Clinical characteristics and natural history of porto-sinusoidal vascular disease: A cohort study of 234 patients in China.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) is an under-recognized and under-diagnosed disease. The purpose of this study was to investigate the clinical features and prognosis of PSVD. METHODS: The patients who underwent liver biopsies were analyzed retrospectively. The clinical and pathological data were reviewed and screened according to the latest diagnostic criteria of PSVD. RESULTS: A total of 234 patients were diagnosed as PSVD, including 103 patients presented with portal hypertension (PH) and 131 patients without PH. At baseline, the alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT) levels were higher in the no-PH group. The liver stiffness increased in the PH group. In histological review, obliterative portal venopathy, sinusoidal dilatation and architectural disturbance were more common in the PH group, while portal tract abnormalities were more widely distributed in the no-PH group. After a median follow-up of 43.6 months, the survival rate of patients with baseline liver decompensation was 76.0%, and that of patients at a liver compensated stage in the PH group was 98.7%. First variceal bleeding occurred in 13.8% of patients with gastric-oesophageal varices. None of the patients in the no-PH group developed portal hypertension during follow-up. CONCLUSIONS: PSVD can manifest as PH or mild liver enzyme abnormalities. There are significant differences in pathological features among patients with different clinical manifestations. Recurrent ascites are the main cause of death in PSVD patients. However, patients without PH have a slow disease progression, with recurrent elevated GGT levels being their main clinical feature.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

Background/Aims: : The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases.

BACKGROUND AND AIMS: There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. METHODS: From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. RESULTS: A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation. CONCLUSIONS: ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.

Transjugular liver biopsy: enlarge the indications for liver biopsy with reliable diagnostic quality.

BACKGROUND: Complications and diagnostic efficiency for liver biopsy are main concerns for clinicians. This study aimed to assess the safety and efficacy of transjugular liver biopsy (TJLB) compared with percutaneous liver biopsy (PLB) when patients had equal level of liver function and number of passes, using propensity score matching (PSM). METHODS: The clinical and pathological data of patients who received TJLB or PLB between January 2012 and October 2022 were collected. Matching factors included age, gender, cirrhosis, portal hypertension, liver function, creatinine, number of passes, hemodialysis, history of anti-coagulation and anti-platelet, and comorbidities. Coagulation indexes were not considered as matching factors due to different indications of the two techniques. RESULTS: 2711 PLBs and 30 TJLBs were evaluated. By PSM, 75 patients (50 PLBs, 25 TJLBs) were matched. The complication rates for TJLB and PLB were 4.0% (1/25) and 10.0% (5/50) (P > 0.05). Two PLBs had hepatic hemorrhage, one of which required only close monitoring (Grade 1) and the other needed hemostasis and rehydration therapy (Grade 2). The other 3 cases presented with mild abdominal pain (Grade 1). And only one TJLB presented with mild pain. The median number of complete portal tracts were 6.0 and 10.0 for TJLBs and PLBs (P < 0.05). Moreover, the median length of sample for TJLBs and PLBs were 10.0 and 16.5 mm (P < 0.05). The diagnostic efficiency of hepatopathy of unknown etiology of TJLB versus PLB groups before and after matching were 96.4% vs. 94.1% and 95.7% vs. 93.2%, respectively (P > 0.05). CONCLUSION: TJLB is an effective invasive diagnostic procedure that expands indications for liver biopsy with reliable diagnostic quality.

Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

BACKGROUND: Aberrant cytokeratin 7 expression by hepatocytes (CK7+Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients. METHODS: The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0. RESULTS: Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7+Hs (2 +), CK7+Hs (1 +), and CK7-Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7-Hs and CK7+Hs (2 +) (P < 0.05). The ductopenia grade was also significantly different between patients with CK7+Hs (2 +) and CK7+Hs (1 +) according to sex (P < 0.05). Upon merging the data of CK7+Hs (2 +) and CK7+Hs (1 +) into CK7+Hs, we found significant differences in AMA, AMA-M2, anti-gp210, TB, DB, ALP, TA, IgM, fibrosis, and ductopenia grade between CK7+Hs and CK7-Hs (P < 0.05). The odds ratios (ORs) (and 95% confidence intervals (CIs)) of CK7+Hs according to anti-gp210, ductopenia grade, and interface activity were 6.413 (95% CI 1.363-30.162), 4.145 (95% CI 1.898-9.052) and 3.247 (95% CI 1.556-6.775), respectively (P < 0.05). Spearman's rank correlation according to interface activity and ductopenia grade in patients with CK7+Hs (2 + , 1 + , 0) was r = 0.359 (P = 0.001) and r = 0.396 (P < 0.001), respectively. CONCLUSION: CK7+Hs serves as a cholestasis index of PBC and are associated with the ductopenia grade and interface activity. Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

Early predictors of acute hepatitis B progression to liver failure.

BACKGROUND AND AIMS: 1~4% of acute hepatitis B (AHB) cases in adults progresses to acute liver failure (ALF).The predictors of ALF and prognosis for patients with ALF are not clear. This study investigated some of predictive and prognostic factors for AHB progression to ALF. METHODS: A retrospective analysis was used to assess the clinical and laboratory features of 293 patients diagnosed with AHB; the patients were divided into the following two groups: ALF (n = 13) and non-ALF (n = 280). RESULTS: In total,13 of the 293 (4.43%) patients developed ALF (10 recovered、3 died). The variables of age, anti-HBc IgM titers≥10 S/CO, HBeAg negativity, and total bilirubin (TB) at admission were significantly higher in ALF patients than in non-ALF patients. Compared to non-ALF patients, ALF patients had significantly lower values for prothrombin time activity (PTA), serum albumin, and HBV DNA. At discharge, ALF patients had lower TB normalization rates and much faster clearance of HBsAg, HBeAg and HBVDNA than non-ALF patients. In multivariate analysis, TB≥5×upper limit of normal (ULN) and HBeAg negative status were independent predictors for ALF development at admission, with 84.6% sensitivity, 85.7% specificity, a likelihood ratio of 5.91 and an area under the receiver operating characteristics curve (AUROC) of 0.850.Those who died had lower levels of peak PTA (<20%) and higher levels of peak hepatic encephalopathy (HE) grade (III-IV) than those who recovered. CONCLUSIONS: Of the patients with ALF, 23.1% died. TB≥5×ULN and HBeAg negative status were the most effective and practicable factors distinguishing ALF from AHB at admission before the onset of encephalopathy. Peak PTA<20% and/or HE grade III-IV were independent predictors of a high probability of death or a need for transplantation.

Radiological characteristics of pulmonary cryptococcosis in HIV-infected patients.

BACKGROUND: Current understanding of human immunodeficiency virus (HIV)-associated pulmonary cryptococcosis (PC) is largely based on studies performed about 2 decades ago which reported that the most common findings on chest radiograph were diffuse interstitial infiltrates. Few studies are available regarding the computed tomography (CT) findings. The aim of this study was to characterize chest CT features of HIV-associated PC. METHODS: HIV patients with cryptococccal infection and pulmonary abnormalities on Chest CT between September 2010 and May 2016 in the Second Affiliated Hospital of the Southeast University were retrospectively analyzed. Confirmed cases of tumors, mycobacterial infections and other fungal infections were excluded from the analysis. RESULTS: 60 cases were identified. The median CD4 T-cell counts were 20 cells/µL (range, 0-205 cells/µL). Chest CT scans demonstrated nodular lesions in 93.3% of the studied patients. Those nodular lesions were usually cavitated and solitary nodule was the most common form. Pleural effusions and pneumonic infiltrates occurred in 11.6% and 31.7% of the cases respectively. Those lesions were usually had co-existing nodular lesions. Etiological analysis suggested that 76.8% of the nodular lesions could have a relationship with PC that 12.5% of the nodular lesions were "laboratory-confirmed" cases, 48.2% were "clinically confirmed" cases and 16.1% were "clinically probable" cases. 85.7% of the pleural effusions could be "clinically confirmed" cases of PC. At least, 38.5% of the diffuse pneumonic infiltrates may be clinically attributed to pneumocystis pneumonia. CONCLUSIONS: This study suggested that pulmonary nodules but not diffuse pneumonia are the most common radiological characteristics of HIV-associated PC. HIV-infected patients with pulmonary nodules on Chest CT should particularly be screened for cryptococcal infection.

Solitary cavitary pulmonary nodule may be a common CT finding in AIDS-associated pulmonary cryptococcosis.

BACKGROUND: Previous studies have demonstrated that the most common chest radiologic finding in acquired immune deficiency syndrome (AIDS)-associated pulmonary cryptococcosis (PC) is diffuse interstitial infiltrates. The aim of this study was to provide additional radiologic characterization of PC in AIDS patients. METHODS: AIDS patients from the Second Affiliated Hospital of the Southeast University who were diagnosed with cryptococcosis between February 2009 and May 2012 and who had undergone chest computed tomography (CT) scans before or at the time of diagnosis were retrospectively analyzed. RESULTS: Twelve patients met eligibility criteria. The median CD4 T-cell count was 23 cells/µl (range 2-79 cells/µl). Eleven patients had pulmonary abnormalities on imaging. Initial chest CT scans demonstrated solitary cavitary pulmonary nodules in 9 patients, pleural effusions in 2 patients, bilateral ground-glass opacities in 6 patients, patchy opacities in 1 patient, and bronchiectasis in 1 patient. Bilateral ground-glass opacities appeared to be associated with Pneumocystis pneumonia, while the presence of a pleural effusion was predictive of PC. Of the 9 solitary cavitary pulmonary nodules, 7 were PC and the other 2 were probable cases of PC. These nodules were predominantly in the peripheral lung and were either asymptomatic or caused only mild pulmonary symptoms. CONCLUSIONS: Solitary cavitary pulmonary nodule may be a common CT finding in AIDS-associated PC. All AIDS patients with solitary cavitary pulmonary nodules on chest CT should be screened for Cryptococcus infection.

Clinical characteristics and chronicity of acute hepatitis B induced by lamivudine-resistant strains.

Whether resistant hepatitis B virus (HBV) strains are transmissible and can lead to chronic infection remains to be studied. The aim of this study was to investigate the clinical characteristics of patients with acute hepatitis B caused by lamivudine (LAM)-resistant strains. Sera were collected from 234 Chinese patients with acute hepatitis B. LAM-resistance mutations were identified by direct polymerase chain reaction (PCR) sequencing. LAM-resistant HBV variants were detected in 11 of the 234 (4.7%) patients. Among these patients, six harbored the rtM204I mutation, two harbored the rtL180M + rtM204I mutations, one harbored the rtM204I + rtM204V mutations, one harbored the rtL80I + rtM204I mutations, and one harbored the rtV173L + rtL180M + rtM204V mutations. Three patients were infected with genotype B HBV and eight patients were infected with genotype C HBV. Two patients infected with viruses with LAM-resistance mutations developed severe acute hepatitis. One patient developed chronic hepatitis B. This patient was infected with genotype C HBV that had LAM-resistance mutations (rtL180M + rtM204I). The patient was diagnosed with an occult hepatitis B virus infection based on the presence of HBV DNA in the liver and the absence of detectable hepatitis B surface antigen (HBsAg) in the serum. LAM-resistant HBV strains in China are transmissible, can cause acute hepatitis B, and can even progress to chronic infection in China.

Complete remission of hepatitis B virus-related membranous nephropathy after entecavir monotherapy.

We reported a case of Hepatitis B virus-related membranous nephropathy (HBV-MN) with improvement under an ongoing 4.5-year of entecavir monotherapy. A 37 years old man with a 5 years' history of chronic hepatitis B (CHB) who was taken to our department because of proteinuria and microscopic haematuria. A renal biopsy led to a diagnosis of HBV-MN with mesangioproliferative. Interferon-alpha 2b (IFN-α2b) was stopped after 24 weeks due to the increasement of HBV-DNA and sustained HBeAg positive. Therefore, we started using 0.5mg entecavir per day. After 2 months' treatment, HBV-DNA was not detected in the blood, and the ALT and AST decreased to normal degree. After 3 years of entecavir therapy, virological tests revealed HBeAg seroconversion. With no further intervention during the next one and a half years, there was improvement of proteinuria gradually. This suggested that entecavir monotherapy may induce and maintain complete remission of membranous nephropathy associated with hepatitis B.

Long-term efficacy of interferon alpha therapy on hepatitis B viral replication in patients with chronic hepatitis B: a meta-analysis.

BACKGROUND/AIMS: Interferon (IFN) alpha has been used in the treatment of chronic hepatitis B for decades. Beneficial effects including hepatitis B e antigen (HBeAg)/HBV DNA seroclearance have been documented. However, it remains unclear whether interferon has long-term efficacy on inhibiting hepatitis B viral replication. So we conducted a meta-analysis of available literature to assess the evidence obtained on the efficacy of IFN treatment in chronic HBV infection. METHODS: Seven clinical controlled trials, including 1550 patients and comparing IFN to no treatment, were selected. Data on the incidence of HBV DNA seroclearance, HBeAg seroclearance, and HBsAg seroclearance in IFN treated and untreated patients were extracted from each study. The evaluation of effectiveness was performed with an intention-to-treat (ITT) method. We used the relative risk (RR) and 95% confidence interval (CI) of the main outcomes as the measure of efficacy. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity. Analyses were performed with STATA version 9.0 and Review Manager Version 4.2. RESULTS: Four studies including the data of HBeAg seroclearance with significant heterogeneity were analyzed by random-effect method; six studies including the data of HBsAg seroclearance without significant heterogeneity were analyzed by fixed-effect method. A different incidence of HBeAg seroclearance and HBsAg seroclearance was observed between treated and untreated patients. The RR of HBeAg seroclearance and HBsAg seroclearance was 0.66 (95% CI: 0.44, 0.99) and 0.28 (95% CI: 0.17, 0.46), respectively. CONCLUSIONS: In conclusion, the results of this meta-analysis indicate that IFN increases the incidence of HBeAg seroclearance and HBsAg seroclearance after long-term follow-up of three to seven years.

[Comparison of curative effect of low flow rate plasma exchange combined with hemofiltration for treatment of liver failure].

OBJECTIVE: To investigate the effect of plasma exchange (PE) combined with hemofiltration (HF) on liver failure. METHODS: Seventy-seven inpatients with liver failure admitted during January 2006 to August 2007 were randomly assigned to receive PE combined with HF (PE+HF group, 38 cases), or PE alone (PE group, 39 cases). Forty-one inpatients with liver failure who had not received artificial liver support treatment were assigned to serve as control group. The survival rates and biochemical parameters of three groups were compared. RESULTS: There was no significant difference in biochemical parameters before treatment among three groups. Compared with pre-treatment values, albumin (Alb), cholinesterase (ChE) and prothrombin activity (PTA) of both PE group and PE+HF group were significantly increased after treatment, and total bilirubin (TBIL), alanine transaminase (ALT), aspartate transaminase (AST) of both PE group and PE+HF group were significantly decreased after treatment (P<0.05 or P<0.01). The survival rate of PE group, PE+HF group and control group was 48.7% (19/39), 68.4% (26/38), and 29.3% (12/41) respectively. The survival rate of PE+HF group was significantly higher than that of control group (chi(2)=12.11, P<0.01). The rate of recovery of consciousness of patients with hepatic encephalopathy in PE+HF group was higher than that of PE group (42.8% vs. 0, P<0.05). Compared with PE alone, the result was better when it was combined with HF in correction of electrolyte disturbance and acid-base imbalance (19/23 vs. 0/21, P<0.05). CONCLUSION: Treatment of liver failure by PE combined with HF is safe and effective, and its efficacy is higher than PE alone.

Mycophenolate mofetil prevents lethal acute liver failure in mice induced by bacille Calmette-Guérin and lipopolysaccharide.

BACKGROUND/AIMS: To investigate the effect of mycophenolate mofetil (MMF) on acute liver injury induced by bacille Calmette-Guérin (BCG) and lipopolysaccharide (LPS). METHODS: Acute liver failure was induced in male Kunming strain mice by injecting the animals with BCG 2.5 mg per mouse, and LPS 10 microg per mouse 10 days later. The mice in the treatment groups were given MMF 2 h before, simultaneous with, or 2 h after administration of LPS, and the mice in the control group were given the same dose of saline. The 24-h survival rate, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were compared. Serum levels of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 6 (IL-6) were measured and the expressions of TNF-alpha, IFN-gamma, and IL-6 mRNA in the liver tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). Concanavalin A (Con A)-induced splenocyte proliferation were determined by methods of methyl thiazolyl tetrazolium. RESULTS: Injecting a small dose of LPS into BCG-primed mice caused a lethal hepatic injury mimicking acute hepatitis, from which 16 of the 20 mice died within 24 h (20% survival rate). Massive necrosis of parenchymal hepatocytes with marked inflammatory cell infiltration was observed by histological examination. In parallel, serum ALT and TNF-alpha, IFN-gamma, and IL-6 levels were increased. Expression of TNF-alpha, IFN-gamma, and IL-6 mRNA in the liver were significantly increased also. Treatment with MMF markedly reduced the death rate in a dose-dependent manner. It reached its maximal effect at the dosage of 150 mg per kg of body weight when pretreated 2 h before LPS injection, with improvement of histological feather and survival rate (84.2%, 16/19). MMF significantly inhibited serum levels of TNF-alpha, IFN-gamma, and IL-6, and significantly reduced TNF-alpha, IFN-gamma, and IL-6 expression in the liver, which increased after BCG and LPS injection. Moreover, splenocyte proliferation response induced by Con A was also inhibited by MMF treatment. CONCLUSIONS: Treatment with MMF has a protective effect on endotoxin-induced fatal liver failure by regulating the production of inflammatory cytokines and T-cell proliferation.