Metabolism of porphyrins in patients with hepatic cirrhosis]

The article analyses the results of the study of porphyrins metabolism in 53 patients with chronic hepatic diffuse diseases at the stage of hepatic cirrhosis (HC). HC of viral etiology was diagnosed in 16 patients, and HC of ethanol etiology--in 9 patients. As many as 11 patients were diagnosed with primary biliary cirrhosis (PBC), and 10 patients--with idiopathic hemochromatosis (IHC). As many as 3 patients with manifested late skin porphyria developed secondary hemochromatosis, and 4 patients have manifested late skin porphyria with HC. Nonspecific disorders of porphyrins metabolism were revealed in 14 patients suffering from viral HC, 7 patients with ethanol HC, 9 ones with PBC and 8 suffering from IHC. Altogether 38 patients (82.6%) of the entire group of examined patients had pathological abnormalities. Porphyrins metabolism disorders manifested various combinations of biochemical features. Increased values of all porphyrin fractions in urine and faces were the most common characteristics (15 patients) as well as secondary coproporphyrinuria (15 patients). Symptoms of the growth of porphyrins in faces was less frequent (8 patients). Porphyrins metabolism disorders were assessed as a negative factor as the accumulation of the excessive amount of porphyrins in hepatocytes results in a rapid progress of hepatocellular deficiency. The dynamic assessment of porphyrins metabolism values is considered to be an important prognostic criterion for HC. The tested reduction of the porphyrin level can be a sign of hepatic deficiency with a serious prognosis.     

Determination of 15N-ammonia by chemical ionization mass spectrometry.

The tracing of ammonium nitrogen is important in hepatic diseases, especially in liver cirrhosis with hyperammonemia. In this paper, a new convenient method is described for determining stable isotope 15N-labeled ammonia using the Conway apparatus and chemical ionization mass spectrometry. The minimum quantity of ammonia necessary for reliable measure of 15N content was 0.1 muMol. The average error was 5.3%. In clinical application, 4 ml of blood after oral administration of 1 g of 15NH4Cl was sufficient for measurement.     

Metabolism of orally administered tauroursodeoxycholic acid in patients with primary biliary cirrhosis.

The metabolism of tauroursodeoxycholic acid orally administered and its effects on the bile acid pool of patients with asymptomatic/mildly symptomatic primary biliary cirrhosis is described. Patients were randomly assigned 500, 1000, or 1500 mg/day of tauroursodeoxycholate for six months. Biliary and serum bile acids were measured before and during treatment by gas chromatography-mass spectrometry and by high performance liquid chromatography. During tauroursodeoxycholate administration, the proportion of total ursodeoxycholate in bile reached mean (SEM) 34.4 (4.5)%, 32.8 (2.8)%, and 41.6 (3.0)% with doses of 500, 1000, and 1500 mg/day, respectively. Significant decreases in the proportions of chenodeoxycholate and cholate resulted. The glycine/taurine ratio of the biliary bile acid pool decreased from 1.9 at baseline, to 1.1 with the highest dose. Ursodeoxycholate in bile was conjugated with glycine and taurine, indicating that tauroursodeoxycholate undergoes significant deconjugation and reconjugation during its enterohepatic recycling. The proportion of lithocholate in bile remained unchanged. Fasting serum conjugated ursodeoxycholate concentration positively correlated with the tauroursodeoxycholate dose, and the increased proportion of ursodeoxycholate was accompanied by substantial decreases in the endogenous bile acids. Compared with previously published data for ursodeoxycholic acid therapy, these findings indicate that the shift toward a more hydrophilic bile acid pool is greater and potentially more favourable with tauroursodeoxycholate, and this is because of the reduced intestinal biotransformation of tauroursodeoxycholate.     

夜间加餐对肝硬化患者影响的Meta分析

目的 系统评价晚间加餐(LES)对肝硬化(LC)患者的疗效和安全性.方法 在PubMe d、EMbase、The Co-chrane Library、中国知网、万方数据库、维普数据库,结合手工检索进行了系统检索2000年1月至2020年8月发表的相关研究论文.应用RevMan5.3对这些研究进行了统计合并和分析.结果 ...     

Reactivation of cytomegalovirus in patients with cirrhosis: analysis of 122 cases.

Human cytomegalovirus causes severe and often fatal infections in immunocompromised patients. After organ transplantation cytomegalovirus in peripheral blood mononuclear cells is thought to be activated by alloreaction and to spread because of immunosuppression, and it may cause endogenous cytomegalovirus diseases. Patients with cirrhosis, one group of candidates for liver transplantation, often show various grades of immunosuppression before transplantation. To evaluate the status of cytomegalovirus infection in cirrhotic patients and its relevance to the degree of immunosuppression, we examined the presence of cytomegalovirus in mononuclear cells by polymerase chain reaction and immunocytochemical analysis. We studied 122 patients with definite cirrhosis and 43 normal volunteers. All cirrhotic patients (100%) and 40 (93%) of 43 normal controls were seropositive for cytomegalovirus. Cytomegalovirus DNA was detected by polymerase chain reaction in 77 (63.1%) of 122 seropositive cirrhotic patients, but in only 1 (2.5%) of 40 seropositive normal controls (p < 0.01). Cytomegalovirus antigen could not be detected in mononuclear cells by immunocytochemical staining with monoclonal antibodies. Cytomegalovirus DNA-positive patients have a greater impairment of liver function than do cytomegalovirus DNA-negative patients; this fact is manifested by delayed indocyanine green retention rates and elevated serum bilirubin levels (p < 0.05). Lymphocyte proliferative response induced by phytohemagglutinin and natural killer cell activity were also significantly lower in cytomegalovirus DNA-positive patients as compared with cytomegalovirus DNA-negative patients (p < 0.01). Our data suggest that the reactivation of cytomegalovirus may have already occurred in patients with cirrhosis before transplantation.     

Acute exacerbation in patients with liver cirrhosis: a clinicopathological study.

The incidence, clinicopathologic features and etiology of acute exacerbation occurring in patients with liver cirrhosis were assessed prospectively among 332 hepatitis B surface antigen (HBsAg) positive and 71 HBsAg negative patients. During an 11-year period and a mean follow-up duration of 26.8 months, 148 acute exacerbation occurred in 107 HBsAg positive patients and 32 episodes occurred in 18 HBsAg negative patients. The calculated annual incidence was 11.5%. The clinical, laboratory and histologic features were similar to those in patients with chronic hepatitis. Confluent hepatic necrosis and alphafetoprotein elevation over 100 ng/ml occurred frequently, particularly in HBeAg positive patients. In general, acute exacerbations in HBsAg negative patients were less severe than their HBsAg positive counterparts. Of the exacerbations in HBsAg positive patients, 54.8% of the HBeAg positive ones and 38.6% of the HBeAg negative ones were attributable to hepatitis B virus reactivation, while 4.8% and 7.9%, respectively, were due to hepatitis delta virus superinfection. The others might be the results of hepatitis non-A, non-B virus superinfection or increased piecemeal necrosis. The immediate outcome of acute exacerbations in cirrhotic patients was usually good, although 13.8% developed hepatic decompensation and 4.4% died. Further follow-up study is required to evaluate the long-term effect of the frequent occurrence of bridging hepatic necrosis, high elevation of alphafetoprotein and hepatic decompensation during acute exacerbation in cirrhotic patients.     

Serum uric acid levels in patients with cirrhosis: a reevaluation.

It has been reported that the serum uric acid levels in patients with cirrhosis were decreased compared with healthy subjects. These studies suggested that the lower serum uric acid levels in cirrhotic patients were attributed mainly to an increased effective vascular volume, and consequently to an excessive renal clearance of uric acid. However, the previous observations are challenged by a recent hypothesis for the pathogenesis of hyperdynamic circulation and formation of ascites in cirrhosis. The current study was undertaken to reevaluate serum uric acid levels in patients with cirrhosis. Ninety-eight cirrhotic patients with normal renal functions were included in this study. All biochemical and hemodynamic data were utilized for analysis. The mean serum uric acid level (mean, 6.1+/-1.2 mg/dL; range, 2.7-9.1 mg/dL) was higher than that of the age- and sex-matched healthy control subjects (mean, 5.5+/-1.3 mg/dL; range, 2.9-8.1 mg/dL; p = 0.018). Using multiple regression analysis it was determined that the serum uric acid level was not related to the severity of liver disease, cardiac index, systemic vascular resistance, and hepatic venous pressure gradient but was related closely to age (r = 0.210, p = 0.026) and effective renal plasma flow (r = -0.677, p < 0.0001). Compared with cirrhotic patients without ascites, those with ascites had a significantly higher serum uric acid level (6.7+/-1.6 mg/dL vs. 5.6+/-1.7 mg/dL, p < 0.05) and lower effective renal plasma flow (396+/-125 mL/min vs. 445+/-149 mL/min, p < 0.05). In conclusion, for cirrhotic patients with normal serum creatinine levels, the current study shows that the mean serum uric acid level is higher than that of healthy control subjects. It is not related to the severity of liver failure and systemic and portal hemodynamics, but is related closely to renal functions, especially the renal plasma flow.     

Bioelectric impedance analysis: experience with male patients with cirrhosis

Bioelectric impedance analysis is a new, convenient and portable method used to estimate total body water and to assess body composition in healthy people. We used the tetrapolar bioelectrical impedance analysis method in 58 cirrhotic patients to assess its clinical applicability. Whole-body resistance, reactance and impedance were measured and compared with those of 30 healthy volunteers matched for age and sex. The resistance and impedance values of ascitic cirrhotic patients (resistance = 461 +/- 80 omega; impedance = 462 +/- 80 omega) and nonascitic cirrhotic patients (resistance = 487 +/- 96 omega; impedance = 489 +/- 97 omega) were comparable with the resistance (488 +/- 44 omega) and impedance (491 +/- 44 omega) of controls. However, a significant (p less than 0.05) reduction in whole body reactance was found in patients with ascites and in those without ascites (34 +/- 9 omega vs. 47 +/- 12 omega) as compared with healthy subjects (56 +/- 7 omega). In 10 ascitic patients total body water was determined both before and after paracentesis; the volume of intraperitoneal fluid removed (7.9 +/- 3.8 L) could not be fully accounted for but only detected as an average volume of 1.9 +/- 1.0 L independently of the initial volume of the ascites. Our data clearly demonstrate that tetrapolar bioelectric impedance analysis is not adequate for measuring variations of "compartmentalized" fluid in the abdomen.     

Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: a cost-utility analysis

OBJECTIVES: Screening for hepatocellular carcinoma (HCC) is advocated in cirrhotic patients to optimize early detection and treatment. However, the cost-effectiveness is not well defined. Our objective was to perform a cost-utility analysis from a third-party payer's perspective of no screening, alpha-fetoprotein (AFP) concentration measurement alone, abdominal ultrasound (US) and AFP, abdominal three-phase CT and AFP, and abdominal magnetic resonance imaging (MRI) and AFP. METHODS: A Markov model was constructed simulating the natural history of hepatitis C-related cirrhosis in a cohort of patients age 50 yr over a time horizon of their remaining life expectancy. Transition probabilities were obtained from published data and U.S. vital statistics. Costs represented Medicare reimbursement data. Costs and health effects were discounted at a 3% annual rate. RESULTS: Screening with ultrasonography and AFP concentration measurement was associated with an incremental cost-utility ratio of 26,689 US dollars per quality-adjusted life year, whereas screening with abdominal three-phase CT and AFP concentration measurement was associated with an incremental cost-utility ratio of 25,232 US dollars per quality-adjusted life year compared with no screening. Compared with three-phase CT and AFP, magnetic resonance and AFP imaging costs 118,000 US dollars per quality-adjusted life year. Sensitivity analysis demonstrated that the results are most sensitive to the annual incidence of HCC, proportion of tumors amenable to treatment, and to transplant candidacy, whereas the choice of screening strategy is most sensitive to the test characteristics and cost. CONCLUSIONS: Screening for HCC with CT is a cost-effective strategy in transplant-eligible patients with cirrhosis secondary to chronic hepatitis C viral (HCV) infection, comparable with other commonly accepted screening interventions such as mammography and colonoscopy.     

53例原发性胆汁性肝硬化临床和病理分析

目的分析原发性胆汁性肝硬化（PBC）患者的临床表现、实验室检查及病理特征。方法回顾性分析53例PBC患者的临床表现、实验室检查及病理特征。结果53例PBC患者中女性46例（86．8％），发病至确诊时间（中位数）28个月，主要症状包括反复肝功能异常、乏力、黄疸、瘙痒、肝脾肿大等；53例患者GGT、ALP均有明显升高；73．6％（39／53）患者AMA和（或）AMA-M2亚型阳性，另14例血清AMA和AMA-M2亚型阴性，经病理检查证实为PBC；53例患者中Ⅰ期为13例（24．5％），Ⅱ期20例（37．7％），Ⅲ期16例（30．2％），Ⅳ期4例（7．5％）；Ⅰ期、Ⅱ期（33例）与Ⅲ期、Ⅳ期（20例）患者肝功能等计量资料只有GGT、ALP差异有显著性意义（P〈0．05），病理改变严重者GGT、ALP升高明显。结论临床判断PBC患者病情的轻重应综合分析临床症状、生化改变（尤其是GGT、ALP）、自身抗体检测以及组织学检查等，而不应局限于用黄疸作为衡量指标。     

Management of solitary 1 cm to 2 cm liver nodules in patients with compensated cirrhosis: a decision analysis.

OBJECTIVES: Current guidelines, based on expert opinion, recommend that suspected 1 cm to 2 cm hepatocellular carcinoma (HCC) detected on screening be biopsied and, if positive, treated (eg, resection or transplantation). Alternative strategies are immediate treatment or observation until disease progression occurs. METHODS: A Markov decision model was developed that compared three management strategies - immediate resection, biopsy and resection if positive, and ultrasound surveillance every three months until disease progression - for a single 1 cm to 2 cm liver nodule suspicious for HCC following ultrasound screening and computed tomography confirmation. The cohort included 55-year-old patients with compensated cirrhosis and no significant comorbidities. The model used in the present study incorporated the probabilities of false-positive and false-negative results, needle-track seeding, HCC recurrence, cirrhosis progression and death. The quality-adjusted life expectancy (LE) and the unadjusted LE were evaluated and the model's strength was assessed with sensitivity analyses. RESULTS: In the base case analysis, biopsy, resection and surveillance yielded an unadjusted LE of 60.5, 59.7 and 56.6 months, respectively, and a quality-adjusted LE of 46.6, 45.6 and 43.8 months, respectively. In probabilistic sensitivity analyses, biopsy was the preferred strategy 69.5% of the time, resection 30.5% of the time and surveillance never. Resection was the optimal decision if the sensitivity of biopsy was very low (less than 0.45) or if the accuracy of the imaging tests resulted in a high percentage of HCC-positive patients (greater than 76%) in the screened cohort, as with expert interpretation of triphasic computed tomography. CONCLUSIONS: The present model suggests that biopsy is the preferred management strategy for these patients. When postimaging probability of HCC is high or pathology expertise is lacking, resection is the best alternative. Surveillance is never the optimal strategy.     

Retrospective analysis of complications related to endoscopic retrograde cholangio-pancreatography in patients with cirrhosis vs patients without cirrhosis

BACKGROUNDThere is minimal objective data regarding adverse events related to endoscopic retrograde cholangio-pancreatography (ERCP) in patients with cirrhosis compared to those without cirrhosis and even fewer data comparing complications among cirrhosis patients based on severity of cirrhosis.AIMTo determine if patients with cirrhosis are at increased risk of adverse events related to ERCP: mainly pancreatitis, bleeding, perforation, cholangitis, and mortality; And to see if higher Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) score are associated with higher post-ERCP complications.METHODSWe performed a retrospective analysis of 692 patients who underwent ERCP and analyzed the impact of cirrhosis etiology, gender, type of sedation used during procedure, interventions performed, and co-morbidities on the rate of complications in cirrhosis patients as compared to non-cirrhosis patients.RESULTSOverall complications were higher in those with cirrhosis as compared to those without cirrhosis (P = 0.015 at significance level of 0.05). CP class, especially CP class C, was shown to be associated with a significantly higher rate of ERCP complications as compared to CP class A and CP class B (P = 0.010 at significance level of 0.05). CONCLUSIONThe results of our study reaffirm that liver cirrhosis has an impact on the occurrence of complications during ERCP. Our study shows that CP class seems to be more reliable as compared to MELD score in predicting complications of ERCP in cirrhosis patients.     

原发性胆汁性肝硬化早期诊断15例

目的:提高早期原发性胆汁性肝硬化的诊断水平.方法:回顾性分析1994/2007-06云南大理学院临床学院附属医院收治确诊的早期原发性胆汁性肝硬化患者15例的临床及实验室资料,总结其诊断依据和诊断方法.结果:15例早期原发胆汁性肝硬化患者中仅有2例有皮肤瘙痒和轻度黄疸,其余13例无任何临床表现,所有病例均以ALP、GGT增高为突出表现,病程越长ALP、GGT增高越明显.AMAF阳性对早期原发胆汁性肝硬化的诊断特异性高,有重要的诊断价值.结论:早期原发性胆汁性肝硬化缺乏临床表现,ALP、GGT增高和AMA阳性是早期原发性胆汁性肝硬化的主要表现和诊断依据.     

Long-term prognosis of patients with alcoholic liver cirrhosis: a 15-year follow-up study of 100 Norwegian patients admitted to one unit

BACKGROUND: Most follow-up studies in patients with alcoholic liver cirrhosis have been for a 5-year period or less. The aim of this study was to assess the long-term mortality and causes of death among patients with alcoholic liver cirrhosis and to identify predictors of mortality. METHODS: One hundred patients with alcoholic liver cirrhosis, consecutively admitted to one medical department, were included in the study from May 1984 until December 1988. All patients had a history of alcohol abuse of at least 100 g ethanol daily for several years. The study comprised 65 men and 35 women with a median age of 58 years (range 34-82). Percutaneous liver biopsies and/or autopsies were obtained on 89 patients. Sixty-seven had ascites at admission and 34% had bleeding oesophageal varices. All patients were followed prospectively until death or until October 2000. RESULTS: During the follow-up period 90% of the patients died, 68 of whom (76 %) had been autopsied. The cumulative actuarial mortality after 1, 3, 6 and 12 months was 18%, 28%, 36% and 49%, respectively and after 5, 10 and 15 years 71%, 84% and 90%, respectively. None of the patients underwent liver transplantation during the study. The causes of death were bleeding, liver failure or a combination of these two conditions in 52 of 90 patients (58%), while 9 (11%) died of hepatocellular carcinoma 0.5 to 73 months after inclusion in the study. Using the Cox regression analysis, age, alcohol abuse and alkaline phosphatase were independent and significant predictors of mortality, but Child-Pugh class was not. CONCLUSIONS: The mortality in a group of patients with advanced alcoholic cirrhosis was extremely high with 5 and 15 years' mortality in 71% and 90%, respectively. Independent predictors of a poor prognosis were high age, continuous alcohol consumption of more than 10 g ethanol per day and high levels of alkaline phosphatase.     

肝硬化伴肝源性糖尿病临床分析

目的分析肝硬化伴肝源性糖尿病的临床特征。方法回顾性分析45例肝硬化伴肝源性糖尿病患者的临床资料。结果 45例患者中,乙型肝炎肝硬化31例（68.9%）;空腹血糖7.3±2.9mmol/L,餐后2h血糖16.2±4.7mmol/L,空腹血糖水平与Child-Pugh分级呈正相关（Spearman等级相关系数rs=0.48,P〈0.01）;通过饮食控制、口服α葡萄糖苷酶抑制剂或皮下注射胰岛素,大部分患者血糖控制在正常水平或接近正常水平;7例死亡病例均死于肝硬化并发症。结论肝硬化伴肝源性糖尿病患者的糖尿病症状多不典型,以餐后高血糖为特征,血糖水平与肝功能的损害程度密切相关,应用胰岛素治疗效果较好,不良预后主要与肝硬化相关。