Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients

Background/Aims@#Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). @*Methods@#Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. @*Results@#The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. @*Conclusions@#The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Perinatal management and genetic testing and for a puerperant affected with ATP7B gene variation in Wilson disease / 中国综合临床

Objective:To explore the perinatal management of patients with WD during pregnancy, and to determine its genetic etiology and the possibility of fetal morbidity using the genetic detection of amniotic fluid and umbilical cord blood.Method:In terms of fine management during the perinatal period, a case of K-F ring was found in the Ophthalmology Department of Beijing Friendship Hospital, Capital Medical University in March 2019 due to eye astringency and eye swelling, and the hepatology department further diagnosed WD for one artificial abortion. After the second pregnancy in October 2020, multidisciplinary consultation and standardized treatment during pregnancy including gynecology and obstetrics, liver disease center, anesthesiology department, gastroenterology department and nutrition department were carried out. The genomes of patients' venous blood, amniotic fluid and umbilical cord blood were extracted and analyzed for ATP7B gene variation by Sanger sequencing.Result:Through multi-disciplinary collaborative management, the patient gave birth successfully in the case of pregnancy complicated with liver cirrhosis, portal hypertension, splenomegaly with hyperfunction, thrombocytopenia, anemia, esophageal and gastric varices and other complications. The phenotype of the newborn was normal, and the Apgar score was 10-10-10. Sequencing results showed that the patient had ATP7B p.Arg778Leu and p.Val890Met, which were missense heterozygous variants reported in the mutation database, and ACMG was classified as pathogenic variants. The results of amniotic fluid and umbilical cord blood showed that the fetus had only p.Arg778Leu single heterozygous variation, and it was predicted that there would be no clinical phenotype of WD.Conclusion:Perinatal multidisciplinary collaborative management has important protective significance for the successful pregnancy of patients with WD. Genetic screening of amniotic fluid and umbilical cord blood is conducive to early detection of fetal WD.

Etiological and non-etiological therapies for cirrhotic portal hypertension / 临床肝胆病杂志

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.

Direct intrahepatic portosystemic shunt in treatment of Budd-Chiari syndrome / 中华肝胆外科杂志

Objective:To study the efficacy of direct intrahepatic portosystemic shunt (DIPS) in treatment of Budd-Chiari syndrome (BCS).Methods:From January 1, 2015 to June 31, 2017, consecutive patients with BCS who were treated with DIPS at the Department of Interventional Therapy of Beijing Shijitan Hospital, the Liver Disease Research Center of Beijing Friendship Hospital and the General Surgery Department of Beijing Ditan Hospital were retrospectively analyzed. The symptoms, physical signs (including abdominal distension, ascites, pleural effusion, splenomegaly, hepatic encephalopathy) and perioperative laboratory results of these patients were collected and analyzed. Biochemical indicators including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), and portal pressure gradient were compared before and 2 weeks after treatment. The patients were followed up for at least 3 years to assess their clinical symptoms, patency of shunt, oncological status and survival.Results:Of 67 patients with BCS who were included in the study, there were 45 males and 22 females, aged (38.12±23.22) years. The BCS classification of these patients were hepatic vein type ( n=65), including 62 patients with complete hepatic vein obstruction, 3 patients with hepatic vein occlusion due to thrombosis, and 2 patients with mixed hepatic vein and inferior vena cava occlusion. All 67 patients underwent DIPS with 93 stents being implanted. In addition, 43 patients underwent gastric coronary vein embolization, and 2 patients with mixed type of BCS underwent inferior vena cava stenting. The portal pressure gradient decreased from (22.17±9.16) mmHg (1 mmHg=0.133 kPa) to (9.87±4.75) mmHg, the difference was statistically significant ( P<0.05). Abdominal distension was relieved, at one month and ascites completely subsided in 3 months after operation. The liver congestion and swelling were obviously relieved. Comparison of patients 2 weeks after operation and before operation, ALT decreased from (65.28±27.75) U/L to (28.43±13.46)U/L, AST from (68.75±29.23) U/L to (26.92±13.33)U/L, TBil from (175.31±80.48)μmol/L to (45.08±26.54)μmol/L, DBil from (127.55±44.65)μmol/L to (35.12±10.77)μmol/L, and albumin increased from (31.56±7.22) g/L to (44.18±11.36)g/L, the difference was statistically significant (all P<0.05). All patients were followed up for at least 3 years. Shunt stenosis was detected in 5 patients (7.46%) with shunt expansion being performed, variceal bleeding in 2 patients (2.99%), ascites recurrence in 4 patients (5.97%) and hepatic encephalopathy in 2 patients (2.99%). No patients were diagnosed with hepatic cancer, and no patients died. Conclusion:DIPS was efficacious, safe and reliable to that BCS patients. It rapidly reduced portal venous pressure, relieved liver congestion, and restored liver morphology and liver function in these patients.

Clinical diagnosis, staging, and therapeutic principles of liver cirrhosis / 临床肝胆病杂志

With in-depth studies on the pathogenesis, pathophysiology, treatment, and prognosis of liver cirrhosis in recent years, there have been great changes in staging and treatment concepts among scholars in China and globally. Besides the traditional staging system of compensated and decompensated liver cirrhosis, liver cirrhosis can be divided into five stages based on ascites, variceal bleeding, and severe infection, which highlights the features of this disease in different disease stages and this provides potential targets and basis for treatment. At present, the comprehensive management of liver cirrhosis, including etiological treatment, treatment targeting key pathogenesis and major complications, nutritional support, exercise guidance, and lifestyle adjustment (smoking cessation, alcohol withdrawal, and improvement of oral hygiene), is the key to delaying disease progression and improving prognosis, and liver transplantation remains the most effective approach for end-stage liver cirrhosis.

Definition, etiology, and epidemiology of liver cirrhosis / 临床肝胆病杂志

Liver cirrhosis is the leading cause of liver-related death globally, and the most common causes of liver cirrhosis are chronic hepatitis B and C, alcoholic liver disease, and nonalcoholic fatty liver disease. Recent studies have shown that despite an increase in the number of deaths due to liver cirrhosis around the world, there is a reduction in age-standardized death. In China, there are increases in number of patients with liver cirrhosis, prevalence rate of liver cirrhosis, number of deaths due to liver cirrhosis, and mortality rate of liver cirrhosis, while there are reductions in age-standardized prevalence rate and mortality rate; chronic hepatitis B remains the main cause of liver cirrhosis, with a gradual increase in the proportion of liver cirrhosis cases caused by alcoholic and nonalcoholic fatty liver diseases.

Value of hepatic venous pressure gradient in predicting clinical end events in liver cirrhosis / 临床肝胆病杂志

Liver cirrhosis is the end stage of liver disease, and decompensated liver cirrhosis has the significant feature of portal hypertension. At present, hepatic venous pressure gradient (HVPG) remains the “gold standard” for evaluating portal hypertension and thus has great significance in clinical practice. This article elaborates on the value of HVPG in predicting end events in compensated and decompensated liver cirrhosis and the application of HVPG in evaluating the therapeutic effect of drugs in the treatment of portal hypertension, so as to provide a basis for early prediction, early prevention, and early intervention of portal hypertension in clinical practice.

Hemochromatosis International: therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr homozygous genotype / 中华肝脏病杂志

Hereditary hemochromatosis is a kind of hereditary metabolic liver disorders. It is caused by mutations in genes related to hemochromatosis, which leads to over deposition of iron in the liver, pancreas, skin, hypophysis, gonad and other organs and tissues of the whole body and is manifested as cirrhosis, diabetes, skin pigmentation, and low libido. Physicians of our country have inadequate understanding and familiarity with this disorder. Both the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases have issued guidelines for the diagnosis and treatment of hemochromatosis, but these two guidelines are complicated and difficult for Chinese clinical physician to comprehend. In 2018, Hepatology International published therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr homozygous genotype developed by Hemochromatosis International, these recommendations were objective, simple, and practical. We believe the above-mentioned guideline is understandable and helpful for clinicians and patients without medical education background. Therefore, herein the recommendations are translated into Chinese language, with a view to being able to be clinical work guide for the majority of Chinese hepatologists.

Diagnosis and treatment of portal hypertension caused by rare diseases / 临床肝胆病杂志

Portal hypertension caused by rare diseases is mostly presinusoidal (prehepatic) or posthepatic. It is non-cirrhotic portal hypertension in most cases, so hepatic venous pressure gradient cannot accurately reflect the portal venous pressure of such patients, which causes difficulties in clinical diagnosis and treatment. There are many diseases in this category. This article introduces the advances in the pathogenesis and treatment of portal hypertension caused by six rare diseases and summarizes the current status of treatment, in order to help improve the awareness of these diseases among clinicians.

Comparison of FibroTouch and FibroScan for the assessment of fibrosis in chronic hepatitis B patients / 中华实验和临床病毒学杂志

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.

An analysis of clinical characteristic and related risk factors in 208 cirrhotic patients complicated with infections / 中华内科杂志

Objective To analyze the clinical features and risk factors of cirrhotic patients complicated with infections. Methods The clinical and laboratory characteristics of cirrhotic patients complicated with infections hospitalized from April 2014 to June 2017 were retrospectively analyzed. Relevant risk factors for infection and mortality were explored. Results The overall incidence of infections was 17.6％ in 1670 hospitalized cirrhotic patients. Among the recruited 208 patients in this study, alcoholic, viral hepatitis B or C and autoimmune liver diseases accounted for 29.8％ (62/208), 26.0％ (54/208), and 22.1％ (46/208), respectively. The most common infection site was respiratory tract (70.2％ ), followed by urinary tract, intestinal and intra-abdomen. Forty-six pathogens were isolated from 32 patients, including 22 (47.8％ ) Gram negative bacteria, 16 (34.8％ ) Gram positive bacteria and 2(4.3％ ) mycobacterium tuberculosis, 5 (10.9％) fungi and 1 (2.2％) mycoplasma. The mortality in patients with nosocomial infections (16.7％,7/42) was higher than that in patients with community-acquired infections (6.0％,10/166, P=0.025). All 17 deaths occurred in decompensated cirrhosis. Multivariate analysis demonstrated that hepatic encephalopathy and prothrombin time were independent risk factors of mortality. Conclusions Patients with decompensated cirrhosis are more susceptible to infections. Hepatic encephalopathy and prothrombin time are independent risk factors for death.

Qualitative pathological assessment of liver fibrosis regression after antiviral therapy in patients with chronic hepatitis B / 中华肝脏病杂志

Objective@#To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression.@*Methods@#Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment.@*Results@#A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness.@*Conclusion@#This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.

The importance of hyperdynamic circulation in the progression of liver cirrhosis and its therapeutic strategies / 中华肝脏病杂志

Portal hypertension is one of the main performance of liver cirrhosis, in addition to anatomical factors, hyperdynamic circulatory status caused by abnormal splanchnic vascular tension is also very important in this procession. We summarised the mechanism and treatment strategies of hyperdynamic circulation in cirrhosis, so as to provide some recommendation for clinical practice.

Comparison of FibroTouch and FibroScan for the assessment of fibrosis in chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To perform a comparative assessment of the performance of FibroTouch and FibroScan in patients with hepatitis B.</p><p><b>METHODS</b>A total of 211 patients with hepatitis B, including cases of chronic hepatitis B (CHB) and of compensated cirrhosis, were enrolled for study between June and November of 2013. The patients underwent FibroScan testing (group 1) and FibroTouch testing (group 3), after which the operator examined a time motion ultrasound image from the FibroScan test and located a specific liver portion for focused FibroTouch testing (group 2). The consistency between the two tests' results was investigated by Pearson's correlation analysis, and the difference of liver stiffness between CHB patients and compensated cirrhosis patients was investigated by the two independent samples t-test or Mann-Whitney U test.</p><p><b>RESULTS</b>The values of liver stiffness were 5.30 (4.30,8.65) in group 1,6.10 (4.70,8.90) in group 2, and 5.70 (4.50, 8.00) in group 3 (all P < 0.05); the Pearson correlation coefficients were all more than 0.8 (P < 0.05) and there was no statistically significant difference found between the results from FibroScan and FibroTouch.The values of liver stiffness were significantly different between the CHB patients and the compensated cirrhosis patients (P < 0.05). The rates of successful detection were 100% for FibroTouch and 97% for FibroScan.</p><p><b>CONCLUSION</b>FibroTouch and FibroScan have good consistency in the evaluation of the degree of liver fibrosis. FibroTouch has a higher rate of successful detection than FibroScan.</p>

Nursing of hand-foot syndrome by oral intake of Nexavar in one patient with liver cancer / 中国实用护理杂志

Objective To summarize nursing measures of one liver cancer patient with hand-foot syndrome by onral intake of Nexavar. Methods Care focused on close observation of disease condition changes,strengthening skin care,psychological support,life care,health education and dietary care. Results The patient was discharged crred after two-week treatment.Through intensive care,the patient was discharged from hospital after 2 weeks. Conclusions To teach patients self-observation and prevention measures of hand-foot syndrome can ensure early detection,early treatment and early recovery of them.

A noninvasive diagnostic model of liver fibrosis using serum markers in primary biliary cirrhosis / 中华内科杂志

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).

The clinicopathological analysis of 88 patients with abnormal liver function test of unknown etiology / 中华内科杂志

Objective To evaluate the clinical and histological features of patients with abnormal liver tests of unknown etiology, and then to investigate the diagnosis and differential diagnosis. Methods Patients with abnormal liver function test hospitalized and had liver biopsies during 2008-2009 constituted this retrospective study cohort. After excluding those patients diagnosed with hepatotropic viral hepatitis,space occupying lesions of the liver, alcoholic liver disease and obstruction of bile duct caused by stone or malignancy and AMA/AMA-M2 positive of primary biliary cirrhosis ( PBC ), the clinical and histological characteristics were evaluated. Results Out of the 180 patients who underwent liver biopsy, 88 patients were included in the present analysis. The final diagnosis involved 15 categories of diseases, with druginduced liver injury ( DILI ) [34. 09% ( 30/88 )], autoimmune liver diseases [22.73% ( 20/88 )], and nonalcoholic fatty liver disease (NAFLD) [12. 50% ( 11/88 )] being the most common causes, following by genetic and other rare diseases. Conclusion DILI, autoimmune liver disease and NAFLD were the most common causes of abnormal liver tests in these non-viral liver diseases. Some rare diseases such as hereditary metalbolic liver disease also represent a considerable proportion in patients with abnormal liver function test.