A real-world study of the efficacy and safety of sofosbuvir and velpatasvir in the treatment of HCV-infected patients in a county in northern China / 中华肝脏病杂志

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.

Detection of hepatic progenitor cells in patients with severe hepatitis and their distribution / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To identify hepatic progenitor cells (HPCs) in patients with severe hepatitis (SH) by detecting their markers and investigate the features of their distribution and location.</p><p><b>METHODS</b>Liver tissues taken from 59 SH patients were tested for the receptor of stem cell factor (c-kit), pi-class glutathione S-transferase (GST-pi), cluster of differentiation 34 (CD34), cytokeratin 19 (CK19), cytokeratin 18 (CK18) and alpha fetoprotein (AFP) by immunohistochemistry (IHC). Meanwhile, 58 patients with acute or chronic hepatitis were also detected to act as controls.</p><p><b>RESULTS</b>Hepatic progenitor cells could be seen in SH patients. Most of them existed as ductular cells that had been called "typical ductular proliferation (ADP)" or "typical ductular reaction" in previous research. These ductular cells were mainly located at the portal areas, fibro septa, periportal parenchyma and the border of the pseudolobuli and inflammatory foci. Further, c-kit, GST-pi, CK19 and CK18, but not CD34 and AFP could be detected in these cells. Another kind of HPC was the small hepatocyte-like cell (SHLC), which could express c-kit, GST-pi, and CK18, but not CK19, CD34 and AFP. The semi-quantitative analysis showed that the scope of ADP in SH patients was significantly larger than that in acute and chronic hepatitis patients (chi2= 63.62, P<0.05), and the scope of ADP in subacute severe hepatitis and chronic severe hepatitis patients was also significantly larger than that in acute severe hepatitis patients.</p><p><b>CONCLUSION</b>In the course of regeneration of viral hepatitis, different types of pathology have different features. In acute and chronic hepatitis (G1-2), the regeneration is mainly owing to the proliferation of mature hepatocytes, and in chronic hepatitis (G3-4), there is the participation of HPCs, although they are limited. In severe hepatitis, however, since the replicative capacity of normal hepatocytes is impaired or prohibited, liver regenerates and restores mainly by the means of hepatic stem cells activation and proliferation. But the hepatic stem cells don't differentiate into their mature functional compartments directly at all. There are several intermediary or transition populations. In human severe hepatitis, they are mainly ductular cells, and parts of them are small hepatocyte-like cells.</p>

Clinical features of severe acute respiratory syndrome in forty-one confirmed health care workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the clinical features of severe acute respiratory syndrome (SARS).</p><p><b>METHODS</b>Forty-one medical care workers (aged 23 - 55 years, with a average of 32 years; men/women = 8/32) who were admitted to our hospital and diagnosed with SARS during March and April, 2003 were retrospectively analyzed.</p><p><b>RESULTS</b>Thirteen of all the patients were physicians and the rest were nurses. The disease was mainly transmitted through air droplet in a short distance, and overwork induced tiredness was involved in disease stimulation. Seventy-three percent of the patients presented fever as their first symptom. Ten patients complained inertia and myalgia. One patient showed no clinical symptoms, and bilateral infiltrates was found in his chest X-ray. Among the 41 cases, 6 (15%) were diagnosed as severe type. At the first week, the counts of white blood cells (WBCs), lymphocyte and platelets were (4.4 +/- 1.5) x 10(9)/L, 0.22 +/- 0.12 and (143 +/- 37) x 10(9)/L, which were significantly lower when compared with those at the 2nd to 4th week. Abnormal liver function was found in 27 cases (mostly with elevated serum ALT), with 70% occurred at the 3rd or 4th week. In terms of CT, 30 patients (73%) showed pathological changes in lungs, and bilateral lung involvement was found in 35.59%. Of 36 cases treated with steroids, 86% received middle or low dosage (80 - 240 mg/d). Artificial ventilation was used for twenty-seven patients, and air pipe mechanical ventilation was used for 1 case. Mortality in this study was 5%.</p><p><b>CONCLUSIONS</b>Inertia and myalgia may be the earlier symptoms of health care workers with SARS include, which are parallel to CT manifestations. There is no objective index for the assessment of the severity of the disease at early stage. The medicine associated toxicities may be the main reason of liver lesions. damages. Middle or low dosage of steroid was reasonable to be used as early as possible.</p>

A clinicopathological study on nonalcoholic steatohepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the pathological and clinical characters of nonalcoholic steatohepatitis (NASH).</p><p><b>METHODS</b>Liver biopsy tissues taken from 97 patients negative for common viral detection with serological test and immunohistochemistry as well as in situ hybridization, were observed by routine light microscopic examination. And the clinical data of patients with NASH was analyzed.</p><p><b>RESULTS</b>Among the chronic hepatitis patients with unknown etiology, the detection rate of NASH was 15.5% (15/97). The characteristic lesions in NASH patients included macrovesicular steatosis in zone 3 of lobules, hepatocytes ballooning degeneration, lobules diffused with acute and chronic inflammation, and perisinusoidal fibrosis. Grading and staging according to Brunt's method, histological lesions could be accounted for G1S1 in 7 patients, G2S2 in 3 patients, G3S1 in 4 patients and G3S2 in 1 patient. There were 14 patients with mild to moderate elevation of transaminase, 10 with hyperlipemia, 8 with diabetes and 9 with fatty liver by ultrasonography.</p><p><b>CONCLUSION</b>Nonalcoholic steatohepatitis is a common form of unknown etiology chronic liver disease with certain clinic-pathological features.</p>