Effect of portacaval shunt on drug disposition in patients with cirrhosis

To examine the consequences of liver blood flow variations on drug disposition in cirrhosis, we studied the effects of portacaval shunt on drug clearance in 35 cirrhotic patients. Lidocaine clearance and bioavailability, indocyanine green (ICG) clearance, aminopyrine breath test, and hepatic blood flow were measured before and 18 months after surgery. The patients were divided into two groups according to severity of disease: 14 patients (group 1) had slight liver dysfunction (ICG extraction ratio greater than 0.25) and 21 patients (group 2) had severe liver disease (ICG extraction ratio less than 0.25). After portacaval shunt the decrease in hepatic blood flow was similar for both groups (-65%). In group 1, ICG systemic clearance decreased from 9.10 +/- 0.68 to 4.40 +/- 0.34 ml/min . kg (p less than 0.05), whereas ICG intrinsic clearance remained unchanged; lidocaine systemic clearance decreased from 7.93 +/- 0.93 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05), whereas lidocaine intrinsic clearance remained unchanged; bioavailability increased from 0.601 +/- 0.076 to 1, resulting in an abrupt reduction of oral clearance from 18.01 +/- 4.90 to 5.09 +/- 0.33 ml/min . kg (p less than 0.05). In group 2, ICG systemic clearance decreased slightly from 3.90 +/- 0.39 to 2.28 +/- 0.16 ml/min . kg (p less than 0.01) and ICG intrinsic clearance was not modified; lidocaine systemic and intrinsic clearance remained unchanged; and bioavailability increased from 0.779 +/- 0.229 to 1, resulting in a decrease of oral clearance from 7.68 +/- 1.65 to 4.23 +/- 0.37 ml/min X kg (p less than 0.05). The aminopyrine breath test was not affected by surgery in either group. We conclude that reduction of hepatic blood flow after portacaval shunt has only minimal effects on drug disposition in patients with severe liver disease, but results in a notable reduction in the clearance of high-extraction drugs in cirrhotics with mild liver disease.     

Antipyrine Clearance and Metabolite Formation in Primary Biliary Cirrhosis

The disposition of antipyrine is altered and may be a prognostic factor in the presence of various types of hepatic dysfunction. The object of the present study was to investigate whether antipyrine clearance and metabolite formation are useful to detect altered metabolic function in primary biliary cirrhosis. Saliva clearance of antipyrine and the formation clearance of antipyrine metabolites (hydroxymethylantipyrine, HMA; norantipyrine, NORA; and 4-hydroxyantipyrine, OHA) were investigated in a group of 34 women with biopsy-proven PBC (mean age 60 years; range 39–87 years) and in 15 healthy control women (mean age 62 years; range 46–78 years). Parameters of antipyrine clearance of patients in stage I and II were similar to those observed in healthy subjects. When compared to patients in stage I, patients in advanced stages showed a reduction in antipyrine clearance (–29% and –44% in stages III and IV, respectively) and increases in antipyrine half-life (+24% and +75% in stages III and IV, respectively). The reduction in antipyrine clearance was due to a reduction in the formation of all three antipyrine metabolites, with the formation clearance of both HMA and NORA decreasing to a slightly greater extent than that of OHA. Antipyrine clearance correlated significantly with serum bilirubin (P < 0.017) and the Mayo risk score (P < 0.001). Logistic regression analysis indicated that antipyrine clearance was an independent predictor of the histological stage of the disease (P < 0.001). Antipyrine clearance and metabolite formation is a sensitive parameter for assessing hepatic metabolic function in primary biliary cirrhosis.     

A comparison between antipyrine and aminopyrine blood clearances.

The purpose of this study was to investigate the relationship between two quantitative liver functions, that is, antipyrine blood clearance and aminopyrine blood clearance, in normal subjects and in patients with liver cirrhosis. The mean blood clearances of antipyrine and aminopyrine in cirrhotic patients (0.220 +/- 0.085 ml/min/kg and 1.13 +/- 0.56 ml/min/kg; n = 64) was 50% and 38% of that of normal subjects (0.440 +/- 0.110 ml/min/kg and 2.95 +/- 0.59 ml/min/kg; n = 11). While no significant correlation was demonstrated between these two values in normal subjects (n = 11, r = -0.107, p greater than 0.10), a strong positive correlation was observed between antipyrine and aminopyrine blood clearances in cirrhotic patients (n = 64, r = 0.846, p less than 0.001). These results suggest that both antipyrine and aminopyrine blood clearances may be valuable indicators for assessing the total hepatic functioning mass in cirrhotics.     

慢性肝病肝脏储备功能与肝纤维化的关系

目的:研究慢性乙型肝炎及乙肝肝硬化患者的肝脏储备功能及肝纤维化,进一步探讨肝脏储备功能与肝纤维化之间的关系.方法:60例慢性乙肝病毒感染患者,分为慢性乙型肝炎及乙肝肝硬化代偿期两组,利用脉冲式色素浓度图像分析仪(DDG)行吲哚氰绿(ICG)排泄试验,监测ICG血浆清除率(K)和15min滞留率(R15);同时利用Fib...     

HLA-DPB1 Variant Effect on Hepatitis B Virus Clearance and Liver Cirrhosis Development Among Southwest Chinese Population

Background:

Previous studies have shown that genetic variants in HLA-DP genes affect disease progression in hepatitis B virus (HBV) infection.

Objectives:

We aimed to evaluate possible association between HLA-DPB1 rs9277534 polymorphism and different clinical complications of hepatitis B virus (HBV) infection.

Materials and Methods:

Snapshot assay was used to investigate the association of rs9277534 polymorphism in 342 patients with persistent HBV infection and 342 age and gender-matched HBV spontaneous clearance controls. Patients were categorized into asymptomatic HBV carriers (AsC, n = 104), chronic hepatitis B (CHB, n = 116), and liver cirrhosis (LC, n = 122) subgroups.

Results:

There was a significantly higher proportion of the rs9277534 minor allele A in HBV spontaneous clearance control than that in HBV persistent infection group (OR = 0.58, 95%CI = 0.46-0.73, P < 0.0001). Genotypic analysis showed that GA and AA genotypes were associated with HBV spontaneous clearance (GA: OR = 0.56, 95%CI = 0.40-0.79, P = 0.019; AA: OR = 0.24, 95%CI = 0.14-0.44, P < 0.0001). A significant difference was found between AsC and LC groups in the distribution of AA genotype (OR = 9.32, 95%CI = 1.293-67.14, P = 0.027).

Conclusions:

Variant at rs9277534 could affect both the spontaneous clearance of HBV infection and progression from asymptomatic HBV carriers to HBV-related liver cirrhosis in Southwest Han Chinese population.     

慢性肝炎肝硬化和肝衰竭患者吲哚菁绿清除试验的变化及其临床意义

目的 探讨吲哚菁绿(ICG)清除试验对不同程度慢性肝病患者肝脏储备功能的评估价值。方法 2017年11月～2019年8月山西医科大学第一医院感染病科住院治疗的肝病患者87例,其中慢性病毒性肝炎9例,肝硬化69例,慢性肝衰竭9例,使用日本DDG-3300K分析仪及配套分析软件检测ICG15分钟滞留率(ICG-R15)、ICG血浆清除率(K值)和有效肝脏血流量(EHBF),同时检测肝功能、血常规、腹部彩超、腹部CT或MRI,计算肝功能Child-Turcotte-Pugh(CTP)评分并对肝硬化患者分级。结果 慢性肝衰竭组ICG-R15为(54.2±11.6)%,K值为(0.04±0.01)/min,EHBF为(0.2±0.1)L/min,与慢性肝炎组比,差异显著【分别为(7.4±1.7)%、(0.22±0.05)/min和(0.9±0.3)L/min,P<0.05】;11例CTP C级患者ICG-R15为(39.3±8.9)%,K值为(0.06±0.02)/min,EHBF为(0.3±0.1)L/min,与39例CTP B级【分别为(28.8±12.6)%、(0.10±0.03)/min和(0.4±0.2)L/min,P<0.05】或19例CTP A级【分别为(12.2±2.8)%、(0.16±0.05)/min和(0.7±0.2)L/min,P<0.05】比,差异显著。结论 ICG清除试验能动态反映肝脏储备功能,弥补CTP分级的不足,尝试作为早期诊断肝硬化的参考指标,值得进一步研究。     

Human genes involved in hepatitis B virus infection

Persistent hepatitis B virus(HBV)infection is a significant public health problem because it is a major cause of chronic liver disease,cirrhosis,and hepatocellular carcinoma(HCC).Roughly one-third of the world population has been infected with HBV and there are about350 million(5%-6%)persistent carriers.HBV causes80%of all liver cancer cases and is the second most important carcinogen,after smoking tobacco.There is an approximate 90%risk of becoming a persistent carrier following perinatal infection in infants born to e antigen positive carrier mothers and a 30%risk in pre-school children.Only 5%-10%of adults become persistent carriers following infection.Of individuals persistently infected with HBV,10%-30%will develop liver cirrhosis and HCC.These highly variable outcomes in both clearance rates and disease outcomes in persistently infected individuals cannot be fully explained by differences in immunological,viral or environmental factors.Thus,differences in host genetic factors may affect the natural history of hepatitis B.     

Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C.

BACKGROUND/AIM: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. METHODS: Three hundred and sixty-seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child-Pugh classification for liver cirrhosis. RESULTS: In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. CONCLUSIONS: In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.     

Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis. Lack of correlation with hepatitis C and D virus superinfection

We investigated the frequency of HBsAg clearance and the possible role of viral superinfection in a long-term follow-up of 184 patients with chronic hepatitis B (CHB). Our subjects were 184 patients with chronic hepatitis B and the follow-up was 12–216 months (mean 66.2±53.7 months). The investigative methods used were: immunoenzymatic assays for HBV, HCV, HDV, and HIV markers; polymerase chain reaction (PCR) for HBV DNA; and liver biopsy and immunoperoxidase. During the follow-up, 20 of the 184 patients cleared serum HBsAg. A comparison of patients with persistent HBsAg (group I) and of those who cleared this marker (group II) showed a significant difference in mortality (P=0.002) between the two groups and a tendency to a more severe exacerbation (flare) in group II (P=0.07). Antibodies to hepatitis C and D virus as well as antibodies to HIV were equally distributed in both groups. Thirteen patients (7.9%) from group I, but none from group II, subsequently developed hepatocellular carcinoma. These results suggest that the frequency of spontaneous clearance of HBsAg during chronic HBV infection is low. No determinant factor for the clearance was found, including the presence of liver cirrhosis. Serum HBV DNA was undetectable by PCR after clearance in 16 out of 17 patients. Some of these findings were presented at the Biennial Scientific Meeting of the International Association for the Study of the Liver, held in Brighton, UK, in June 1992.     

Can quantitative tests of liver function discriminate between different etiologies of liver cirrhosis?

Studies comparing quantitative testing of liver function (QTLF) in large numbers of patients with defined etiology of cirrhosis are lacking. In all 316 patients with proven cirrhosis underwent QTLF, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol (SCI), and indocyanine green clearance (ICG). Values were correlated with the Child-Pugh classification (CP) and the etiology of liver cirrhosis. Fifty-five percent of the patients had alcoholic cirrhosis (ALC), 31% cirrhosis due to viral hepatitis (VIC), and 14% primary biliary cirrhosis (PBC). In all three groups there was a decrease of QTLF levels from CP grade A to C, which differed from normal values. QTLF was most compromised in patients with ALC and VIC compared to patients with PBC. In conclusion, QTLF in ALC and VIC patients was more reduced than in patients with PBC. This may be due to saturation of enzymes in ALC and ongoing inflammation in VIC.     

Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C

Abstract: Background/Aim: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. Methods: Three hundred and sixty‐seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child–Pugh classification for liver cirrhosis. Results: In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. Conclusions: In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.     

Parameters of Microsomal and Cytosolic Liver Function But Not of Liver Perfusion Predict Portal Vein Velocity in Noncirrhotic Patients with Chronic Hepatitis C

Our aim was to compare color-coded Doppler sonography (CCDS) and quantitative testing of liver function (QTLF) in patients with chronic hepatitis C. In all, 74 patients with chronic hepatitis C and mild fibrosis underwent QTLF, which included aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SC), and indocyanine green clearance (ICG). Hepatic artery velocity and resistance index (HA-V, HA-RI) as well as portal vein velocity (PV-V) were measured by CCDS. ABT, GEC, and PV-V were significantly reduced, whereas SCl, ICG, HA-V, and HA-RI showed normal levels. There was a significant correlation between reduction in PV-V only with GEC and ABT. QTLF did not correlate with HA-V and HA-RI. In conclusion, in hepatitis C patients with liver fibrosis, ABT and GEC are decreased significantly, which was paralleled by a reduction of PV-V. Unexpectedly SCl and ICG, the classical hepatic perfusion parameters, do not correlate with the parameters measured by CCDS.     

Breath14CO2 after intravenous administration of [14C]aminopyrine in liver diseases

The determination of¹⁴CO₂ in breath after oral administration of [¹⁴C]aminopyrine has been proposed as a quantitative liver function test. In order to shorten the procedure and avoid misinterpretations related to variable rates of intestinal absorption, the [¹⁴C]aminopyrine breath test (ABT) was performed after intravenous administration of [¹⁴C]aminopyrine in 21 controls and 89 patients with biopsy-proven liver disease. The specific activity of the first hour sample corrected for body weight (SA1) was the most discriminant expression of breath data. The SA1 value, expressed as the percentage of the administered dose, was 0.86±0.1% (mean±sd) in controls and significantly less in patients (0.46 ±0.31%). Low values were observed in patients with untreated chronic active hepatitis (0.16±0.13%), alcoholic cirrhosis (0.2±0.15%), and untreated postnecrotic cirrhosis (0.47±0.17%). In contrast, normal values were obtained in chronic persistent hepatitis (0.86±0.13%) and 58% of noncirrhotic alcoholic liver diseases (0.83±0.27%). The results of duplicate studies were reproducible and SA1 correlated with other conventional liver function tests, including 45-min BSP retention. Among these, ABT was the most sensitive screening test for the presence of cirrhosis, especially in alcoholic patients, where it allowed a sharp distinction between cirrhotic and noncirrhotic cases. The results obtained in chronic hepatitis suggested that ABT may provide a reliable index of the activity of the disease. In our hands, intravenous ABT, performed over a 1-hr period, was a fast, sensitive, and discriminant liver function test.     

Antipyrine,Oxazepam, and Indocyanine Green Clearance in Patients with Chronic Pancreatitis and Healthy Subjects

Background: Hepatic drug metabolism was examined in patients with chronic pancreatitis and healthy controls by using a cocktail design with three different model compounds: antipyrine to express phase-I oxidation, oxazepam to express phase-II conjugation, and indocyanine green (ICG), a high-clearance compound. Methods: Eight patients with chronic pancreatitis and seven healthy controls participated. Patients were diagnosed by the presence of typical morphologic changes of the pancreas on imaging and had a moderately but significantly reduced exocrine function and no or only slight impairment of the glucose tolerance. No one had a history or clinical signs of liver disease. Clearance of the three model compounds was estimated after the administration of 1 g antipyrine and 15 mg oxazepam orally and a bolus of indocyanine green, 0.5 mg/kg body weight, intravenously. Results: The antipyrine clearance and ICG clearance were significantly decreased in the patients compared with the controls (mean, 27.2 ml/min; 95% confidence interval (CI), 19.4-35; versus 46.2 ml/min; 34.7-58.7, and 501 ml/min; 401-601, versus 771 ml/min; 677-865 (P &lt; 0.05), respectively). The oxazepam clearance did not differ significantly between the two groups (181 ml/min (145-217) versus 178 ml/min (152-204)). The model drug clearance ratios between the patient and control clearances showed decreased values for antipyrine and ICG compared with the oxazepam data (0.59 and 0.65 versus 1.02, respectively). Patients and controls were characterized by a body weight of 58.2 kg (53.1-63.3) and 83.4 kg (72.7-94.1), respectively, and a body mass index (BMI) of 19.6 kg/m² (17.9-21.3) versus 25.9 kg/m² (23.4-28.4) (P &lt; 0.05 for both). Conclusions: Patients with chronic pancreatitis characterized by a moderately reduced exocrine function and absence of diabetes mellitus and overt liver disease had a decreased antipyrine oxidation and ICG clearance, whereas no difference was seen in oxazepam conjugation when compared with healthy volunteers. In chronic pancreatitis the hepatic phase-I oxidation is reduced compared with the phase-II conjugation, as shown by the model drug clearance ratios. The clearance of ICG was also affected, pointing at a reduced hepatic plasma flow, provided that the hepatic extraction fraction is normal for these patients.     

Association of single nucleotide polymorphisms in microRNAs with susceptibility to hepatitis B virus infection and HBV‐related liver complications: A study in a Saudi Arabian population

The aim of this study was to evaluate the association of 10 SNPs in different microRNAs (miRNAs) with susceptibility to hepatitis B virus (HBV) infection, HBV clearance, persistence of chronic HBV infection, and progression to liver cirrhosis and hepatocellular carcinoma (HCC). Patients were categorized into the following groups: inactive HBV carrier, active HBV carrier, HBV‐cleared subject and cirrhosis+HCC. Samples were analysed for 10 SNPs in microRNAs using either PCR‐based genotyping or the TaqMan assay. We found that rs1358379 was associated with susceptibility to HBV infection, HBV clearance, persistent chronic HBV infection and liver cirrhosis+HCC. In addition, we found that rs2292832 and rs11614913 were associated with risk of HBV infection, viral clearance and cirrhosis+HCC, whereas rs2910164 was associated with proneness to HBV infection, and ability to clear the virus. There was evidence of associations between rs6505162 and HBV clearance and the development of liver disease, whereas a single association was found between rs2289030 and HBV clearance. Similarly, rs7372209 and rs4919510 were specifically associated with the development of HBV‐induced liver complications. SNPs in miRNAs affect the susceptibility, clearance and progression of HBV infection in Saudi Arabian patients. We found, using Gene Ontology or pathway analyses, that these genes may contribute to the pathophysiology of HBV infection and related liver complications. However, differences in the association of examined SNPs with various clinical stages indicate variations in the respective functional roles of these polymorphisms and their miRNAs, and thus, further investigation to fully explore their therapeutic potential is warranted.     

Inducibility of microsomal liver function may differentiate cirrhotic patients with maintained compared with severely compromised liver reserve

BACKGROUND AND AIM: Quantitative tests of liver function (QTLF) can be modulated by enzyme-inducing agents. The objective of the study was to examine changes in QTLF after treatment with Phenobarbital, a potent cytochrome P450-inducing agent. METHODS: Forty-six consecutive patients with liver cirrhosis Child-Pugh score B and C (34 alcoholic, 12 hepatitis C) and a compromised aminopyrine breath test (ABT) were included. Thirty-six patients (group I) received phenobarbitone (150 mg) for 7 days. Ten patients (group II) received a placebo. The QTLF, which included ABT (microsomal liver function), galactose elimination capacity (GEC, cytosolic liver function), sorbitol clearance (SCl, liver plasma flow) and indocyanine green clearance (ICG, liver perfusion) was carried out before and after pharmacological induction. RESULTS: Group I showed a basal ABT of 0.18 +/- 0.11% dose.kg/mmol CO2 (normal >0.6%), which increased significantly after induction (172%, P < 0.05), whereas in group II the ABT values did not change. In group IB, a subgroup of group I which exceeded the basal threshold value of 0.30% after stimulation (n = 22), the ABT values increased significantly to 0.44 +/- 0.17% (244%, P < 0.01). The GEC, SCl and ICG remained unchanged before and after induction. CONCLUSIONS: After pharmacological induction, microsomal liver function increased significantly in a subgroup of patients with liver cirrhosis, whereas the GEC, SCl and ICG remained unchanged. Inducibility of the microsomal liver function could be used as a novel parameter of functional hepatic reserve and prognosis in cirrhosis.     

Determinants of drug disposition in patients with cirrhosis

The effects of alterations of the hepatic blood flow, the intrinsic clearance, and the anatomy of the portal circulation on drug disposition were investigated in 53 cirrhotic patients with portal hypertension using indocyanine green (ICG) and lidocaine as model drugs. ICG disposition was studied by sampling from an artery and one hepatic vein following i.v. injection, with determination of systemic and intrinsic clearances and hepatic blood flow. Lidocaine disposition was studied following i.v. and oral administration from peripheral vein disappearance curves, with determination of systemic and intrinsic clearances and systemic availability. The shunted fraction of intestinal blood flow (f) was measured from the combined ICG and lidocaine disposition studies. In the 53 patients, systemic clearances of ICG and lidocaine varied widely and were significantly correlated with each other (r = 0.725, p less than 0.001). The systemic clearances of both ICG and lidocaine were not related to hepatic blood flow but were significantly correlated to their respective intrinsic clearances (for ICG: r = 0.948, p less than 0.001; for lidocaine: r = 0.873, p less than 0.001). Lidocaine systemic availability was also found to vary widely from 0.2 to 1.0. In 28 patients, f was less than 0.1 indicating minimal extrahepatic shunting and in these patients, lidocaine systemic availability was related to its intrinsic clearance (r = -0.717, p less than 0.001); in the 25 other patients with significant extrahepatic shunting (f greater than 0.1), the extent of lidocaine systemic availability was related to both intrinsic clearance (r = -0.819, p less than 0.001) and extrahepatic shunting (r = 0.913, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term follow-up of non-A, non-B (type C) post-transfusion hepatitis

One hundred and thirty-five patients who developed non-A, non-B post-transfusion hepatitis mostly after cardiac surgery, were followed for a mean (±S.D.) of 90±41 months (range: 13–180) to evaluate clinical and histological outcome.Thirty-one cases resolved within 12 months, while 104 (77%) progressed to chronicity. Twenty-one of 65 (32%) biopsied patients developed cirrhosis at the end of the follow-up, and one further progressed to hepatocellular carcinoma. One patient had a complete histological remission (1%). The remaining cases had chronic active (37%), chronic persistent (27%) or chronic lobular hepatitis (3%). About half of the cases with cirrhosis developed portal hypertension, and three of these died due to esophageal varices hemorrhage, one due to liver failure, and one due to hepatocellular carcinoma. Out of 26 patients with the initial histologic diagnosis of chronic hepatitis that were rebiopsied during follow-up, 13 (50%) progressed to cirrhosis. These patients were significantly older than patients who did not develop cirrhosis (mean age 57 and 45 years respectively; p<0.01).During acute hepatitis anti-HCV was positive in all but one of the 114 patients tested. Percentages were similar for patients who recovered (95%) and those who developed chronic hepatitis (100%). However, during follow-up, 71% of the 1st generation and 21% of the 2nd generation ELISA test patients with acute resolved hepatitis became anti-HCV negative, while the same figures in chronic cases were only 8.5% (p<0.0001) and 1.4% (p=0.012). This suggests a correlation between anti-HCV antibody activity, hepatitis C virus replication, and the development of chronic liver disease.     

Long‐term outcome of hepatitis B virus‐related Chronic Hepatitis under protracted nucleos(t)ide analogues

Long‐term outcome of patients with chronic hepatitis B virus (HBV) infection under continuous nucleos(t)ide analogues (NUCs) has been poorly elucidated. We enrolled 121 anti‐HBe‐positive patients into a prospective surveillance programme while on (>36 months) NUCs therapy. HBV‐DNA clearance, add‐on therapy and safety were evaluated. Development of cirrhosis, events of liver decompensation and hepatocellular carcinoma (HCC) during the follow‐up were the main endpoints, as the complication‐free survival. At baseline, 74 patients (61%) had chronic hepatitis, the remainders a cirrhotic liver. HBV‐DNA levels >38 000 IU/mL were discovered in 103 patients. At enrolment, 79 patients were naïve to NUCs treatment. Lamivudine monotherapy (n = 70) or a different NUC (n = 51) was administered. At month 6 of therapy, HBV‐DNA clearance was documented in 88 patients (73%). Treatment schedule was modified in 52 patients due to breakthrough or suboptimal response. During a mean follow‐up of 6 ± 3 years, viral clearance was achieved in the majority of patients. Ten of 74 patients (13.5%) with chronic hepatitis progressed to cirrhosis, 1 patient developed a HCC. In the 47 patients with cirrhosis at presentation, HCC occurred in 14 (30%) and liver decompensation in 5 (11%). The 5 and 10‐year event‐free survivals were, respectively, 89.3% (95% CI, 81.7 ?96.9) and 75.6% (95% CI, 61.5 ?89.7) for patients with chronic hepatitis, and 70.2% (95% CI, 56.3 ?84.1) and 40.4% (95% CI, 16.9 ?63.9) for those with cirrhosis. Protracted, effective treatment with oral NUCs affects the natural history of chronic HBV infection by reducing the incidence of cirrhosis and risk of complications, but does not guarantee against the development of HCC in cirrhosis at presentation.     

Chronic persistent hepatitis type B can be a progressive disease when associated with sustained virus replication

In 44 hepatitis B virus (HBV) carriers with chronic persistent hepatitis (CPH), serial liver biopsies were available. At presentation 38 patients had HBV-DNA in their serum including 31 HBeAg positive and seven anti-HBe positive cases. The remaining six patients were anti-HBe positive and HBV-DNA negative. During a mean histologic follow-up of 4.2 years, 12 (32%) of the 38 HBV-DNA positive patients progressed to chronic active hepatitis (six cases) or to active cirrhosis (six cases), while 26 patients showed either unchanged features of CPH (21 cases), or histologic improvement to normal liver (five cases). Persistence of HBV-DNA in serum, independently of HBeAg/anti-HBe events, was significantly (p less than 0.01) associated with deterioration of liver disease, while termination of HBV replication correlated significantly (p less than 0.05) with spontaneous biochemical remission and with unchanged or improved histology. None of the six anti-HBe positive patients without serologic markers of hepatitis B virus replication showed histologic deterioration. These findings indicate that continuing HBV replication is a marker which predicts unfavourable evolution of chronic persistent hepatitis and frequent transition to chronic active hepatitis or cirrhosis.