Post-partum acute exacerbation of chronic hepatitis in a hepatitis C-carrier mother

Hepatitis C virus infection is a global health problem; however, the interaction between pregnancy and chronic hepatitis C remains controversial. A Taiwanese woman with chronic hepatitis C had an uncomplicated pregnancy and gave birth to a female baby through spontaneous vaginal delivery. The serum levels of alanine aminotransferase and hepatitis C virus (HCV) RNA were measured before pregnancy, in the first and third trimesters, 1 and 3 months after delivery, respectively. During her pregnancy, the serum aminotransferase levels became normalized, while the serum HCV-RNA levels declined significantly and consecutively with the lowest viral load in the third trimester. One month after delivery, she had an abrupt elevation of serum HCV-RNA level, paralleling a hepatitis flare with serum aminotransferase level more than 20-fold the upper normal limit. The serum HCV-RNA levels declined thereafter, and serum aminotransferase levels became normalized 3 months postdelivery. She was infected with HCV genotype 1a throughout the entire follow-up period, and other causes of hepatitis flare were excluded. In conclusion, post-partum acute exacerbation of chronic hepatitis may occur in HCV-carrier mothers, and an abrupt elevation of serum HCV-RNA level may be associated with the acute exacerbation.     

Vertical transmission of hepatitis C virus in a hospital in southern Brazil

BACKGROUND: There still are controversies concerning the vertical transmission of hepatitis C virus. AIM: To evaluate the prevalence of antibodies against hepatitis C virus in pregnant women, as well as the rate of vertical transmission of this virus. PATIENTS AND METHODS: Between August 1998 and November 1999, 1,090 consecutive pregnant women were screened for anti-hepatitis C virus; positive results were confirmed by the polymerase chain reaction assay. Patient's viral load was evaluated by the branched deoxyribonucleic acid assay. Hepatitis C virus genotype was identified by direct sequencing of the polymerase chain reaction amplification products. The same tests were performed in the children born from infected mothers at the 1st and 6th month of life. RESULTS: Of the 1,090 mothers surveyed, 29 were positive for anti-hepatitis C virus (prevalence of 2.66%). Twenty-five patients presented with hepatitis C virus RNA, with a median hepatitis C virus viral load of 3.132 +/- 5.891 MEq/mL. Twenty-two patients (six human immunodeficiency virus-coinfected) were followed and gave birth to 23 children; 18 of them had blood samples tested at the 1st month of life, and 22, at the 6th month. Vertical transmission rate was 5.56%; it affected a girl who had hepatitis C virus RNA detectable only in the 1st month sample (41.570 MEq/mL). The mother who transmitted hepatitis C virus was coinfected with human immunodeficiency virus and presented with an hepatitis C virus viral load of 3.765 MEq/mL, with 100% homology with her daughter's hepatitis C virus genotype. CONCLUSION: These results suggest that the prevalence of hepatitis C virus infection in pregnant women should not be neglected, and early diagnosis of vertical transmission and the follow up of infected children should be emphasized.     

干扰素治疗慢性丙型肝炎的持续应答与复发相关因素的研究

目的 探讨丙型肝炎病毒（HCV）基因型、RNA含量与肝组织炎症活动的相关性，慢性丙型肝炎患者经干扰素治疗后复发的相关因素。方法 对慢性丙型肝炎患者的血清进行丙氨酸氨基转移酶（ALT）检测，采用Cobas Amplicor Monnitour Test．version 2．0试剂进行HCVRNA定量和Simmonds酶切分型方法进行HCV基因分型检测。对聚乙二醇化干扰素α-2a（PEG—IFN α-2a）与干扰素α-2a治疗24周结束时，取得病毒学应答的慢性丙型肝炎患者进行24周随访观察，对临床特征、病毒学特征、治疗药物等因素与复发的相关性进行分析。结果 208例丙型肝炎患者基础HCVRNA含量与ALT水平无相关性（r=0．093，P〉0．05），HCV基因1型与非基因1型之间ALT的水平差异无统计学意义，HCV基因型与RNA含量无相关性；在治疗结束取得病毒学应答的119例患者中，随访24周持续应答者61例（51．3％），复发58例（48．7％）。患者的性别、年龄、HCV感染途径、既往干扰素治疗史、天冬氨酸氨基转移酶／ALT比值、血小板计数和血清基础HCV载量等因素均与复发率无显著相关性。基因1型患者复发率（54．5％）显著高于非1型（32．1％）（x^2=4．265，P=0．039）。PEG-IFNα-2a组复发率（47．0％）低于IFNα-2a组（52．8％），但差异无统计学意义。结论 病毒基因型与慢性丙型肝炎干扰素治疗后的病毒复发显著相关。     

Mother-to-child transmission of hepatitis C virus detected by nested polymerase chain reaction.

Serum samples from eight pregnant women and their offspring were studied by nested polymerase chain reaction (PCR) for detection of hepatitis C virus (HCV) RNA to evaluate mother-to-child transmission of this virus. The mothers were all infected with human immunodeficiency virus (HIV); none showed symptoms of HCV infection. Anti-HCV antibodies were tested for by recombinant immunoblot assay. HCV viral sequences were found in five of the mothers and four of eight children, three of them at birth. Viremia was persistent in one infant who had chronic transaminase elevation and persistently remained anti-HCV-positive. The other three babies had intermittent viremia; all were asymptomatic and lost anti-HCV antibodies during follow-up. This loss of antibodies was also observed in PCR-negative infants. Thus, these results demonstrate transmission of HCV from mother to child by women coinfected with HCV and HIV. They indicate the usefulness of PCR for direct and early detection of HCV viremia in neonates.     

SEN virus co-infection among HCV-RNA-positive mothers, risk of transmission to the offspring and outcome of child infection during a 1-year follow-up

SEN is a newly discovered blood-transmissible virus. Among its variants, SENV-D and -H are most often associated with non-A, -E hepatitis. Very little is known about the risk of vertical transmission of the virus. By using polymerase chain reaction with specific primers for SENV-D and -H, we investigated the prevalence of SENV-H and -D infection, the transmission rate of SENV infection and clinical features of SENV-infected children in 89 hepatitis C virus (HCV)-positive human immunodeficiency virus type 1-negative mothers. SENV infection was found in 36 (40%) mothers, and SENV-D was more frequent than SENV-H infection (34/36, 94%vs 5/36, 14%, P < 0.01). No difference in SENV infection rates was found between injection drug user (IDU) mothers (17/51, 33%) and mothers with no risk for bloodborne infection (19/38, 50%, P = ns). SENV-H infection was found only in IDU mothers and mothers with HCV genotype1b. Both SENV-D and -H can be transmitted to the offspring with an overall rate of 47%. Vertical transmission of HCV does not facilitate SENV infection of the offspring. Among 17 SENV-infected children, none was co-infected with HCV. Maternal HCV genotype or viral load does not interfere with mother-to-infant transmission of SENV. Persistence of SENV infection was demonstrated in 100% of infected children after 1-year follow-up, but none had clinical evidence of liver disease.     

Transmission of hepatitis C virus to infants of human immunodeficiency virus-negative intravenous drug-using mothers: rate of infection and assessment of risk factors for transmission

The risk of perinatal transmission of hepatitis C virus (HCV) from a cohort of 95 human immunodeficiency virus (HIV)-negative intravenous drug users (IVDU) is described, 89 of whom were positive for antibodies to HCV (anti-HCV). Infection, defined as the presence of HCV RNA in a serum sample collected from an infant at any time during follow-up, was detected in six of 63 (9.5%) infants born to HCV antibody-positive viraemic mothers. No mother who was HCV RNA negative at delivery transmitted HCV to her infant. Hepatitis C virus antibodies became undetectable in uninfected infants by 15 months, but persisted in all HCV-infected infants throughout follow-up. An abnormal alanine aminotransferase (ALT) level was observed on at least one occasion in all HCV-infected infants and in six occasions in uninfected infants. Two of the six HCV-infected infants became HCV RNA negative during follow-up by 27 and 29 months. Both of these infants had a large ALT elevation (mean peak ALT 398Ul^–1) at around 12 months of age. Analysis of a range of potential risk factors revealed that maternal HCV RNA load was important in predicting transmission, but suggested that other factors play a role in perinatal transmission from mother to child. No difference was found between mothers who transmitted HCV to their infants and those who did not for HCV genotype, duration of drug use, duration of methadone use, methadone dose, history of alcohol abuse, past hepatitis B virus (HBV) infection, mode of delivery, maternal and gestational age, birth weight and incidence of breast-feeding. Mothers who transmitted HCV to their infants had a longer duration between membrane rupture and delivery than the mothers who did not transmit ( P =0.03). HCV RNA was not detected in breast milk and colostrum samples from 38 viraemic mothers, including two who transmitted HCV to their infant.     

妊娠期病毒性肝炎对围产儿的影响

目的 探讨妊娠期病毒性肝炎对围产儿的影响。方法 测定４７名正常孕妇和４９５例病毒性肝炎孕妇所生新生儿Ａｐｇａｒ评分和出生时体重,并检测新生儿血清肝炎病毒标志。结果 肝炎孕妇所生新生儿Ａｐｇａｒ评分和出生时体重均显著低于对照组（均Ｐ〈０．０１）,急性肝炎孕妇所生新生儿１ｍｉｎ Ａｐｇａｒ评分和出生时体重均显著低于乙型肝炎病毒（ＨＢＶ）携带和慢性肝炎组（均Ｐ〈０．０１）,甲型肝炎未见宫内感染。ＨＢＶ,     

Hepatitis C virus RNA present in saliva but absent in breast-milk of the hepatitis C carrier mother

In order to examine whether saliva and breast-milk are mediators of the vertical transmission of hepatitis C virus (HCV) from an HCV carrier mother, serum, saliva, and breast-milk samples from 11 HCV carrier mothers were collected at the time of delivery, and at approximately 1- to 3-month intervals for as long as 30 months postpartum. Serum was also sampled from their children. All samples were analysed for the presence of HCV RNA, using the nested polymerase chain reaction method. No HCV RNA was detected in any breast-milk samples. In saliva, HCV RNA was detected in four of the 11 mothers (36%). These four mothers also had liver function abnormalities. Hepatitis C virus RNA was not detected in any serum samples of the children, and all children had normal liver function. The children were monitored for periods from 2 to 44 months. During this period, there was no evidence of virus transmission. Breast-milk is not likely to be a source of mother-to-child transmission of HCV. Maternal saliva may harbour HCV, but it may not result in infant infection.     

Hepatitis C virus genotypes and hepatic fibrosis regulate 24-h decline of serum hepatitis C virus RNA during interferon therapy in patients with chronic hepatitis C

BACKGROUND AND AIMS: Recently, hepatitis C virus (HCV) dynamics during interferon (IFN) therapy have been studied in detail. We examined factors that regulate the viral kinetics and the relationship between the viral kinetics and clinical effect of IFN therapy. METHODS: Eighty-eight patients with chronic hepatitis C entered this study. All patients had been treated with 3 MU of IFN-beta twice a day for the first 2-4 weeks, then IFN-alpha for the next 20-22 weeks (three injections per week). The levels of serum HCV RNA were determined by Amplicor HCV Monitor version 1.0, before and 24 h after the first injection of IFN; then the decline of HCV was calculated. Liver inflammation and fibrosis were scored as 0 (none), 1 (mild), 2 (moderate) or 3 (severe) using biopsy specimens. RESULTS: The decline of serum HCV RNA was 1.42 +/- 0.65 log copies/mL in genotype 1b and 1.83 +/- 0.72 in genotype 2a or 2b (P < 0.01). By a logistic regression model, genotype (1b, 2a or 2b) and hepatic fibrosis (0 or 1, 2 or 3) associated with 24-h decline of serum HCV RNA, independently. As the predictor of IFN therapy, the decline of serum HCV RNA and serum HCV RNA levels before IFN therapy were the independent significant factors (P < 0.001). CONCLUSIONS: The decline of serum HCV RNA during the first 24 h of IFN therapy was regulated by genotypes and hepatic fibrosis. The decline of serum HCV RNA and initial HCV load were independent factors that can be the predictor of the subsequent sustained viral response to IFN therapy.     

Comparative analysis of quantification of viral load in patients infected with hepatitis C virus: quantiplex HCV RNA assay and amplicor monitor assay.

OBJECTIVE: two standardized techniques, Quantiplex HCV RNA 2.0 (bDNA) and Amplicor Monitor, were evaluated for the quantification of hepatitis C virus (HCV) load. Our objectives were: 1) to determine the relationship between viral load and genotype, and 2) to evaluate viral load in serial serum samples and in patients with normal or slightly elevated liver enzyme values in an area with a high prevalence of genotype 1. RESULTS: the viral loads detected with the two methods correlated significantly (r = 0.7, p < 0.0001), but viral load was smaller with the Monitor than with the Quantiplex assay, and was independent of genotype. The Monitor/Quantiplex ratio was lower in patients with a non-1 genotype than in patients with genotype 1b. Virological characteristics were similar in patients with normal or slightly elevated enzyme levels and in patients with elevated enzyme values. Neither method showed a relationship between viral load and age, sex, duration of the infection, mode of transmission, or histological activity index. CONCLUSION: viral load was not dependent on genotype. Measurement of viral load in a single serum sample adequately reflected the viral load measured in several serum samples from patients with chronic HCV infection. Patients with normal liver enzyme levels are not good candidates, in virological terms, for treatment with interferon.     

Clarification of interspousal hepatitis C virus infection in acute hepatitis C patients by molecular evolutionary analyses: Consideration on sexual and non‐sexual transmission between spouses

Aim: Previous studies evaluating the possibilities of interspousal sexual transmission of hepatitis C virus (HCV) have yielded many conflicting results. The aim of this study was to clarify the source of HCV infection in acute hepatitis C patients using phylogenetic analyses of nucleotide sequences of HCV E1 region. Methods: Four acute hepatitis C patients were hospitalized in 2002–2007. The diagnosis was based on medical records, laboratory tests including HCV markers, and ultrasonographic examination of the liver. In each spouse of four patients, serum HCV antibody was assayed. In the subjects whose serum HCV antibody was positive, additional tests on HCV viral load and genotype were carried out. Then phylogenetic analyses of nucleotide sequences of partial HCV E1 region (440 nucleotides) of the patients and their spouses were performed. Results: Hepatitis C virus antibody changed from negative to positive in the course of hospitalization and HCV RNA could be detected in every patient. Therefore they were diagnosed as acute hepatitis caused by HCV infection. In every spouse of four patients, HCV antibody and HCV RNA were positive. Three of four couples had the identical genotype and homogeneity of nucleotide sequences of HCV E1 region in three couples ranged from 97.9% to 100%. The results of phylogenic analyses suggested that interspousal HCV infection occurred in the three couples. Conclusion: In conclusion, interspousal infection might be one of the important sources of acute HCV infection in Japan. The usefulness of phylogenetic analysis of nucleotide sequences of HCV E1 region for clarifying interspousal HCV infection was validated.     

Optimal follow-up time to determine the sustained virological response in patients with chronic hepatitis C receiving pegylated-interferon and ribavirin

Background and Aim: This study evaluated whether the assessment of hepatitis C virus (HCV)‐RNA at 12 weeks (FW+12) post‐treatment follow‐up was as applicable as FW+24 to evaluate sustained virological response (SVR) using the highly sensitive real‐time polymerase chain reaction (PCR) HCV assay. Methods and Results: Two hundred and twenty‐two patients with chronic hepatitis C were included in this study. Pegylated interferon (Peg‐IFN) and ribavirin were administered for 24–72 weeks based on the genotype and viral load. Serum HCV‐RNA was measured using real‐time PCR at pretreatment, the end of treatment, FW+4, FW+8, FW+12, FW+16, FW+20 and FW+24. Two hundred patients had a virological response at the end of treatment. One hundred and forty‐eight of 200 (74.0%) patients with a virological response at the end of treatment had an SVR at the FW+24. The positive predictive value (PPV) to identify patients with SVR at FW+4, FW+8, FW+12 was 87.1, 96.1, 98.0%, respectively. The viral load showed a reversion to the basal level as early as 8 weeks in relapse patients. There were only three patients who relapsed after FW+12 and all three of these patients were females with genotype Ib and a high viral load. Conclusion: The assessment of serum HCV‐RNA FW+12, using the highly sensitive real‐time PCR assay, is almost as effective as FW+24 to predict SVR. However, there are false negatives in female patients with a high viral load of genotype Ib when the SVR is predicted by FW+12. The current standard with FW+24 is reasonable, but the assessment of serum HCV‐RNA FW+12 may be effective in most patients.     

Mother-to-infant transmission of hepatitis C virus.

OBJECTIVE: To describe the rate of perinatal transmission of hepatitis C virus (HCV). DESIGN: Follow-up study of newborn children of mothers with chronic HCV infection. SETTING: A university hospital in Sweden. PARTICIPANTS: Fourteen women with chronic HCV infection and their 21 newly born children. MAIN OUTCOME MEASURES: Detection of HCV RNA in serum by the polymerase chain reaction and detection of anti-HCV antibody by second generation assays. RESULTS: All mothers were found to be positive for anti-HCV antibody both by second-generation enzyme-linked immunosorbent assay (ELISA) and by second-generation recombinant immunoblot assay (RIBA-2); all also had detectable serum HCV RNA. Two children had long-lasting alanine aminotransferase (ALT) elevations, and one of them became HCV RNA positive. None of the other children developed biochemical hepatitis. However, two additional children had temporary viremia. Only the child with biochemical and biopsy-proven hepatitis and detectable HCV RNA in multiple blood samples actively produced anti-HCV antibody. CONCLUSIONS: Mother-to-infant transmission of HCV infection from chronically infected women without human immunodeficiency virus (HIV) infection seems to be uncommon.     

Different outcomes of vertical transmission of hepatitis C virus in a twin pregnancy

The risk of vertical transmission of hepatitis C virus (HCV) from mother to infant has been well documented, but the exact mode of transmission is still unclear. In a set of monochorionic diamniotic monozygous twins, only the second baby was infected with HCV from the mother who was positive for serum HCV-RNA. The babies had an uncomplicated vaginal delivery 3 min apart and they were both bottle fed from the outset. The second baby developed clinical hepatitis that persisted to 30 months follow up. The intrauterine environment should have been identical for these twins, and therefore, the maternal HCV factors, including viral load are not the sole determining factors for mother-to-infant transmission of HCV.     

Immediate virological response predicts the success of shortterm peg-interferon monotherapy for chronic hepatitis C

AIM:To investigate the efficacy of short-term peginterferon(PEG-IFN)monotherapy for chronic hepatitis C patients who achieved an immediate virological response.METHODS:Defining an“immediate virological response(IVR)“as the loss of serum hepatitis C virus(HCV) RNA 7 d after the first administration of PEG-IFNα,we conducted a 12-wk course of PEG-IFNα2a monotherapy without the addition of ribavirin for 38 patients who had low pretreatment HCV RNA load and exhibited IVR.The patients included 21 men and 17 women...     

Leptin has no role in determining severity of steatosis and fibrosis in patients with chronic hepatitis C

OBJECTIVE: The presence of steatosis is a common histological finding in patients with chronic hepatitis C (CHC). The causes of the severity of this condition are not yet clear, although both metabolic and viral factors supposedly are involved. In this study our aim was to examine the possible influence that leptin levels, hepatitis C virus (HCV) RNA levels, and hepatitis G virus (HGV) infection have on the severity of steatosis and on the presence and degree of fibrosis in patients with CHC. METHODS: One hundred eighty-two CHC patients with histological findings of steatosis were chosen from among a cohort of patients referred to our center for staging of liver disease. Among them 48 CHC patients were accurately selected so as to rule out possible confounding factors for the presence of steatosis (diabetes mellitus, hyperlipemia, obesity, alcohol). Leptin levels, HCV RNA levels, and HCV genotype, and the presence of HGV RNA were assessed in these patients and related to histological findings. RESULTS: We found that leptin levels in CHC patients were similar to those in healthy subjects. No relationship was found between leptin levels and severity of steatosis. HCV RNA levels, HCV genotype, and the presence of HGV infection were no different among CHC patients with various degrees of steatosis. Leptin was not related to different degrees of fibrosis, whereas higher viral load was the only parameter associated to higher fibrosis scores. CONCLUSIONS: These findings suggest that the degree of steatosis in patients with CHC does not seem to depend on serum leptin levels or on viral factors, at least as far as HCV viremia and genotype and HGV infection are concerned. The severity of fibrosis does not seem to be influenced by leptin levels, whereas HCV viral load does seem to play some role.     

Predicting the response to 48‐week combination therapy with peginterferon α‐2b plus ribavirin from the estimated HCV RNA load index after negative serum change in genotype 1b hepatitis C patients

Aim: We estimated viral dynamics after serum hepatitis C virus (HCV) RNA became negative and assessed the relation between the estimated viral load at the end of treatment (EVE) index and the response to the combination therapy with peginterferon α‐2b plus ribavirin. Methods: Patients with chronic HCV, genotype 1b, and a high viral load were treated with this combination therapy for 48 weeks, and serum HCV RNA was measured frequently during the treatment period. In the patients showing an end‐of‐treatment response (ETR), the viral load profile from the start of treatment until serum HCV RNA became negative was expressed by an approximate curve. Then the EVE index was calculated by using the expression obtained from the curve, and differences between the sustained virologic response (SVR) and relapse groups were investigated. Results: The SVR rate increased as the EVE index became lower, and the EVE index was significantly lower in the SVR group than in the relapse group. The SVR rate was higher for those in whom the EVE index was below the cut‐off point. Conclusion: Prediction of SVR and relapse from the EVE index is more useful than prediction from viral dynamics at the time when HCV RNA becomes negative or when HCV RNA shows a decrease of 2‐log or more.     

Viral load in HCV RNA-positive pregnant women

OBJECTIVES: The risk of hepatitis C virus (HCV) infection in the newborn is estimated to be around 5%, but becomes very high in the case of coinfection with HIV. One of the main factors associated with the vertical transmission of HCV is the viral load. Our objective was to investigate the behavior of HCV viral load during pregnancy in relation to HIV coinfection, liver enzymes, and vertical transmission. METHODS: Three thousand seven hundred forty-eight women seen consecutively in their first trimester of pregnancy were screened for HCV infection. Sixty-five were found to be anti-HCV+/HCV RNA+ and were followed up with clinical and serological assessment (i.e., transaminases and quantitative polymerase chain reaction [PCR] for viral load) in their second and third trimesters and 6 months after delivery. All were anti-HIV and hepatitis B surface antigen negative. HCV RNA was 12.0+/-19.9 x 10(6) copies/ml in the first trimester and 10.9+/-13.3 x 10(6) in the second, but increased to 19.5+/-25.1 x 10(6) in the third trimester. Six months after delivery the viral load returned to the baseline levels; the changes in viral load did not reach any statistical significance, however. Transaminases tended toward a reduction from the baseline during the second and third trimesters, and then an increase in both AST and ALT was recorded 6 months after delivery. However, when the group whose AST/ALT were found abnormal at the first test was considered, no significant changes were recorded during the follow-up. The overall rate of vertical transmission was 4.6 CONCLUSIONS: With HCV+ mothers monitoring transaminases during pregnancy is unnecessary, and testing liver enzymes at the beginning of pregnancy is sufficient. Qualitative PCR should be done once during the pregnancy, but any staging of the liver disease should be taken after delivery. Quantitative PCR testing is expensive and pointless. Any decision for elective cesarean section in HCV RNA+ mothers should be confirmed by other studies.