[Clinical safety and professional liability claims in Orthopaedic Surgery and Traumatology]. / Seguridad clínica y reclamaciones por responsabilidad profesional en Cirugía Ortopédica y Traumatología.

The specialist in orthopaedic and traumatological surgery, like any other doctor, is subject to the current legal provisions while exercising their profession. Mandatory training in the medical-legal aspects of health care is essential. Claims against doctors are a reality, and orthopaedic and traumatological surgery holds first place in terms of frequency of claims according to the data from the General Council of Official Colleges of Doctors of Catalonia. Professionals must be aware of the fundamental aspects of medical professional liability, as well as specific aspects, such as defensive medicine and clinical safety. The understanding of these medical-legal aspects in the routine clinical practice can help to pave the way towards a satisfactory and safe professional career. The aim of this review is to contribute to this training, for the benefit of professionals and patients.

[Guideline to prevent claims due to medical malpractice, on how to act when they do occur and how to defend oneself through the courts]. / Guía para prevenir las reclamaciones por presunta mala praxis médica, de cómo actuar cuando se producen y cómo defenderse judicialmente.

Claims due to presumed medical malpractice are increasing in all developed countries and many of them have no basis. To prevent legal complaints, the physicians should know the reasons why complaints are made by their patients and adopt the adequate preventive measures. In the case of a complaint, it is essential to follow the guidelines that allow for adequate legal defense and the action of the physician before the judge that inspires confidence and credibility. The risk of the claims can be reduced with adequate information to the patient, the following of the clinical guidelines, control of the risk factors and adoption of verification lists in each invasive procedure. In case of complication or serious adverse effect, explanations should be given to the patient and family and it should be reported to the facility where one works and to the insurance company. If the physician received a claim, he/she should report it to the insurance compare so that it can name a lawyer responsible for the legal defense who will advise the physician regarding the appearance in court before the judge.

Assessment of liver fibrosis before and after antiviral therapy by different serum marker panels in patients with chronic hepatitis C.

BACKGROUND: Liver biopsy is the reference standard to assess liver fibrosis in chronic hepatitis C. AIM: To validate and compare the diagnostic performance of non-invasive tests for prediction of liver fibrosis severity and assessed changes in extracellular matrix markers after antiviral treatment. METHODS: The performances of Forns' score, AST to platelet ratio index (APRI), FIB-4 index and Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent antiviral therapy. These scores were determined 24 weeks after treatment in 161 patients. RESULTS: Forns' score, APRI, FIB-4 and ELF score showed comparable diagnostic accuracies for significant fibrosis [area under the receiver operating characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively]. To identify cirrhosis, FIB-4 index showed a significantly better performance over APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score decreased significantly in patients with sustained virological response (SVR) (P < 0.0001) but remained unchanged in nonresponders. Non-1 hepatitis C virus (HCV) genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol levels were independently associated with SVR. CONCLUSIONS: Simple panel markers and ELF score are accurate at identifying significant fibrosis and cirrhosis in chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects the impact of viral clearance in hepatic extracellular matrix and probably in the improvement of liver fibrosis.

Adverse reactions during transfusion of thawed haematopoietic progenitor cells from apheresis are closely related to the number of granulocyte cells in the leukapheresis product.

BACKGROUND AND OBJECTIVES: The infusion of thawed haematopoietic progenitor cells from apheresis (HPC-A) is associated with minor but frequent adverse reactions (ARs), which has been mainly attributed to dimethyl sulphoxide (DMSO). Nevertheless, other factors may play a role in the pathogenesis of such toxicity. MATERIALS AND METHODS: The ARs on a cohort of 423 cryopreserved HPC-A infusions for 398 patients in HPC transplantation program were analysed. RESULTS: ARs were reported in 105 graft infusions (24·8%) and most of them were graded as mild to moderate. The most frequently reported ARs were gastrointestinal and respiratory, and three patients presented epileptic seizure. The volume of DMSO/kg (P < 0·001), volume of red-blood-cells/kg (P = 0·02), number of nuclear cells (NCs)/kg (P <0·001) and number of granulocytes/kg (P<0·001) in the infused graft were significant in the univariate analysis for the occurrence of ARs. The amount of granulocytes/kg remained significant in the multivariate analysis (P<0·001). The grade of ARs also correlated with the amount of cryopreserved granulocytes. CONCLUSION: The incidence and grade of ARs during infusion of cryopreserved HPC-A are related to the amount of granulocytes in the graft.

Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene.

Wilson disease (WD) is a copper metabolism disorder characterized by hepatic and/or neurological damage. More than 200 mutations in the ATP7B gene causing this autosomal recessive defect have been reported. In certain populations, a high prevalence of particular mutations allows rapid screening and diagnosis of the disease. We identified the ATP7B alterations in Spanish patients with WD. Mutations in the ATP7B gene were analysed in a total of 64 individuals from 40 different WD families by PCR amplification, single-strand conformation polymorphism (SSCP) analysis and sequencing. Twenty-one different ATP7B gene mutations were identified, eight of which were novel. 74% of the disease alleles were characterized among the 40 unrelated probands. We identified a prevalent mutation in our population (Met645Arg), present in 55% of this 40 patients. The frequency of the remaining ATP7B alterations was low. In addition, 17 different polymorphic variants were found. There is remarkable allele heterogeneity in WD in the Spanish population. Nevertheless, SSCP screening for the most frequent mutations in our population is feasible and leads to the detection of about 74% of the mutated chromosomes. Molecular diagnosis of WD is very useful in clinical practice to confirm or support clinical suspicion.

[Hypertransaminasemia greater than 400 U/l in adults seen at a tertiary hospital. Prospective study of etiology]. / Hipertransaminasemia superior a 400 U/l en adultos atendidos en un hospital terciario. Estudio prospectivo de su etiología.

AIM: To investigate the frequency of distinct causes of elevated transaminase levels in the range of acute viral hepatitides in patients attended in a hospital. PATIENTS AND METHOD: Patients attended in a tertiary hospital over a 3-month period who had elevation of transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) above 400 U/l were identified and their medical records were reviewed to determine etiology. RESULTS: A total of 106 patients were studied, of which 22 had undergone liver transplantation. In these patients, the causes of hypertransaminasemia were ischemic/reperfusion injury in 6 (27%), ischemic hepatitis in 4 (18%), acute hepatitis in 2 (9%), cellular rejection in 3 (14%), chronic hepatitis C in 4 (18%) and cholestasis in 3 (14%). In the 84 patients who did not undergo transplantation, the causes were hepatic ischemia in 24 (28%), chronic viral hepatitis in 19 (22%), toxic hepatitis in 12 (14%), pancreatico-biliary disease in 11 (13%), acute viral or bacterial hepatitis in 10 (12%), liver tumor in 3 (4%), cholestasis of pregnancy in one and unknown in 4 (5%). Ischemic lesions and pancreatico-biliary disease were more frequent in hospitalized patients while acute and chronic hepatitides were more frequent in outpatients. The worst outcomes were found in ischemic lesions and pancreatico-biliary disease. CONCLUSION: Marked elevation of transaminase levels has multiple causes. Acute viral hepatitides were a relatively infrequent cause. In transplant recipients, the most frequent causes were ischemia/reperfusion injury, while in non-transplanted patients the most frequent causes were ischemic hepatitides and acute episodes of chronic viral hepatitides. The AST/ALT ratio did not contribute to etiologic diagnosis.

Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary-care center.

BACKGROUND/AIMS: The natural history of chronic hepatitis C (HCV) is not completely understood. This study was aimed to evaluate the long-term outcome of the disease over a prolonged period of time and to identify factors associated with progression. METHODS: One hundred and sixteen patients with non-cirrhotic chronic non-A, non-B hepatitis consecutively diagnosed at a tertiary hospital between 1971 and 1977 were followed until December 1998 or until death. Patients with significant alcohol intake were excluded from the study. Variables obtained at the time of diagnosis, including epidemiological, clinical, laboratory, and histological data were recorded to determine risk factors associated with the development of liver cirrhosis and hepatic decompensation. RESULTS: Based on complete follow-up data, the development of liver cirrhosis and hepatic decompensation was evaluated in 94 and 114 of the 116 patients, respectively. Thirty-seven (39.3%) of 94 patients developed liver cirrhosis; an aspartate aminotransferase (AST) value higher than 70 IU/L was associated with development of cirrhosis (odds ratio (OR) 4.22, 95% CI 1.3-13.8). Hepatic decompensation occurred in 12 (10.5%) of 114 patients, its cumulative probability being 2.8% at 10 years, 5.2% at 15 years and 19.8% at 20 years. The only factor independently associated to the development of hepatic decompensation was the presence of fibrosis (stage 2 or 3) in the initial liver biopsy (OR 4.1, IC 95% 1.22-13.9). Liver-related death occurred only in seven (6%) of 114 patients. In comparison with the 116 patients diagnosed in the 1970's, patients with chronic hepatitis C diagnosed in 1999 were younger, more often asymptomatic, had lower AST and alanine aminotransferase (ALT) values and had significantly lower grade and stage histological scores. CONCLUSIONS: In summary, chronic hepatitis C had a high rate of progression to liver cirrhosis over a prolonged follow-up. However, this might be related to the fact that two decades ago the diagnosis was made at a significantly more advanced stage of the disease. Patients at high risk of progression can be identified by biochemical and histological variables at the time of diagnosis.

Hepatic familial amyloidosis caused by a new mutation in the apolipoprotein AI gene: clinical and pathological features.

OBJECTIVE: Recently, we reported a nondescribed deletion/insertion mutation in the apolipoprotein AI gene as the cause of hereditary amyloidosis with hepatic presentation. We describe the clinical and pathological features of this type of amyloidosis in one affected family. METHODS: Demographic, clinical, and biochemical data were obtained from 33 members of the family in whom the apolipoprotein AI gene was studied. Diagnosis was based on the detection of the apolipoprotein AI gene mutation, scintigraphy using radioionated serum amyloid P component, and histological and immunohistochemical studies. RESULTS: Eight members with the mutation had hepatic involvement. Six patients were practically asymptomatic, presented with an elevation of alkaline phosphatase and gamma-glutamyl transpeptidase, and remained stable during follow-up (7.6 +/- 4.9 yr). One patient had jaundice, developed ascites and encephalopathy, and died of hepatorenal syndrome a few months after diagnosis. Jaundice and portal hypertension appeared in the remaining patient, who died 4 yr later. CONCLUSION: This form of familial amyloidosis is characterized by elevation in serum alkaline phosphatase and gamma-glutamyl transpeptidase secondary to amyloid deposits in the portal tracts. Patients remain stable and asymptomatic for many years, but portal hypertension and liver failure can develop later in life and lead to death. Thus, patients should be observed regularly and liver transplantation should be indicated when progression is detected.

Complete characterization of the 3' region of the human and mouse hereditary hemochromatosis HFE gene and detection of novel splicing forms.

The human HFE gene was identified in 1996 as the gene whose mutations are responsible for hereditary hemochromatosis in most patients. Expression analysis by Northern blot indicated that the gene was approximately 4.1 kb in length. However, the cDNA reported was only 2716 bp. These results implied that at least 1.4 kb of the mRNA remained to be identified. In the present study, we detected several 3' EST clones while screening the genomic region of the gene in search of potential additional HFE mRNA sequences. Subsequent sequencing of these EST clones and RT-PCR experiments revealed that exon 7 of the HFE gene has, in fact, a length of 1944 bp and it presents two polyadenylation signals. The new human HFE exon 7 region has been screened in non-C282Y HH patients in search for new putative mutations. Mouse 3' RACE experiments also further extend the previously reported mouse HFE exon 6 sequence. Additionally, we report two novel end forms of the human HFE gene detected by 3' RACE experiments and several novel splicing forms identified in the HepG2 cell line.

[Hepatocellular carcinoma in a patient with hereditary hemochromatosis without cirrhosis]. / Carcinoma hepatocelular en una paciente afectada de hemocromatosis hereditaria sin cirrosis.

Hepatocellular carcinoma in patients with hereditary hemochromatosis in the cirrhotic phase is one of the complications causing greatest mortality and may present in spite of removal of excess iron by bloodletting. Hepatocellular carcinoma is usually considered to occur in cirrhotic livers and consequently measures for the early diagnosis of this complication are only recommended in this type of patient. We present the case of a 69-year-old female patient with non-cirrhotic hemochromatosis who, 6 years after undergoing successful treatment, developed hepatocellular carcinoma. This observation should be added to the 12 cases published in the literature. Criteria should be established for the early diagnosis of hepatocellular carcinoma in patients with hereditary hemochromatosis, irrespective of whether they have cirrhosis.

Assessment of genotype and molecular evolution of hepatitis C virus in formalin-fixed paraffin-embedded liver tissue from patients with chronic hepatitis C virus infection.

Drawbacks of hepatitis C virus (HCV) RNA detection in paraffin-embedded liver tissue have satisfactorily been solved by RT-PCR amplification of the 5'non-coding region (5'NCR). However, detection of this highly conserved region does not provide information on epidemiological or pathogenetic aspects of HCV infection. This study explores whether other functionally important genetic regions of HCV, such as the hypervariable region 1 (HVR-1) and the interferon sensitivity-determining region (ISDR), can be retrieved from paraffin-embedded liver specimens by RT-PCR, and whether the amplified material is suitable for further molecular analyses. RT-PCR amplification of 5'NCR, HVR-1, and ISDR was assessed in RNA extracted from 50 formalin-fixed, paraffin-embedded liver specimens, including 23 needle liver biopsies (11 from patients with non-A, non-B chronic hepatitis diagnosed between 1971 and 1985, 8 from subjects with normal liver histology and 4 from sequential biopsies from a patient with HCV recurrence after liver transplantation), and 27 liver explants from patients undergoing transplantation between 1988 and 1996 (16 with HCV-related cirrhosis and 11 with other disorders). The 5'NCR was successfully amplified in 8 of 11 (73%) non-A, non-B chronic hepatitis biopsies and in all of the specimens from patients with serological documentation of HCV infection. There were no false-positive results. HCV genotype was identified by RFLP analysis of the 5'NCR in the 13 cases analyzed. HVR-1 and ISDR were amplified in 24 of 28 (86%) samples, which were positive for the 5'NCR. Efficient amplification was inversely related to the time of storage. The evolutionary changes of HVR-1 and ISDR were successfully analyzed by direct sequencing of amplificates from the explanted liver and from the sequential liver biopsies in a patient with HCV infection recurrence after transplantation. These observations indicate that paraffin-embedded liver tissue, even when stored for more than 20 years, is appropriate for advanced studies on the molecular biology of HCV.

[Autoimmune hepatitis associated with thyroiditis and hypophysitis. A case report]. / Hepatitis autoinmune asociada a tiroiditis e hipofisitis. Presentación de un caso.

Autoimmune hepatitis primarily affects women and 40% of cases are associated with extrahepatic autoimmune dysfunction. Thyroiditis, ulcerative colitis and rheumatoid arthritis are the most commonly implicated entities. We present a 46-year-old woman with type-II autoimmune hepatitis and Graves disease who presented deterioration in level of consciousness, her symptoms mimicking severe liver failure. Hormone studies and nuclear magnetic resonance imaging revealed hypophysitis, which led to hypothyroidism and metabolic encephalopathy. The syndrome was resolved with hormone replacement therapy.

Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver.

BACKGROUND/AIM: The aim of this study was to assess the efficacy of ursodeoxycholic acid (UDCA) for primary biliary cirrhosis in a randomized, double-blind placebo-controlled trial. METHODS: Consecutive patients (n=192) were randomized to receive 14-16 mg UDCA/kg/day or placebo. Patients underwent a complete history, physical examination, liver chemistries, immunological determinations and liver biopsy at entry and at the end of the trial, which lasted for at least 2 years. Patients were seen every 3 months and the median follow-up was 3.4 years (range 0.3 to 6.1 years). RESULTS: Patients receiving UDCA (99) or placebo (93) were comparable with regard to age, sex, biochemical parameters and liver histology. UDCA treatment was associated with decreases in alkaline phosphatase, gammaglutamyl transferase, alanine aminotransferase, and cholesterol levels, effects which were conspicuous after 3 months of treatment and remained similar during the follow-up. During the study 31 patients (10 receiving UDCA and 21 placebo) discontinued the trial because of noncompliance (n=11), voluntary withdrawal (n=19) or adverse effects (n=1). Treatment failure (death or liver transplantation) was observed in 17 patients receiving UDCA and in 11 patients receiving placebo. Times to death or liver transplantation and to clinical complications were not significantly different in patients receiving UDCA or placebo. Histological analysis indicates that UDCA improved portal inflammation and prevented histological stage progression. By contrast, histological stage as well as ductular proliferation and ductopenia progressed in patients receiving placebo. CONCLUSIONS: Although UDCA treatment did not significantly affect time to death or liver transplantation and to clinical complications, the effects on both cholestasis and liver histology suggest that UDCA is safe and may be useful for preventing the progression of primary biliary cirrhosis.

[The progression of hepatic fibrosis in chronic hepatitis C]. / Progresión de la fibrosis hepática en la hepatitis C crónica.

UNLABELLED: The natural history of liver fibrosis in 47 untreated patients with chronic hepatitis C and no cirrhosis, as well as the factors associated with its progression, were evaluated by examining two consecutive liver biopsies, separated by an average interval of 64.8 +/- 62.9 months (12-244). In all the biopsies, the degree of necroinflammation and the stage of fibrosis were determined on a scale from 0+ to 4+. In 53% of the patients, liver fibrosis did not progress. The interval between biopsies was significantly higher in those who progressed from one stage to another (85 +/- 77 months) than in those who did not (41 +/- 27 months), p = 0.014. Two factors were independently associated with a greater risk of fibrosis progression: a history of daily alcohol intake > or = 80 g (p = 0.02) and having acquired an infection through a known parenteral mechanism such as blood transfusion, major surgery or hemodialysis (p = 0.018). Necroinflammation was significantly diminished in the second biopsy due to a lesser necrosis and inflammation of the lobules. IN CONCLUSION: a) liver fibrosis progression is independent of necroinflammation; b) progression is related to the duration of the disease and with the mechanism of transmission, and c) it is aggravated by excessive alcohol consumption.

[Steatosis and nonalcoholic steatohepatitis. A comparative analysis]. / Esteatosis y esteatohepatitis no alcohólica. Análisis comparativo.

Liver biopsies with a main histological diagnosis of steatosis were selected from 3,422 liver biopsies carried out in our department between January 1995 and December 1998. Patients with known risk factors for steatosis, such as excessive alcohol consumption, hepatitis C infection, treatment with amiodarone, perhexiline maleate, tamoxifen, antiviral drugs (didanosine, zidovudine) methotrexate, sodium valproate or total parenteral nutrition, Wilson's disease and organ transplant were subsequently excluded. Of the 43 liver biopsies finally included in the study, 23 showed simple steatosis and 20 steatohepatitis. Eighty-one per cent of the patients were male (mean age of 44 years) and the majority were asymptomatic. The most frequent indication for liver biopsy was hypertransaminasemia. No differences were observed between the two groups in terms of frequency and severity of classical risk factors for steatosis (diabetes mellitus, dyslipemia and obesity). Thirty-five percent of patients with steatohepatitis and 26% of those with simple steatosis had none of these risk factors. Patients with steatohepatitis were older than those with simple steatosis. They presented more severe symptomatology, the degree of steatosis was more intense and laboratory investigations showed greater alterations. These results suggest that simple steatosis and nonalcoholic steatohepatitis are two different phases of the same disease. The difficulty in clinical differentiation justifies carrying out liver biopsy, especially in patients with more severe symptomatology whose laboratory results show greater alterations, since these patients present more marked histological lesions, are at risk of developing liver cirrhosis and require therapy.

Prospects for vaccination against hepatitis A and B in Catalonia (Spain).

Catalonia is in an area of intermediate endemicity for hepatitis A virus (HAV) infection. An Expert Committee has recently proposed the implementation of universal hepatitis A vaccination for 12-year-olds, based on the fact that no risk factors can be identified for hepatitis A in 50% of cases, and also that selective vaccination targeted at high-risk groups has a limited potential to reduce the incidence of hepatitis A. The well-established programme of hepatitis B vaccination of pre-adolescents in Catalonian schools has high levels of vaccination coverage. This will provide a means to introduce hepatitis A vaccination in a cost-effective way in schools, by replacing the single vaccine with the combined hepatitis A and B vaccine. High-risk groups will also continue to be targeted. A pilot programme has commenced in the 1998/1999 school year and will be evaluated after 3 years. If it is successful, it will be extended indefinitely.

Hepatic fibrogenic activity in chronic alcoholic pancreatitis.

The prevalence and the mechanisms of hepatic fibrosis in chronic alcoholic pancreatitis remain uncertain. The aim of this study was to investigate the fibrogenic activity of the liver in patients with chronic pancreatitis and its relation with either the alcohol or cholestasis. Liver biopsies were obtained from 16 patients with chronic pancreatitis at the time of surgery and from 10 organ donors. Samples were processed for histologic examination to assess the presence and extent of fibrosis, inflammatory reactions, and cholestasis- and alcohol-related lesions. In other samples, the collagen content was measured by morphometry, and prolylhydroxylase activity was determined. Liver-function tests, ultrasonography, and endoscopic retrograde cholangiopancreatography were performed before surgery in all the patients. Of patients with chronic pancreatitis, 75% had significantly greater hepatic fibrosis and prolylhydroxylase activity than the control group. Moreover, prolylhydroxylase activity in patients with chronic pancreatitis was higher in those with cholestasis or partial obstruction of the common bile duct than in those without cholestasis or partial obstruction of the common bile duct. Both the fibrogenic activity and the collagen content in the livers of patients with chronic alcoholic pancreatitis are significantly increased, even in those without histologic lesions, and these alterations may be secondary to a partial occlusion of the common bile duct.

[Severe hepatitis from therapeutic doses of paracetamol in an alcoholic patient]. / Hepatitis grave por dosis terapéuticas de paracetamol en un paciente alcohólico.

The case of a 36-year-old chronic alcoholic patient who came to the hospital for presenting general bad shape, arthromyalgia and jaundice and who developed severe hepatitis with an extreme elevation in the transaminase levels following the consumption of therapeutic doses of paracetamol (3 g/day for 4 days). The possibility of other causes of hepatitis were duly discarded. Liver biopsy showed confluent centrolobular necrosis compatible with the diagnosis of toxic hepatitis. The patient was discharged from hospital in stable condition and with a slight alteration in the transaminase levels. Recognizing hepatotoxicity by paracetamol in alcoholics is simple if the clinical history, the marked transaminase elevation and the history of paracetamol intake are adequately evaluated. Lower doses of paracetamol or even avoidance of this drug is recommended in circumstances in which the toxicity of the drug may be potentiated by chronic alcohol consumption or by the lack of appetite associated with deficient alimentation.