肝炎肝硬化合并免疫性血小板减少症临床特点分析（附8例报道）

目的总结分析肝炎肝硬化血小板明显下降患者的临床表现及其原因,藉此探讨和交流诊治经验。方法对8例肝炎肝硬化合并进行性血小板下降的息者,回顾分析其肝功能指标、凝血指标及免疫学指标以及各指标之间的相关性。结果8例患者血小板进行性下降与其肝硬化严重程度不成比例,并能够除外严重感染、弥漫性血管内凝血、再生障碍性贫血、淋巴瘤、血栓性血小板减少性紫癜等血液系统疾病,抗血小板抗体阳性,诊断为免疫性血小板减少症,应用丙种球蛋白、激素治疗后血小板明显升高。结论肝炎肝硬化患者血小板短期内明显下降时,应考虑合并免疫性小板减少症,并予以相应的治疗。     

Liver transplantation for hepatitis C-associated cirrhosis in a single Australian centre: Referral patterns and transplant outcomes

During the study period, 63 patients with hepatitis C virus (HCV) cirrhosis were referred to our unit for liver transplantation. All cases referred and transplanted were retrospectively examined. Eighty-six per cent of referred patients were male, 35% consumed alcohol in the harmful hazardous range, 13% were infected with hepatitis B and 7% had hepatocellular carcinoma. Patients with sporadic infection were more likely to be born outside Australia and were an average of 10 years older than those with HCV acquired via intravenous drug use (P< 0.001). However, patients were an average of 12 years younger at referral if they consumed harmful amounts of alcohol than if they abstained (P = 0.002). We examined the impact of HCV on the outcome of 28 patients who underwent liver transplantation (mean follow up 25 months; range 3–76 months). The use of OKT3, HCV genotype and hepatitis B status were examined for their effect on HCV-related graft dysfunction. Three year survival was 84%, equivalent to a control group. Chronic HCV-related graft dysfunction occurred in 15 (56%) patients, of whom 10 had an asymptomatic elevation in serum amino transferase, two had cholestatic hepatitis and three had severe hepatitis C that progressed onto chronic rejection. Hepatitis C virus genotype 1b tended to be associated with HCV graft dysfunction (5/6 type 1b vs 10/16 in non-type 1b). In conclusion, HCV is an increasingly common-indication for liver transplantation. Alcohol and hepatitis B were frequently occurring cofactors in the referral cohort. Most patients referred were male, although the reason why is not clear. Transplantation offers a good medium-term outcome, despite the high incidence of HCV-associated graft dysfunction.     

Comparison of outcomes between patients with alcoholic cirrhosis and those with hepatitis C virus-related cirrhosis

Background and Aim:  The natural history of alcoholic cirrhosis, especially in Asian countries, has not been completely understood thus far.
Methods:  We retrospectively compared the outcomes of compensated cirrhosis between Japanese alcoholic and hepatitis C virus (HCV)-infected patients.
Results:  A total of 227 patients (75 alcoholic and 152 HCV-infected patients) with compensated cirrhosis were enrolled. The median follow-up period was 4.9 years. The cumulative rates of hepatocellular carcinoma (HCC) development were significantly lower in the alcoholic patients than in the HCV-infected patients (6.8% vs 50.3% at 10 years, P  = 0.0003), while the cumulative rates of hepatic decompensation (37.4% vs 51.7% at 10 years) and survival (53.8% vs 47.4% at 10 years) did not significantly differ between the two groups (Kaplan-Meir analysis). The main causes of death were hepatic failure and non-hepatic diseases in the alcoholic patients and HCC and hepatic failure in the HCV-infected patients. Multivariate analyses using the Cox proportional hazard model revealed that the risk of HCC was lower in alcoholic cirrhosis than in HCV-related cirrhosis (hazard ratio (HR), 0.46), while the risk of hepatic decompensation and mortality was the same. Predictors of decreased survival were non-abstinence (HR, 2.53) in the alcoholic patients and low serum albumin level (1.58) in the HCV-infected patients.
Conclusions:  Survival of patients with alcoholic cirrhosis was similar to that of patients with HCV-related cirrhosis. The risk of HCC development was lower in alcoholic cirrhosis than in HCV-related cirrhosis. Abstinence from alcohol was important for improving the survival of patients with alcoholic cirrhosis.     

Abstinence in patients with alcoholic liver cirrhosis: A follow-up study

Aim:  To investigate the proportion of patients with alcoholic cirrhosis who abstained from alcohol after contact with a hepatology unit, the predictors for abstinence, and the role of clinical and psychosocial factors in short-term mortality in these patients.
Methods:  Eighty-seven consecutive patients with alcoholic cirrhosis from a transplant center were included. Data on cirrhosis severity and complications, as well as on abstinence and psychosocial factors were collected. Patients were followed up for 19 (12–25) months. Data on abstinence during follow up, alcohol abuse treatment, psychiatric contact, severity of cirrhosis, mortality, and liver transplantation were analyzed.
Results:  Prior to inclusion, 53/87 (61%) patients had abstained from alcohol for 24 months (interquartile range: 18–33). Twenty percent had a history of other substance abuse, 47% had undergone alcohol abuse treatment, and 21% had a previous psychiatric diagnosis. Forty-eight percent lived with a partner, 23% worked/studied, and 53% were pensioners. During follow up, 26% died, 20% received a liver transplant, 55% abstained from alcohol, 47% received alcohol abuse treatment, and 33% had psychiatric contact. In a multivariate analysis, abstinence during follow up was found to be related to abstinence upon inclusion in the study, to the model for end-stage liver disease (MELD) score at follow up, and to no abuse treatment in a detoxification unit, whereas mortality was related to index MELD and alcohol abuse treatment during follow up. Neither abstinence nor mortality was related to psychosocial factors.
Conclusion:  More than half of patients with alcoholic cirrhosis were found to abstain from alcohol during follow up, which was related to prior documentation of abstinence and cirrhosis severity. Cirrhosis severity (expressed as the MELD) and alcohol abuse treatment during follow up were related to short-term mortality.     

Liver transplantation in HIV-positive patients

This article reviews the worldwide evolution of liver transplantation as a therapeutic intervention in HIV-infected patients. Since the introduction of highly active antiretroviral therapy (HAART), liver disease secondary to viral hepatitis has become a leading cause of morbidity and mortality among HIV-positive individuals. The authors contrast survival data from pilot studies in the pre-HAART era to those data emerging from more recent trials. Particular emphasis is placed on current selection criteria for HIV-positive transplant candidates. Additional consideration is given to the effect of prolonged transplant waiting time on survival outcome. The complexity of the post-transplant medication regime, including drug interactions, optimal immunosuppression and most appropriate HAART regimes, are discussed in detail. Postoperative challenges including optimal management of hepatitis B virus and recurrent hepatitis C virus post-transplant are reviewed separately. The ethical and practical arguments relating to the use of a scarce and valuable resource in this population are debated. The authors conclude with several recommendations to assist pretransplant assessment and postoperative management of such complex patients and speculate on the direction and evolution of this field in the coming years.     

Pathogenesis of liver cirrhosis in alcoholic patients: histological evidence for hepatitis C virus responsibility

ABSTRACT— Hepatitis C virus (HCV) has been proposed to be a cofactor in the pathogenesis of cirrhosis in patients with chronic alcoholism. The demonstration of a different liver histological pattern in anti-HCV positive patients might provide additional evidence. We studied 164 patients with chronic alcoholism, and histologically proven cirrhosis. For all of them, serum samples were collected at the time of a liver biopsy and stored at –80°C. Testing for anti-HCV antibodies was done using the Ortho Diagnostic Systems Anti-HCV ELISA test. Only reproducible results were considered positive. A semi-quantitative assessment of seven histological parameters was made independently on liver biopsy samples. In the study group, 29 patients (18%) had anti-HCV antibodies. When compared with anti-HCV negative patients, both groups had similar ALT and AST seric activities. Anti-HCV positive patients had a greater score of mononuclear cells infiltrate (0.71±0.57 vs 0.41 ±0.52; p<0.05) and a lesser score of alcoholic hepatitis (0.19 ±0.57 vs 0.74 ±0.74; p<0.005). The scores for steatosis, perisinusoidal and perinodular fibrosis, and hepatocellular necrosis were similar in the two groups. In anti-HCV positive patients, with a clearly positive recombinant immunobinding assay (RIBA, Chiron-Ortho Diagnostic Systems), a greater score for hepatic necrosis and a lesser one for fibrosis were demonstrated. Among the seven patients with active cirrhosis, six were anti-HCV positive. Therefore, HCV is likely to play a role in the pathogenesis of liver damage in a few patients with alcoholic cirrhosis, especially, those with active cirrhosis.     

Effect of drinking on the outcome of cirrhosis in patients with hepatitis B or C

Survival rates were calculated for 251 patients with cirrhosis of the liver but without hepatocellular carcinoma, primary biliary cirrhosis, or autoimmune cirrhosis who underwent laparoscopy during the past 21 years at the authors' hospital. The survival rates were calculated by the Kaplan-Meier method. Stored serum was assayed for hepatitis B surface antigen (HBsAg) and antibodies to the hepatitis C virus (HCV). Patients with alcoholic cirrhosis had significantly better survival rates than patients with HBsAg, HCV, or both. Differences in survival rates between patients with hepatitis B and C were insignificant. In both groups, habitual drinkers had a significantly lower survival rate. The results suggested that alcohol accelerates liver damage in subjects with viral hepatitis.     

Factors associated with cirrhosis development in chronic hepatitis C patients from an area of low prevalence

The aim of this study was to evaluate the importance of different endogenous and exogenous factors associated with cirrhosis development among heptatitis C virus (HCV)-positive individuals from an area of low prevalence. We studied 106 consecutive HCV RNA positive patients who had undergone liver biopsy. Each patient was assessed with special attention to risk factors for hepatitis C infection, average daily alcohol consumption and analysis of plasma levels of α₁-antitrypsin (α₁AT) and α₁-antichymotrypsin (α₁ACT). Viral RNA, amplified from serum with the polymerase chain reaction (PCR) technique, was used for genotyping. Liver biopsies were assessed according to conventional histopathological criteria, and for necroinflammatory activity (grade) and fibrosis (stage) according to a numerical scoring system. The presence of cirrhosis (stage 4) was used as the dependent variable in multivariate logistic regression analysis. Alcohol abuse ( P =0.007), age at entry ( P <0.001), immigrant status ( P =0.017) and a low α₁ACT level ( P =0.008) were all independent determinants of progression to cirrhosis whereas HCV genotype 1, estimated duration of HCV infection and positivity for antibodies to hepatitis B core antigen (HBcAb) were not. Cirrhosis occurred at a significantly younger age ( P =0.005) among alcohol abusers. Hence, both endogenous and exogenous factors such as subnormal α₁ACT levels and alcohol appear to contribute to the rate of progression to cirrhosis among HCV-positive patients.     

Bacteremia in patients with cirrhosis of the liver

ABSTRACT— Infections are frequent in patients with liver cirrhosis, as their defenses against infectious agents are altered. But bacteremia occurring in cirrhotic patients has seldom been reported in the literature. From 1981 to 1986, we collected 197 cases with 228 episodes of bacteremia for this retrospective study. The incidence of bacteremia in cirrhotic patients was 8.8%; no significant difference was noted between cirrhotic patients with variant etiologies of HBV(+), HBV(–) and alcohol. But the incidence increased with the severity of the disease (1%, 4.8%, 17.1% in Child's A, B, C groups, respectively). Gram-negative bacteria were the predominant microorganisms of bacteremia (75.6%). Among them, Escherichia coli, Klebsiella pneumoniae and Aeromonas hydrophilia were the three most commonly detected microorganisms. Gram-positive bacterias were detected in 21.2% of patients with bacteremia, with predominance of the Streptococcus group and Staphylococcus aureus. In about 26.3% of cases the infectious sources were the same by bacteria cultures as from blood. The most common sources were spontaneous bacterial peritonitis, urinary tract infection, pneumonia and biliary tree infection. In cirrhotic patients with and without bacteremia, the mortality rate increased significantly in the bacteremia group (54.8% vs 23.2%, P<0.05). By Child's classification, the mortality of patients with classes B and C increased significantly after onset of bacteremia. There was no significant difference in mortality between bacteremic patients in the HBV(+), HBV(–) and alcohol groups. In conclusion, bacteremia is a severe complication of liver cirrhosis and a sign of a poor prognosis.     

Reduced ubiquinone plasma levels in patients with liver cirrhosis and in chronic alcoholics

Ubiquinone (CoQ₁₀ coenzyme) is part of the respiratory chain in mitochondria, and acts as a scavenger in oxidative stress in cell membranes. Ubiquinone is mainly synthesized in the liver and partly derived from the diet; its plasma levels significantly correlate with tissue levels in experimental animals and in pathological states in man. By means of an original high-performance liquid chromatography technique, we measured ubiquinone plasma levels in 10 healthy subjects, in 27 patients with cirrhosis and in 22 chronic alcoholics with normal liver function. Ubiquinone levels were markedly reduced in cirrhosis (0.25 [SD 0.21] μg/ml vs. 0.92 [0.38] in controls; P<0.001), without any difference between alcohol- and non-alcohol-related disease. Also, in chronic alcoholics ubiquinone levels were nearly halved (0.49 [0.24]). In cirrhosis, ubiquinone plasma levels significantly correlated with cholesterol (P<0.05), and with total bilirubin levels (P<0.01). Our study highlights a remarkable deficiency in ubiquinone levels in patients with cirrhosis and in chronic alcoholics, to which both reduced hepatic synthesis and nutritional defects may contribute.     

直接作用抗病毒药物治疗丙型肝炎肝硬化和肝移植术后丙型肝炎复发的初步临床观察

目的观察直接作用抗病毒药物(direct-acting antiviral agents,DAAs)治疗丙型肝炎(丙肝)肝硬化和肝移植术后丙肝复发的安全性和临床效果。方法入组丙肝肝硬化7例(5例失代偿)和肝移植术后丙肝复发7例(移植后时间6~44个月,中位时间17个月),年龄26~69岁(中位年龄55岁),HCV RNA分型均为基因1b型,HCV RNA载量为6.90×104~4.34×107IU/ml。DAAs治疗方案为索菲布韦(sofosbuvir)+息米普韦(simeprevir)(3例)和harvoni(sofosbuvir+ledipasvir)(11例),疗程12周。治疗过程中观察HCV RNA、肝功能、安全性指标及不良反应。结果除1例肝移植术后患者4周时HCV RNA为5.60×10 IU/ml,其余患者均获快速病毒学应答,HCV RNA最快5 d低于检测值下限。所有患者均获得治疗结束时病毒学应答和持续病毒学应答,ALT和AST下降,ALB水平升高。移植术后患者他克莫司血药浓度未见明显变化。不良反应轻,主要为头痛(1例)、乏力(2例)和关节痛(1例)。结论 DAAs治疗丙肝肝硬化和肝移植术后丙肝复发安全性好,疗效肯定。对失代偿期丙肝肝硬化的远期疗效待观察。     

Clinical characteristics and outcome of patients with cirrhosis and refractory ascites.

BACKGROUND: In patients with cirrhosis, refractory ascites is associated with a poor prognosis and is an indication for liver transplantation. However, factors that determine prognosis remain unclear. AIMS: To investigate the predictive factors of prognosis in patients with refractory ascites. METHODS: Seventy-five patients with refractory ascites were followed-up for 18+/-13 months (mean+/-SD) and survival was analyzed. RESULTS: The 1-year probability of survival was 52%. Univariate analyses showed that older patients, hepatocellular carcinoma and diabetes, all assessed at entry, were associated with significantly increased risk ratios of death. The risk ratio of death was significantly lower in abstinent alcoholics than in patients with nonalcoholic cirrhosis. The risk ratio of death did not significantly differ between patients with nonalcoholic cirrhosis and nonabstinent alcoholics. Child-Pugh score at entry had no prognostic value. Multivariate analysis showed that older age, hepatocellular carcinoma, diabetes and abstinence were independent prognostic factors. CONCLUSIONS: In patients with cirrhosis and refractory ascites, older age, hepatocellular carcinoma and diabetes, but not Child-Pugh score at entry, were independent predictive factors of poor survival while abstinence was an independent predictive factor of good survival. These findings should be taken into account when deciding on liver transplantation in patients with refractory ascites.     

重视肝硬化患者门静脉压力的检测——从研究工具到临床应用

肝硬化是各种致病因素长期作用于肝脏引起肝细胞损伤、纤维化和结节再生的结果.肝硬化逐渐进展所产生的并发症如食管胃静脉曲张破裂出血、肝性脑病、肝肾综合征、肝细胞癌等才是造成患者死亡的主要原因. 了解肝硬化的自然病史以及寻找预测其预后的指标对于检测肝硬化进展、预防其并发症的发生有重要意义. 用Child - Pugh分数评估肝硬化严重度,从而预测Child -Pugh A、B、C级患者的预后;用终末期肝硬化MELD或MELD- Na等评分系统预测终末期肝硬化预后并对肝移植器官分配需求做出判断已得到大家的公认.肝活检及企图替代肝活检的多种无创检测手段对肝纤维化的诊断有一定作用,但它们均不能对慢性肝病进展到肝硬化及其并发症进行预测.     

Hazardous drinking is associated with an elevated aspartate aminotransferase to platelet ratio index in an urban HIV-infected clinical cohort

Objectives

The aim of the study was to determine the relationship between alcohol consumption and liver fibrosis as assessed by aspartate aminotransferase to platelet ratio index (APRI) in HIV‐infected adults and to explore the relative contributions of alcohol and hepatitis C virus (HCV) to APRI among HIV/HCV‐coinfected adults.

Methods

We performed a cross‐sectional analysis of data from an observational clinical cohort. Alcohol consumption was categorized according to National Institute on Alcohol Abuse and Alcoholism guidelines. We defined significant liver disease as APRI>1.5, and used multinomial logistic regression to identify correlates of increased APRI.

Results

Among 1358 participants, 10.4% reported hazardous drinking. It was found that 11.6% had APRI>1.5, indicating liver fibrosis. Hazardous drinking was associated with increased APRI [adjusted relative risk ratio (RRR) 2.30; 95% confidence interval (CI) 1.26–4.17]. Other factors associated with increased APRI were male gender, viral hepatitis, and HIV transmission category of injecting drug use. Among coinfected individuals, 18.3% had APRI>1.5, and hazardous drinking was not associated with APRI. Among non‐HCV‐infected individuals, 5.3% had APRI>1.5 and hazardous drinking was associated with increased APRI (adjusted RRR 3.72; 95% CI 1.40–9.87).

Conclusions

Hazardous drinking is an important modifiable risk factor for liver fibrosis, particularly among non‐HCV‐infected patients. Clinicians and researchers must address alcohol use as the burden of liver disease increases among HIV‐positive individuals.     

Measurement of carboxy terminal peptide of type I procollagen in sera of patients with viral hepatitis and liver cirrhosis

In the present investigation, a radioimmunoassay for carboxy terminal peptide of human type I procollagen (type 1 C-peptide) was developed. Its clinical implication for serodiagnosis of hepatic fibrosis in 85 patients with viral hepatitis, 45 patients with post-hepatitic liver cirrhosis and 37 patients with alcoholic liver diseases was evaluated in comparison with that of the previously established amino terminal peptide (type III N-peptide) assay. Anti-sera against type I procollagen was obtained by immunization of rabbit with purified type I procollagen from culture medium of IMR-90. The serum level of type I C-peptide in normal subjects was found to be 42 ng/ml (s.d. = 19). Type I C-peptide levels in patients with acute hepatitis were within normal range, while in chronic hepatitis, the mean type I C-peptide level increased as the grade of fibrosis advanced from grade I to III. However, there was no statistically significant difference between the mean type I C-peptide level of grade III and that of liver cirrhosis. Increments of type I C-peptide levels were also observed in alcoholic liver fibrosis (fatty liver with fibrosis and liver cirrhosis). On the other hand, type III N-peptide assay appeared to reflect not only the degree of hepatic fibrosis, but also the degree of hepatic inflammation, giving the high levels in acute viral hepatitis. Collectively, the results indicate the usefulness of type I C-peptide assay for monitoring hepatic fibrosis in viral hepatitis as well as in alcoholic liver disease.     

Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study

BACKGROUND/AIMS: A study was undertaken of liver biopsy samples from 229 consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996 to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma. METHODS: Hepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed. RESULTS: 130 patients had detectable iron at enrollment. During follow up (57 (28) months), 95 patients died and 39 patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p = 0.007) by the log rank test but not in patients with hepatitis C virus related (p = 0.71) or mixed (p = 0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p = 0.009; relative risk = 2.27; 95% confidence interval 1.2 to 4.19) or the continuous values (p = 0.002). CONCLUSIONS: These results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus.