Musculoskeletal pain and fatigue are associated with chronic hepatitis C: a report of 239 hepatology clinic patients

OBJECTIVE: The aim of this study was to identify the frequency of fatigue and musculoskeletal pain in hepatitis C compared with other liver diseases. METHODS: Hepatology outpatients were evaluated by questionnaire for musculoskeletal pain and fatigue. Charts were reviewed for diagnoses, aminotransferases, histology, treatment, and presence of hepatitis C by second generation ELISA and/or polymerase chain reaction. The frequency of symptoms in patients with and without hepatitis C were compared. RESULTS: In 239 patients (mean age 46.7 +/- 11.6 yr; 52% male) musculoskeletal pain was present in 70% for 6.7 +/- 8.3 yr and fatigue in 56% for 3.3 +/- 5.1 yr. Backache was the most common complaint (54%), followed by morning stiffness (45%), arthralgia (42%), myalgia (38%), neck pain (33%), pain "all over" (21%), and subjective joint swelling (20%). Diffuse body pain was present in 23% on a pain diagram and was strongly associated with fatigue. There was a significant association between hepatitis C positivity and the presence of musculoskeletal pain (81% of HCV-positive compared with 56% of HCV-negative patients, respectively; p = 0.0001), and fatigue (67% compared with 44%; p = 0.001). Musculoskeletal pain was more frequent among patients with isolated hepatitis C infection than among patients with isolated hepatitis B or alcoholic liver disease (91%, 59%, and 48%, respectively; p = 0.004). Similarly, fatigue was more frequent among patients with isolated hepatitis C than among those with isolated alcoholic liver disease or hepatitis B (66%, 30%, and 29%, respectively; p = 0.004). There was no relationship between musculoskeletal complaints and possible route of acquiring hepatitis C, levels of aminotransferases, liver disease severity on biopsy, or interferon treatment. CONCLUSIONS: Musculoskeletal pain and fatigue are frequent in hepatology clinic attendees, particularly those with hepatitis C and are unrelated to severity of liver disease, route of infection, or interferon therapy.     

Hepatitis C virus RNA quantification in right and left lobes of the liver in patients with chronic hepatitis C

Summary. Quantification of hepatitis C virus RNA in liver tissue is likely to be useful in the study of the natural history, pathogenesis, progression and treatment of hepatitis C virus-associated liver disease. Quantitative measurements of hepatitis C virus RNA in liver biopsy samples using the branched DNA (bDNA) signal amplification assay were carried out. The aims of this study were threefold: first, to assess the level of hepatitis C virus RNA in biopsy samples from the right and left lobes of the liver; second, to evaluate the correlation between hepatitis C virus RNA levels in serum and liver; and third, to investigate the relationship between serum and liver hepatitis C virus RNA levels and the severity of hepatic histology in non-cirrhotic patients with chronic hepatitis C. There was a strong correlation ( r = 0.92, P < 0.01) between hepatitis C virus RNA levels in the right and left lobes of the liver as well as a strong correlation between hepatitis C virus RNA levels in liver and serum ( r = 0.82, P < 0.01). However, there was no significant correlation between the severity of hepatic histology and levels of hepatitis C virus RNA in serum and liver among patients with chronic active hepatitis classified according to Knodell's hepatic activity index (KI). Our results indicate that hepatitis C virus RNA quantification from a single liver biopsy is representative of both lobes in patients with chronic hepatitis, and suggest that serum hepatitis C virus RNA levels are a meaningful reflection of hepatitis C virus RNA levels in the liver.     

Impaired health-related quality of life in patients with chronic hepatitis C and persistently normal aminotransferase levels

A significant impact of hepatitis C virus (HCV) infection on health-related quality of life (HRQOL) has been previously described. However, comprehensive data on the quality of life in patients with chronic hepatitis C and persistently normal aminotransferase levels (PNAL) are currently not available. One hundred fifteen patients with chronic hepatitis C (45 with persistently normal aminotransferases and 70 with elevated aminotransferases) and 50 healthy subjects were enrolled. Emotional and psychological states were assessed by Profile of Mood States (POMS) scale and HRQOL was assessed by the 'Everyday Life' questionnaire (EDLQ), a validated questionnaire related to the SF-36 Health Survey. An impairment in HRQOL was observed in patients with chronic hepatitis C showing PNAL compared with healthy subjects with significant differences for the factor scores depression and anger in the POMS scale as well as for the items body, relationship to partner, self-confidence and zest of life in the EDLQ. No differences in any questionnaire were observed between patients with chronic hepatitis C showing PNAL or elevated aminotransferase levels except of a worse mean level for factor score anger in POMS scale in patients with persistently normal aminotransferases. No association of quality of life with severity of liver disease was found. Impairment of HRQOL by chronic infection with HCV is similar in patients with PNAL and those with elevated aminotransferase levels.     

Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy

BACKGROUND & AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a unique episomal replicative intermediate responsible for persistent infection of hepatocytes. Technical constraints have hampered the direct study of cccDNA maintenance and clearance mechanisms in patients. The aim of this study was to develop a sensitive and specific assay for quantifying cccDNA in biopsy samples from chronic hepatitis B patients during different natural history phases and in patients undergoing antiviral therapy. METHODS: Intrahepatic cccDNA levels were quantified by a specific real-time PCR assay. Ninety-eight liver biopsy samples from patients in the major phases of the natural history of chronic hepatitis B and 32 pairs of samples from patients receiving adefovir dipivoxil (ADV) therapy were assessed. RESULTS: cccDNA was detected, at levels ranging over 3 orders of magnitude, in patients in different phases of the natural history of chronic hepatitis B. cccDNA levels were strongly correlated with levels of total intracellular HBV DNA and serum HBV DNA. Forty-eight weeks of ADV therapy resulted in a significant 0.8 log decrease in cccDNA copies/cell. Changes in cccDNA were correlated with a similar reduction in serum HBsAg titer but not with a decrease in the number of HBV antigen-positive cells during ADV treatment.CONCLUSIONS: cccDNA persists throughout the natural history of chronic hepatitis B, even in patients with serologic evidence of viral clearance. Long-term ADV therapy significantly decreased cccDNA levels by a primarily noncytolytic mechanism.     

Fatigue Complicating Chronic Liver Disease

Fatigue is common and can be profound in patients with chronic liver diseases, such as primary biliary cirrhosis (PBC) and chronic hepatitis C. The pathogenesis of fatigue in such patients is unknown; it may be related to infection with the hepatitis C virus or the pathophysiology of cholestasis in PBC, to a psychological reaction to knowledge of the diagnosis, or to the presence of chronic liver disease. A major problem in evaluating a treatment for fatigue in a randomized controlled trial is the inherent subjectivity of fatigue and the lack of a satisfactory objective quantitative primary efficacy endpoint. Experimental studies in rats and male athletes have implicated the serotonin neurotransmitter system in fatigue of central origin. Administration of the 5-HT3 serotonin receptor subtype antagonist, ondansetron, has been associated with substantial sustained clinical ameliorations of profound fatigue in at least some patients with chronic liver disease.     

Subclinical impairment of brain function in chronic hepatitis C infection

BACKGROUND/AIMS: Central nervous system abnormalities such as fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in many other causes of chronic liver disease. The finding that fatigue is unrelated to activity of hepatitis or mode of infection could indicate an independent effect of HCV on brain function. This study tested the hypothesis of a subclinical cognitive dysfunction in HCV-infected patients. METHODS: One-hundred untreated HCV-RNA positive biopsy-proven patients were investigated by P300 event-related potentials, a sensitive electrophysiologic test of cognitive processing. Health-related quality of life and fatigue were assessed using the SF-36 questionnaire and the Fatigue Impact Scale, respectively. RESULTS: Cognitive brain function was subclinically impaired in the cohort of HCV-infected patients as indicated by significantly prolonged P300 latencies (P=0.01 for comparison to matched healthy subjects) and reduced P300 amplitudes (P<0.001, respectively). Seventeen of the 100 HCV-infected patients had P300 latencies outside the age-adjusted normal range. Abnormal P300 characteristics were not related to the degree of histologic or biochemical activity of hepatitis, severity of fatigue or mental health impairment. CONCLUSIONS: This study demonstrates that patients with HCV infection showed a slight but significant neurocognitive impairment, possibly indicating a further extrahepatic manifestation of chronic hepatitis C.     

Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?!

One of the most disabling symptoms of hepatitis C virus (HCV) infection is chronic fatigue. While this is accepted for HCV polymerase chain reaction (PCR)‐positive patients, a relationship between HCV infection and chronic fatigue is questioned after successful virus eradication. As fatigue is a subjective criterion, we aimed to evaluate in addition mood alterations and cognitive function in HCV‐exposed patients with only mild liver disease and to assess a) possible interrelationships between these factors and health‐related quality of life and b) the impact of viremia and former interferon treatment. One hundred and fifty‐nine anti‐HCV‐positive individuals without advanced liver disease answered health‐related quality of life (HRQoL), fatigue and depression questionnaires and underwent a battery of attention and memory tests. Accompanying diseases which could distort the results of the study such as HIV co‐infection or drug addiction were exclusion criteria. The patients were subdivided into four groups according to their viremia status and interferon treatment history. Patients' data were evaluated with respect to norms given in the respective test manuals and in addition compared to those of 33 age‐matched healthy controls. Eighty‐five per cent of the patients had chronic fatigue, 50‐60% mild depression or anxiety, 45% memory deficits and 30% attention deficits, irrespective of their HCV viremia status or treatment history. HRQoL correlated negatively with chronic fatigue (P<.001), while cognitive deficits—especially memory function—were independent from fatigue and depression. HCV infection may cause long‐standing cerebral dysfunction that significantly impairs HRQoL and may even persist after clearance of the virus.     

Are hepatitis G virus and TT virus involved in cryptogenic chronic liver disease?

BACKGROUND: Hepatitis G virus can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. Little is known about the relation of another newly discovered agent, the TT virus, with chronic liver disease. AIM: To investigate the rate of infection with hepatitis G virus and TT virus in patients with cryptogenic chronic liver disease. PATIENTS: A total of 23 subjects with chronically raised alanine transaminase and a liver biopsy in whom all known causes of liver disease had been excluded, and 40 subjects with hepatitis C virus-related chronic liver disease. METHODS: Evaluation of anti-hepatitis G virus by enzyme immunoassay. Hepatitis G virus-RNA by polymerase chain reaction with primers from the 5' NC and NS5a regions. TT virus-DNA by nested polymerase chain reaction with primers from the ORF1 region. Results. Hepatitis G virus-RNA was detected in 4 out of 23 patients with cryptogenic chronic hepatitis and in 6 out of 40 with hepatitis C virus chronic hepatitis (17.4% vs 15% p=ns). At least one marker of hepatitis G virus infection (hepatitis G virus-RNA and/or anti-hepatitis G virus, mostly mutually exclusive) was present in 6 out of 23 patients with cryptogenic hepatitis and 16 out of 40 with hepatitis C virus liver disease (26. 1% vs 40% p=ns). T virus-DNA was present in serum in 3 subjects, 1 with cryptogenic and 2 with hepatitis C virus-related chronic liver disease. Demographic and clinical features, including stage and grade of liver histology, were comparable between hepatitis G virus-infected and uninfected subjects. Severe liver damage [chronic hepatitis with fibrosis or cirrhosis) were significantly more frequent in subjects with hepatitis C virus liver disease. CONCLUSIONS: In Southern Italy, hepatitis G virus infection is widespread among patients with chronic hepatitis, independently of parenteral risk factors. Its frequency in subjects with cryptogenic liver disease parallels that observed in hepatitis C virus chronic liver disease, thus ruling out an aetiologic role of hepatitis G virus. TT virus infection is uncommon in patients with cryptogenic or hepatitis C virus-related liver disease who do not have a history of parenteral exposure.     

Functional connectivity alterations in patients with chronic hepatitis C virus infection: A multimodal MRI study

Chronic hepatitis C virus (HCV) infection is associated with fatigue and depression. Cognitive impairments are also reported in a smaller number of HCV‐positive patients. Recent studies linked HCV to low‐grade inflammation in brain. Here, we test the hypothesis that chronic HCV is associated with 3T‐neuroimaging‐derived grey matter volume (GMV) and functional connectivity alterations in a sample of chronic HCV (1b), without severe liver disease. Regional GMV and resting‐state fMRI‐derived eigenvector centrality (EC) were compared between 19 HCV‐positive patients and 23 healthy controls (all females, 50‐69 and 52‐64 years, respectively), controlling for white matter hyperintensities and age. Standard tests were used to assess fatigue, depression and cognitive performance. Also, liver fibrosis stage and viral load were quantified among patients. In comparison with controls, HCV‐positive patients had higher scores in fatigue and depression, and worse alertness scores. The groups performed similarly in other cognitive domains. We report higher EC in a cluster in the right anterior superior parietal lobule in patients, while no differences are found in GMV. Post hoc functional connectivity analysis showed increased connectivity of this cluster with primary and secondary somatosensory cortex, and temporal and occipital lobes in patients. Higher mean EC in the superior parietal cluster, adjusted for mean framewise displacement, was associated with better memory and attention performance, but not with fatigue, depression, viral load or level of liver fibrosis, among patients. These results suggest a compensatory mechanism in chronic hepatitis C and explain equivocal results in the literature about cognitive deficits in infected persons. Further studies should define the relation of these connectivity changes to the brain's inflammatory activity.     

A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection

Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue, depression and impairments in health-related quality of life, which are independent of the severity of liver disease. Although there are a large number of potential explanations for these symptoms, including a history of substance abuse and associated personality types, or the effect of the diagnosis of HCV infection itself, there has been recent interest in the possibility of a biological effect of HCV infection on cerebral function. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be wholly attributed to substance abuse, co-existent depression or hepatic encephalopathy. Impairments are predominantly in the domains of attention, concentration and information processing speed. Furthermore, in-vivo cerebral magnetic resonance spectroscopy studies in patients with hepatitis C and normal liver function have reported elevations in cerebral choline-containing compounds and reductions in N-acetyl aspartate, suggesting that a biological mechanism may underlie the cognitive findings. The recent detection of HCV genetic sequences in post-mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment.     

Psychological issues in the treatment of asthmatic patients

Recently published research contends that anxiety and depression are more common in asthmatic patients than in the general population. Particular psychological profiles could even be a risk factor contributing to deaths caused by asthma. The purpose of our research was to evaluate the anxiety and depression level in a population of 80 asthmatic patients who were treated in our department, and to judge whether data collected on psychological profiles of these asthmatic patients can be of any significance when dealing with their pathology. The study consisted of 40 patients suffering from chronic viral hepatitis B or C, and 40 healthy subjects who served as a control group. Both sets of patients were homogeneous with regard to sex, age and education. All subjects were tested for anxiety and depression levels with the S.T.A.I. and Zung questionnaires. A structured questionnaire was employed to assess the daily approach to living with the disease only in asthmatic patients. The anxiety and depression levels were noticeably higher in asthmatic patients than in patients with chronic liver disease and healthy subjects. In particular, 34 asthmatic patients scored higher than the S.T.A.I. cut-off (40/80) and 27 attained the same results in the Zung questionnaire. Results from the asthmatic population and healthy subjects illustrated that women had a higher incidence of anxiety and depression compared to men, although no statistically significant relationship between sex and questionnaire results was apparent in patients with liver disease. In the year before assessment, hospitalization and emergency treatment due to asthmatic exacerbation was correlated in females with a high incidence of anxiety. Additionally, the asthmatic population's level of education is significantly related to the incidence of anxiety and depression. With higher education, incidence of depression and anxiety decreased. This result was not apparent in control groups. The results of our study were: (1) we confirmed that asthmatic pathology is associated with an increase in incidence of anxiety and depression, whose presence and seriousness should be taken into consideration in therapeutic programmes when dealing with a patient; (2) we indicated that a specific approach towards therapy is crucial when dealing with an asthmatic patient; (3) we suggested how important it is to identify categories of patients that require more care because of their psychological profile. These findings should provide for the optimal use of informational resources with important applications for educational programmes and the future treatment of the asthmatic population.     

病毒性肝炎患者疲劳的影响因素研究

目的:调查病毒性肝炎患者疲劳现状及其影响因素,为患者进行心理健康干预提供依据。方法:采用多维疲劳量表、匹兹堡睡眠质量量表、HAD量表及一般资料、疾病相关资料进行问卷调查。结果:202例病毒性肝炎患者疲劳得分为(57.866±9.886)分,疲劳得分在性别、年龄、婚姻状况、医疗费用来源、有无肝病家族史、症状体征个数、焦虑、抑郁、睡眠质量方面有显著性差异(P<0.05),多元线性回归结果显示症状体征个数、焦虑、睡眠质量、有医保是病毒性肝炎患者疲劳的影响因素。结论:症状体征个数、焦虑、睡眠质量、医保是影响病毒性肝炎患者疲劳水平的主要因素。     

The liver biopsy in chronic hepatitis C: a view from the other side of the microscope

The liver biopsy has long been the gold standard for the evaluation of the state of liver disease in patients with chronic hepatitis C. Although a liver biopsy continues to be a recommended part of the work-up of this disease, its routine use is challenged by the increasing effectiveness of therapy and by surrogate biochemical tests that give information about the stage of disease. Nevertheless, recent studies have shown that histological features other than stage may have predictive value for disease progression and therapeutic response to interferon-based regimens. Pathologists can increase the relevance and utility of the liver biopsy in chronic hepatitis C by the systematic reporting of steatosis and iron accumulation in addition to stage and grade, and by identifying certain potential confounding liver diseases, such as steatohepatitis and hereditary hemochromatosis. Clinicians can then make best use of the information derived from the liver biopsy to help them advise patients on the natural history of their disease and the therapeutic options that are available.     

Natural history of initially mild chronic hepatitis C

The hepatitis C virus is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in western countries. Chronic hepatitis C is highly heterogeneous and many patients present with a mild form of liver disease. Population-based studies have indeed demonstrated that around 50% of hepatitis C virus carriers have persistently normal ALT and two-third have mild histological liver lesions. Studies on the natural history of initially mild chronic disease indicate that the short-term outcome is always benign. However, progression of liver fibrosis can be observed at long-term (>5-7 years) follow-up, particularly in those cases who have elevated and/or fluctuating transaminase levels. Observational prospective studies and outcome modelling projections indicate that the risk of liver disease progression towards severe fibrosis/cirrhosis is minimal at 10-15 years in hepatitis C virus carriers with persistently normal ALT, around 5-10% in patients with elevated ALT and F0 (no fibrosis) in the initial biopsy but >30-40% in chronic carriers with elevated ALT and F1 (portal fibrosis) in the initial biopsy. Cofactors like age at infection, alcohol, coinfections and liver steatosis accelerate disease progression. On the basis of these findings, patients with initially mild chronic hepatitis C and elevated ALT should be proposed for antiviral therapy in the absence of contraindications.     

Hepatitis C,iron status,and disease severity: relationship with HFE mutations

BACKGROUND & AIMS: Mild to moderate hepatic iron loading is common in patients with chronic hepatitis C. We sought to determine whether mutations in the hemochromatosis gene, HFE, are associated with iron overload and acceleration of disease progression in hepatitis C patients. METHODS: A total of 316 patients with chronic hepatitis C were studied: 198 consecutive patients undergoing liver biopsy for compensated liver disease and 118 who underwent liver transplantation for end-stage liver disease. Serum iron studies, quantitative hepatic iron concentration, histologic activity index, and HFE genotype were determined. RESULTS: Among patients with compensated liver disease, the presence of HFE mutations was independently associated with elevations in serum iron level, serum transferrin-iron saturation, serum ferritin level, and hepatic iron index (P < 0.05). After adjustment for duration of infection with hepatitis C virus, HFE mutations were also independently associated with the presence of bridging fibrosis or cirrhosis (odds ratio, 18; 95% confidence interval, 1.7-193). HFE mutations were not independently associated with iron loading in patients with end-stage liver disease. There was no significant difference in the prevalence of HFE mutations between patients with compensated and end-stage liver disease (42% vs. 33%, respectively; P = 0.67). CONCLUSIONS: The presence of HFE mutations is independently associated with iron loading and advanced fibrosis in patients with compensated liver disease from chronic hepatitis C, especially after controlling for duration of disease. These results suggest that HFE mutations accelerate hepatic fibrosis in hepatitis C but may not be responsible for progression to end-stage liver disease.     

Morbidity of Chronic Hepatitis C as Seen in a Tertiary Care Medical Center

We studied the morbidity of chronic hepatitis Cin patients referred to a tertiary care medicalfacility. The medical records of 500 consecutive casesof chronic hepatitis C were examined for the following: (1) source and time of exposure, (2) signs andsymptoms of liver disease, (3) degree of alcohol intake,(4) liver biopsy findings, (5) extrahepatic diseasemanifestations, and (6) coexisting illnesses that could have an impact on morbidity. Morbidityand histologic findings were evaluated in relation tothe duration of hepatitis C. The onset of infectioncould be determined in 376 patients (75%). A close relationship between the length of infectionand disease features was not observed. Fatigue wascommon at all stages of infection. Whereas cirrhosisoccurred more frequently in patients with disease of long duration, 15-24% of patients had signs ofadvanced liver disease (ascites, encephalopathy,thrombocytopenia) within six years of exposure. Overtextrahepatic manifestations of chronic hepatitis Coccurred infrequently, and depression was reported in24% of untreated patients. In conclusion, in patientsreferred to a tertiary care setting, chronic hepatitisC is often associated with significantmorbidity.     

Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study

BACKGROUND AND AIMS: There are no available effective therapies for fatigue associated with chronic hepatitis C (CHC). The serotonin antagonist ondansetron has been shown to be effective in the chronic fatigue syndrome. In this randomised, placebo controlled, double blind trial, we investigated the effect of orally administered ondansetron on fatigue in CHC. METHODS: Thirty six patients with CHC were included if fatigue was their predominant symptom and they scored more than 4 on a visual analogue scale (0-10). During the study, fatigue and depression were measured on days 0, 15, 30, and 60 using a validated self report questionnaire (fatigue impact scale and Beck depression inventory). Patients were randomised to receive ondansetron tablets 4 mg twice daily or placebo for one month followed by an additional four weeks of observation. RESULTS: Fatigue score was 85.4 (28.2) and 98.2 (26.9) in the ondansetron and placebo groups, respectively (NS). Ondansetron significantly reduced the fatigue score with more than 30% improvement on day 15 (57.1 (38.9); p<0.01), day 30 (54.5 (37.6); p<0.01), and day 60 (60.8 (37.3); p<0.01) whereas placebo did not. Overall, the reduction in fatigue was significantly higher with ondansetron compared with placebo (ANOVA for repeated measurements) for the whole follow up period (p = 0.03) or for the treatment period only (p = 0.04). Ondansetron also significantly reduced depression scores. CONCLUSIONS: The 5-hydroxytryptamine receptor type 3 antagonist ondansetron had a significant positive effect on fatigue in CHC. These observations support the concept that fatigue involves serotoninergic pathways and may encourage further evaluations of the efficacy of ondansetron on fatigue in chronic liver diseases.     

Serum Hepatitis C Virus RNA Levels and Liver Injury in Volunteer Blood Donors

Objectives: Liver histology in volunteer blood donors positive for serum hepatitis C virus RNA was investigated in relation to hepatitis C virus viremia levels. Methods: Twenty-one volunteer blood donors positive for serum hepatitis C virus RNA by polymerase chain reaction were monitored for at least 1 yr by monthly routine liver function tests and underwent liver biopsy. Liver histology findings were correlated with hepatitis C virus viremia levels assessed hy a quantitative branched DNA assay. Results: Liver histology showed the features of chronic hepatitis in 20 (95%) patients. Only one of the seven patients with persistently normal aminotransfer-ase levels during follow-up had normal liver histology, and the others had chronic hepatitis. Sera ohtained the same day of the liver biopsy were shown to contain hepatitis C virus RNA of 10^5.7–10^7.6 equivalent/ml (median 10^6.7). The total histological activity index score (median 2, range 0–15) and the scores of portal inflammation (median 1, range 0–3), lobular inflammation (median 1, range 0–4) and piecemeal necrosis (median 0, range 0–5) correlated with viremia levels ( r = 0.64, p < 0.01; r = 0.60, p < 0.01; r = 0.48, p < 0.05; and r = 0.49, p < 0.05, respectively). Conclusions: These findings suggest that chronic hepatitis is frequently caused by hepatitis C virus infection irrespective of the serum amino-transferase levels, and high level hepatitis C virus replication is a contributory cause for liver injury in volunteer blood donor populations.     

Aspartate aminotransferase to platelet ratio index in patients with alcoholic liver fibrosis

OBJECTIVE: Aspartate aminotransferase (AST) to platelet ratio index (APRI) has been proposed as an easily determined and accurate noninvasive marker of liver fibrosis in chronic hepatitis C. To validate APRI in hepatitis C and to determine its usefulness in other liver diseases, we evaluated APRI in patients with liver fibrosis due to excessive alcohol consumption with or without viral hepatitis C. METHODS: A total of 1,308 subjects from two VA cooperative studies of alcoholic liver disease were evaluated. Liver biopsy was available from 781 noncirrhotic patients while a history of decompensation was present in 527. Alcohol intake was determined by self-report. Hepatitis C was confirmed by PCR. RESULTS: Ninety-eight percent were men with a mean age of 51.5 yr. Alcohol intake averaged 19 drinks/day for 20.6 yr. One hundred thirty-three (10.2%) were hepatitis C positive. In the HCV-positive subgroup, APRI had a sensitivity of 35.6% and a specificity of 29.7% for significant fibrosis. Of 64 patients classified as significant fibrosis, 21 (32.8%) were incorrectly classified. In the 507 HCV negative patients with biopsy confirmed fibrosis, the sensitivity of APRI for significant fibrosis was 13.2% and the specificity was 77.6%. Twenty percent were classified incorrectly. CONCLUSION: APRI has low sensitivity and specificity for the diagnosis of significant fibrosis in patients with alcoholic liver disease, including patients who have hepatitis C. Given the frequent history of alcohol use in patients with hepatitis C, APRI may be of limited usefulness in the diagnosis of fibrosis in many patients.     

Detection of male DNA in the liver of female patients with primary biliary cirrhosis

BACKGROUND/AIMS: Primary biliary cirrhosis is a chronic cholestatic liver disease characterized by progressive inflammatory destruction of bile ducts, with eventual hepatic fibrosis and cirrhosis. Since primary biliary cirrhosis affects predominantly middle-aged women and has pathological similarities to hepatic graft-versus-host-disease, we investigated whether fetal cell microchimerism might be involved in the development of this disease. METHODS: The presence of Y-chromosome-specific sequences was analyzed by polymerase chain reaction using peripheral blood mononuclear cells from women with primary biliary cirrhosis (n=18) and healthy (control) women (n=18), and by in situ hybridization of liver biopsy sections from women with primary biliary cirrhosis (n=19) and women with chronic hepatitis C or alcoholic liver disease (n=20). RESULTS: Male cells were detected in liver biopsy specimens of 8 of 19 patients (42%) with primary biliary cirrhosis. Y-chromosome-containing cells were not seen in any of the liver biopsy specimens from women with chronic hepatitis C or alcoholic liver disease. Male cells were detected in peripheral blood mononuclear cells from one healthy control at a level of 1 male cell per 10(6) female cells, but were not detected in peripheral blood mononuclear cells of women with primary biliary cirrhosis. CONCLUSIONS: The presence of male cells in the liver of women with primary biliary cirrhosis raises the possibility that fetal cell microchimerism may be involved in the pathogenesis of this chronic liver disease.