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Hepatitis B virus (HBV) infection was highly endemic in China, where the prevalence of HBsAg was 9.7% in 1992. Comprehensive strategies, including universal infant hepatitis B vaccination with emphasis on timely birth-dose and 3-dose coverage, dramatically reduced the mother-to-infant transmission and early childhood acquisition of HBV, resulting in estimated HBsAg prevalence rates of 5.6% and 0.1% in the general population and among children aged <5 years in 2022, respectively. Clinical guidelines on the prevention and treatment of chronic hepatitis B have been periodically updated based on emerging evidence from clinical research. The continuously improved reimbursement policy and the massively reduced price of antiviral drugs through government negotiation and central procurement have increased treatment accessibility and affordability. However, due to the low rates of diagnosis and treatment, China still faces a large challenge in achieving the 2030 goal of lowering HBV-related mortality by 65%. A public health approach involving concerted efforts from the government, medical community, industry, and society as a whole would be necessary to increase the uptake of HBV tests and treatment to achieve the global goal of eliminating viral hepatitis as a public health threat by 2030.
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Liver biopsy is a key method for clarifying the diagnosis of liver diseases and has an important value in determining disease severity, deciding treatment timing, and predicting treatment response and prognosis. By recognizing the pattern of liver pathological injury, pathologists evaluate the nature of lesions as the basis of diagnosis and differential diagnosis, and among these patterns, liver tissue with "normal appearance" requires careful observation of easily overlooked pathological changes, so as to reduce misdiagnosis or missed diagnosis. This article mainly introduces the thoughts in the pathological diagnosis of liver tissue with normal appearance and the key points in differential diagnosis.
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Objective To investigate the clinical features, liver histological features, and diagnostic and treatment methods for patients with myeloproliferative neoplasms (MPN) with portal hypertension as the main manifestation. Methods A retrospective analysis was performed for related data of the patients who attended the hospital due to portal hypertension and were finally diagnosed with MPN in Liver Research Center, Beijing Friendship Hospital, from January 2019 to February 2022, including clinical manifestation, liver pathological features, treatment, and follow-up results. Results Nine patients were included in this study, and all the patients had splenomegaly and esophageal and gastric varices, while portal vein thrombosis was observed in eight patients. All patients had normal or slightly abnormal liver function and routine blood test results. Six patients underwent liver biopsy, without the formation of fibrous septum and pseudolobule, and hepatic extramedullary hematopoiesis was observed in two patients. All nine patients underwent bone marrow biopsy and genetic testing, among whom six had essential thrombocythemia and three had primary myelofibrosis, and genetic testing revealed JAK - 2V617F gene mutation in seven patients and CALR gene mutation in two patients. Conclusion MPN is one of the rare causes of portal hypertension and has the clinical manifestations of esophageal and gastric varices, splenomegaly, and even megalosplenia, without the manifestations of hypersplenism such as leukopenia and thrombocytopenia. Detection of the JAK - 2V617F and CALR genes can improve the diagnostic rate of MPN.
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The clinical characteristics of pregnancy with portal hypertension are complicated, which seriously affects the safety of pregnancy. We summarized the classification of portal hypertension, the clinical evidence and expert consensus of pregnancy with portal hypertension, and summarized the clinical characteristics and management strategies of pregnancy with portal hypertension. Pregnancy aggravates portal hypertension and its complications. Portal hypertension increases the incidence of adverse pregnancy events. Patients with stable portal hypertension could be pregnancy under the care of multidisciplinary teams., Choosing the right timing of endoscopic examination, the treatment of high-risk esophageal gastric varices, screening risk factors for thrombosis and pulmonary hypertension. During pregancy, to prevent and treat the complications of portal hypertension, to take delivery timing and mode individually.
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Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The clinical characteristics, management and prognosis of pregnancy in WD are special and less reported, which are the key and difficult problems concerned by clinicians. Regardless of whether they receive treatment or not, pregnant women with WD may have disease progression or even death, and their fetuses are also faced with the risk of genetic disease, malformation and death. Domestic and foreign guidelines suggest that during pregnancy, drugs such as D penicillamine and zinc should continue to be taken to remove copper, however breast-feeding is not recommended now. Although the safety of treatment drugs and breastfeeding in WD needs to be further evaluated, the benefits of appropriate copper removal treatment still outweigh the disadvantages. Most women of childbearing age with WD can successfully conceive and deliver after receiving appropriate copper removal treatment and pre pregnancy consultation.
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Portal hypertension is a serious complication of liver cirrhosis resulting from the increases in portal vascular resistance and portal blood inflow. Both etiological and non-etiological therapies can effectively reduce portal venous pressure to a certain degree, but with an unsatisfactory effect in improving prognosis. New therapeutic drugs targeting the reduction in intrahepatic vascular resistance may help to achieve the reversal of portal hypertension. Based on the pathogenesis of cirrhotic portal hypertension, this article summarizes the current pharmacotherapies from the aspects of etiological and non-etiological therapies, so as to provide a comprehensive theoretical and evidence-based basis for clinical treatment options.
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Objective:To assess the performance of liver and spleen stiffness measured by MR elastography (MRE) and their combined model in diagnosing liver fibrosis.Methods:From November 2018 to November 2019, 104 patients with chronic liver disease were prospectively enrolled in Beijing Friendship Hospital, all patients underwent MRE scans. Liver and spleen stiffness were measured from MRE elastograms. Liver biopsy was used to identify fibrosis stage (F0—F4). The differences among different fibrosis stages were analyzed by one-way ANOVA or independent samples t test. The Spearman rank correlation analysis was used to evaluate the correlation with fibrosis stages. Liver and spleen stiffness combined model was established by logistic regression. The ROC curve was used to evaluate the performance of the liver, spleen stiffness and combined model in staging fibrosis (≥F1), significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4).The area under the ROC curve(AUC) was compared using Delong test. Results:The liver and spleen stiffness both showed significant differences among the 5 fibrosis stages ( F=64.058, 32.890, both P<0.001). The liver and spleen stiffness were positively associated with fibrosis stage ( r s=0.89, 0.69, both P<0.001). The AUC of liver stiffness in staging ≥F1, ≥F2, ≥F3 were 0. 91, 0.97, 0.93, respectively. The corresponding AUCs of the spleen stiffness were 0.81, 0.82, 0.85, respectively, which were statistically lower than those of liver stiffness ( Z=2.283, 4.085, 2.314, P=0.022,<0.001, 0.021). In diagnosing F4, the AUCs of liver and spleen stiffness were both 0.95. The AUCs of the liver and spleen combined model were 0.92, 0.97, 0.93, 0.96 in diagnosing ≥F1, ≥F2, ≥F3 and F4, with no significantly differences from liver stiffness (all P>0.05). Conclusions:The liver stiffness measured with MRE have better diagnostic performance than spleen stiffness in staging fibrosis. Parameters combined model slightly improves diagnostic value but without significant difference with liver stiffness in staging early fibrosis. Spleen stiffness evaluation is feasible in detecting cirrhosis.
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Sunscreen products have been widely used with the increase in public awareness of sun protection. As sunscreens are structurally stable and resistant to degradation, the concern for their biotoxicity and impact on marine environment has been heightened increasingly, and several countries and regions have successively issued bans on relevant sunscreen products. However, these bans have not yet affected the key international rules and regulations related to sunscreen products. The risks of different sunscreens to marine ecosystems and potential risks to human themselves still need to be evaluated through further multidisciplinary researches.
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ObjectiveTo investigate the diagnostic efficiency of FibroTouch, FibroScan, and acoustic radiation force impulse (ARFI) for liver fibrosis in patients with primary biliary cholangitis (PBC). MethodsA retrospective analysis was performed for the patients who underwent liver biopsy and were then diagnosed with PBC in Beijing Friendship Hospital, Capital Medical University, from September 2014 to October 2018, and the METAVIR scoring system was used to evaluate the degree of liver fibrosis and inflammation. Within 1 week after liver biopsy, FibroTouch, FibroScan, and ARFI were used to measure liver stiffness (LS); with pathological results as the gold standard, the area under the ROC curve (AUC) was used to compare the value of FibroTouch, FibroScan, and ARFI in the diagnosis of liver fibrosis in PBC patients, and related influencing factors were analyzed; Youden index was used to calculate the cut-off values of LS for different degrees of liver fibrosis. The Kruskal-Wallis H test was used for comparison between multiple groups, and P value corrected by the Bonferroni method was used for further comparison between two groups. A Spearman correlation analysis was performed, and a multiple linear regression model was used for multivariate analysis. ResultsA total of 68 patients with PBC were enrolled in the study, among whom 13 had F0 liver fibrosis, 15 had F1 liver fibrosis, 18 had F2 liver fibrosis, 12 had F3 liver fibrosis, and 10 had F4 liver fibrosis. LS obtained by FibroTouch (FT-LS), LS obtained by FibroScan (FS-LS), and LS obtained by ARFI (ARFI-LS) were strongly positively correlated with the degree of liver fibrosis (r=0.798, 0.782, and 0.742, all P＜0.001). FT-LS had AUCs of 0.922, 0.881, and 0.926, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 10.5 kPa, 15.8 kPa, and 17.5 kPa, respectively; FS-LS had AUCs of 0.918, 0.878, and 0.939, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 10.1 kPa, 12.9 kPa, and 18.2 kPa, respectively; ARFI-LS had AUCs of 0.904, 0.869, and 0.928, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 1.45 m/s, 1.83 m/s, and 2.08 m/s, respectively. There was no significant difference in diagnosing the same stage of liver fibrosis between FibroTouch, FibroScan, and ARFI (P＞0.05). The multivariate analysis showed that degree of liver fibrosis (β=0.399, P＜0.001), total bilirubin (β=0.466, P＜0.001), and prothrombin time activity (β=-0.195, P=0.020) were influencing factors for FT-LS; degree of liver fibrosis (β=0370, P＜0.001), aspartate aminotransferase (β=0.450, P＜0.001), prothrombin time activity (β=-0.303, P=0.001), and alkaline phosphatase (β=-0.187, P=0.042) were influencing factors for FS-LS; degree of liver fibrosis (β=0.489, P＜0.001), aspartate aminotransferase (β=0.467, P＜0.001), and platelet count (β=-0.188, P=0.028) were influencing factors for ARFI-LS. ConclusionFibroTouch has similar efficiency to FibroScan and ARFI in the diagnosis of liver fibrosis in PBC patients, with relatively high diagnostic efficiency for significant liver fibrosis (F≥2) and liver cirrhosis (F=4), and therefore, it can be used as a reliable method for the diagnosis of liver fibrosis in PBC patients.
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Objective To summarize the incidence, diagnostic and therapeutic experience of hepatic sinusoidal obstruction syndrome (HSOS) after liver transplantation. Methods Clinical data of 4 patients with HSOS after liver transplantation were retrospectively analyzed. The incidence, clinical manifestations, imaging and pathological characteristics of HSOS after liver transplantation were collected, and the treatment methods and clinical outcomes of patients with HSOS were analyzed. Results The incidence of HSOS after liver transplantation was 0.8%(2/239), and the median time of onset was 4.5(1.7, 9.0) months after liver transplantation. The clinical manifestations of HSOS mainly included abdominal distension, ascites, hepatomegaly, increased bilirubin, and renal insufficiency in partial cases. Enhanced abdominal CT scan of 4 patients with HSOS showed uneven spot-like enhancement and the liver histopathological examination mainly showed the signs of hepatic sinusoidal dilatation complicated with congestion. Four patients were administered with an adjusted regime of immunosuppressant by replacing tacrolimus (Tac) with ciclosporin and adding anticoagulant therapy with warfarin. One patient received transjugular intrahepatic portosystemic shunt (TIPS). After treatment, the symptoms of 3 patients were completely relieved, and 1 patient died. One of the 3 surviving patients died from pulmonary infection and gastrointestinal bleeding. Conclusions HSOS is a rare and fatal complication after liver transplantation. Timely diagnosis and treatment can avoid the incidence of graft failure and improve clinical prognosis of the patients.
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Idiosyncratic (unpredictable) drug-induced liver injury (iDILI) is one of the most challenging liver diseases encountered by hepatologists due to its diverse clinical and pathological manifestations and lack of specific diagnostic markers. An increasing awareness of iDILI diagnosis and carefully excluding liver damage induced by other causes is the key to a proper diagnosis of iDILI. However, delayed diagnosis, inappropriate monitor and care leads to serious clinical consequences, such as acute liver failure or even liver-related death. In addition, there is presently no effective treatment for iDILI. Herein, we presented the main recommendations of the recent EASL published first DILI guidelines into Chinese language to facilitate liver disease authors and health workers to understand the latest research progress of DILI.
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Liver biopsy has been regarded as the gold standard for the assessment of liver fibrosis regression. In 2017, Liver Research Center, Beijing Friendship Hospital, proposed a new classification called PIR classification for the evaluation of liver fibrosis regression in patients with chronic hepatitis B after antiviral therapy, which was also called “Beijing classification”. This classification is new breakthrough based on conventional staging and grading systems, quantitative assessment methods for liver fibrosis, and the concept of liver biopsy. This article discusses the prospects and shortcomings of PIR classification.
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Objective@#To explore the diagnostic values of FibroTouch and FibroScan for liver fibrosis in patients with chronic hepatitis B(CHB).@*Methods@#This study enrolled patients with CHB who was accepted liver biopsy at Beijing Friendship Hospital, Capital Medical University between March 2014 to December 2017. FibroTouch and FibroScan were performed among these patients at same time. Liver stiffness measurement(LSM), optimal cut-off value, receiver operating characteristic(ROC) were compared.@*Results@#In our 103 patients, there were no significantly different between FibroTouch and FibroScan in LSM. The threshold of the optimal cut-off value for FibroTouch and FibroScan were 5.45 versus 5.55 kPa (≥S1), 7.10 versus 6.65 kPa (≥S2), 11.05 versus 9.20 kPa (≥S3), 15.50 versus 15.45 kPa (S4), respectively. The area under the ROC curve for the prediction of the stage1, stage2, stage2, stage 4 of liver fibrosis in these patients were 0.858 versus 0.765 (P=0.54), 0.812 versus 0.801 (P=0.68), 0.863 versus 0.878 (P=0.45), and 1.0 versus 0.99 (P=0.38) respectively.@*Conclusions@#FibroTouch and FibmScan have a good consistency in the evaluation of the degree of liver fibrosis in patients with CHB.
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Inherited metabolic liver disease is a kind of metabolic disorders caused by the interactions between host and environmental factors because of genetic defects. The incidence of inherited metabolic liver disease is low and its clinical manifestations are complex and diverse, which initiates difficulties in clinical diagnosis. In addition, hereditary hemochromatosis and Wilson's disease are common types of metabolic abnormalities, often seem in clinical practice, and early diagnosis and treatment can improve the prognosis. Benign recurrent intrahepatic cholestasis in cholestatic liver disease is a benign phenotype of progressive familial intrahepatic cholestasis and progressive familial intrahepatic cholestasis type 3 can progress to adulthood with a poor outcome. The incidence of Gilbert’s syndrome is higher in congenital metabolic diseases, and the prognosis is good in absence of special treatment but most importantly, it should be differentiated from Crigler-Najjar syndrome and Dubin-Johnson syndrome. Presently the general characteristic of inherited metabolic liver disease in Chinese population is still vague.
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Objective@#To improve the diagnostic quality of hepatolenticular degeneration by summarizing the clinicopathological features.@*Methods@#A retrospective analysis of 21 cases that were diagnosed as hepatolenticular degeneration with liver biopsy in our hospital from January 2013 to August 2018 was reviewed, and then their clinicopathologic features were analyzed. The pathomorphological differences between liver biopsy and liver biopsy after transplantation, and the relationship between histopathological patterns and biopsy types and clinical indicators were analyzed by Fisher's exact test.@*Results@#Of the 21 patients with hepatolenticular degeneration, 10 patients had liver biopsy, and 11 patients underwent liver biopsy after liver transplantation. Among them, four cases were presented as simple fatty liver pattern (19.0%, 4/21), eight cases as steatohepatitis pattern (38.1%, 8/21), four cases as inflammatory necrosis without cirrhosis pattern (19.0%, 4/21), and five cases as inflammatory necrosis with cirrhosis pattern (23.9%, 5/21). Twelve cases had copper deposition in the liver (57.1%, 12/21), and the pattern of copper distribution in the liver was uneven.@*Conclusion@#A clinicalpathological features of hepatolenticular degeneration mainly manifests in four patterns, but lack characteristic changes. Hence, comprehensive judgment should rely on clinical history, laboratory examination, genetic test results and liver histopathological changes.
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Hepatic vascular diseases are a group of heterogeneous diseases which affect blood circulation in the liver. Although hepatic vascular diseases have a low incidence rate, they remain an important cause of portal hypertension. Patients often develop these diseases at a younger age, and misdiagnosis and/or mistreatment may greatly reduce their life expectancy. A good understanding of clinical manifestations, imaging features, and pathological features of hepatic vascular diseases is of vital importance in clarifying diagnosis and developing reasonable treatment strategies. This article introduces the pathological features of common hepatic vascular diseases and key points in differential diagnosis.
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The incidence rate of drug -induced liver injury (DILI) tends to increase in recent years, and early accurate diagnosis and eval -uation of the degree of liver injury are great challenges in diagnosis and treatment .The pathomorphological features of DILI are determined by the structure and metabolic features of hepatic lobules .The basis of pathological injury pattern is injury of related targets , i.e., hepatocytes,biliary epithelium, and blood vessel endothelium, which determines the distinct features of DILI.Although DILI has various pathological features,it has major injury patterns of acute hepatitis type , chronic hepatitis type, acute cholestatic type, chronic cholestatic type, and cholestatic hepatitis type.The degree of the pathological injury of DILI is associated with the disease severity and prognosis of patients , and pathology helps to identify small bile duct injury and vascular endothelial injury caused by drugs as early as possible .The liver histological features of DILI overlap with other diseases, and related clinical indices should be used to make an objective , accurate, and timely diagnosis of DILI.This article reviews the pathomorphological features and patterns of DILI and elaborates on the significance of liver histological examination in the diagnosis and treatment of DILI.
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Muscle cramp is one of the common symptoms of patients with liver cirrhosis and significantly affects patients' quality of life.In general,the research on liver cirrhosis mainly focuses on the management and prevention of causes or common complications,and there are relatively few studies on the treatment of muscle cramp.Therefore,it is very important to find safe and effective therapeutic regimens.This article describes the pathogenesis and manifestations of muscle cramp in patients with liver cirrhosis,summarizes the therapeutic regimens with clinical value,including new drugs such as baclofen,L-carnitine,and taurine,and further elaborates on the protective effect of taurine against liver fibrosis via its activation of extracellular matrix and hepatic stellate cells,in order to provide new evidence for the treatment of muscle cramp in liver cirrhosis.
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Purpose Liver fibrosis is the common pathological process of cirrhosis developed by chronic liver disease.This study aims to explore the application of microvascular change in assessing the liver fibrosis induced by bile duct ligation based on X-ray phasecontrast computed tomography (PCCT).Materials and Methods Ten rats were equally divided into the group of bile duct ligation-induced liver fibrosis and the control group at random.Then ten excised liver tissues were imaged at beamline BL13W1 of Shanghai Synchrotron Radiation Facility in China.After the imaging studies,the liver samples were stained with Sirius red and immunostained with antibodies against cytokeratin 19 (CK19).The microvasculature in livers was reconstructed via PCCT,and the correlation analysis on microvascular density and the proportion of fibrosis area was performed.Results The microvasculature including blood vessels,dilated bile ducts and ductular proliferation were clearly revealed by PCCT technology.Moreover,the 3D microvascular density and proportion of fibrosis area in the liver fibrosis group increased significantly compared with those in the control group (P＜0.01),and the correlation between them was obvious (r=0.812,P＜0.01).Conclusion Microvascular 3D characteristics of liver fibrosis are well demonstrated by PCCT,and 3D microvascular density is significantly correlated with the proportion of fibrosis area.Those findings indicate that microvascular change is closely related to the degree of liver fibrosis induced by bile duct ligation,and thus it provides a novel means to assess the severity of liver fibrosis through microvascular change.
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Objective To verify and assess diagnostic value of noninvasive diagnostic model of liver fibrosis in primary biliary cirrhosis (PBC) based on conventional laboratory markers.Methods Seventythree patients with PBC diagnosed by liver biopsy between January 2003 and June 2011 in Beijing Friendship Hospital,Capital Medical University were recruited in this study.Correlation analysis and logistic regression analysis between the conventional laboratory markers and histology stages were assessed.A liver fibrosis diagnostic model was established based upon aforementioned biomarkers and verified by its sensitivity and specificity for predicting the liver fibrosis.Results The predictive model ( H index) consisting of five conventional laboratory markers,i.e.,platelet count,serum cholinesterase,albumin,HDL-C and prothrombin time activity,could predict advanced fibrosis ( stages Ⅲ-Ⅳ ) with an AUCROC of 0.861.The sensitivity of predicting the absence of advanced fibrosis using H index ＜ - 2.20 was 96.6％ and the specificity of predicting the presence of advanced fibrosis using H index ＞ 0.41 was 93.2％.Conclusion The established noninvasive diagnostic model consisting of five laboratory markers could accurately distinguish pathological changes of early stage PBC ( stages Ⅰ - Ⅱ ) from advanced stage PBC ( stages Ⅲ-Ⅳ).