Raised Serum Transaminases Research Articles

A Phase I, Dose-Finding Study of Sorafenib in Combination with Gemcitabine and Radiation Therapy in Patients with Unresectable Pancreatic Adenocarcinoma: A Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) Study

PurposeSorafenib, an oral inhibitor of B-raf, VEGFR2, and PDGFR2-beta, acts against pancreatic cancer in preclinical models. Due to the radio-sensitization activity of both sorafenib and gemcitabine, we designed a multicenter, phase I trial to evaluate the safety profile and the recommended dose of this combination used with concomitant radiation therapy.MethodsPatients with biopsy-proven, unresectable pancreatic adenocarcinoma (based on vascular invasion detected by computed tomography) were treated with gemcitabine (300 mg/m2 i.v. weekly ×5 weeks) concurrently with radiation therapy (45 Gy in 25 fractions) and sorafenib (escalated doses in a 3+3 design, from 200 to 800 mg/day). Radiation portals included the primary tumor but not the regional lymph nodes. Patients with planning target volumes (PTV) over 500 cc were excluded. Cases not progressing during chemoradiation were allowed to continue with sorafenib until disease progression.ResultsTwelve patients were included. Three patients received 200 mg/day, 6 received 400 mg/day, and 3 received 800 mg/day; PTVs ranged from 105 to 500 cc. No dose-limiting toxicities occurred. The most common grade 2 toxicities were fatigue, neutropenia, nausea, and raised serum transaminases. Treatment was discontinued in one patient because of a reversible posterior leukoencephalopathy. There were no treatment-related deaths.ConclusionThe addition of sorafenib to concurrent gemcitabine and radiation therapy showed a favorable safety profile in unresectable pancreatic adenocarcinoma. A dose of 800 mg/day is recommended for phase II evaluation.Trial RegistrationEudraCT 2007-003211-31 ClinicalTrials.gov 00789763

P.15.9 An X-linked dominant mutation in LAMP2 causing Danon disease associated with myotonia expanding the spectrum

We describe a family with strong family history of cardiomyopathy. The mother has dilated cardiomyopathy with symptoms onset around 40 years old requiring treatment for both heart failure and atrial fibrillation. She does not have muscle weakness and her creatine kinase level was normal. The elder son has hypertrophic cardiomyopathy with symptoms onset at 20 years old, a mildly elevated creatine kinase of 1000 U/L but no muscle weakness. The younger brother with limited intelligence was asymptomatic all along. At the age of 15 with an incidental finding of raised serum transaminase levels he was referred for further investigations. Initial consultation confirmed mild proximal weakness, calves hypertrophy, creatine kinase up to 3500 U/L and echocardiogram confirmed hypertrophic cardiomyopathy. Needle electromyography showed myotonia after ice application. Nerve conduction study with short exercise test showed compound muscle action potentials decrement confirming myotonia. Metabolic workup, DMD gene and CTG repeat mutation study were all negative. The muscle biopsy of the elder brother showed vacuolar myopathy. Subsequent LAMP2 mutation study on exome sequencing confirmed Danon Disease. Mother has subsequently undergone heart transplantation, and vacuolar myocytes are noted in the cardiac muscles. This report describe a family with Danon disease, a rare X-linked dominant condition, but an important differential diagnosis for patient with cardiomyopathy, myopathy and learning difficulty, having a strong family history of cardiomyopathy. While skeletal muscles biopsy showed vacuolar myopathy, these abnormal vacuolar changes also extended to the cardiac muscles. Diagnostic confirmation is important when counseling the long term prognosis for this family. While symptomatic treatment is available for the heart failure, with a progressive course of cardiomyopathy the ultimate cure is heart transplantation.

Hemostatic dysfunction is increased in patients with hepatosplenic schistosomiasis mansoni and advanced periportal fibrosis.

BackgroundSchistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n = 55) correlate with the severity of their periportal fibrosis.Methodology/Principal FindingsBlood samples were used for liver function tests, hemogram and prothrombin time (International Normalized Ratio, INR). The blood coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa (ATIIa), plasminogen activator inhibitor 1 (PAI-1) and D-dimer were measured by photometry or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of 483 ng/mL. Standard liver function tests were all abnormal in the patient group compared to healthy controls (n = 29), including raised serum transaminases (p<0.001) and lower levels of albumin (p = 0.0156). Platelet counts were 50% lower in patients, while for coagulation factors there was a 40% increase in the INR (p<0.001) and reduced levels of Factor VII and protein C in patients compared to the controls (both p<0.001). Additionally, patients with more advanced fibrosis (n = 38) had lower levels of protein C compared to those with only central fibrosis (p = 0.0124). The concentration of plasma PAI-1 in patients was one-third that of the control group (p<0.001), and D-dimer levels 2.2 times higher (p<0.001) with 13 of the 55 patients having levels above the cut-off.Conclusion/SignificanceThis study confirms that hemostatic abnormalities are associated with reduced liver function and increased liver fibrosis. Of note was the finding that a quarter of patients with hepatosplenic schistosomiasis and advanced periportal fibrosis have hyperfibrinolysis, as judged by excessive levels of D-dimer, which may predispose them to gastrointestinal bleeding.

Raised Serum Aminotransferase Levels and Muscle Pseudohypertrophy Caused by Hypothyroidism

Raised Serum Aminotransferase Levels and Muscle Pseudohypertrophy Caused by Hypothyroidism

The ETR (End Treatment Response) of Chinese Brand Human recombinant interferon alpha 2a plus Ribavirin in chronic hepatitis C patients selected from Combined Military Hospitals in Pakistan

This Study was carried out to determine the End of Treatment Response (ETR) of a Chinese Source Human Recombinant Interferon Alpha 2a and Ribavirin in chronic hepatitis C affected patients, selected from different combined military hospitals in Pakistan. In this study hepatitis affected noncirrhotic patients from different combined military hospitals in Pakistan were selected from September 2010 to April 2011. Sixty seven patients were selected based on the inclusion exclusion criteria. Fifty seven patients completed the 24 weeks therapy for Hepatitis C. The Patients (n=57) had persistently raised serum aminotransferase (ALT), positive HCV antibodies by 3rd generation ELISA, positive HCV RNA by polymerase chain reaction. Study group patients underwent 24 weeks therapy with a Chinese source Interferon and Ribavirin and subsequently followed up for the End of Treatment Response by the assay of HCV RNA by polymerase chain reaction at 24 weeks. Patients of chronic hepatitis C (44 males and 13 females) had age range 20-56 years. After 24 weeks of therapy with a Chinese source Interferon and Ribavirin, 73.7% patients showed a favourable ETR manifested by Negative HCV RNA polymerase chain reaction.Treatment with a Chinese source Interferon and Ribavirin combination therapy for 24 weeks produces a favourable End of Treatment Response in patients of chronic hepatitis C from different military hospitals in Pakistan.

Plasmodium vivax malaria complicated by acute kidney injury: experience at a referral hospital in Uttarakhand, India

Acute kidney injury (AKI) is a serious complication of Plasmodium vivax malaria, worsening its prognosis. This prospective study assessed the incidence, clinical spectrum, prognostic factors and outcome of AKI in P. vivax malaria. During 2010-2011, 195 patients with vivax malaria diagnosed by positive peripheral blood film and rapid malaria test were studied for AKI using RIFLE criteria. AKI occurred in 63 patients (32%), with maximum RIFLE class R (Risk), class I (Injury) and class F (Failure) in 27 (43%), 23 (37%) and 13 (21%) patients, respectively. AKI was associated with oliguria/anuria (48%), anaemia (70%), thrombocytopenia (84%), hepatic dysfunction (48%), gastrointestinal manifestations (33%), acute respiratory distress syndrome (ARDS) (14%), cerebral malaria (6%), disseminated intravascular coagulation (8%) and shock (11%). All 63 patients with AKI received artesunate and 12 (19%) received quinine after failure of response to artesunate. Fourteen patients (22%) underwent haemodialysis. Patients with maximum RIFLE class R, I and F had mortality rates of 3.7%, 4.3% and 30.7%, respectively. Poor prognostic factors were delayed diagnosis, anaemia, severe AKI, shock, ARDS, need for ventilatory support, raised serum transaminases and metabolic acidosis. AKI is now common in vivax malaria and has significant mortality. Its early recognition and management can improve the outcome.

English

BACKGROUND: Thyroid hormones regulate Basal Metabolic Rate (BMR) and calorigenesis in tissues, including hepatocytes and thereby modulate hepatic function. The liver in turn metabolizes the thyroid hormones and regulates their systemic endocrine effect. Raised serum transaminase activities in absence of any overt liver dysfunction can therefore be attributed to primary thyroid dysfunction. The aim of this study is to assess the impairment in liver function by estimating serum Aspartate Transaminase (AST) and Alanine Transaminase (ALT) in patients with hypothyroidism. MATERIALS AND METHODS: 50 patients diagnosed with thyroid disorders irrespective of duration of the disease and treatment were taken as cases and 50 healthy adults were taken as control. Estimation of T3, T4, TSH, serum AST and serum ALT were carried out. RESULTS: Serum AST and serum ALT were within reference range in both cases and controls. CONCLUSION: The likelihood of abnormal serum transaminases levels in hypothyroid patients is minimal. Early detection and better management of the thyroid diseases in recent times might be attributed as one of the factors for the same.

Extremely high serum ferritin levels as a main diagnostic tool of adult-onset Still’s disease

Adult-onset Still's disease is a rare systemic inflammatory disease of unknown aetiology characterised by typical symptoms including daily high spiking fever, evanescent salmon-pink rash, sore throat, arthritis/arthralgias and polyserositis. The laboratory findings usually show neutrophilic leucocytosis, seronegativity and raised serum transaminases. We describe six typical cases. All of them had serum ferritin above 5,000 µg/L. Although there are few theories about the origin of the high ferritin level, an extremely high serum ferritin above 5,000 µg/L should be the main diagnostic tool of adult-onset Still's disease.

HEV Infection as an Aetiologic Factor for Acute Hepatitis: Experience from a Tertiary Hospital in Bangladesh

Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004-December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 micromol/L, raised serum transaminases, and prothrombin time >3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in cirrhotics in Bangladesh. Sewerage contamination of piped water following floods may contribute to the higher incidence of HEV infection.

Clinical Features of Human Influenza A (H5N1) Infection in Vietnam: 2004–2006

The first cases of avian influenza A (H5N1) in humans in Vietnam were detected in early 2004, and Vietnam has reported the second highest number of cases globally. We obtained retrospective clinical data through review of medical records for laboratory confirmed cases of influenza A (H5N1) infection diagnosed in Vietnam from January 2004 through December 2006. Standard data was abstracted regarding clinical and laboratory features, treatment, and outcome. Data were obtained for 67 (72%) of 93 cases diagnosed in Vietnam over the study period. Patients presented to the hospital after a median duration of illness of 6 days with fever (75%), cough (89%), and dyspnea (81%). Diarrhea and mucosal bleeding at presentation were more common in fatal than in nonfatal cases. Common findings were bilateral pulmonary infiltrates on chest radiograph (72%), lymphopenia (73%), and increased serum transaminase levels (aspartate aminotransferase, 69%; alanine aminotransferase, 61%). Twenty-six patients died (case fatality rate, 39%; 95% confidence interval, 27%-51%) and the most reliable predictor of a fatal outcome was the presence of both neutropenia and raised alanine aminotransferase level at admission, which correctly predicted 91% of deaths and 82% of survivals. The risk of death was higher among persons aged < or =16 years, compared with older persons (P < .001), and the risk of death was higher among patients who did not receive oseltamivir treatment (P = .048). The benefit of oseltamivir treatment remained after controlling for potential confounding by 1 measure of severity (odds ratio, 0.15; 95% confidence interval, 0.026-0.893; P = .034). In cases of infection with Influenza A (H5N1), the presence of both neutropenia and raised serum transaminase levels predicts a poor outcome. Oseltamivir treatment shows benefit, but treatment with corticosteroids is associated with an increased risk of death.

Hepatitis A, B and C viral co-infections among HIV-infected adults presenting for care and treatment at Muhimbili National Hospital in Dar es Salaam, Tanzania

BackgroundTanzania is currently scaling-up access to anti-retro viral therapy (ART) to reach as many eligible persons as possible. Hepatitis viral co-infections are known to influence progression, management as well as outcome of HIV infection. However, information is scarce regarding the prevalence and predictors of viral hepatitis co-infection among HIV-infected individuals presenting at the HIV care and treatment clinics in the country.MethodsA cross-sectional study conducted between April and September 2006 enrolled 260 HIV-1 infected, HAART naïve patients aged ≥18 years presenting at the HIV care and treatment clinic (CTC) of the Muhimbili National Hospital (MNH). The evaluation included clinical assessment and determination of CD4+ T-lymphocyte count, serum transaminases and serology for Hepatitis A, B and C markers by ELISA.ResultsThe prevalence of anti HAV IgM, HBsAg, anti-HBc IgM and anti-HCV IgG antibodies were 3.1%, 17.3%, 2.3% and 18.1%, respectively. Dual co-infection with HBV and HCV occurred in 10 individuals (3.9%), while that of HAV and HBV was detected in two subjects (0.8%). None of the patients had all the three hepatitis viruses. Most patients (81.1%) with hepatitis co-infection neither had specific clinical features nor raised serum transaminases. History of blood transfusion and jaundice were independent predictors for HBsAg and anti-HBc IgM positivity, respectively.ConclusionThere is high prevalence of markers for hepatitis B and C infections among HIV infected patients seeking care and treatment at MNH. Clinical features and a raise in serum alanine aminotransferase were of limited predictive values for the viral co-infections. Efforts to scale up HAART should also address co-infections with Hepatitis B and C viruses.

Aetiology of Acute Hepatitis in Bangladeshi Pregnant Women in the Third Trimester: Experience from a Tertiary Hospital in Bangladesh

Introduction: Acute hepatitis in pregnancy in not uncommon in Bangladesh. There has been a rise in acute viral E hepatitis in Bangladesh after the 2004 floods. At that time most of the country was under water for more than a month leading to sewerage contamination of water supply. The aim of this study was to see the aetiology of acute hepatitis in pregnant women in the third trimester in Bangladesh. Materials and Methods: In this retrospective study, 31 pregnant women in their third trimester with acute hepatitis were included. Only those patients who presented with prodromal features like icterus, nausea and vomiting, fever and raised serum bilirubin and raised serum transaminase levels were included in this study. They were all previously healthy and came to the Unit from all over Bangladesh. Patients were tested for markers for common hepatotrophic viruses. Relevant history was taken. Patient Record Book of the Unit was reviewed and patients who fulfilled the criteria were included in this retrospective study. Results: 45.16% (14/31) had HEV infection. They were all anti-HEV IgM positive by ELISA. HBV infection was detected in 6.45% (2/31). All these later patients tested positive for either HBsAg or anti-HBs IgM by ELISA. Both anti-HEV IgM and HBsAg were positive in 9.38% (3/31) patients. No viral marker could be detected in 38.7% (12/31) patients. Overall 54.84% (17/31) patients had HEV and 16.12% (5/31) had HBV infection. No patient had history of drug or alcohol intake. Conclusion: Acute viral E hepatitis is the leading cause of acute hepatitis in pregnancy in Bangladesh. Sewerage contamination of water supply following flood contributed to the higher incidence of HEV infections. Hepatitis B virus infection is also important.

Miositis eosinofílica en un niño de 9 años

Eosinophil infiltration of skeletal muscle is rare, but often no etiological factor can be identified and these are isolated eosinophilic myositis. They may be associated with parasite infections or drugs, or be features of rare systemic disorders of hypereosinophilia, such as the myalgia eosinophilia syndrome and the idiopathic hypereosinophilic syndrome. The eosinophilic myopathies should be distinguished from the commoner inflammatory myopathies such as polymyositis and dermatomyositis. A nine year old boy with slight motor clumsiness but normal psychomotor development and neurological findings. Laboratory findings showed slightly raised serum transaminases (SGOT 271, SGPT 157 UI/L), CPK 7517 UI/L and eosinophilia (707/mL). Investigations for myoglobin cysticercosis, trichinosis, hydatidosis and toxicariasis were negative. No parasites were found in the faeces. The gammaglobulins were normal. Anti smooth muscle, antinuclear and anti KLM antibodies were negative. Cardiological studies were normal. His father, mother and two siblings had normal results of laboratory tests. Muscle biopsy showed inflammatory myopathy with abundant eosinophils, no evidence of parasites, no alteration of membrane proteins: dystrophin, sarcoglycan and merosine. Two years later he remains asymptomatic, maintains raised muscle enzyme levels in all tests with figures for CPK between 3,065 and 9,616UI/L, and eosinophilia ranging between 634 and 1,026/mL. Corticosteroid treatment was tried but no response obtained. We consider this to be a case of eosinophilic polymyositis which gives rise to many questions regarding etiopathogenesis, management and prognosis.

Coeliac disease hidden by cryptogenic hypertransaminasaemia

Hypertransaminasaemia of unknown, cryptogenic, origin occasionally has been found to be the only sign of coeliac disease. Raised concentrations of transaminases, or aminotransferases, have been retrospectively observed in about a half of patients with coeliac disease who are on a gluten-containing diet. We aimed to establish the overall prevalence of coeliac disease among patients with cryptogenic hypertransaminasaemia. Of the 600 consecutive patients referred to our outpatient clinic for liver disease due to raised serum transaminases from September, 1995, to June, 1997, 55 were classified as having cryptogenic hypertransaminasaemia after the exclusion of every known cause of liver disease. These patients were tested by indirect immunofluorescence for IgA to endomysium and for IgA and IgG to gliadin. Five patients were positive for both IgA to endomysium and IgG to gliadin, whereas IgA to gliadin was only found in four patients. IgG to gliadin was also present in another patient who was not positive for antibodies to endomysium. The six antibody-positive patients had duodenal biopsy that showed a subtotal villous atrophy consistent with coeliac disease in the five patients with antibodies to endomysium. The patient with only IgG to gliadin had a normal small-intestine mucosa. None of the five patients with coeliac disease had gastrointestinal symptoms. Liver biopsy samples were taken from three of the five patients with flat mucosa and showed a histological picture of nonspecific reactive hepatitis. Transaminase concentrations reverted to normal within 6 months in four patients with coeliac disease who followed a strict gluten-free diet. Our results show that about 9% of patients with cryptogenic hypertransaminasaemia are affected by symptom-free coeliac disease. Gluten-sensitive enteropathy and antibody screening for coeliac disease by means of antibodies to endomysium and gliadin should be considered in these patients.

Hepatitis G virus infection in chronic dialysis patients and kidney transplant recipients.

The cloning of the hepatitis G virus (HGV), a novel RNA virus of the Flaviviridae family, has been very recently developed. HGV is known to be parenterally transmitted and has been detected in several patients with cryptogenic hepatitis. However, little information exists about the epidemiology of HGV infection in renal patients. We studied 178 chronic dialysis patients and 11 renal transplant individuals to evaluate prevalence, risk factors, and clinical manifestations of HGV infection in this population. Hepatitis G virus infection has been detected by a modified PCR technology which incorporates digoxigenin-labelled nucleotides into the amplicon. Primers from the non-coding region and the NS-5 region of HGV are utilized for a single round amplification. Using a streptavidin surface and a biotin-labelled capture probe, the labelled nucleic acid is bound through the capture probe to the surface, and the amplified nucleic acid is detected using antibody to digoxigenin. HGV RNA was detected in 6% of chronic haemodialysis (HD) patients (11/172), 36% of renal transplant recipients (4/11), and 17% (1/6) of patients on peritoneal dialysis treatment (CAPD). There were no significant differences between HGV positive and negative patients on chronic HD treatment with regard to several demographic, biochemical and virological features. However, the frequency of anti-HCV antibody was significantly higher in HGV-positive than HGV-negative patients (9/11 (82%) vs 51/161 (32%), P = 0.006). In the whole group of HGV RNA-positive patients, 78% (11/14) had a history of blood transfusion requirements, 14/16 (87%) had co-infection with HCV, and 1 (6%) had co-infection with HBsAg. There was no significant association between HCV genotypes and HGV RNA positivity. Six (37.5%) of 16 HGV RNA-positive patients showed raised aminotransferase values in serum. Patients on maintenance dialysis and kidney transplant recipients are at increased risk of HGV infection; HGV is very frequently associated to hepatitis C co-infection, regardless of HCV genotype. HGV may be transmitted by blood transfusions but transmission routes other than transfusion are possible; 37.5% of HGV RNA-positive patients showed raised serum aminotransferase levels. Further investigations are necessary to clarify the role of HGV infection in the development of liver disease in this clinical setting.

HGV: hepatitis G virus or harmless G virus?

The discovery of the hepatitis G virus (HGV) has given hepatologists a new lease on life. Just when they were becoming frustrated with the slow rate of progress in unravelling the pathobiological consequences of hepatitis B and C virus infections, along comes another candidate virus. HGV, a single-stranded ribonucleic acid (RNA) virus that belongs to the Flaviviridae family, has a global distribution. The virus is present in 1–2% of blood donors in the USA, a frequency higher than that of either HCV or hepatitis B virus (HBV) (Alter). Even more striking is the seroprevalence of 15.2% reported in West African residents (J Med Virol 1996; 50: 97). HGV exists in a chronic carrier state. The virus is transmitted parenterally and is often present in patients who have received multiple transfusions or who are on haemodialysis (N Engl J Med 1996; 334: 1485), and in intravenous drug users. There is preliminary evidence for perinatal transmission (Lancet 1996; 347: 615). HGV RNA sequences have been identified in serum from patients with non-A-E acute and chronic hepatitis and cirrhosis. Impressive data comes from Brescia, Italy, where 35% of patients with acute hepatitis and 39% of those with chronic hepatitis were positive for HGV RNA (Fiordalisi). Among blood donors the virus is more common in those with raised serum amino transferase concentrations (3.9%) than in those with normal concentrations (0.8%) (J Med Virol 1996; 50: 97). These findings imply that HGV is a human pathogen, but is it? Other information is more consistent with HGV being an innocent passenger. The great majority of individuals who become HGV-RNA positive after blood transfusion have normal serum amino transperase concentrations and neither they, nor those found positive for HGV RNA in other circumstances, develop liver disease during prolonged follow-up (Alter). Moreover, when serum enzyme concentrations are raised they seldom accord with levels of viraemia. HGV and HCV are often, and HGV and HBV less often, found together in serum. In those coinfected with HGV and HCV, amino transterases run parallel to HCV rather than HGV, and the presence of the latter seems to have no effect on outcome. HGV usually accounts for only a minority of cases of acute non-A-E hepatitis, and there is no evidence yet of progression over time to chronic hepatitis, cirrhosis, or hepatocellular carcinoma, as occurs with HBV and HCV. Although severe (even fulminant) cases of community-acquired acute hepatitis G have been reported, some of the patients had histories suggestive of earlier exposure to HGV and HGV RNA has persisted for a long time after clinical and biochemical recovery, so one possibility is that they were chronic carriers of the virus and the acute liver injury had another cause. HGV positivity rates in patients with chronic non-A-E hepatitis are not usually higher than in patients with non-viral hepatitis. Inclusion of HGV among the hepatitis viruses may have been premature. Furthermore, it is obvious that at least one virus that causes clinically significant liver disease is still out there waiting to be identified. Several other important observations appeared during 1996. Ursodeoxycholic acid, long known to improve the symptoms and disturbed biochemistry in patients with primary biliary cirrhosis, was finally shown to improve long-term survival as well. Ecstasy (3,4 methyl-enedioxymethamphetamine) unsurprisingly proved to be hepatotoxic. Eight patients with severe acute liver failure were reported: all but one required liver transplantation and six died.

Liver disease in dialysis patients with antibodies to hepatitis C virus

Eighty-three patients with chronic end-stage renal failure, including 65 on haemodialysis and 18 on intermittent peritoneal dialysis, were evaluated for hepatitis B virus profile and antibodies to hepatitis C virus (HCV). All those positive for HBsAg were excluded from the study. Nineteen patients were found to be positive for antibodies to HCV by the ELISA II test. Eight cases were already positive for HCV antibody when they started dialysis in our unit, the other 11 became positive during dialysis in our unit. Only one of the patients on peritoneal dialysis was positive for HCV. A liver biopsy was obtained from 17 patients, who consented to the procedure. All the cases were evaluated for the number of blood transfusions received, HIV infection and the approximate time of contracting the HCV infection. Liver enzymes were determined every month. Only three patients had abnormally raised serum aminotransferase at the time of biopsy. The various histopathological lesions detected were chronic active hepatitis ( n =3, including one with changes consistent with cirrhosis), chronic persistent hepatitis ( n = 4), non-specific hepatitis ( n = 3) and haemosiderosis ( n =3); four biopsy samples were normal. There was no correlation between the biochemical and histopathological changes. Moreover, patients with normal serum aminotransferase levels had abnormal histopathological changes. All were negative for HIV and none of the patients had received a renal graft. Twelve patients had received blood transfusions varying from 2 to 12 units, four had not received any blood, and in one the history of blood transfusion could not be confirmed. The four patients with anti-HCV antibodies who had not received blood transfusion had relatively mild disease-non-specific hepatitis ( n =2) or normal biopsy ( n =2). One patient with cirrhosis died 30 months after liver biopsy from hepatic insufficiency and three received renal transplants. Others are continuing on dialysis and their biochemical tests are within normal limits 12−45 (30± 14) months after biopsy. In conclusion, biochemical tests are poor indicators of liver disease, and liver biopsy is a definitive way of evaluating the patients of dialysis with positive HCV antibodies for prognosis.

Liver disease in dialysis patients with antibodies to hepatitis C virus.

Eighty-three patients with chronic end-stage renal failure, including 65 on haemodialysis and 18 on intermittent peritoneal dialysis, were evaluated for hepatitis B virus profile and antibodies to hepatitis C virus (HCV). All those positive for HBsAg were excluded from the study. Nineteen patients were found to be positive for antibodies to HCV by the ELISA II test. Eight cases were already positive for HCV antibody when they started dialysis in our unit, the other 11 became positive during dialysis in our unit. Only one of the patients on peritoneal dialysis was positive for HCV. A liver biopsy was obtained from 17 patients, who consented to the procedure. All the cases were evaluated for the number of blood transfusions received, HIV infection and the approximate time of contracting the HCV infection. Liver enzymes were determined every month. Only three patients had abnormally raised serum aminotransferase at the time of biopsy. The various histopathological lesions detected were chronic active hepatitis (n = 3, including one with changes consistent with cirrhosis), chronic persistent hepatitis (n = 4), non-specific hepatitis (n = 3) and haemosiderosis (n = 3); four biopsy samples were normal. There was no correlation between the biochemical and histopathological changes. Moreover, patients with normal serum aminotransferase levels had abnormal histopathological changes. All were negative for HIV and none of the patients had received a renal graft. Twelve patients had received blood transfusions varying from 2 to 12 units, four had not received any blood, and in one the history of blood transfusion could not be confirmed. The four patients with anti-HCV antibodies who had not received blood transfusion had relatively mild disease--non-specific hepatitis (n = 2) or normal biopsy (n = 2). One patient with cirrhosis died 30 months after liver biopsy from hepatic insufficiency and three received renal transplants. Others are continuing on dialysis and their biochemical tests are within normal limits 12-45 (30 +/- 14) months after biopsy. In conclusion, biochemical tests are poor indicators of liver disease, and liver biopsy is a definitive way of evaluating the patients of dialysis with positive HCV antibodies for prognosis.

Persistent hepatitis C viremia after acute self-limiting posttransfusion hepatitis C

Persistent viremia after clinical or subclinical hepatitis C virus (HCV) infection is believed to occur in patients with chronic hepatitis C, but little is known about the duration of HCV replication in patients with acute hepatitis who have recovered or the relation of HCV viremia with the kinetics of antibodies to HCV (anti-HCV). We tested HCV-RNA and anti-HCV in serial serum samples from 41 patients with posttransfusion non-A, non-B hepatitis, followed for an average of 6 years after transfusion. Serum HCV-RNA was measured by nested polymerase chain reaction, which used primers from the 5' untranslated region of the HCV genome. Anti-HCV were tested with first- and second-generation enzyme-linked immunosorbent assays (ELISA 1 and ELISA 2), and with a second-generation recombinant immunoblot assay. Of the 41 patients, 10 recovered and 31 progressed to chronic liver disease. HCV-RNA was detected in serum before or simultaneously with the onset of hepatitis in all cases, and lasted between 2 and 6 weeks in 5 of the 10 patients who recovered, whereas it persisted for the entire follow-up period in every case with chronic hepatitis and in the remaining 5 patients with self-limiting hepatitis. Anti-HCV were detected with ELISA 2 in the first serum sample, with raised serum transaminases in 57% of patients, but in only 6% with ELISA 1. In the sample obtained 1 month after the onset of hepatitis, anti-HCV were detected with ELISA 2 in 94% of patients, but in 34% with the ELISA 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistent Hepatitis C viremia after acute self-limiting posttransfusion Hepatitis C

Persistent viremia after clinical or subclinical hepatitis C virus (HCV) infection is believed to occur in patients with chronic hepatitis C, but little is known about the duration of HCV replication in patients with acute hepatitis who have recovered or the relation of HCV viremia with the kinetics of antibodies to HCV (antiHCV). We tested HCV-RNA and anti-HCV in serial serum samples from 41 patients with posttransfusion non-A, non-B hepatitis, followed for an average of 6 years after transfusion. Serum HCV-RNA was measured by nested polymerase chain reaction, which used primers from the 5′ untranslated region of the HCV genome. Anti-HCV were tested with first- and second-generation enzyme-linked immunosorbent assays (ELISA 1 and ELISA 2), and with a second-generation recombinant immunoblot assay. Of the 41 patients, 10 recovered and 31 progressed to chronic liver disease. HCV-RNA was detected in serum before or simultaneously with the onset of hepatitis in all cases, and lasted between 2 and 6 weeks in 5 of the 10 patients who recovered, whereas it persisted for the entire follow-up period in every case with chronic hepatitis and in the remaining 5 patients with self-limiting hepatitis. Anti-HCV were detected with ELISA 2 in the first serum sample, with raised serum transaminases in 57% of patients, but in only 6% with ELISA 1. In the sample obtained 1 month after the onset of hepatitis, anti-HCV were detected with ELISA 2 in 94% of patients, but in 34% with the ELISA 1. Anti-HCV (anti C-33 and anti-c22) were cleared in the five patients with transient hepatitis C viremia, but remained detectable in those with chronic viremia. In conclusion, serum HCV-RNA is detected at the onset of acute posttransfusion hepatitis C and persists in patients progressing to chronic hepatitis. Some patients with self-limiting hepatitis become HCV-RNA negative soon after the onset of hepatitis, whereas in others it persists throughout follow-up, suggesting the development of a silent carrier state.