysis patients were enrolled in this study. We found hepatitis C seroconversion in 94 patients (27.8%), all of which occurred after regular dialysis was started. Vascular access type (OR 42.07, 95% CI 5.757-307.472) and dialyzer reuse (OR 8.324, 95% CI 4.319-16.044) were showing a statistically significant association with hepatitis C seroconversion. A separate analysis on each dialysis unit found common evidence that the duration of dialysis was significantly associated with hepatitis C infection among hemodialysis patients.

Conclusion: Hepatitis C seroconversion among dialysis patients remains high. Factors related to the dialysis procedure itself played a major role in transmitting the virus.