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The liver disorders unique to pregnancy include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, and preeclampsia-associated hepatic impairment, specifically hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP). Their importance lies in the significant maternal and fetal/neonatal morbidity and mortality. Expeditious diagnosis and clinical evaluation is critical to ensure timely, appropriate care and minimize risks to the pregnant woman and her fetus/baby. A multidisciplinary approach is essential, including midwives, maternal-fetal-medicine specialists, anesthetists, neonatologists, and hepatologists., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Liver disease presenting in pregnancy may be due to a pregnancy-specific liver disorder, due to previously unrecognised pre-existing liver disease, or de novo liver disorders coincidentally presenting in a pregnant woman. The pregnancy-specific liver diseases can span from mild disease with limited impact on maternal and foetal health to severe disorders that can result in significant morbidity and mortality for mother and foetus. Swift identification of these disorders is essential to allow timely and appropriate management via a multi-disciplinary approach. The pregnancy-specific conditions, including their presentation, investigations, and management are reviewed in this chapter in detail., Competing Interests: Declaration of competing Interest DK has no conflicts of interest to declare. RW has no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier Ltd.)

Sarcoidosis is a multisystem inflammatory disorder associated with non-caseating granulomas in affected organs, most commonly the lungs. Involvement of extrapulmonary organs is common, but lack of pulmonary involvement is rare and is called non-pulmonary sarcoidosis (NPS). Like pulmonary sarcoidosis, a definitive diagnostic test for NPS does not exist. Instead, the diagnosis of sarcoidosis requires the following elements: clinical and radiographic manifestations of sarcoidosis, histopathological detection of non-caseating granulomas and the exclusion of other diseases that may present similarly. Because of the experience with corticosteroids in pulmonary sarcoidosis, they are generally considered first-line therapy for NPS too. Ursodeoxycholic acid can be used to reduce cholestasis in NPS, but is inferior to corticosteroids in reducing inflammation. We hereby present a case that is particularly notable for its rare presentation of NPS as a granulomatous hepatitis with cholestatic liver function tests., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with sickle cell disease can develop liver disease as a result of intrahepatic sickling of erythrocytes, viral hepatitis and iron overload secondary to multiple blood transfusions, and gallstone disease as a result of chronic hemolysis. The spectrum of clinical liver disease is wide and often multifactorial. Some patients develop cirrhosis that may progress to end-stage liver failure. Limited evidence exists for medical treatments. Exchange blood transfusions may improve outcomes in the acute liver syndromes. Liver transplantation may be an option for chronic liver disease. The role for prophylactic cholecystectomy in preventing complications of gallstone disease is controversial., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Indeterminate biliary strictures pose a diagnostic and therapeutic challenge. Although underlying malignancy is a primary concern, biliary strictures may result from benign processes. An accurate diagnosis is paramount to define the treatment strategy and minimize morbidity. The limitations of traditional endoscopic retrograde cholangiopancreatography-based tissue acquisition with cytology brushings are well-documented. Endoscopic retrograde cholangiopancreatography is generally unable to determine a stricture's etiology. Complementary advanced endoscopic imaging and multimodal tissue acquisition have evolved. Careful consideration of the clinical presentation, location of the stricture, and interpretation of imaging constitute the most optimal approach for diagnosis and management., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The mother's immune system has to adapt to pregnancy accepting the semi-allograft fetus and preventing harmful effects to the developing child. Aberrations in feto-maternal immune adaptation may result in disease of the mother, such as liver injury. Five pregnancy-associated liver disorders have been described so far, however, little is known concerning immune alterations promoting the respective disease. These liver disorders are pre-eclampsia, hemolysis, elevated liver enzymes, low platelet count (HELLP), acute fatty liver, hyperemesis gravidarum, and intrahepatic cholestasis of pregnancy. On the other hand, pre-existing autoimmune liver injury of the mother can be affected by pregnancy. This review intends to summarize current knowledge linking feto-maternal immunology and liver inflammation with a special emphasis on novel potential biomarkers.

Pregnancy associated liver diseases affect up to 3% of pregnant women and are the most frequent cause of liver dysfunction in pregnancy. When severe, they are associated with significant morbidity and mortality for both mother and infant. A rapid evaluation to distinguish them from non-pregnancy related liver dysfunction is essential, in order to facilitate appropriate management. Liver disease unrelated to pregnancy can present de novo in pregnancy, or pregnancy can occur in women with preexisting liver pathology (Table 1). Research and subsequent advances in medical care have resulted in improved but still not satisfactory maternal and fetal outcomes. In this review we provide an overview of the liver diseases specific to the pregnant state and an update on their pathogenesis, treatment and outcomes. The risks of pregnancy in women with pre-existent liver pathology is detailed and recent advances in our understanding of specific risks and outcomes are discussed.

Unlabelled: The intercellular adhesion molecule 1 (ICAM-1) is induced in mouse liver after bile duct ligation (BDL) and plays a key role in neutrophil-mediated liver injury in BDL mice. ICAM-1 has been shown to interact with cytoskeletal ezrin-radixin-moesin (ERM) proteins that also interact with the PDZ protein, Na(+) /H(+) exchanger regulatory factor 1 (NHERF-1/EBP50). In NHERF-1(-/-) mice, ERM proteins are significantly reduced in brush-border membranes from kidney and small intestine. ERM knockdown reduces ICAM-1 expression in response to tumor necrosis factor alpha. Here we show that NHERF-1 assembles ERM proteins, ICAM-1 and F-actin into a macromolecule complex that is increased in mouse liver after BDL. Compared to wild-type (WT) mice, both sham-operated and BDL NHERF-1(-/-) mice have lower levels of activated ERM and ICAM-1 protein in the liver accompanied by significantly reduced hepatic neutrophil accumulation, serum alanine aminotransferase, and attenuated liver injury after BDL. However, total bile acid concentrations in serum and liver of sham and BDL NHERF-1(-/-) mice were not significantly different from WT controls, although hepatic tetrahydroxylated bile acids and Cyp3a11 messenger RNA levels were higher in NHERF-1(-/-) BDL mice., Conclusion: NHERF-1 participates in the inflammatory response that is associated with BDL-induced liver injury. Deletion of NHERF-1 in mice leads to disruption of the formation of ICAM-1/ERM/NHERF-1 complex and reduction of hepatic ERM proteins and ICAM-1, molecules that are up-regulated and are essential for neutrophil-mediated liver injury in cholestasis. Further study of the role of NHERF-1 in the inflammatory response in cholestasis and other forms of liver injury should lead to discovery of new therapeutic targets in hepatic inflammatory diseases., (© 2015 by the American Association for the Study of Liver Diseases.)

We report the case of a 50-year-old woman who was admitted to the hospital for acute abdominal pain with nephrotic proteinuria, rapidly progressive renal failure, and moderate anemia. Laboratory tests showed mild Bence Jones (λ) proteinuria with negative serum immunofixation and a mild increase in λ free light chains. A bone marrow biopsy and a fat tissue aspirate showed multiple myeloma and amyloidosis. Because of the end-stage renal disease, the patient began regular dialysis treatment and was started on bortezomib 1.3 mg/m2 plus dexamethasone 40 mg on days 1, 4, 8 and 11 of 21-day cycles. Ten days later she complained of a new episode of abdominal pain with jaundice. A CT scan and an MRI scan ruled out all secondary causes of cholangitis including cancer. Acute intrahepatic cholestasis due to amyloid deposition was then hypothesized. After 4 well tolerated cycles of bortezomib and dexamethasone, blood tests showed a complete hematological response with full reversal of cholestasis. After three months, a new episode of abdominal pain occurred and this time the patient was operated on and found to have an intestinal volvulus. Because of the jaundice, a transjugular liver biopsy was performed showing no evidence of amyloid deposits. Two months later the patient died of septic shock. Although no autopsy was performed and the ultimate cause of the cholestasis could not be ascertained, amyloidosis remains the major culprit in this unfortunate case.

Purpose: Dependence on total parenteral nutrition in intestinal failure or short bowel syndrome patients can lead to many complications. The most significant complication is progressive liver injury leading to liver failure. This study assesses the potential of hepatocyte growth factor (HGF) in modulating the hepatic response in a rat cholestatic liver injury model., Methods: Female Sprague-Dawley rats were divided into 3 groups: control (n = 5), chronic liver injury (alpha-naphtylisocyocyanate [ANIT] every 3.5 days at 75 mg/kg; n = 5), and chronic liver injury plus HGF (ANIT + HGF at 250 microg kg(-1) d(-1); n = 5). The rats initially underwent massive (80%) small bowel resections. Seven days later, they were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic minipump for continuous intravenous saline or HGF. Intraperitoneal saline or ANIT injections were subsequently administered every 3.5 days to create a chronic cholestatic model. After 14 days, the animals were euthanized, and liver biopsies were obtained. The liver biopsies were evaluated by histology, immunofluorescence staining for interleukin-6 and tumor necrosis factor alpha, and assessment of apoptosis by terminal dUTP-transferase-mediated nick end labeling (TUNEL) technique., Results: In this chronic liver injury model, HGF did not effect the grade of inflammation. However, HGF did induce retention of the ductal structures and avoided ductal proliferation, damage, and evidence of primary sclerosing cholangitis (P < .05). Hepatocyte growth factor induced less interleukin-6 (P < .011) and tumor necrosis factor alpha (P < .01) expression. Apoptotic activity was also significantly less in the HGF group (P < .01)., Conclusion: Hepatocyte growth factor preserved the hepatic ductal system, modulated the hepatic inflammatory response, and reduced the apoptotic index in this chronic cholestatic liver injury model. It may diminish or prevent liver damage in patients with total parenteral nutrition-induced liver injury., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: Intestinal failure (IF)-associated liver disease (IFALD) complicates the treatment of children with IF receiving parenteral nutrition (PN). We hypothesized that prevention or resolution of IFALD was possible in most children and that this would result in improved outcomes., Methods: We reviewed prospectively gathered data on all children referred to the intestinal rehabilitation and transplantation center at our institution. Total bilirubin level (TB) was used as the marker for IFALD. Patients were grouped based on TB at referral and at subsequent inpatient stays and outpatient visits. Standard treatment consisted of cycling of PN, limiting lipid infusion, enteral stimulation, use of ursodeoxycholic acid, and surgical intervention when necessary. Outcomes such as mortality, dependence on PN, and need for transplantation were assessed. Statistical analyses were performed using Fisher's exact, Mann-Whitney U, and Wilcoxon signed rank tests., Results: Ninety-three patients with intestinal failure and on PN were treated at our center from 2003 to 2009. Median age at referral was 5 months (0.5-264 months). Prematurity was a complicating factor in 63 patients and necrotizing enterocolitis was the most common diagnosis. Eighty-two children had short bowel syndrome, whereas the remaining 11 had extensive motility disorders. 97% of children required significant alteration of their PN administration. At referral, 76 of 93 children had TB 2.0 mg/dL or higher, and 17 had TB below 2.0 mg/dL. TB normalized in 57 of 76 children with elevated TB at referral, and TB remained elevated in 19. Normalization of TB was associated with a mortality of 5.2%, and transplantation was needed in 5.2%. Conversely, when TB remained elevated, mortality was 58% (P = .0002 vs TB normalized), and transplantation occurred in 58% owing to failure of surgical and medical rehabilitation., Conclusions: Most children referred for treatment of IF have IFALD. A dedicated IF rehabilitation program can reverse IFALD in many children, and this is associated with improved outcome., (Copyright 2010 Elsevier Inc. All rights reserved.)

We describe a 71-year-old man with an inflammatory tumor arising in segment 5 of the liver. The patient was admitted because of acute pain in the right upper quadrant of the abdomen and fever. Initial laboratory tests revealed the following: serum alkaline phosphatase concentration, 634 IU/L; serum gamma glutamic transpeptidase concentration, 1,378 IU/L; serum C-reactive protein concentration, 0.89 mg/dL; and total bilirubin concentration, 8.9 mg/dL. Abdominal ultrasonography, computed tomography (CT), and magnetic resonance imaging showed a mass, 3 cm in diameter, in segment 5 of the liver. Magnetic resonance cholangiopancreatography showed a lesion of moderate-to-high signal intensity on T2-weighted images of segment 5. Endoscopic retrograde cholangiopancreatography revealed a common bile duct stone. The intrahepatic bile ducts of segment 5 could not be visualized after the use of contrast material. Endoscopic sphincterotomy was performed to remove the common bile duct stone. Antibiotics were administered soon after stone removal, and fever gradually resolved. Positron emission tomography revealed hot spots in segment 5 of the liver. Three weeks after discharge, the patient was readmitted with an acute pain in the right upper quadrant of the abdomen. Abdominal ultrasonography, CT, and magnetic resonance imaging showed enlargement of this area. Inflammatory changes of segment 5 due to cholangitis with intrahepatic bile duct stones was diagnosed. Because malignant disease could not be completely ruled out, segment 5 of the liver was resected. Macroscopic examination of the resected specimen revealed a gray, fibrotic, solid tumor associated with intrahepatic bile duct stones. Microscopic examination of the tumor showed proliferation of spindle-shaped myofibroblastic cells in a mixed myxoedematous, dense fibrotic stroma, associated with infiltration by various acute and chronic inflammatory cells. The postoperative course was uneventful, and the patient was discharged on postoperative day 16.

Hypothesis: Primary intrahepatic lithiasis occurs frequently in East Asia but is rare in Western countries. Biliary pain and episodes of cholangitis are the most common presenting symptoms, whereas intrahepatic cholangiocarcinoma represents a long-term unfavorable complication of the disease. When a single liver lobe or segment is involved, partial hepatectomy may be regarded today as an effective method of treatment., Design: Retrospective study., Setting: Hepatobiliary unit in a tertiary care hospital., Patients: The clinical records of 35 patients treated for primary intrahepatic lithiasis between January 1, 1992, and December 31, 2005, were reviewed and clinical data, cholangiograms, operative procedures, and early and late results were examined., Interventions: Thirty-four patients underwent liver resection; left hepatectomy (18 patients) and left lateral segmentectomy (10 patients) were the most frequently performed procedures. A cholangiocarcinoma was found in 3 patients (8.6%): 2 underwent liver resection and 1, who was found unresectable at surgery, underwent only explorative laparotomy., Main Outcome Measures: Survival, quality of life, laboratory data, and need for further treatments., Results: There was no postoperative mortality. Morbidity was 20.0% with a prevalence of infectious complications related to bile leakage. Long-term results, assessed in 26 patients with follow-up longer than 12 months (range, 12-170 months; mean, 63 months), were good or fair in 24 patients (92.3%), including 3 patients who needed subsequent endoscopic removal of biliary stones., Conclusions: Primary intrahepatic lithiasis more commonly involves 1 single liver segment or lobe. Partial hepatectomy is a safe and effective procedure, allowing definitive treatment of the disease and prevention of cancer.

Sickle cell hepatopathy is a well-documented entity that ranges from the self-limiting hepatic right upper quadrant syndrome to the potentially lethal intrahepatic cholestasis and acute hepatic sequestration syndromes. We describe a 26-year-male with homozygous sickle cell disease who had this unique hepatic presentation and was documented to have characteristic findings of cholestasis, portal inflammation and sinusoidal dilatation on histopathology.

Sarcoidosis is a multisystem disease of unknown aetiology. Histological evidence of non-caseating granulomas represents the main finding. It affects mostly young people, targeting primary the lung and hilar lymph nodes although liver involvement is often encountered. Hepatic sarcoidosis covers a broad spectrum from asymptomatic hepatic granulomas formation and slightly deranged liver function tests to clinically evident disease with cholestasis or, in advanced cases, cirrhosis and portal hypertension. Other granulomatous diseases (mainly systemic infections like tuberculosis) should be excluded prior to treatment, as longstanding corticosteroid administration is the main stem of therapy. In advanced cases, liver transplantation represents the ultimate therapeutic option.

Objective: Hepatic dysfunction is an important but poorly understood component of sepsis. In severe sepsis, liver dysfunction is characterized by cholestasis, steatosis, hepatocellular injury, impaired regeneration, a decreased response to the cytokine interleukin-6, and high mortality. To determine whether loss of interleukin-6 activity caused hepatic dysfunction and mortality, we induced sepsis in wild-type (interleukin-6 +/+) and interleukin-6 knockout (interleukin-6 -/-) mice. We hypothesized that sepsis in interleukin-6 -/- mice would increase cholestasis, steatosis, hepatocellular injury, and mortality and impair hepatocyte regeneration., Design: Randomized prospective experimental study., Setting: University medical laboratory., Subjects: Male adolescent C57Bl6 interleukin-6 +/+ and interleukin-6 -/- mice., Interventions: Mild sepsis was induced using cecal ligation and single puncture (CLP). Severe, lethal sepsis was induced using cecal ligation and double puncture (2CLP). Some mice received recombinant human interleukin-6 at the time of CLP/2CLP. All animals were fluid resuscitated at the time of surgery and every 24 hrs thereafter. In survival cohorts, mortality at 16, 24, 48, and 72 hrs was recorded. In separate cohorts, surviving animals were killed at 24 and 48 hrs, and liver tissue was harvested. A separate cohort of mice received bromodeoxyuridine for detection of regeneration., Measurements and Main Results: 2CLP was 100% fatal within the first 12 hrs in interleukin-6 -/- mice. Mortality from 2CLP in interleukin-6 +/+ mice before 24 hrs was nil but was 90% by 72 hrs. At 72 hrs, CLP was 40% fatal in interleukin-6 +/+ mice but 90% in interleukin-6 -/- mice. CLP induced cholestasis, steatosis, and hepatocellular injury in interleukin-6 -/-, but not interleukin-6 +/+, mice. Regeneration was absent following CLP in interleukin-6 -/- animals but occurred in interleukin-6 +/+ mice. Early administration of recombinant human interleukin-6 did not reverse abnormalities in interleukin-6 -/- mice., Conclusions: The absence of interleukin-6 is an important determinant of hepatic dysfunction and mortality in sepsis.

Hepatic involvement in primary amyloidosis (AL type) is not rare but is often clinically silent. However, presentation with jaundice in AL-type amyloidosis is rare, with an incidence of less than 5% reported in the literature. It is considered to be a preterminal sign. We herein report on a case of primary hepatic amyloidosis presenting with severe intrahepatic cholestasis. Viral, drug, alcohol, and autoimmune etiologies were all excluded. A liver biopsy was performed because of unexplained cholestatic jaundice for 3 months. The pathology showed hepatic amyloidosis with extensive amyloid deposition in the expanded portal tracts and sinusoidal space. The patient received supportive treatment only, because of persistent jaundice, coexistent colon cancer with para-aortic lymph node metastasis, and possibly peritoneal carcinomatosis. Unfortunately, the patient died of sepsis 10 months after the onset of jaundice. We suggest that hepatic amyloidosis must be considered in the differential diagnosis of unexplained cholestatic jaundice.

The liver is frequently involved by amyloidosis, but hyperbilirubinemia and liver failure are uncommon features. A mild elevation of the serum alkaline phosphatase value and, less frequently, hepatomegaly are the most common findings. Usually the patients have no symptoms related with the liver involvement; the clinical manifestation and the long term prognosis depends on the renal and cardiac disease. We report an unusual clinical presentation of primary amyloidosis in a previously asymptomatic 65 years old woman who was admitted to the hospital because of ictericia and ascitis mimicking a drug induced acute hepatic failure.

Background/aims: Acute serious liver disease which is unrelated to infectious, obstructive, or metabolic disease is uncommon. Many drugs have been implicated. Data on its epidemiology are scarce. We performed a population-based prospective study of acute serious liver disease in Catalonia (Spain)., Methods: A collaborating hospital network was set up. All patients with acute serious liver disease and negative viral hepatitis serological markers, without an obvious cause of liver disease, were included., Results: The incidence of acute serious liver disease was 7.4 per 10(6) inhabitants per year (95% CI; 6.0-8.8), which increased with age. The incidence of hepatocellular acute serious liver disease (3.84 per 10(6) per year) was greater than that of cholestatic and mixed patterns. The case-fatality ratio was 11.9% and mortality 0.8 per million person-years. The risk of death was similar among patients with hepatocellular and cholestatic patterns. Non-steroidal antiinflammatory drugs, analgesics, and antibacterials were the most frequently used drugs., Conclusions: Acute serious liver disease which is unrelated to infectious, obstructive, or metabolic disease is rare. Its incidence increases with age. The prognosis of cholestatic acute serious liver disease does not significantly differ from that of the hepatocellular pattern. Non-steroidal antiinflammatory drugs, analgesics, and antibacterials were the most common drugs likely to be responsible for acute liver disease., (Copyright 2002 European Association for the Study of the Liver)

Clinical Symptoms: We report of a 52-year-old man from Egypt who suffered from 20 kg weight loss within 6 months, jaundice, macrohematuria, and impaired renal function., Investigations and Therapy: Due to the ultrasound and the CT scan of the abdomen, a kidney tumor was suspected. A nephrectomy was planned but the biopsy of the kidney and liver intraoperatively revealed amyloid deposits. A plasma cell dyscrasia of 15% was found by bone marrow biopsy. Immunfixation showed an IgG-kappa light chain in plasma and urine. There was no osteolysis throughout the skeletal system. Thus, the patient had a plasmacytoma Stage II associated with IgG-kappa light chain AL-amyloidosis which was treated by chemotherapy (melphalan and prednisolone)., Conclusion: This unusual case presents a cholestatic liver disease due to bile duct obstruction secondary to amyloid deposits. Although AL-amyloidosis is easily diagnosed by certain criteria, the disease is often recognized too late with consequently poor prognosis.

Background: Liver cholestasis can be a life-threatening complication during home parenteral nutrition and may lead to combined liver-intestinal transplantation., Objective: To assess the prevalence of home parenteral nutrition-related liver disease and its contributing factors in patients with permanent intestinal failure., Design: Prospective cohort study., Setting: Two approved home parenteral nutrition centers., Patients: 90 patients with permanent intestinal failure who were receiving home parenteral nutrition were enrolled from 1985 to 1996., Intervention: Clinical, biological, endoscopic, and ultrasonographic follow-up. Histologic examination of the liver was done in 57 patients (112 liver biopsies)., Measurements: The Kaplan-Meier method was used to determine the actuarial occurrence of chronic cholestasis and complicated home parenteral nutrition-related liver disease (bilirubin level > or =60 micromol/L [3.5 mg/dL], factor V level < or =50%, portal hypertension, encephalopathy, ascites, gastrointestinal bleeding, or histologically proven extensive fibrosis or cirrhosis). Contributing factors were assessed by using univariate and multivariate (Cox model) analysis., Results: 58 patients (65%) developed chronic cholestasis after a median of 6 months (range, 3 to 132 months), and 37 (41.5%) developed complicated home parenteral nutrition-related liver disease after a median of 17 months (range, 2 to 155 months). Of these patients, 17 showed extensive fibrosis after 26 months (range, 2 to 148 months) and 5 had cirrhosis after 37 months (range, 26 to 77 months). The prevalence of complicated home parenteral nutrition-related liver disease was 26%+/-9% at 2 years and 50%+/-13% at 6 years. Six patients died of liver disease (22% of all deaths). In multivariate analysis, chronic cholestasis was significantly associated with a parenteral nutrition-independent risk for liver disease, a bowel remnant shorter than 50 cm in length, and a parenteral lipid intake of 1 g/kg of body weight per day or more (omega-6-rich long-chain triglycerides), whereas complicated home parenteral nutrition-related liver disease was significantly associated with chronic cholestasis and lipid parenteral intake of 1 g/kg per day or more., Conclusion: The prevalence of complicated home parenteral nutrition-related liver disease increased with longer duration of parenteral nutrition. This condition was one of the main causes of death in patients with permanent intestinal failure. Parenteral intake of omega-6-rich long-chain triglycerides lipid emulsion consisting of less than 1 g/kg per day is recommended in these patients.

Selection of a method of contraception in patients with liver disease can be complicated. Tubal ligation should be considered in the setting of chronic liver disease for those patients who have completed families. Multiple reversible methods of contraception are currently available but may affect hepatic disease. Estrogen-containing contraceptive methods are contraindicated in patients with acute liver disease. Progestin contraceptives appear to be safe and multiple delivery systems are available. With rare exception, barrier methods and the intrauterine device may be offered as alternative methods.

A quarter of patients with erythropoietic protoporphyria develop mild to severe cholestatic liver disease. The determination of early indicators of hepatobiliary involvement are of pivotal importance to select patients for choleretic therapy. Porphyrin parameters were studied during ursodeoxycholic acid treatment in eight patients with protoporphyrin-associated liver disease and eight patients with liver failure before and after liver transplantation. The patients with intrahepatic cholestasis exhibited excessive protoporphyrinemia (27 mumol/l) compared with controls (normal < 0.64 mumol/l). Fecal protoporphyrin excretion decreased in patients with deterioration of liver function, whereas urinary coproporphyrin increased up to 2290 nmol/24 h (normal < 119 nmol/24 h). Coproporphyrin isomer I proportion increased to 71 +/- 10% (mean +/- SD, n = 8) in patients with terminal liver failure (normal < 31%). During therapy with ursodeoxycholic acid biochemical improvement occurred but without clinical remission in most cases. Eight patients underwent liver transplantation between 1987 and 1997. One patient died of liver failure. Two transplant recipients are in a good condition since 8 and 9 years, respectively. All explanted livers revealed micronodular cirrhosis and high protoporphyrin levels of about 25,000-fold (mean, n = 3). Immediately after liver transplantation protoporphyrin in erythrocytes decreased to 46-96% of pre-operative values. Coproporphyrin remained moderately elevated due to post-operative cholestasis. A post-operative rise in fecal protoporphyrin elimination reflected sufficient biliary clearence of protoporphyrin by the transplant. In conclusion, moderate coproporphyrinuria with isomer I is the earliest sign of liver complications in erythropoietic protoporphyria. Progression of protoporphyrin induced toxic liver injury is indicated by excessive protoporphyrinemia and coproporphyrinuria with an isomer I proportion > 71 +/- 10%, and reduction of fecal protoporphyrin excretion. Results suggest that therapy of intrahepatic cholestasis with ursodeoxycholic acid is only effective in the initial stages of liver disease in erythropoietic protoporphyria. In patients with severe cholestatic hepatic failure, liver transplantation is the treatment of choice.

In primary amyloidosis the gastrointestinal tract and the liver are commonly involved, but clinical features and prognosis are mainly determined by the extent of cardiac and renal involvement. We review two cases with primary amyloidosis of the gastrointestinal tract and the liver. The predominant symptoms were malabsorption and hepatomegaly with cholestasis. The clinical aspects, diagnosis, treatment and prognosis of primary amyloidosis of the gastrointestinal tract and the liver are discussed in the context of the current literature.

We describe a subcapsular hematoma of the liver and pylethrombosis in a patient who developed cholestasis 4 days after severe burn injury. On the 44th hospital day, severe anemia suddenly appeared with no determinable cause. This was the initial manifestation of hepatic hematoma. Cholestatic liver injury of unknown cause lasted throughout the clinical course. The patient subsequently died of hepatic failure 27 months after the burn injury. An autopsy confirmed pylephlebitis and pylethrombosis, which were considered to have contributed to the hepatic failure. This was a rare case of hepatic hematoma and pylephlebitis and pylethrombosis that developed after burn injury.

Cholestasis syndromes are characterized by a reflux of compounds usually excreted with bile. ATP dependent carriers and cytoskeleton proteins guarantee physiological bile flux. There are several clinical conditions in which this system is affected. Intrahepatic cholestasis is characterized by damage to hepatocytes or intrahepatic bile ducts. Primary biliary cirrhosis and primary sclerosing cholangitis represent examples of cholestatic chronic liver disease. The pathogenesis of these two conditions seems to be mediated by immunological reactions. Moreover, hepatitis viruses are able to induce cholestasis.

We report a case of obstructive jaundice caused by a large hepatic cyst which was successfully treated by percutaneous drainage and instillation of minocycline hydrochloride. An 88-year-old man presented with obstructive jaundice and upper abdominal fullness. Abdominal CT and ultrasonography revealed a large hepatic cyst and intrahepatic bile duct dilatation. After the percutaneous drainage of the cyst, minocycline hydrochloride was instilled as a sclerosant via a catheter into the cyst cavity. Liver enzyme levels returned to normal and the jaundice disappeared. Nine months after the treatment, the large cyst and dilatation of the intrahepatic bile duct had disappeared. The patient has remained healthy without symptoms.

During parenteral nutrition hepatic complications are seen in about 15% of patients. They are characterized by steatosis, cholestasis and formation of sludge and bile stones. These hepatic complications depend on the duration as well as on the concept and mode of application of parenteral nutrition. They are more frequent after treatment periods of > 1-2 weeks, in response to a carbohydrate rich and low fat parenteral nutrition and in patients with extensive intestinal resection. Clinically, hepatic complications are frequently observed in new-borns and children, patients with inflammatory bowel disease, after ileum resection and in patients with hepatic malignancies. The exact pathophysiology of these phenomena is presently unknown. Enteral instead of parenteral nutrition, meeting the demand of nutrients, increasing fat supply (up to 50% of energy supply), "cyclic" parenteral nutrition and the addition of "semi-essential" nutrients (like L-glutamine, carnitin, cholin) are considered as possible strategies for the prevention and therapy of hepatic complications during parenteral nutrition.

We have reviewed all available data related to the development of liver dysfunction in patients receiving total parenteral nutrition (TPN). It seems that TPN-related liver dysfunction is multifactorial. Among all factors involved, two are most significant in the development of liver dysfunction, i.e. underlying disease and illness severity. In most cases, liver dysfunction is both self-limiting and reversible after cessation of TPN.

There are many causes of granulomas of the liver including infections, immunological aberrations, enzyme defects, drugs and other chemicals, and neoplasia (Table I). The commonest causes are tuberculosis, sarcoidosis, schistosomiasis and intrinsic liver disease. About 10 per cent of granulomas remain unidentified. In sarcoidosis, liver granulomas are usually inconspicuous and featureless. They are not associated with symptoms or abnormal physical signs. Sarcoidosis of the liver has three well-recognised clinical syndromes-chronic intrahepatic cholestasis, portal hypertension and the Budd-Chiari Syndrome.

Inducing positive nitrogen balance and weight gain in patients fed exclusively parenterally was documented first by Dudrick et al. in 1968. Since that time, total parenteral nutrition (TPN) has become commonplace both in acutely ill patients and in those with severe chronic gastrointestinal disease. Clear nutritional benefits accrue, but certain complications associated with TPN have become apparent. In the following discussion we review clinical, biochemical, and pathophysiologic abnormalities of the hepatobiliary system associated with TPN, particularly hepatic dysfunction and gallbladder disease and their management.

Liver transplantation is the therapy of choice in the final stage of PBC, PSC and biliary atresia. UDCA leads to remission of the symptoms and the clinic in the early stages not only of these diseases but of cholestasis of pregnancy and of cholestasis in cystic fibrosis as well. In benign intermittent cholestasis only phenobarbital but not UDCA seems to be efficacious. The efficacy of UDCA in chronic active hepatitis and alcoholic hepatitis is not yet guaranteed.

There are three types of disorders which may produce jaundice during pregnancy: 1) acute or chronic coexistent or pre-existent liver disease (acute and chronic hepatitis, liver cirrhosis etc.), 2) acute and chronic hemolytic disorders, 3) jaundice directly or indirectly related to pregnancy. Among the later group, intrahepatic cholostasis, gravidic hyperemesis with jaundice represent exacerbations of physiologic gravidic cholostasis. Hepatic steatoses of pregnancy are the result of toxic metabolites or drugs on the liver parenchyma. Severe forms of eclampsia may induce jaundice of hemolytic and parenchymal origin. Hypercoagulability may also induce, in the first post-partum days Budd-Chiari's syndrome with accompanying jaundice.

Despite the fact that hepatic involvement is frequently seen in systemic amyloidosis, major clinical symptoms or impaired hepatic functional capacity are rare. We describe a patient with primary hepatic amyloidosis, severe intrahepatic cholestasis and portal hypertension, a combination previously reported only three times in the literature. In case of an unexplained intrahepatic cholestasis or portal hypertension the possibility of amyloidosis should be considered and a Congo red staining should be performed.

In order to determine the extent of liver abnormalities occurring during acquired immunodeficiency syndrome, the available histological analyses of liver samples (32 biopsies, 52 autopsies) from 71 AIDS patients, for the period 1982-1986, were studied retrospectively. Hepatomegaly was the most common clinical symptom (23 patients, 32.4%), while jaundice was rare, being seen in only 5 cases (7%). Progressive anicteric cholestasis was the most frequently observed biological anomaly (29/52, 55.7%). Ten patients had liver infections: 2 Mycobacterium tuberculosis, 8 Mycobacterium avium intracellulare. Cytomegalovirus was present in 3 patients and 1 individual was infected with Cryptococcus neoformans. Granulomatous hepatitis was associated with these infectious agents in 11 patients, but remained unexplained in 11 others. Three patients had cholangitis (2 with CMV inclusions, 1 unexplained). Among the 32 biopsies, 5 elucidated the origin of unexplained fever. Kaposi's sarcoma of the liver was found in 10/52 autopsy samples (19%) and hepatic lymphoma in 2 cases. Non-specific histological lesions were common: inflammation of the portal spaces (48 cases, 67.6%), steatosis (32 patients, 45%), peliosis hepatis (9 cases, 12.6%) and sinusoidal dilations (39 cases, 54.9%).

The authors had 302 patients with focal lesions of the liver, 232 of them were operated on. Radical operations were carried out on 96 and palliative operations on 136 patients. Operations were performed for a second time in 35 patients, radically in 24 of them. A previously conducted exploratory laparotomy is still no evidence of inoperability of the process. In alveococcosis of the liver with no clinical signs of biliary stasis, it is advisable to consider resection of the liver after a previously conducted bile-draining operation. Patients who had been subjected to cavernotomy may also be operated on radically. The appearance of jaundice in the late-term periods after resection-fragmentation of the liver indicates growth of the remaining area of the parasitic nodus and dictates the indications for a bile-draining operation. Obstructive jaundice is considered the main indication for undertaking a palliative operation for the second time. Five patients died after surgery.

Retention cysts may arise from periductal glands of the hepatic ducts. These cysts are usually asymptomatic. Presented here is the first case with jaundice secondary to obstruction of the hepatic ducts by periductal cysts. Two other cases involved asymptomatic cysts in the presence of cirrhosis, portal vein thrombosis, and hepatocellular carcinoma. This confirms the previously noted association of cysts and portal vein thrombosis. The possibility of obstruction caused by benign cysts should be considered when investigating patients with intrahepatic bile duct obstruction.

Immunotherapy with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells (LAK) has become a new form of therapy that has been shown to induce remissions in patients with renal cell carcinoma and melanoma. Despite encouraging results, this form of therapy has been associated with increasing toxicity, often requiring therapy in an intensive-care unit. In this report severe intrahepatic cholestasis occurred in two patients receiving rIL-2 and LAK cells. This form of cholestasis appeared to be directly related to rIL-2 administration at a doses of 2 x 10(6) U/m2 and 3 x 10(6) U/m2 t.i.d. A liver biopsy showed moderate hepatocellular bile stasis, with lobular and portal inflammation. All other studies for potential cause of this cholestasis were negative, including studies for metastatic disease. When therapy was discontinued, evidence for cholestasis and bile stasis resolved. We conclude that rIL-2 is a drug with a potential to induce severe hepatic injury that is reversible upon cessation of therapy with rIL-2. Further care should be exercised when rIL-2 is administered to patients with abnormal liver function.