Ammonia is associated with liver-related complications and predicts mortality in acute-on-chronic liver failure patients.

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

AARC score determines outcomes in patients with alcohol-associated hepatitis: a multinational study.

BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients. METHODS: Prospectively collected data from the AARC database were analyzed. RESULTS: Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p < 0.001); extrahepatic organ failure [66.9% vs. 41.8% vs. 35.4%; p < 0.001] respectively. The AARC score better discriminated 90-day mortality. Harrell's C-index was 0.72 compared to other scores. CONCLUSION: Nearly 4 of 5 patients with AH present with ACLF. Such patients have a higher risk of infections, organ failures, lower response to CS, and higher mortality. Patients with AH and ACLF with AARC grade 3 should be considered for an early liver transplant.

Clinical and pathological characteristics of chronic hepatitis B patients with normal alanine aminotransferase and not receiving antiviral therapy / 中华微生物学和免疫学杂志

Objective:To analyze the clinical and pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and not receiving antiviral therapy.Methods:This study retrospectively included CHB patients diagnosed by liver biopsy at the Third Hospital of Hebei Medical University from January 2008 to December 2022. According to the HBV DNA and HBeAg status of "immune tolerance period and immune control period", these patients were divided into three groups: chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group including the patients that did not meet the inclusion criteria of the above two groups. Kruskal-Wallis H test was used for comparison of continuous data between multiple groups. Mann-Whitney U test was used for comparison of continuous data and ordered categorical data between two groups. Chi-square test or Fisher′s exact test was used for comparison of categorical data between two groups. Results:A total of 284 CHB patients with normal ALT were enrolled. There were 64, 88 and 132 cases in the chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group, respectively. Histopathological analysis revealed that there were 182 (64.08%) cases with pathological inflammation grade (G) and/or fibrosis stage (S)≥2, 155 (54.58%) with S≥2 and 120 (42.25%) with G≥2. The proportion of patients with G and/or S≥2 in the indeterminate group [70.45% (93/132)] was higher than that in the chronic HBV carrier group [48.44% (31/64)] and inactive HBsAg carrier group [65.91% (58/88)] (both P<0.05). Patient′s age and the ratio of patients with S≥2 in the chronic HBV carrier group [33 years old, 39.06% (25/64)] were smaller than those in the inactive HBsAg carrier group [39 years old, 56.82% (50/88)] and the indeterminate group [39 years old, 60.61% (80/132)] (all P<0.05). Patients in the inactive HBsAg carrier group (19 U/L) had lower ALT levels than those in the chronic HBV carrier group (26 U/L) and the indeterminate group (23 U/L) (both P<0.05). The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 [73.08% (57/78) vs 32.08% (17/53), P<0.05], and the proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg increased gradually with age. The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 in the chronic HBV carrier status and indeterminate groups [93.33% (28/30) vs 43.33%(13/30), P<0.05; 59.46% (22/37) vs 12.50% (2/16); both P<0.05]. There was a statistically significant difference in the incidence of significant liver injury between patients≤ 30 years old and >30 years old [52.7% (39/74) vs 68.1% (143/210), P<0.05]. Conclusions:Significant liver injury occurred in 64.08% (182/284) of CHB patients with normal ALT not receiving antiviral therapy, which required the attention of clinicians. Among CHB patients with normal ALT, the expression site of HBcAg in hepatocytes was related to the occurrence of significant liver injury and could be expected to serve as an important indicator for predicting the patient′s status and the necessity of antiviral treatment. CHB patients with positive HBV DNA who were older than 30 years required antiviral treatment, and CHB patients≤30 years with normal ALT and significant hepatic tissue damage also required antiviral treatment.

A study on the diagnostic value of GP73 in liver fibrosis among patients with chronic liver disease / 中华内科杂志

Objective:This study aimed to evaluate the diagnostic value of serum Golgi protein 73(GP73) alone and GP73 combined with liver stiffness measurement (LSM), aspartate aminotransferase/platelet ratio index (APRI), and 4-factor-based fibrosis index (FIB4) in diagnosing liver fibrosis in patients with chronic liver disease of different etiologies.Methods:A diagnostic test. A total of 68 patients who underwent liver biopsy in the Department of Traditional and Western Medical Hepatology of the Third Hospital of Hebei Medical University from October 2019 to December 2020 were selected to detect serum GP73 levels. iLivTouch was used to assess liver stiffness measurement (LSM). In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels, and peripheral platelet (PLT) counts were assayed. The correlation between GP73 and the above indexes was assessed, and APRI and FIB-4 were calculated. SPSS 21.0 statistical software was used for statistical analysis. The area under the receiver operating characteristic curve was calculated to evaluate diagnostic efficacy of GP73 in identifying hepatic fibrosis stages. Furthermore, the difference between GP73 and liver stiffness, as well as APRI and FIB4 in diagnosing significant fibrosis was assessed.Results:Based on liver biopsy, 13, 18, 17, and 20 cases were diagnosed as stages S0-1, S2, S3, and S4, respectively. The AUC of GP73 diagnosing hepatic fibrosis stage S≥3 and S=4 were 0.806 and 0.844 at cut-off points of 2.06 and 3.27 μg/L, and the sensitivity and specificity were 93.5%, 61.5%, 90.0%, 70.3%, respectively. In addition, GP73 levels were positively correlated with the degree of liver fibrosis ( r=0.547, P<0.001). Conclusions:The efficacy of serum GP73 level in diagnosing the degree of liver fibrosis in patients with chronic liver disease from different causes was significantly higher than that of APRI, FIB4, and LSM. The combination of GP73 and FIB4 can further improve the accuracy of diagnosis of liver fibrosis staging S≥3 and S=4, which is a reliable serological marker for the diagnosis of fibrosis in patients with chronic liver disease.

Acute variceal bleeding portends poor outcomes in patients with acute-on-chronic liver failure: a propensity score matched study from the APASL ACLF Research Consortium (AARC).

BACKGROUND AND AIMS: Limited data exist regarding outcomes of acute variceal bleeding (AVB) in patients with acute-on-chronic liver failure (ACLF), especially in those with hepatic failure. We evaluated the outcomes of AVB in patients with ACLF in a multinational cohort of APASL ACLF Research Consortium (AARC). METHODS: Prospectively maintained data from AARC database on patients with ACLF who developed AVB (ACLF-AVB) was analysed. This data included demographic profile, severity of liver disease, and rebleeding and mortality in 6 weeks. These outcomes were compared with a propensity score matched (PSM) cohort of ACLF matched for severity of liver disease (MELD, AARC score) without AVB (ACLF without AVB). RESULTS: Of the 4434 ACLF patients, the outcomes in ACLF-AVB (n = 72) [mean age-46 ± 10.4 years, 93% males, 66% with alcoholic liver disease, 65% with alcoholic hepatitis, AARC score: 10.1 ± 2.2, MELD score: 34 (IQR: 27-40)] were compared with a PSM cohort selected in a ratio of 1:2 (n = 143) [mean age-44.9 ± 12.5 years, 82.5% males, 48% alcoholic liver disease, 55.7% alcoholic hepatitis, AARC score: 9.4 ± 1.5, MELD score: 32 (IQR: 24-40)] of ACLF-without AVB. Despite PSM, ACLF patients with AVB had a higher baseline HVPG than without AVB (25.00 [IQR: 23.00-28.00] vs. 17.00 [15.00-21.75] mmHg; p = 0.045). The 6-week mortality in ACLF patients with or without AVB was 70.8% and 53.8%, respectively (p = 0.025). The 6-week rebleeding rate was 23% in ACLF-AVB. Presence of ascites [hazard ratio (HR) 2.2 (95% CI 1.03-9.8), p = 0.026], AVB [HR 1.9 (95% CI 1.2-2.5, p = 0.03)], and MELD score [HR 1.7 (95% CI 1.1-2.1), p = 0.001] independently predicted mortality in the overall ACLF cohort. CONCLUSION: Development of AVB confers poor outcomes in patients with ACLF with a high 6-week mortality. Elevated HVPG at baseline represents a potential risk factor for future AVB in ACLF.

Clinical and pathological features of children with glycogen storage disease: An analysis of 10 cases / 临床肝胆病杂志

Objective To investigate the clinical and pathological features of children with glycogen storage disease (GSD). Methods A retrospective analysis was performed for ten children with GSD who were admitted to the Third Hospital of Hebei Medical University and The Fifth Medical Center of Chinese PLA General Hospital from January 2002 to January 2022, based on medical history, liver biochemistry, and liver biopsy, and population characteristics, clinical manifestations, biochemical parameters, and liver histopathological characteristics were compared and analyzed. Results All ten children had developmental retardation and a short stature, with the manifestations of abnormal liver function, mild weakness, poor appetite, yellow urine, and yellow eyes, and four children had hepatosplenomegaly. Among the ten children, six had the clinical manifestations of hypoglycemia, and one had bilateral gastrocnemius hypertrophy and positive Gower sign. Two children had positive CMV IgG. Liver histopathological manifestations included diffuse enlargement of hepatocytes, light cytoplasm, and small nucleus in the middle like plant cells, with or without fibrous tissue proliferation. Conclusion Most patients with GSD have developmental retardation and abnormal aminotransferases, and liver pathological examination shows specific pathological features.

Dynamic assessments of hepatic encephalopathy and ammonia levels predict mortality in acute-on-chronic liver failure.

BACKGROUND: We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence. METHODS: ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted. RESULTS: Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I-II in 981 (74.6%) and grades III-IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p < 0.05; each). The progressive course of HE was noted in 10.0% of patients without HE and 8.2% of patients with HE at baseline, respectively. Independent predictors of progressive course of HE were AARC score (≥ 9) and ammonia levels (≥ 85 µmol/L) (p < 0.05; each) at baseline. A final grade of HE was achieved within 7 days in 70% of patients and those with final grades III-IV had the worst survival (8.9%). Ammonia levels were a significant predictor of HE occurrence, higher HE grades and 30-day mortality (p < 0.05; each). The dynamic increase in the ammonia levels over 7 days could predict nonsurvivors and progression of HE (p < 0.05; each). Ammonia, HE grade, SIRS, bilirubin, INR, creatinine, lactate and age were the independent predictors of 30-day mortality in ACLF patients. CONCLUSIONS: HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients.

Current status of the research on low-level viremia in chronic hepatitis B patients receiving nucleos(t)ide analogues / 临床肝胆病杂志

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

Role of microRNAs in the development and progression of nonalcoholic steatohepatitis / 临床肝胆病杂志

Nonalcoholic steatohepatitis (NASH) has become the second leading cause of hepatitis and can further progress to liver fibrosis, liver cirrhosis, and even liver cancer; however, the detailed pathogenesis of NASH remains unclear, and there is still a lack of effective therapeutic drugs. MicroRNAs (miRNAs) are a class of non-coding, post-transcriptionally regulated, and highly conserved small RNAs in the body and play an important role in a variety of liver diseases. This article mainly reviews the role of miRNAs in the development and progression of NASH.

Research progress in prognostic biomarkers of liver failure / 中国综合临床

Liver failure is a group of serious clinical syndrome, which develops rapidly and has a dangerous prognosis.In recent years, there are many biomarkers to evaluate the prognosis of patients with liver failure at home and abroad, such as neutrophil/lymphocyte ratio, alpha fetoprotein, galactose lectin-3, osteopontin, Golgi protein 73, human β - defensin-1, etc.these biomarkers are of great significance for early identification of patients with liver failure, accurate evaluation of their prognosis, and formulation of effective treatment plan.

Research progress in prognostic biomarkers of liver failure / 中国综合临床

Liver failure is a group of serious clinical syndrome, which develops rapidly and has a dangerous prognosis.In recent years, there are many biomarkers to evaluate the prognosis of patients with liver failure at home and abroad, such as neutrophil/lymphocyte ratio, alpha fetoprotein, galactose lectin-3, osteopontin, Golgi protein 73, human β - defensin-1, etc.these biomarkers are of great significance for early identification of patients with liver failure, accurate evaluation of their prognosis, and formulation of effective treatment plan.

A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection / 中华肝脏病杂志

Objective@#To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.@*Methods@#Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.@*Results@#132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death.@*Conclusion@#Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Application of heme oxygenase 1 in the diagnosis of non-alcoholic fatty liver disease / 中华肝脏病杂志

Objective@#To explore the clinical value of plasma heme oxygenase 1(HO-1) in the development of non-alcoholic fatty liver disease(NAFLD).@*Methods@#Patients with NAFLD were selected from the Physical examination center and the Department of Traditional and Western Medical Hepatology of Third Hospital of Hebei Medical University. A combination of ultrasound and liver elastography was used to screen NAFLD patients and healthy persons. General clinical characteristics, peripheral blood cell count and liver biochemical test results were collected synchronously, plasma samples were retained, and plasma HO-1 level was detected by enzyme-linked immunosorbent assay. SPSS21.0 statistical software was used for statistical analysis, multivariate logistic regression analyses was used to analyse the independent risk factors affecting the incidence and progression of NAFLD. The diagnostic efficacy of indicators related to development of NAFLD was assessed by the receiver operating characteristic curve(ROC).@*Results@#A total of 328 patients with NAFLD and 113 healthy controls were included. According to the liver biochemical results, the NAFLD group was divided into 148 patients with normal liver enzymes and 180 patients with abnormal liver enzymes. The level of HO-1 in the three groups was 9.09 ± 2.19, 14.38 ± 2.63, 17.00 ± 3.30 ng/ml, and was increased respectively of healthy controls, patients with normal liver enzymes and patients with abnormal liver enzymes. Analyzing plasma HO-1 levels of components associated with metabolic disorders suggests that components without metabolic syndrome(9.83 ± 3.21) < components with 1 metabolic syndrome(13.59 ± 3.72) < components with 2 or more metabolic syndrome(16.09 ± 3.41), P < 0.001. The results of HO-1 level stratification analysis showed that WBC, ALT, AST, GGT, TG increased as HO-1 level increased, and the pairwise difference was statistically significant (P < 0.001). The WBC count of NAFLD is significantly higher than healthy group(6.79 ± 1.62 vs 5.68 ± 1.36, P < 0.001). The univariate and multivariate regression analyses of all the subjects showed that HO-1, TG and BMI were prognostic factors for the occurrence of NAFLD and HO-1, TC, GLU were prognostic factors for the progression of NAFLD, P < 0.05. The ROC analysis showed that HO-1 was reliable markers for predicting the occurrence and progression of NALFD, the sensitivity and specificity were respectively 85.10%, 92.90% and 38.33%, 95.27%.@*Conclusion@#Plasma HO-1 can predict the occurrence and progression of NAFLD and is expected to be a novel molecular diagnostic marker for NAFLD and NASH.

Progress of antiviral therapy for hepatitis C virus-related decompensated cirrhosis / 中华肝脏病杂志

Direct-acting antiviral agents (DAAs) are the main antiviral therapeutics for hepatitis C virus-related decompensated stage cirrhosis. DAAs of NS3/4A protease inhibitors use is not recommended for patients with decompensated cirrhosis due to characteristics of DAAs metabolism in liver. The recent guidelines have recommended sofosbuvir (SOF)-based plan including pan-genotype plan of sofosbuvir(SOF)/velpatasvir (VEL), sofosbuvir combined with daclatasvir (DCV), genotype 1,4,5,6 specific plan of sofosbuvir (SOF) / ledipasvir (LDV) for 24 weeks or above in combination with ribavirin for 12 weeks because NS5B and NS5A inhibitors has no obvious effect on CYP450 enzyme system and achievement of sustained virological response (SVR) rates at 12/24 weeks is achievable in 88% ~ 100%, and liver reserve function improves in 42% ~ 53% of patients. Furthermore, approximately 15.5% ~ 49% of patients waiting for liver transplantation after treatment with DAAs do not require liver transplantation for short-term and 10.3% ~19.2% of patients receiving SOF/LDV, and SOF combined with DCV not needed liver transplantation. Thus, the clinical application of DAAs provides a safe and reliable antiviral treatment plan for hepatitis C virus-related decompensated stage cirrhosis.

Advances in diagnosis and treatment of liver cirrhosis with integrated traditional Chinese and Western medicine / 中华肝脏病杂志

Liver cirrhosis is a chronic progressive liver disease. A non-invasive diagnostic technique for hepatic fibrosis combined with liver biochemistry, molecular biology, and immunology, imaging study, liver histopathological assessment, and traditional Chinese medicine (TCM) syndrome differentiation can accurately diagnose the cause, severity of disease, and determine the prognosis. In clinical practice of Western medicine, there are five-stages of cirrhosis classification, with periods 1 and 2 being compensated stage, and periods 3 to 5 being decompensated stage. Etiological treatment and anti-hepatic fibrosis treatment are the basic measures for different disease severity and complications. Comprehensive application of modern medical technology and traditional Chinese medicine differentiation therapy can improve the treatment effect and survival rate.

Focus on the treatment of chronic hepatitis C in children / 临床肝胆病杂志

Chronic hepatitis C in children has an insidious onset and has few available treatment options.Pegylated interferon alpha (Peg-IFNα) combined with ribavirin (RBV),known as the PR regimen for short,used to be the standard regimen;however,treatment response is often affected by various factors including hepatitis C virus genotype,viral load,and host gene polymorphisms,and some children cannot tolerate the adverse reactions of PR regimen.HCV Guidance:Recommendations for Testing,Managing,and Treating Hepatitis C developed by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD/IDSA) in September,2017 recommended that direct-acting antiviral agents (DAAs) can be used for children with hepatitis C who are aged above 12 years or have a body weight of ≥35 kg.Sofosbuvir combined with ledipasvir is the recommended regimen for children with genotype 1,4,5,or 6 infection,and sofosbuvir combined with RBV is recommended for children with genotype 2 or 3 infection.The course of disease is 12 weeks for previously untreated children with genotype 1 infection,children with genotype 1 infection who were treated by IFNα and do not have liver cirrhosis,or children with genotype 2,4,5,or 6 infection,and 24 weeks for children with genotype 1 infection who were treated by IFNα and have liver cirrhosis or children with genotype 3 infection.Further studies are needed to investigate the type of DAAs used in children with chronic hepatitis C aged ＜ 12 years,related regimens,and their safety.As for special populations including children with chronic hepatitis C complicated by HIV infection and those treated by liver transplantation,individualized treatment regimens should be developed with reference to the status of HIV infection and complications of liver transplantation.

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.

An interpretation of the AASLD practice guideline on the diagnosis and management of nonalcoholic fatty liver disease in 2017 / 中华肝脏病杂志

The American Association for the Study of Liver Diseases (AASLD) updated and published the Practice Guidance for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease (NAFLD) in July 2017, which provides recommendations for the accurate diagnosis, treatment, and effective prevention of NAFLD. Related metabolic diseases should be considered during the initial evaluation of patients suspected of NAFLD. Noninvasive diagnostic techniques including transient elastography, magnetic resonance elastography, and serum biochemical models should be used to evaluate the development and progression of liver fibrosis in patients with NAFLD. Clinical liver pathology report should clearly differentiate between nonalcoholic fatty liver (NAFL), NAFL with inflammation, and nonalcoholic steatohepatitis (NASH) and identify the presence or absence of liver fibrosis and its degree. Early medication for NAFLD can only be used in patients with pathologically confirmed NASH and liver fibrosis, and it is not recommended to use pioglitazone and vitamin E as the first-line drugs for patients with NASH which has not been proven by biopsy or non-diabetic NASH patients. Foregut bariatric surgery can be considered for obese patients with NAFLD/NASH who meet related indications. It is emphasized that the risk factors for cardiovascular disease should be eliminated for NAFLD patients. Statins can be used for the treatment of dyslipidemia in patients with NAFLD/NASH, but they cannot be used in patients with decompensated liver cirrhosis. Routine screening or hepatocellular carcinoma surveillance is not recommended for NASH patients without liver cirrhosis. Cardiovascular disease should be taken seriously during liver transplantation evaluation. There is still no adequate clinical evidence for the treatment of NAFLD in children and adolescents, and intensive lifestyle intervention is recommended as the first-line therapy for such patients.

Mechanism of action of Yiqi Huoxue Recipe in regulating autophagy and reversing liver fibrosis / 中华肝脏病杂志

Objective@#To investigate the role and mechanism of action of Yiqi Huoxue Recipe (YQHXR) in regulating autophagy and reversing liver fibrosis in rats with carbon tetrachloride (CCl4)-induced liver fibrosis.@*Methods@#Healthy male Wistar rats were intraperitoneally injected with a mixture of CCl4 (30%) and olive oil (70%) twice a week for 8 weeks to establish a rat model of liver fibrosis. The rats administered normal diet were used as control group. Furthermore, YQHXR or Fuzheng Huayu Recipe (FZHYR) was intragastrically administered to the rats. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automatic biochemical analyzer. Hematoxylin-eosin (HE) staining and Masson staining were performed to observe the degree of fibrosis in rat liver. The protein expression of α-smooth muscle actin (α-SMA) and type I collagen α1 chain (Col1A1) in liver tissue was measured by immunohistochemistry. Furthermore, the mRNA and protein expression of α-SMA, Col1A1, autophagy-related protein 7 (Atg7), microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (SQSTM1/p62) were determined using qRT-PCR and Western blotting, respectively. Comparison between multiple groups was made by one-way analysis of variance, and comparison between any two groups was made using the LSD test. P < 0.05 was considered as statistically significant.@*Results@#The YQHXR group and FZHYR group had significantly lower serum levels of ALT and AST than the model group (ALT: 66.8±10.42 U/L and 73.2±10.33 U/L vs 106.80±18.24 U/L, F = 31.672, P < 0.001; AST: 122.6±16.65 U/L and 125.4±16.92 U/L vs 278.4±66.14 U/L, F = 25.539, P < 0.001). The pathological grades of hepatic fibrosis were S5.64±0.22, S3.70±0.35, and S3.90±0.34 in the model group, YQHXR group, and FZHYR group, respectively (F = 362.188, P < 0.001). Compared with the control group, the YQHXR group and FZHYR group had significantly reduced mRNA and protein expression of α-SMA, Col1A1, Atg7, and LC3B and significantly increased expression of p62 (all P < 0.05), and the differences were greatest in the YQHXR group.@*Conclusion@#YQHXR and FZHYR can prevent or reverse liver fibrosis by regulating hepatocyte autophagy and inhibiting hepatic stellate cell activation and collagen deposition.

Current status and perspectives of diagnosis and treatment of complications related to liver cirrhosis / 中华肝脏病杂志

Liver cirrhosis is the severe period of chronic liver diseases, especially decompensated liver cirrhosis and its complications, such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, acute kidney injury, and hepatocellular carcinoma, which greatly affect patients’ quality of life and even threaten their lives. Early prevention and treatment of the causes of development and progression and pathogenic mechanism may slow down or reverse liver cirrhosis and its severe complications. Once the disease progresses to portal hypertension and related complications, it is very important to select preventive measures for acute exacerbation of different complications, as well as the methods and timing for treatment in acute stage, which may help to save patients’ lives and improve their prognosis.