Signs Of Liver Cirrhosis Research Articles

Upper Gastrointestinal Endoscopic Findings and Their Clinical Correlates in Patients With Liver Cirrhosis in Northern Ghana.

Background and study aim Liver cirrhosis causes portal hypertension that leads to dysfunction of the gastrointestinal tract, which may result in complications including upper gastrointestinal (UGI) bleeding. This study sought to determine the prevalence and the clinical correlates of these UGI abnormalities in patients with liver cirrhosis receiving care at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. Patients and methods One hundred and forty-five participants with liver cirrhosis were consecutively sampled and clinically evaluated for symptoms and signs of liver cirrhosis and then underwent esophagogastroduodenoscopy (EGD). Results The mean age of the respondents was 46.50 ± 12.14 years, with the majority being males (106, 73.10%) and in Child-Pugh class C (111, 76.55%). Fatigue (128, 88.28%) and ascites (127, 87.59%) were the most common symptoms and signs, respectively. Fatigue, itch, and ascites were significantly correlated with the severity of liver cirrhosis, with an adjusted odd ratio (AOR) (confidence interval (CI)) of 3.56 (1.11-11.47), p-value of 0.03, 4.35 (1.34-14.18), p-value of 0.02 and 22.50 (4.88-103.77), p-value < 0.01, respectively. Esophageal varices were the most common UGI endoscopic findings, occurring in 102 (70.34%) patients, and correlated with the severity of liver cirrhosis, AOR (CI) of 5.19 (1.70-15.87), p-value of 0.01. Other common findings included gastritis in 71 (48.97%), portal hypertensive gastropathy in 67 (46.2%), duodenitis in 49 (33.79%), and peptic ulcer in 46 (31.72%). Conclusions Fatigue, ascites, and esophageal varices were the most common symptoms, signs, and EGD findings, respectively. Fatigue, itch, ascites, esophageal varices, duodenitis, and gastric antral vascular ectasia correlate with the severity of liver cirrhosis.

Epidemiological and Clinical Aspects of Simple Steatosis and Non-Alcoholic Steato- Hepatitis Among Newly Diagnosed Type 2 Diabetes Patients at The Central Hospital in Yaoundé, Cameroon

Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic comorbidities like type 2 diabetes mellitus (T2DM). The aim of this study was to determine the proportion of simple steatosis and non-alcoholic steatohepatitis, which are components of NAFLD, among newly diagnosed T2DM patients. This cross-sectional study was undertaken at the Central Hospital, Cameroon from March 2020 to September 2020 and it included all recently diagnosed T2DM patients, who had an alcohol consumption &lt;140g (14 drinks/week) for women and &lt;210g (21 drinks/week) for men, and without any signs of liver cirrhosis on abdominal ultrasound. All patients underwent a clinical examination with blood samples taken for lipid profile and transaminases measurements and an abdominal ultrasound assessment using a LOGIQ V5 Expert ultrasound machine. A total of 98 (53 males and 45 females) out of 128 eligible patients consented to participate in the study. The mean age was 50.31±10.51. NAFLD was present in 56.1% (55/98) patients; with mild and homogeneously diffused in 92.7% (51/55) and 94.5% (52/55) respectively. There were no significant differences in lipids profiles and transaminases between those with or without steatosis. Factors associated with fatty liver disease were body mass index ≥ 30 kg / m2 (P = 0.0002), waist circumference ≥ 94 cm for men or ≥ 80cm for women (P = 0.004). In conclusion, NAFLD is a common feature in newly diagnosed T2DM in our setting. There is a need for more attention towards NAFLD by primary care physicians, specialists and health policy makers

Wilson-Konovalov disease in a patient after COVID-19 infection

We present a rare clinical case of Wilson-C onovalov disease in a patient after a new coronavirus infection. The development of her neurological symptoms, which allowed to specify the etiology of the already existing liver damage, may have been provoked by the COVID-19 infection, in which the central nervous system is frequently involved in the pathological process. Wilson-C onovalov disease was suspected due to the presence of neurological manifestations and signs of liver cirrhosis. Subsequently, the diagnosis was confi rmed genetically, copper metabolism disorders were identifi ed and pathogenetic therapy was prescribed to eliminate excess copper from the body.

Grazing Ecology of Sheep and Its Impact on Vegetation and Animal Health on Pastures Dominated by Common Ragwort (Senecio jacobaea L.)—Part 2: Animal Health

Simple SummaryCommon ragwort (Senecio jacobaea L.) contains potentially toxic pyrrolizidine alkaloids (PA). Occurring on sites of roughage production, it contaminates the harvest. Regardless of fresh or dried intake, ragwort may result in fatal liver cirrhosis in livestock animals. Controlling ragwort, especially without biocides in nature conservation areas, is difficult. Since sheep seemed more resistant to PA in experiments, we tested how this animal species copes with ragwort under field and free-choice conditions. On a ragwort-rich pasture with a stocking density of 12 sheep/hectare, animals grazed for six months over two grazing seasons. From 70 sheep in the beginning, seven were slaughtered every six weeks for analysis of liver parameters, including seven control animals in the beginning of each grazing season. We addressed two questions: (1) To what extent do sheep voluntarily ingest ragwort on contaminated pastures? (2) Which impact on animal health does this grazing behavior have? Sheep ingested large amounts of ragwort, exceeding the assumed lethal dose established under experimental conditions by up to 200%. Behavior, body condition, and liver enzymes mainly remained unchanged. From the point of view of animal health and nature conservation, sheep grazing might be an option to reduce the amount of ragwort on pastures.Common ragwort (Senecio jacobaea L.) naturally occurs on species-rich grasslands. Containing pyrrolizidine alkaloids (PA), it endangers livestock health through contaminated feed. Although in vitro studies showed a detoxification capacity of PA in sheep, few field data are available on the ability of grazing sheep to cope with ragwort. During two grazing seasons on a ragwort-rich pasture, we studied: (1) To what extent do sheep voluntarily ingest ragwort and (2) What impact their grazing behavior has on animal health. Ragwort intake was monitored by counting missing plant parts and calculating their weight. From 70 sheep, seven were slaughtered at the beginning and in six-week intervals at the end of each grazing period to monitor blood parameters and liver tissue. Sheep continuously preferred ragwort. The daily intake was above the currently assumed lethal dose, varying between 0.2–4.9 kg per sheep. Clinical, hematologic, and blood biochemistry parameters mostly remained within the reference limits. Initially elevated liver copper content declined over time. The liver of all 70 animals displayed slight to moderate hepatitis, fibrosis, and proliferation of the bile ducts, but no morphological signs of liver cirrhosis. Sheep preferred and tolerated ragwort, making their grazing an option to control ragwort from both an animal health and nature conservation perspective.

A relation between T cell phenotypic profile and virus genotype in patients with chronic viral hepatitis (before and after treatment with direct antiviral agents)

The aim of the study was to investigate the phenotype of effector T lymphocytes in patients with chronic viral hepatitis C (CVHC) before and after of treatment with direct antiviral drugs depending on the genotype of the virus. 50 patients with CVHC without signs of liver cirrhosis were examined. The diagnosis was made on the basis of epidemiological and clinical laboratory data as recommended by the European Association for the Study of the Liver when specific serological markers of CHCV and RNA of hepatitis C virus (HCV) were detected (EASL, 2016). The determination of HCV RNA was carried out by the method of quantitative polymerase chain reaction in real time. The degree of liver fibrosis in patients with CVHC was assessed using ultrasound elastography. Patients were treated for 3 months with direct antiviral drugs according to the recommendations of the European Association for the Study of the Liver (2016). The control group included 46 practically healthy individuals with severe chronic diseases of various organs and systems excluded during a routine examination, no health complaints, having normal clinical and biochemical blood tests in the absence of markers for viral hepatitis B and C, antibodies to opisthorchis and denying history of alcohol abuse. The study of the subpopulation composition of helper and cytotoxic T lymphocytes was carried out by direct immunofluorescence of whole peripheral blood. We obtained a 100% sustained virological response in patients with 1, 2 and genotypes of CHCV without signs of liver cirrhosis when using therapy with Sofosbuvir (400 mg) and Daclatasvir (60 mg) for 12 weeks. It was found that in CVHC patients were found characteristic features in the phenotypic composition of effector T lymphocytes before and after treatment with direct antiviral drugs in depending on the genotype of HCV. Patients with HCV genotypes 1 and 3 had an increase in the content of terminal differentiated effector (TEMRA) T helpers and effector memory (EM). Only patients with HCV genotype 2 had a decrease in the level of EM T-helper cells in the blood. A decrease in the relative number of T helpers of central memory (СM) was independent of the HCV genotype. The level of effector subpopulations of cytotoxic T lymphocytes in patients with CVHC was consistent with or exceeded control levels in depending on the genotype of HCV. The level of all investigated subpopulations of effector cytotoxic T lymphocytes in patients with HCV genotype 1 was equal to the control values. The number of naïve cytotoxic T cells and CM in peripheral blood in patients with HCV genotype 2 was increased. The content of naïve cytotoxic T lymphocytes, CM and TEMRA in patients with genotype 3 HCV in the blood was increased. The highest viral load was detected in patients with CVHC with genotype 1 HCV. Liver fibrosis was most pronounced in patients with CVHC infection with HCV genotypes 2 and 3. After 3 months of treatment with direct antiviral drugs the patients with CVHC had a reduced content of CM T helpers regardless of the HCV genotype. In addition, patients with HCV genotypes 1 and 3 had a decrease in the number of naïve T helpers and patients with HCV genotypes 2 and 3 had a normalization of the content of naïve cytotoxic T lymphocytes.

Multiparametric Ultrasound in the Diagnosis of Hepatocellular Carcinoma in Patients without Cirrhosis (Clinical Case)

Purpose: To demonstrate the capabilities of a complex of multiparametric ultrasound and MRI with intravenous contrast in the detection and characterization of atypical hepatocellular carcinoma with the example of a clinical case of a middle-aged patient without liver cirrhosis.Material and methods: Comprehensive study of medical history, outpatient records, results of clinical, laboratory, instrumental and morphological methods with independent retrospective analysis of the histological preparation of focal liver lesion.Results: Diagnostic search data are presented in a 48-year-old patient with hepatocellular carcinoma without signs of liver cirrhosis. The diagnosis required 1.5 months of examination in gastroenterological department, repeated review of the histological preparation by morphologists. The disease debuted with weakness after physical exertion, which was noted during a planned multiparameter abdomen ultrasound examination. During the study, multiple focal formations with uneven fuzzy contours, an inhomogeneous structure were visualized. Stiffness of the parenchyma in focal liver lesion is 108.29 kPa due to 2D-SWE. Further tactics consisted of hospitalization with further laboratory examination and abdomen MRI with intravenous contrast enhancement. Considering the results of instrumental examination, the patient was prescribed a puncture aspiration biopsy of focal liver lesion under ultrasound control followed by morphological verification.Conclusion: The presented clinical observation demonstrates the need of use an integrated approach in instrumental imaging methods in the diagnosis of atypical hepatocellular carcinoma.

Hepatopulmonary Syndrome in a Thirteen Year Old Boy: A Case Report

Hepatopulmonary syndrome (HPS) is a late complication associated with liver cirrhosis. Recent studies have suggested that it can also occur in non-cirrhotic portal hypertension. The criteria that need to be met for making the diagnosis of HPS include chronic liver disease, impaired gaseous exchange leading to hypoxemia and intrapulmonary vascular dilation. The pathophysiology of this disease includes mediators like nitric oxide (NO), and endothelial growth factors which play an important role in intrapulmonary dilation of vessels. This, in turn, leads to ventilation-perfusion mismatch which is the main etiology of pulmonary symptoms associated with this syndrome. The classical symptoms include dyspnea, orthodeoxia and platypnea. Contrast echocardiography has emerged to be a very sensitive test for its diagnosis. The timing of appearance of microbubbles help to differentiate between intracardiac and intrapulmonary shunting, with the latter being the hallmark of HPS. The only curative treatment available is liver transplantation. Here we present a case of a 13-year-old patient who presented in Nishtar hospital in Multan, Pakistan. He initially presented with signs of liver cirrhosis but no definite cause could be found. The patient didn’t come for a follow-up after that. Now he presented with signs of HPS and acute decompensated liver disease. HPS was confirmed on contrast echocardiography. This is a rare presentation of HPS in this age group.

Correlation of polymorphous variants (ApaI, TagI, BsmI) of the VDR receptor gene with the vitamin D level and liver fibrosis in children with autoimmune hepatitis

The aim. To study the correlation of the frequency distribution of alleles, genotypes and their combinations for the allelic variants of ApaI, TagI, BsmI of the Vitamin D receptor gene (VDR) with the vitamin D levels and the stage of fibrosis in children with autoimmune hepatitis.Materials and methods. 51 children with autoimmune hepatitis were examined between 2016 and 2018. In all children, the diagnosis was confirmed in accordance with the International Guidelines for the study of liver diseases (European Association for the Study of Liver (EASL) Clinical Practice Guidelines: Autoimmune Hepatitis, 2015). In the examined children, the elastography of the liver parenchyma was performed by the shear wave method. Needle biopsy of the liver with histological examination of the specimens was performed in 42 children. The disease activity was determined using the histological activity index (HAI) by Knodell based on the results of a morphological study of the liver biopsy and biochemical parameters. The stage of the disease was evaluated by the histological index of fibrosis using the METAVIR scoring system and semi-quantitatively using the share wave elastography of liver parenchyma. A level of 25(OH)D was determined in the blood serum. The determination of the ApaI, TagI, BsmI polymorphic loci of vitamin D receptor (VDR) was carried out using the molecular-genetic method. The association of polymorphic variants of the VDR gene with the level of vitamin D and the stage of liver fibrosis in children with autoimmune hepatitis has been evaluated.Results. 72.0 % of the examined children had advanced severe liver fibrosis (F3-4 by the METAVIR score), among them 34.0 % of children had signs of liver cirrhosis. Children with advanced severe fibrosis (F3–4 by the METAVIR score) had the CC genotype of the polymorphic version of the TagI of the VDR gene significantly more often (χ2 = 3.953; P &lt; 0.05), and the genotype AA/CC/AA according to the investigated allelic variants of the VDR gene (χ2 = 3.953; P &lt; 0.05). In 72.5 % of the examined children, there was a deficiency of vitamin D. In children with severe fibrosis (F3–4 by the METAVIR score) vitamin D deficiency was significantly more frequent as compared to children with less severe fibrosis (F1–2 by the METAVIR score) (χ2 = 5,207; P = 0.023). The genotype GA of the BsmI polymorphic variant was associated with a decrease in serum vitamin D levels (P &lt; 0.05). At the AC/TC/GA combination of the ApaI, TagI and BsmI allelic variants of the VDR gene, vitamin D deficiency was registered significantly more frequently (P &lt; 0.05).Conclusions. The level of vitamin D in children with autoimmune hepatitis was dependent on the stage of fibrosis. Children with severe fibrosis had a genetically determined vitamin D deficiency significantly more often. Vitamin D deficiency was associated with the CC genotype presence of the TagI polymorphic variant of the VDR gene in patients as well as the GA genotype of the BsmI polymorphic variant and the AC/TC/GA genotype of the three allelic variants of the gene studied.

Ultrasonic evaluation of the hepatic parenchyma in the end-stage cirrhosis in children with rare metabolic diseases

There were examined 209 children, agedfrom 3 months to 18years with metabolic liver diseases (MLD) of various etiology. The diagnosis of MLD was based on data of totality of clinical laboratory indices and data of molecular genetic studies. By means of ultrasonic (US) methods there was performed an evaluation both of the structure of the liver parenchyma and the grade of the pronouncement offibrosis with the use of traditional US method and non-invasive method for the quantitative assessment of the structure of liver parenchyma Acoustic Structure Quantification (ASQ) with the determination of density index (DI). At that US data were compared with morphological observations. According to data of the traditional US examination the signs of liver cirrhosis were of the «streaking» of the hepatic image, cirrhotic nodes and signs of portal hypertension. According to ASQ data in the end-stage cirrhosis DI was in the range of from 2.77 to 4.58 in dependence on etiologic factor: in glycogen storage disease in the average accounted of 2.88, in patients with Wilson disease -3.08, in hereditary tyrosinemia type 1 (HT-1) - 3.37, in cystic fibrosis patients - 3.89 and in congenitalfibrosis - 4.18. Comparative analysis of US and morphological data showed the expediency of complex non-invasive US observations in the assessment of the pronouncement of the stage of liver fibrosis in MLD children.

Idiopathic portal hypertension with regard to thiopurine treatment.

Idiopathic portal hypertension (IPH) is an infrequent adverse reaction to the use of thiopurines that tends to be overlooked. Herein, we present a patient with ileocolic Crohn's disease treated with azathioprine who presented ascites, esophageal varices and splenomegaly without any signs of liver cirrhosis. A portal hemodynamics study revealed a normal portosystemic gradient compatible with presinusoidal portal hypertension. Finally, IPH was diagnosed after a liver biopsy. IPH secondary to thiopurines is due to a 6-thioguanine nucleotide (6-TGN)-dependent reaction and occurs predominantly between three months and three years after the start of treatment. The onset is usually insidious and thrombocytopenia is the first manifestation. The definitive diagnosis is obtained by liver biopsy.

Non-communicable diseases at a regional hospital in Nepal: Findings of a high burden of alcohol-related disease.

Recent global burden of disease reports find that a major proportion of global deaths and disability worldwide can be attributed to alcohol use. Thus, it may be surprising that very few studies have reported on the burden of alcohol-related disease in low income settings. The evidence of non-communicable disease (NCD) burden in Nepal was recently reviewed and concluded that data is still lacking, particularly to describe the burden of alcohol-related diseases (ARDs). Therefore, here we report on NCD burden and specifically ARDs, in hospitalized patients at a regional hospital in Nepal. We conducted a retrospective chart-review that included detailed information on all discharged patients during a four month period. A local database that included sociodemographic information and diagnoses at discharge was established. All doctor-assigned discharge diagnoses were retrospectively assigned ICD-10 codes. A total of 1,139 hospitalized adult patients were included in the study and one third of these were NCDs (n=332). The main NCDs were chronic obstructive pulmonary disease (COPD) (n=148, 45%) and ARDs (n=57, 17%). Patients with ARD often presented with signs of liver cirrhosis and were typically younger men, with a median age at 43 years, from specific ethnic groups. These data demonstrate that severe alcohol-related organ failure in relatively young men contributed to a high proportion of NCDs in a regional hospital in Nepal. These findings are novel and alarming and warrant further studies that can establish the burden of ARDs and alcohol use in Nepal and other similar low-income countries.

Correlation between patatin-like phospholipase domain-containing protein 3 gene polymorphisms and liver cirrhosis in a chinese han population with chronic hepatitis B.

Background:A single nucleotide polymorphism (SNP) of patatin-like phospholipase domain-containing 3 (PNPLA3) genes (rs738409) is associated with the severity of fibrosis and cirrhosis in patients with fatty liver disease. However, in a small group of Italian patients, there was no significant correlation between the rs738409 SNP and hepatitis B virus (HBV) infection-associated liver cirrhosis.Objectives:This study aimed to investigate whether PNPLA3 polymorphisms are a risk factor for liver cirrhosis in a Chinese Han population with chronic hepatitis B (CHB).Patients and Methods:The study population consisted of 344 Chinese Han patients with CHB, among which 203 presented with liver cirrhosis (LC group) and 141 had no sign of liver cirrhosis (CHB group). TaqMan genotyping assay was used to investigate the association of two PNPLA3 SNPs (rs738409 and rs2281135) with the risk of liver cirrhosis.Results:The allele and genotype distributions of PNPLA3 rs738409 and rs2281135 were not significantly different between the CHB and LC groups. After segregation on the basis of sex, no significant correlation between PNPLA3 (rs738409 and rs2281135) genotypes/alleles and liver cirrhosis was detected. Moreover, none of the haplotypes in PNPLA3 (rs738409 and rs2281135) was found to be statistically different between the two groups.Conclusions:Our results showed no association between PNPLA3 polymorphisms (rs738409 and rs2281135) and the susceptibility to HBV-related liver cirrhosis in a Chinese Han population.

Estudio del paciente con sospecha de Osteoporosis

Introduction: Spider naevi are traditionally considered a sign of liver cirrhosis, particularly in patients with alcoholism. However, systematic evaluation of their diagnostic value in alcoholic patients has been scarcely performed. The aim of this study was to determine the diagnostic accuracy of the presence of spider neavi for liver disease detection in alcoholics using percutaneous liver biopsy as the reference standard. Methods: Cross-sectional study of 229 alcoholics admitted to the hospital (67% males) undergoing percutaneous liver biopsy. Results: Spiders were least prevalent in patients with fatty liver (4/104 cases, 4%). The prevalence of spiders was greater in patients with alcoholic hepatitis (15/80, 19%) than in patients with fatty liver (P=0.002). Prevalence was even higher in patients with cirrhosis (6/21, 29%, P<0.001), and was highest in patients with cirrhosis and superimposed alcoholic hepatitis (11/24, 46%, P<0.001). The presence of spiders had a sensitivity of 25% (95% CI 18-34%), a specificity of 95% (95% CI 90-99%), and a positive likelihood ratio of 6.6 (95% CI 2.4-18.2) for the diagnosis of severe underlying liver disease (alcoholic hepatitis, liver cirrhosis, or both). The presence of spiders was associated with biological markers of liver dysfunction and with additional cutaneous stigmata (facial telangiectasia and palmar erythema). Conclusion: The presence of spiders in an alcoholic patient strongly indicates the presence of severe underlying liver disease (liver cirrhosis and/or alcoholic hepatitis).

Laparoscopic findings of congenital hepatic fibrosis: A case report and review of the published work

A 33-year-old man visited a hospital after vomiting blood. Emergent esophagogastroduodenoscopy revealed the presence of varices in the lower esophagus. The patient did not have a past history of alcohol consumption and was negative for hepatitis B and C viruses. He was referred to our hospital for closer examination. Portal hypertension was detected by conventional imaging modalities, but signs of liver cirrhosis, thrombosis, stenosis, malformation of the portal vein and bile duct abnormalities were not observed. We performed laparoscopy-guided liver biopsy to examine the cause of portal hypertension. In addition to prominent development of collateral vessels on hepatic ligaments and the omenta, marbled whitish markings with black-green spots were dispersed over the liver surface, but nodular formation and lymphatic vesicles were not found. Biopsied specimen demonstrated severe dense fibrosis in portal areas and von Meyenburg complexes (vMC). Based on these findings, the diagnosis of congenital hepatic fibrosis (CHF) was made. Post-biopsy hemostasis was confirmed under laparoscopy and no major complications occurred after biopsy. We reviewed 11 cases of CHF which had undergone laparoscopy in Japan, including our case. Marbled whitish markings, black-green spots and collateral vessels were seen in 11, five and seven cases, respectively. When we encounter the patients having portal hypertension of unknown etiology, laparoscopy-guided liver biopsy should be considered as a safe and useful diagnostic procedure. Black-green spots in marbled whitish markings, which reflect vMC in broad fibrotic areas, are laparoscopic characteristics of CHF.

FATE OF PATIENTS WITH LATE-DETECTED HEPATITIS C INFECTION - CASE REPORTS

Chronic hepatitis C virus infection represents an insidious disease that is often detected with signs of liver cirrhosis or hepatocellular carcinoma. It is practicaly impossible to achieve a significant therapeutic progress in these patients without performing a liver transplantation. However, due to underdeveloped program of organ donations, this kind of intervention, as the last helpful procedure, is often not realized. This study presents three patients (out of 121 treated patients) followed during a two-year period. The patients had been initially registered when the stage of their disease became severe: liver failure with signs of decompensation. Antiviral therapy (pegylated interferon and ribavirin) in these patients have no use, hence only a corrective therapy is administered. Pathohistological findings in two patients revealed hepatocellular carcinoma, and in one case lethal outcome was the result of severe hepatic decompensation, hepatopulmonary and hepatorenal syndromes, as well as developed cardiopulmonary failure. Lethal outcome occurred in the period of 2 to 14 months after the first visit to a doctor. One patient was on the list for liver transplantation; however, surgery was not performed and soon after a fatal outcome ensued. Acta Medica Medianae 2011;50(2):49-52.

Clinical and Virological Improvement of Hepatitis B Virus--Related or Hepatitis C Virus--Related Chronic Hepatitis with Concomitant Hepatitis A Virus Infection

We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). We enrolled 21 patients with acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13 patients who were positive for hepatitis B surface antigen (case B group), 8 patients who were anti-HCV positive (case C group), and 21 patients with acute hepatitis A without a preexisting liver disease (control A group). Two control groups of patients with chronic hepatitis B (control B group) or C (control C group) were also chosen. All control groups were pair-matched by age and sex with the corresponding case group. Fulminant hepatitis A was never observed, and hepatitis A had a severe course in 1 patient in the case B group and in 1 patient in the control A group. Both patients recovered. On admission, HBV DNA was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the control B group; HCV RNA was found in no patient in the case C group and in 16 patients (81.2%) in the control C group. Of 9 patients in the case B group who were followed up for 6 months, 3 became negative for hepatitis B surface antigen and positive for hepatitis B surface antibody, 2 remained positive for hepatitis B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA with a low viral load [corrected] Of 6 patients in the case C group who were followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently low viral loads. Concomitant hepatitis A was always self-limited, associated with a marked inhibition of HBV and HCV genomes, and possibly had a good prognosis for the underlying chronic hepatitis.

Liver cirrhosis as a consequence of iron overload caused by hereditary nonspherocytic hemolytic anemia

Nonspherocytic hereditary anemias are occasionally accompanied by significant iron overload but the significance for the development of chronic liver disease is not clear. We described two cases of patients with chronic liver disease and severe iron overload due to chronic hereditary hemolysis. Both patients have had signs of liver cirrhosis and severe hemolysis since childhood. A hereditary pyruvate kinase deficiency (PKD) was discovered as the underlying reason for the hemolysis. Sequencing of the pyruvate kinase gene showed a mutation within exon 11. Liver histology in both patients revealed cirrhosis and a severe iron overload but primary hemochromatosis was excluded by HFE-gene analysis. An iron reduction therapy with desferrioxamine led to significant decrease of serum ferritin and sustained clinical improvement. PKD-induced hemolysis may cause severe iron overload even in the absence of HFE-genotype abnormalities. This secondary iron overload can lead to chronic liver disease and cirrhosis. Therefore, the iron metabolism of PKD patients has to be closely monitored and iron overload should be consequently treated.

Subacute Liver Necrosis after Experimental Infection with Rabbit Haemorrhagic Disease Virus (RHDV)

Rabbit haemorrhagic disease (RHD) is usually peracute to acute, while subacute to chronic disease is rare. This paper describes gross and histopathological findings in four out of 20 rabbits aged 14 weeks, experimentally infected with one of two German field isolates of RHD virus. Eight rabbits survived the infection for 10 days and were killed after four of them, infected with 100 to 10 000 haemagglutination units, had started to develop progressive jaundice. Histopathologically, icteric livers showed severe subacute centrilobular bridging necrosis with calcification, and proliferation of periportal hepatocytes and bile ducts. Positive-strand RHDV RNA was detected by in-situ hybridization, mainly in periportal macrophages. Loss of the normal hepatic architecture, reparation (fibrosis) and hepatocellular regeneration, together with moderate inflammatory reaction, are signs of liver cirrhosis. These signs, observed in young rabbits given small doses of RHD virus, are interpreted as an unusual outcome of experimental inoculation.

Risk factors of cholestasis in very low-birth-weight infants.

To evaluate the incidence, clinical course, and possible risk factors of cholestasis in very low-birth-weight infants. A retrospective study of 143 very low-birth-weight infants was performed. Cholestasis was defined as direct-reacting bilirubin > 2 mg/dL for more than 14 days. The clinical course of cholestasis was described, and perinatal risk factors were evaluated for associations with the development and severity of cholestasis. Cholestasis was present in 31 infants (21.7%). The mean (SD) age of onset was 30.3(15.3) days after birth or 26.0 (15.6) days after receiving parenteral nutrition, and the mean (SD) duration was 77.1 (33.8) days. In half of the cholestatic infants, bilirubin continued to rise after discontinuing parenteral nutrition. One infant developed signs of liver cirrhosis and died, two infants died with progressive cholestasis, while the other 28 patients recovered. Analysis of risk factors revealed that birthweight and duration of fasting significantly correlated with the development of cholestasis, and that sepsis significantly influenced the severity of cholestasis. Cholestasis is a common complication of extreme prematurity. The clinical course seems benign but long-term sequelae are unknown. Immature liver function and absence of stimuli for intestinal motility and hormonal secretion predispose to decreased bile flow, while sepsis further impairs hepatic ductular secretion and aggravates cholestasis.