Development and validation of a LASSO prediction model for cisplatin induced nephrotoxicity: a case-control study in China.

BACKGROUND: Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy. METHODS: We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike's information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model's performance. RESULTS: The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9. CONCLUSIONS: Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN.

Associations between hepatitis B infection and chronic kidney disease: 10-Year results from the U.S. National Inpatient Sample.

INTRODUCTION: Viral hepatitis infection is associated with negative impacts on renal function that may lead to nephropathy. We investigated associations between chronic hepatitis B virus (HBV) infection and chronic kidney disease (CKD) and/or end-stage renal disease (ESRD) in a large, representative sample from a nationwide U.S. METHODS: This population-based, retrospective observational study extracted data from the U.S. Nationwide Inpatient Sample (NIS) database, including adults ≥18 years old admitted to U.S. hospitals between 2005 and 2014 with records of chronic HBV infection in medical history. The final analytic sample included 70,674 HBV-infected patients and 282,696 matched non-HBV controls. Study endpoints were prevalent CKD and ESRD. Associations between CKD/ESRD and HBV and patients' clinical characteristics were determined by logistic regression analysis. RESULTS: HBV infection was associated with slightly increased risk of prevalent CKD (OR: 1.06, 95% CI: 1.004-1.119) and an approximate 2-times risk of prevalent ESRD (OR: 1.98, 95% CI: 1.880-2.086). HBV infection in both genders was associated with slightly increased risk of CKD (males, OR: 1.09, 95% CI: 1.02-1.16; females, OR: 1.07, 95% CI: 0.98,1.17), and significantly associated with increased risk for CKD among non-diabetic patients (OR: 1.23, 95% CI: 1.15-1.32), white patients (OR: 1.14, 95% CI: 1.06-1.23) and Asian/Pacific Islanders (OR: 1.13, 95% CI: 0.98-1.30). CONCLUSIONS: Chronic HBV infection is associated with slightly increased risk for CKD and greater risk for ESRD in males and females, Whites and Asian/Pacific Islanders and non-diabetic patients.

Prognostic Significance of Elevated Cholestatic Enzymes for Fibrosis and Hepatocellular Carcinoma in Hospital Discharged Chronic Viral Hepatitis Patients.

Chronic viral hepatitis (CVH) is the root cause of liver fibrosis and subsequent hepatocellular carcinoma (HCC). We conducted a cross-sectional, observational study based on medical records and primary data collection from patients with CVH who were admitted in five hospitals across China between February and September 2013 to determine the prevalence of elevated cholestatic enzymes (ALP and/or GGT above ULN) in discharged Chinese patients with CVH as a primary outcome and secondarily evaluated the relationship of these enzymes with fibrosis and disease severity. Majority of the patients (56%) had cholestatic enzyme elevation at discharge, with high prevalence of liver fibrosis (37.6% vs. 20.1%, p < 0.001) and cirrhosis (Child-Pugh B: 56.9% vs. 48.7%; Child-Pugh C: 17.4% vs. 12.5%; p < 0.001) in addition to significantly higher odds of liver fibrosis (OR 1.54; p = 0.024) and a trend towards higher odds of moderate-to-severe cirrhosis (OR 1.24; p = 0.317) compared to those who had normal enzyme levels. Elevated cholestatic enzyme levels serve as important prognosticators of liver fibrosis in CVH patients. Therefore, pre-discharge testing of cholestatic enzymes is recommended to identify CVH patients and provide prophylactic care.

Transient elastography in clinical detection of liver cirrhosis: A systematic review and meta-analysis.

BACKGROUND/AIMS: Transient elastography is a noninvasive method for measuring liver fibrosis. This meta-analysis assesses the diagnostic performance of transient elastography of detecting liver cirrhosis in patients with liver disease. PATIENTS AND METHODS: We searched MEDLINE, Cochrane, EMBASE databases until Jan 31, 2015, using the following search terms: elastography and liver cirrhosis. Included studies assessed patients with a diagnosis of liver cirrhosis, with an index test of transient elastography, and with the reference standard being a histopathological exam by liver biopsy. Sensitivity analysis and assessment of risk of bias and publication bias were performed. RESULTS: Fifty-seven studies were included in the meta-analysis with a total of 10,504 patients. The pooled estimate for the sensitivity of transient elastography for detecting liver fibrosis was 81% and the specificity was 88%. The imputed diagnostic odds ratio (DOR) was 26.08 and the area under the receiver-operating characteristic (AUROC) curve was 0.931. CONCLUSION: Our findings indicate that transient elastography shows good sensitivity, specificity and a high accuracy for detecting liver cirrhosis. Transient elastography can be used as an additional method for the clinical diagnosis of liver fibrosis and cirrhosis.

Fibroscan improves the diagnosis sensitivity of liver fibrosis in patients with chronic hepatitis B.

The aim of the present study was to investigate the diagnostic accuracy of Fibroscan for liver fibrosis in patients with chronic hepatitis B (CHB) with alanine aminotransferase (ALT) levels <2 times the upper normal limit. A total of 263 consecutive patients with CHB and ALT levels <2 times the upper normal limit were enrolled in the present study. Liver biopsies and liver stiffness measurements (LSM) were conducted. Receiver operating characteristic (ROC) analysis was used to determine the predictive ability of LSM for the development of liver fibrosis in patients with stage S1, S2 and S3 liver fibrosis. Bivariate Spearman rank correlation analysis was performed in order to determine the association between liver stiffness value, which was measured by Fibroscan, and liver fibrosis stage, which was measured by liver biopsy. The liver stiffness value was found to be positively correlated with the liver fibrosis stage (r=0.522, P<0.001) and necroinflammatory activity (r=0.461, P<0.001), which was measured by liver biopsy. The optimal cut-off value in the patients with stage S1, S2 and S3 liver fibrosis was 5.5, 8.0 and 10.95 kPa, respectively. The area under the ROC curve for the prediction of the development of liver fibrosis in these patients was 0.696, 0.911 and 0.923, respectively. The threshold of the optimal cut-off value exhibited a high sensitivity and specificity. The results of the present study suggested that Fibroscan may improve the sensitivity of the diagnosis of liver fibrosis in patients with CHB and ALT levels <2 times the upper normal limit, and that this sensitivity may increase with the progression of liver fibrosis.

Hepatic actinomycosis: report of one case and analysis of 32 previously reported cases.

Hepatic actinomycosis is rare, with few published cases. There are no characteristic clinical manifestations, and computed tomography (CT) shows mainly low-density images, making clinical diagnosis difficult, and leading to frequent misdiagnosis as primary liver cancer, metastatic liver cancer or liver abscess. Diagnosis normally requires examination of both the aetiology and pathology. This article reports one male patient aged 55 who was hospitalized because of repeated upper abdominal pain for more than 2 mo. He exhibited no chills, fever or yellow staining of the skin and sclera, and examination revealed no positive signs. The routine blood results were: haemoglobin 110 g/L, normal numbers of leukocytes and neutral leukocytes, serum albumin 32 g/L, negative serum hepatitis B markers and hepatitis C antibodies, normal tumour markers (alpha-fetoprotein and carcinoembryonic antigen). An abdominal CT scan revealed an 11.2 cm × 5.8 cm × 7.4 cm mass with an unclear edge in the left liver lobe. The patient was diagnosed as having primary liver cancer, and left lobe resection was performed. The postoperative pathological examination found multifocal actinomycetes in the hepatic parenchyma, which was accompanied by chronic suppurative inflammation. A focal abscess had formed, and large doses of sodium penicillin were administered postoperatively as anti-infective therapy. This article also reviews 32 cases reported in the English literature, with the aim of determining the clinical features and treatment characteristics of this disease, and providing a reference for its diagnosis and treatment.

[Comparison of liver pathohistological and clinical characteristics between chronic HBV carriers and chronic hepatitis B patients with mild elevation in ALT].

OBJECTIVE: To compare the liver pathohistological and clinical features between chronic HBV carriers and chronic hepatitis B patients with mild elevated in ALT. METHODS: 128 patients were divided into 3 groups according to the ALT: group A: ALT is less than or equal to 0.5*ULN, group B: 0.5*ULN less than ALT is less than or equal to 1*ULN, group C: 1*ULN less than ALT less than 2*ULN. The age, sex, serum HBV DNA, HBeAg status, expression of HBcAg in liver, thickness of spleen, breadth of portal vein ,blood stream speed of protal vein, right liver obliqua diameter, grade of liver inflammation and stage of liver fibrosis were compared in the three groups. RESULTS: Among 128 patients, 57(44.5%) patients had G1 hepatitis and 71 (55.5%) had G2 hepatitis, no G0 hepatitis was found in these patients; 72 patients (56.3%) had S1 fibrosis, 30 (23.4%) patients had S2 fibrosis, and 26 (20.3%) patients did not have liver fibrosis. The liver inflammation in group C was more aggravated than that in group A (P less than 0.05). And there were significant differences in thickness of spleen and right liver obliqua diameter between group C and group A, as well as between group C and B (P all less than 0.01). With the aggravating of liver inflammation, the serum ALT, thickness of spleen, breadth of portal vein and expression of HBcAg in liver were increased obviously (P less than 0.05). With the aggravating of liver fibrosis, the thickness of spleen, breadth of portal vein, right liver obliqua diameter and HBeAg negative patients were increased obviously, while the blood stream speed of portal vein was decreased obviously (P less than 0.01). CONCLUSION: Among the chronic HBV infection patients whose ALT less than 2*ULN, there were 55.5% patients had G2 of liver inflammation and 23.4% patients had S2 of liver fibrosis. The serum ALT, thickness of spleen, breadth and blood stream speed of portal vein, right liver obliqua diameter and expression of HBcAg in liver are associated with pathohistological changes in these patients.

Danshao huaxian capsule in treatment of decompensated cirrhosis resulting from chronic hepatitis B.

BACKGROUND: The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are outweight serious side-effects and the risk of fatal exacerbation of disease. Danshao huaxian capsule rapidly reduces hepatitis B virus (HBV)-DNA in serum to undetectable levels. METHODS: A total of 35 patients with chronic hepatitis B and decompensated cirrhosis were treated with danshao huaxian 1.2 g. p.o. tid daily. Before the treatment, HBV-DNA in serum was positive in all patients. Ten patients had Child-Pugh class B and 25, class C hepatitis B. Seven patients underwent liver transplantation within 6 months of initial treatment. Of the 10 patients of class B, 5 died within 6 months, and the other 5 did not complete the treatment for some reasons; the 25 patients of class C were treated for at least 6 months (mean=19 months). RESULTS: In most of the 25 patients, liver function was improved slowly but markedly after 9 months of treatment, showing a decreased level of serum bilirubin from 67+/-13 to 30+/-4 micromol/L (P<0.05, baseline vs. 6 months), an increased level of serum albumin from 27+/-1 to 34+/-1 g/L (P<0.05) and a decreased level of Child-Pugh score from 10.3+/-0.4 to 7.5+/-0.5 (P<0.05). Three patients developed resistance to danshao huaxian because of a mutation in the YMDD motif, but liver function was not deteriorated. Inhibition of viral replication with danshao huaxian resulted in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term results remain uncertain. CONCLUSION: Danshao huaxian capsule is effective in inhibiting viral DNA replication in patients with decompensated cirrhosis and making clinical improvement.

Effect of Danshao Huaxian capsule on expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in fibrotic liver of rats.

AIM: To investigate the effects of Danshao Huaxian (DSHX) capsules, a preparation of traditional Chinese medicine, on the expression of matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the fibrous livers of rats. METHODS: Eighty male Wistar rats were randomly divided into normal control group (group A), CCl(4)-induced hepatic fibrosis group (group B), non-DSHX-treated group (group C), low dose-treated group (group D), and high dose-treated group (group E). Fibrous liver models in rats were induced by subcutaneous injection of CCl(4), oral administration of alcohol and high-lipid/low-protein diet for 8 wk. After the models were established, the rats in groups D and E were orally given a low dose (0.5 g/kg) and a high dose (1.0 g/kg) of DSHX daily for 8 wk, respectively. Then, the liver indexes, serum hyaluronic acid (HA) and alanine aminotransferase (ALT) were examined. The degree of hepatic fibrosis was evaluated by optical microscopy. Hydroxyproline (Hyp) in the urine was determined, and the expression of MMP-1 and TIMP-1 was detected by immunohistochemical techniques. RESULTS: In groups D and E, the liver indexes, levels of serum HA and ALT reduced and development of hepatic fibrosis weakened significantly. The urinary Hyp and expression of MMP-1 in the liver tissues elevated, but the expression of TIMP-1 decreased obviously, as compared to groups B and C. CONCLUSION: DSHX enhances the expression of MMP-1 but decreases that of TIMP-1 in liver tissues of CCl(4)-induced hepatic fibrotic rats, which may result in its elevated activity that contributes to fighting against hepatic fibrosis.

In vivo effects of Chinese herbal recipe, Danshaohuaxian, on apoptosis and proliferation of hepatic stellate cells in hepatic fibrotic rats.

AIM: To investigate the effects of Danshaohuaxian (DSHX), a Chinese herbal recipe, on the apoptosis and cell cycles of hepatic stellate cells (HSCs) in rat hepatic fibrosis and its possible mechanisms. METHODS: Seventy-six male Wistar rats were randomly divided into normal control group, hepatic fibrosis group, non-DSHX-treated group and DSHX-treated group. Except for the normal control group, rat hepatic fibrotic models were induced by subcutaneous injection of carbon tetrachloride (CCl4), drinking alcohol, giving diet of hyperlipid and hypoprotein for 8 wk. When the hepatic fibrotic models were produced, 12 rats of hepatic fibrosis group (15 rats survived, others died during the 8 wk) were sacrificed to collect blood and livers. HSCs were isolated from the other 3 rats to detect the apoptotic index (AI) and cell cycles by flow cytometry. DSHX was then given to the DSHX-treated group (1.0 g/kg, PO, daily) for 8 wk. At the same time, normal control group and non-DSHX-treated group were given normal saline for 8 wk. At end of the experiment, some rats in these three groups were sacrificed to collect blood and livers, the other rats were used for HSC isolation to detect the apoptotic index (AI) and cell cycles. Then the liver index, serum hyaluronic acid (HA) and alanine aminotransferase (ALT), degree of hepatic fibrosis, urinary excretion of hydroxyproline (Hyp) and expression of collagen types I and III (COL I and III) in these four groups were detected respectively. RESULTS: Compared with the indexes of the hepatic fibrosis group and non-DSHX-treated group, the DSHX-treated group revealed a liver index of (0.0267+/-0.0017 vs 0.0423+/-0.0044, 0.0295+/-0.0019, P<0.05), levels of serum HA (200.78+/-31.71 vs 316.17+/-78.48, 300.86+/-72.73, P<0.05) and ALT (93.13+/-5.79 vs 174.5+/-6.02, 104.75+/-6.54, P<0.01), and stage of hepatic fibrosis (1.30 vs 4.25, 2.60, P<0.01) all reduced. The urinary excretion of Hyp increased (541.09+/-73.39 vs 62.00+/-6.40, 182.44+/-30.83, P<0.01), the COL I and III expression decreased (COL I: 1.07+/-0.96 vs 4.18+/-2.26, 3.22+/-1.44, P<0.01; COL III: 1.09+/-0.58 vs 3.04+/-0.62, 2.23+/-0.58, P<0.01), the HSCs apoptotic index of HSCs (7.81+/-0.47 vs 1.63+/-0.25, 1.78+/-0.4, P<0.05) and the ratio of G0-G1 phase cells increased (94.30+/-1.33 vs 62.27+/-17.96, 50.53+/-2.25, P<0.05). The ratios of S-phase cells (3.11+/-1.27 vs 9.83+/-1.81, 11.87+/-1.9, P<0.05) and G2-M phase cells (2.58+/-0.73 vs 23.26+/-10.95, 13.60+/-1.15, P<0.01) declined. CONCLUSION: DSHX capsule shows certain therapeutic effects on hepatic fibrosis in rats and inhibits abnormal deposition of COL I and III in rat livers by promoting the apoptosis of HSCs and preventing their proliferation.

Effects of Dan-Shao-Hua-Xian on the expression of collagen type I and III in rats with hepatic fibrosis.

BACKGROUND: Hepatic fibrosis is the common pathological change in various chronic liver diseases, and its major cause is the imbalance between the production and degradation of the extracellular matrix, which is mainly composed of collagens. Dan-Shao-Hua-Xian (DSHX) capsule, a traditional Chinese herbal compound, has shown marked preventive effects on hepatic fibrosis in rats in our previous studies. The present study was designed to further investigate its therapeutic actions on hepatic fibrosis in rats and its possible mechanisms. METHODS: Eighty male Wistar rats were randomly divided into normal control group, hepatic fibrosis group, non-DSHX-treated group, low-dose-treated group, and high-dose-treated group. The rat models of hepatic fibrosis were established by subcutaneous injecton of CCl4, drinking alcohol, giving diet of hyperliprosis and hypoprotein for 8 weeks. The two DSHX-treated groups were treated respectively with low dose (0.5 g/kg) and high dose (1.0 g/kg) of DSHX capsule p.o. everyday for 8 weeks. At the end of the experiment, liver indexes were calculated in each group in addition to the levels of the serum hyaluronic acid and alanine aminotransferase. Their degree of hepatic fibrosis and urinary excretion of hydroxyproline and expression of collagen I, III were detected. RESULTS: Comparison of the indexes of the hepatic fibrosis group and non-DSHX-treated group revealed that the liver indexes, levels of serum hyaluronic acid and alanine aminotransferase, and stage of hepatic fibrosis were all significantly reduced in the two DSHX treated groups. The urinary excretion of hydroxyproline was increased and the expression of collagen I and III in liver tissue was lessened. These alterations were more obviously observed in the high-dose-treated group. CONCLUSION: DSHX capsule has certain therapeutic effect on hepatic fibrosis in rats.