Icteric Patients Research Articles

Treatment of subacute hepatitis B with lamivudine: A pilot study in Serbia

The incidence of acute hepatitis B viral (HBV) infection in adults has increased in recent years in Serbia. Most icteric patients with acute hepatitis B resolve their infection and do not require treatment. Fulminant hepatitis B is a severe form of acute infection complicated by encephalopathy and liver failure. Subgroups of fulminant hepatitis B including hyperacute, acute and subacute are defined by the interval between jaundice and encephalopathy. Fulminant hepatic failure or subacute hepatitis B infection we observed in about 1% of all cases. In cases of fulminant hepatic failure or subacute form of HBV infection orthotopic liver transplantation can be life-saving operation, but in our country this procedure is difficult to achieve. Lamivudine has been established as a safe and effective antiviral agent for the treatment of chronic HBV hepatitis. In our pilot study performed at the Institute of Infectious and Tropical Diseases in Belgrade, Serbia in the period between 2002 and 2006 we treated 10 patients with clinically verified subacute HBV infection with lamivudine, 100 mg orally per day. The most of the treated patients (9/10; 90%) survived subacute form of hepatitis B. After a few weeks of the treatment serum aminotransferase levels and other liver-function tests were normalized. Also, after a four-month lamivudine treatment all the patients lost HBsAg. Lamivudine was discontinued after six months in all the patients. In addition, six months after lamivudine was discontinued the patients remained well with normal results on liver-function tests. The obtained results suggest significant efficacy of lamivudine in patients with subacute hepatitis B. Also, we suggest that lamivudine therapy should be administered early in progression of subacute disease since it could be life-saving treatment in some patients, especially in the countries (like Serbia) where orthotopic liver transplantation is difficult to achieve.

Evaluation of protective effects of Chi-Zhi-Huang decoction on Phase I drug metabolism of liver injured rats by cocktail probe drugs

Aim of the study Chi-Zhi-Huang decoction (PGR) is one of the traditional Chinese medicine (TCM) preparations with unique effect on withdrawing jaundice and has been used to treat icteric patients in China for many years. In this research, we aim at to evaluate the potential activity of PGR in restoring hepatic drug metabolism in a damaged liver. Materials and methods A cocktail approach with caffeine (10 mg/kg), dapsone (10 mg/kg) and chlorzoxazone (20 mg/kg) respectively as probe drug of cytochrome P450 (CYP) isoform of CYP 1A2, 3A4 and 2E1 was used to evaluate its possible effects on Phase I oxidative metabolism. Pretreated with three dosages of PGR water extract (0.75, 1.5 and 3 g/kg, po) for 5 days, male Wistar rats (220–240 g) were intoxicated by phenylisothiocyanate (PITC, 100 mg/kg, po) 24 h before probes intravenous injection. The pharmacokinetics of the probes in the blood was determined simultaneously by HPLC, and their non-compartmental parameters were used to evaluate the metabolic difference among the groups. Moreover, the levels of liver enzymes (ALT, AST, ALP) and bilirubins were also measured for insight of liver function. Results The findings in this study suggest that PGR induces CYP 3A4, does not have much effect on CYP 2E1, and inhibits CYP 1A2 at high dosage. Conclusion The current pharmacokinetic approach allowed the protective effects of PGR on oxidative drug metabolism in damaged liver to be systemically examined and will certainly help in the explanation of synergistic effect of the composites formula.

Clinical and regulatory protocol for the treatment of jaundice in adults and elderly subjects: a support for the health care network and regulatory system

Clinical interventions and controlled access to the health care system can be improved by a Regulatory System (RS) and Clinical and Regulatory Protocols (CRPs). The objective of the present paper is to present the methodology used for elaborating the CRPs. The process used to elaborate the CPRs involved a scientific co-operation between university and health care system. Workshops were held and attended by primary care practitioners, RS team, and matrix team (university specialists supporting primary care practitioners). The treatment of jaundice in adults and elderly subjects is amongst the themes selected for elaborating the CRPs since jaundice is a medical sign frequently seen in four clinical scenarios involving distinctive diagnostic and therapeutic interventions which can be performed in different health care settings. Evaluation guidelines as well as the clinical and regulatory procedures were established for different health care settings. The most relevant clinical and regulatory interventions were expressed as algorithms in order to facilitate the use of CRPs by health care practitioners. It is expected that the implementation of this protocol will minimise the imbalance between the icteric patients' needs and the treatment modalities being offered, thus contributing to a more co-operative health care network.

Primary duodenal diffuse large cell non-hodgkin lymphoma with involvement of ampulla of Vater: Report of 3 cases

Primary gastrointestinal system lymphomas constitute about one third of all extranodal lymphomas. Duodenal involvement of the lymphoma is a rare condition. Periampullary lymphoma or lymphomatous involvement of ampulla of Vater is even rarer. Since, periampullary lymphoma is not easy to differentiate from epithelial carcinoma of these sites clinically and radiologically, accurate histopathological diagnosis is essential to plan optimal treatment strategy. Obstructive jaundice and the need for some form of drainage procedure and dose modification of the chemotherapy are additional challenges. In this report, we present three cases of duodenal diffuse large cell lymphoma with involvement of ampulla of Vater, two of whom presented with the initial signs of obstructive jaundice. One of the icteric patients was only diagnosed histopathologically following an explorative laparotomy with the initial diagnosis of carcinoma.

Current antibiotic prophylaxis in pancreatoduodenectomy in Japan

The aim of this study was to investigate the current use of antibiotic prophylaxis (AP) in association with pancreatoduodenectomy (PD) in Japan, and to determine its surgical implications. We surveyed 2331 patients who underwent PD for treatment of disease in the periampullary region. Data, obtained during the period January 2002 through December 2003, from 111 major surgical services associated with the Japanese Society for Pancreatic Surgery, were analyzed with regard to patient characteristics, preoperative complications, AP, and postoperative morbidities. Eighty-five (78.7%) of the 108 eligible institutions chose a first- or second-generation cephalosporin for AP, given for a mean duration of 4.3 days. At all but 1 institution, the first dose was administered prior to surgical incision of the skin. At 42% of the institutions, an additional antibiotic was administered during surgery. The overall rate of wound infection was 6.8% of the 2266 patients for whom data were available. Preoperative jaundice was found in 55.3% of these 2266 patients, and 92.6% of these jaundiced patients were suffering from preoperative infections. In addition, those with preoperative infections were also diagnosed as having biliary infections. The number of patients with preoperative jaundice in combination with preoperative infections was significantly related to the rate of postoperative morbidity (P < 0.0001). Administration of AP in association with PD in Japan seems appropriate. Icteric patients with biliary infections are at high risk for postoperative morbidities and need careful monitoring after surgery.

Delayed treatment of acute hepatitis HCV? Yes, but when, who, and how?

Delayed treatment of acute hepatitis HCV? Yes, but when, who, and how?

SR-BI- and ABCA1-mediated cholesterol efflux to serum from patients with Alagille syndrome

Alagille syndrome is associated with bile duct paucity resulting in liver disease. Patients can be divided into mildly and severely icteric groups, with both groups having altered lipoproteins. The incidence of ischemic heart disease is rare in severely cholestatic children despite increased total cholesterol and decreased high density lipoprotein cholesterol (HDL-C). The present studies examine the impact of altered lipid and lipoproteins on scavenger receptor class B type I (SR-BI)- and ABCA1-mediated efflux to serum from both groups. Efflux was compared with serum from 29 patients (15 with normal plasma cholesteryl ester, 14 with low cholesteryl ester). Efflux via SR-BI and ABCA1 was studied using cell systems having either low or high expression levels of these receptors. SR-BI efflux was lower (P = 0.04) with serum from severely icteric patients (3.9 +/- 1.4%) compared with serum from mildly icteric patients (5.1 +/- 1.4%) and was positively correlated with HDL-C and its apolipoproteins. SR-BI-mediated efflux was not correlated with any particular mature HDL but was negatively correlated with small lipid-poor prebeta-1 HDL. Consistent with severely icteric patients having high prebeta-1 HDL levels, the ABCA1 efflux was significantly higher with their serum (4.8 +/- 2.2%) compared with serum from mildly icteric patients (2.0 +/- 0.6%) and was positively correlated with prebeta-1 HDL. These studies demonstrated that prebeta-1 HDL is the preferred acceptor for ABCA1 efflux, whereas many particles mediate SR-BI efflux.

Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis

Inchin-ko-to (TJ-135) is an herbal medicine used in Japan for treatment of icteric patients with cirrhosis. Its efficacy as an anti-fibrogenic drug was evaluated in relation to stellate cell activation. Liver fibrosis was induced in rats by repeated injections of carbon tetrachloride (CCl4) or pig-serum. Oral administration of TJ-135 improved the mortality of rats given CCl4 with reduced extents of liver necrosis and fibrosis. Similar improvement of liver fibrosis was found in rats given pig-serum showing no liver necrosis. DNA synthesis of stellate cells activated in vitro after isolation from normal rat liver was decreased by culture with TJ-135 in a dose-related manner, accompanied by decreased smooth muscle alpha actin expression and contractility. Such attenuation was not found in the cells cultured with geniposide, an iridoid compound of TJ-135, but genipin, an aglycone of geniposide formed in the gut by action of bacterial flora, markedly decreased stellate cell activation without affecting synthesis of proteins other than collagen. TJ-135 may be useful for treatment of liver fibrosis and portal hypertension through suppression of activated hepatic stellate cell function by genipin, an absorbed form of its component.

Proportion of hepatitis C virus antibodies in icteric patients

A total of 1783 sera from icteric patients (988 male &amp; 795 female), their ages ranged 8-54 years, were tested for the presence of viral hepatitis markers (hepatitis A, B, and C), using the available diagnostic kits (enzyme linked immunosorbant assay). 300 donor sera were also tested as matched control. Among the icteric patients 859 (48,2%) had evidence of acute hepatitis A (HA), 499 (28%) were found to be infected with hepatitis B (HB), and hepatitis C virus (HCV-Ab) was detected in 8.2% of patients that confirmed by recombinant immunoblot assay. The results indicated that the maximum HCV seroprevalence was found in patients more than 30 years old, and there was no difference in the chance of infection in both sexes. The main route of HCV transmission was observed in icteric patients who had received blood, and those underwent surgical intervention. These reflect the fact that some of transfused blood may contain HCV that could not be detected by routine serological tests used in Blood Bank. There is a need to identify HCV carriers and the increased awareness of medical and paramedical personnel regarding the risk of transmitting the disease iatrogenically. Furthermore the need to document the risk of nosocomial transmission and highlight the crucial role of molecular sequence based phylogenetic analysis of cloned viral isolates in the investigation of HCV infection.

Therapy of acute hepatitis C

Acute hepatitis C has a high propensity to become chronic, which provides the rationale for treating patients with acute disease attempting to prevent chronicity. Almost all published studies on therapy of acute hepatitis C have been small in size, uncontrolled, and highly heterogeneous as to patient features, dose and duration of treatment, follow-up evaluation, and criteria used to define efficacy and safety. The published studies on treatment of acute hepatitis C have used standard alfa or beta interferon monotherapy: none have evaluated combination therapy of interferon and ribavirin or peginterferon. Several meta-analyses of published studies have concluded that initiation of interferon monotherapy during the acute phase of hepatitis C virus (HCV) infection significantly reduces (by 30% to 40%) evolution to chronic hepatitis. The tolerability of interferon in acute hepatitis C has been excellent, even in symptomatic and icteric patients; the side effects and adverse events being similar in type and frequency to those seen when treating chronic cases. Thus, currently available data support treatment of patients with acute hepatitis C, but data are insufficient to draw firm conclusions about which patients to treat, when therapy should be started, or what regimen is optimal. Future studies of adequate size and design should focus on efficacy and tolerability of peginterferons and whether therapy should be started immediately after diagnosis or delayed for 2 to 4 months to avoid treatment of patients who spontaneously recover. (Hepatology 2002;36:S195-S200).

Therapy of acute hepatitis C.

Acute hepatitis C has a high propensity to become chronic, which provides the rationale for treating patients with acute disease attempting to prevent chronicity. Almost all published studies on therapy of acute hepatitis C have been small in size, uncontrolled, and highly heterogeneous as to patient features, dose and duration of treatment, follow-up evaluation, and criteria used to define efficacy and safety. The published studies on treatment of acute hepatitis C have used standard alfa or beta interferon monotherapy: none have evaluated combination therapy of interferon and ribavirin or peginterferon. Several meta-analyses of published studies have concluded that initiation of interferon monotherapy during the acute phase of hepatitis C virus (HCV) infection significantly reduces (by 30% to 40%) evolution to chronic hepatitis. The tolerability of interferon in acute hepatitis C has been excellent, even in symptomatic and icteric patients; the side effects and adverse events being similar in type and frequency to those seen when treating chronic cases. Thus, currently available data support treatment of patients with acute hepatitis C, but data are insufficient to draw firm conclusions about which patients to treat, when therapy should be started, or what regimen is optimal. Future studies of adequate size and design should focus on efficacy and tolerability of peginterferons and whether therapy should be started immediately after diagnosis or delayed for 2 to 4 months to avoid treatment of patients who spontaneously recover.

Hepatitis E infection in children: study of an outbreak.

Hepatitis E virus (HEV) is responsible for most of the hepatitis epidemics in the developing world and it frequently affects young adults. Therefore, common perception is that it does not affect children. A group of 20 school children (13 years old) were possibly exposed to hepatitis E virus infection during a 2 day trekking trip. Epidemiological and clinical information was correlated to the presence of the hepatitis E virus genome and antibodies to HEV structural and non-structural proteins found in the blood of the children, using polymerase chain reaction and line immunoassay techniques. Ten children developed icteric hepatitis, seven prodrome-like illness without jaundice while three remained asymptomatic. Immunoglobulin M (IgM) antibodies to open reading frame (ORF)2 protein (pORF2) were detected in all 19 children tested, whereas 11 and 10 of the children were positive for IgM antibodies against ORF1 (pORF1) and ORF3 (pORF3) proteins, respectively. The rate of HEV infection was found to be 85%. Viraemia was observed in 11 children and was present in four of the seven anicteric patients (55%) compared with six of the nine (66%) icteric patients. One child without any symptom also had viraemia. The data obtained indicate a high susceptibility of children for HEV infection and a frequently prolonged viraemia in those infected.

Clinical significance of hepatic dysfunction with jaundice in typhoid fever.

A retrospective case note review was undertaken to assess the clinical significance of hepatic dysfunction with jaundice in typhoid fever. Of the 57 patients, 21 (36.8%) had jaundice, while 36 (63.2%) did not have jaundice. Significantly higher proportions of jaundiced patients were females (P = 0.04). Confusion (P = 0.01), upper abdominal pain (P = 0.02), right upper quadrant tenderness (P = 0.0001), and low prothrombin index (P = 0.04) were statistically significant occurrences in jaundiced patients on admission. Admission mean values of serum bilirubin (P = 0.0001), gamma-glutamyltranspeptidase (GGT; P = 0.009), and alanine aminotransferase (ALT; P = 0.0005) were significantly higher in icteric patients while mean values of total serum protein (P = 0.0009) and albumin (P = 0.0001) were significantly higher in anicteric patients. There were no deaths. Glomerulonephritis occurred significantly (P = 0.001) more frequently in icteric patients. It is concluded that hepatic dysfunction with jaundice in typhoid fever indicates more severe hepatic injury, which may precipitate the development of clinically detectable glomerulonephritis.

Incidence and prognosis of postoperative jaundice in surgical intensive care patients

Jaundice in critically ill patients may be difficult to explain. This study analyzes pathophysiologically relevant data, and discusses the prognostic value of hyperbilirubinemia. A total of 1275 patients were prospectively enrolled; 7.6% developed hyperbilirubinemia of at least 2 mg/dl. Mortality in icteric patients was significantly higher (29%) than in the non-icteric group. Sepsis, shock and the number of blood transfusions are very important in hyperbilirubinemia. Nevertheless, in critically ill patients, jaundice per se is not a sign of poor outcome; indeed it only reflects the underlying disease.

Diclofenac-associated hepatotoxicity: Analysis of 180 cases reported to the food and drug administration as adverse reactions

Diclofenac is a nonsteroidal anti-inflammatory drug approved in the United States in 1988 for the treatment of patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis. To characterize the clinical, biochemical, and histological features and possible mechanisms of hepatic injury associated with its use, a retrospective analysis was undertaken of 180 patients whose cases were reported to the Food and Drug Administration from November 1988 through June 1991, as having had possible adverse reactions to diclofenac. Of the reported 180 cases, 79% were female, 71% were 60 years of age or older, and 77% had osteoarthritis. Sixty-seven percent of the cases were detected by symptoms and the remainder by abnormal laboratory tests. Seventy-five percent of the symptomatic patients (90 of 120) were jaundiced. Seven of the 90 icteric patients died. The biochemical pattern of injury was hepatocellular or mixed hepatocellular in 66% of cases. Only 8% had a pattern of cholestatic injury. The remainder, with modestly increased values of both transaminases and alkaline phosphatase, were considered "indeterminate," i.e., either mild hepatocellular or anicteric "cholestatic" injury. Sections of liver from 21 cases were available for study. Hepatic injury was apparent by 1 month after starting the drug in 24%, by 3 months in 63%, and by 6 months in 85% of cases. The latent period in 12% was 6 to 12 months, whereas in 3% it was greater than 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Diclofenac-associated hepatotoxicity: Analysis of 180 cases reported to the food and drug administration as adverse reactions

Diclofenac is a nonsteroidal anti-inflammatory drug approved in the United States in 1988 for the treatment of patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis. To characterize the clinical, biochemical, and histological features and possible mechanisms of hepatic injury associated with its use, a retrospective analysis was undertaken of 180 patients whose cases were reported to the Food and Drug Administration from November 1988 through June 1991, as having had possible adverse reactions to diclofenac. Of the reported 180 cases, 79% were female, 71% were 60 years of age or older, and 77% had osteoarthritis. Sixty-seven percent of the cases were detected by symptoms and the remainder by abnormal laboratory tests. Seventy-five percent of the symptomatic patients (90 of 120) were jaundiced. Seven of the 90 icteric patients died. The biochemical pattern of injury was hepatocellular or mixed hepatocellular in 66% of cases. Only 8% had a pattern of cholestatic injury. The remainder, with modestly increased values of both transaminases and alkaline phosphatase, were considered “indeterminate”, i.e., either mild hepatocellular or anicteric “cholestatic” injury. Sections of liver from 21 cases were available for study. Hepatic injury was apparent by 1 month after starting the drug in 24%, by 3 months in 63%, and by 6 months in 85% of cases. The latent period in 12% was 6 to 12 months, whereas in 3% it was greater than 12 months. A combination of rash, fever, and eosinophilia, all hallmarks of immunological idiosyncrasy (hypersensitivity), was not reported in any case; additionally, the long latent period in most of the patients led to the inference that the mechanism is probably metabolic idiosyncrasy. The data suggest that diclofenac-related liver injury is particularly likely to involve osteoarthritic females, presenting with jaundice 1 to 6 months after starting diclofenac, with injury that is predominantly hepatocel lular and presumably caused by metabolic idiosyncrasy.

HBV Markers in Gaziantep Region

In this study, 98 HBsAg or anti HBs positive sera which sent to serology laboratory of Gaziantep University Research and Application Hospital between 4.5.1993 and 30.11.1993 were tested by Enzyme-Immunoassay (EIA) for HBV markers. It was studied to make the relation of HBV markers in these patients with age, sex, marital status, operation in the story, icter in the family or contact with the icteric patients. 53 of 98 sera were obtained from male and the rest of 45 sera from female patients. According to these results: it was HBV rnarkers were the most comınon in 20-40 age group (68 cases 69.38%) and more in male (54.08%) than fernale (45.92%) patients and also more common in married couples (67 cases, 68.36%). 23 patients (23.46%) had an operation story; 50 patients (51.02 %) had one or more icteric patients lately in their family or had a direct contact story with icteric patients. Total anti-HBc was found in 92 patients (93.87 %) while anti-HBs positivity was obtained in 20 cases (20.40 %).

Acute hepatitis E infection during the 1988 floods in Khartoum, Sudan

Abstract : Following catastrophic floods in August 1988, physicians in Khartoum and Omdurman, Sudan, observed an outbreak of acute hepatitis. During a period of 2 weeks in October 1988 we conducted a seroepidemiological study of icteric patients presenting to an acute-care clinic at the Omdurman Military Hospital. After informed consent was obtained, a standardized questionnaire was administered to each person and a venous blood sample was obtained. Acute and convalescent sera were tested for immunoglobulin (Ig) M and IgG antibody to hepatitis E virus (anti-HEV) using a Western blot assay. Specimens were also tested for IgM antibody to the hepatitis B core protein and IgM antibody to hepatitis A virus.

Prospective assessment of incidence of fulminant hepatitis in post-transfusion hepatitis: a study of 504 cases.

The incidence of posttransfusion hepatitis and "fulminant" hepatitis was investigated by a plan devised at our hospital in December 1982. Of 2959 blood recipients between January 1982 and December 1988, 504 (22.5%) developed posttransfusion hepatitis, with a mean transfusion volume of 10.2 units. Of the 504 cases of posttransfusion hepatitis, "icteric" (T-Bil > 2.0 mg/dl) and "overt icteric" hepatitis (T-Bil > 5.0 mg-dl) developed in 111 cases (22.0%) and 28 cases (5.6%), respectively. Of the 28 overt icteric hepatitis cases, 13 (2.8%) were thought to be true overt icteric posttransfusion hepatitis because the icterus was caused by other reasons in the other 15 cases (seven neonatal jaundice, four hemolytic anemia, one radiation hepatitis, one halothane-induced hepatitis; two other cases were excluded because chronic liver disease was diagnosed by imaging procedures despite serum ALTs in the normal range before transfusion). The anti-HCV serostatus was investigated in five of the 13 true overt icteric posttransfusion hepatitis patients using blood specimens taken 180 days or more following the onset of posttransfusion hepatitis. Anti-HCV seroconversion occurred in three of the five cases (60%). HCV seroconversions were not seen in the cases in which the icterus was due to other reasons.

Glomerular filtration rate and creatinine production in adult icteric patients

Various methods for serum creatinine determination were compared and validity of the Cockroft-Gault algorithm for calculating creatinine clearance was tested in adult icteric patients. Using conventional Jaffé assays, negative interference is proportional to the serum bilirubin content. Pretreatment of the serum with bilirubin oxidase was more efficient in eliminating bilirubin than pretreatment with potassium ferricyanide. Due to a continued creatine-poor diet and liver dysfunction, erythrocyte creatine levels and creatinine output rate were decreased. Median effect (creatinine equivalent) of non-specific chromogens in the unmodified Jaffé assay was 21 μmol/l (range: 1–108 μmol/l), vs. 19 μmol/l (range: 16–26 μmol/l) for the reference population. In the absence of multi-organ failure, the Cockroft-Gault algorithm could be used for estimating glomerular filtration rate. In patients with multiple organ failure however, we recommend correction for both bilirubin and non-specific chromogens for measuring the serum creatinine concentration.