Common Liver diseases

Common Liver diseases

  • Alcoholic Liver Disease
  • Alpha-1-Antitrypsin (AAT) Deficiency
  • Autoimmune Hepatitis
  • Budd Chiari syndrome
  • Viral hepatitis
  • Hepatocellular cancer
  • Metastatic cancer
  • Nonalcoholic steatohepatitis (NASH)
  • Wilson’s disease
  • Drug induced hepatitis
  • Primary Biliary Cirrhosis
  • Primary Sclerosing cholangitis

Common Biliary diseases

  • Cancers of the gall bladder and bile duct
  • Primary biliary atresia
  • Choledochal cyst
  • Bile duct stones
  • Biliary strictures
  • Bile duct injuries

Alcoholic Liver Disease

This is the most common cause of liver cirrhosis in most parts of the world with 3 distinct clinical phases - acute fatty liver, alcoholic hepatitis and alcoholic cirrhosis and can occur in varying combinations. Acute fatty change progresses to cirrhosis in 20% of patients, alcoholic hepatitis develops only in a small proportion of patients after decades of abuse and may progress to cirrhosis. Once cirrhosis develops it is irreversible and progresses at the rate of 10% every year provided there is no further abuse. Liver cancer can develop in 20% of these cirrhotics.

Presentation
Acute fatty liver

Fatty change occurs after consumption of large amounts of alcohol over a short period of time. Liver tests and clinical liver swelling return to normal after abstaining from alcohol. The fat clearance from the liver takes place in 2-6 weeks. With continued abuse of alcohol this may progress to hepatitis and cirrhosis.

Alcoholic Hepatitis

This can present with mild swelling of the liver to severe jaundice, fluid in the abdomen including hepatic coma. The symptoms include lethargy, anorexia, fatigue, vague abdominal pain and rarely jaundice. Women tend to have more florid illness. Approximately 50% may have fluid collection in the abdomen. Bleeding tendency may manifest as easy bruising of skin. Blood tests show rise in liver enzymes and bilirubin.

Treatment

Stopping alcohol consumption is the most important step in treating AH. Several supportive measures like improving nutrition, anti-oxidants, multi vitamins, anti-inflammatory drugs like steroids, hormonal therapy and pro-regenerative stimulants tend to help in stabilizing and sometimes improving AH. Treating co-morbidities like Diabetes, bacterial infections and renal dysfunction are part of conservative treatment measures. Transplantation of the liver is generally not recommended in active AH as the survival is < 60% and in those who do survive there is a high rate of recidivism. However, transplant is recommended for those with cirrhosis without AH when they have been abstinent from alcohol for more than 6 months.

Alpha-1-Antitrypsin (AAT) Deficiency

It is the one of the 3 most common genetic disorders amongst whites. In this condition the Alpha 1 Antitrypsin molecule is trapped within the liver cells, where it is manufactured. This results in a deficiency that leads to alveolar membrane damage in the lungs, and emphysema and the abnormal accumulation in liver cells results in their destruction, leading to liver cirrhosis. The disease can either present in early childhood or in 4th to 5th decade of life.

Diagnosis

Alpha 1 Antitrypsin level can be measured in the blood. Level less than 80 mg/dl increases the likelihood of the diagnosis.

Treatment

The lung disease has several medical, surgical and genetic treatment available. Liver disease often presents late and would need liver transplantation.

Autoimmune Hepatitis (AIH)

AIH is a disease of unknown cause that results from the immune system (T cells) attacking the liver cells. 70% of those affected are females in the age group of 2 to 50 years.

Diagnosis

This is based on raised liver enzymes, inflammatory pattern in the liver biopsy, raised liver specific autoimmune markers (in 30%) and most importantly ruling out other causes of hepatitis like viral hepatitis. In children establishing the diagnosis is more difficult due to overlap of other cholestatic diseases.

Treatment

When diagnosed early treatment involves steroids (Prednisolone) with or without Azathioprine for a period of 18 to 24 months. Patients experiencing multiple relapses are likely to progress to decompensated cirrhosis. Untreated patients and non-responders can die of liver failure within a year.
Those who develop ascites, coma and jaundice with MELD score over 15 will need a liver transplant. The disease can rarely recur in the new liver.

Budd Chiari Syndrome (BCS)

BCS is a rare disorder wherein there is wide spread clotting of the veins draining the liver. There is blockage of venous outflow from the liver resulting from either hepatic vein or caval thrombosis or caval web or narrowing above the liver (Thrombotic states are responsible for >70% of BCS in the US and Europe while membranous Caval webs are common in Asia). The other causes include liver cancer, polycythemia, myeloproliferative disorders and oral contraceptive usage.

Presentation

Can present acutely with pain in the abdomen and sudden onset liver failure with jaundice and coma or can present insidiously with a chronic course. The chronic phase presents with severe abdominal distension from large fluid accumulation in the belly, fatigue and poor nutritional status.

Diagnosis

Angiography by trans jugular approach and measurement of hepatic wedge pressure are the gold standard to establish the diagnosis. CT scan, MRI and Doppler examination can give equally reliable diagnosis. Serum albumin levels help in determining the severity of liver disease. Peripheral smear and bone marrow biopsy may be required to rule out myeloproliferative disorders.

Treatment

Non-surgical therapies with anticoagulation are seldom successful. In the absence of supracaval obstruction, porto-caval or meso-caval shunts are useful. Early in the disease process it may be ideal to consider TIPSS (Trans jugular Intrahepatic Porto Systemic Shunt). Acute BCS with fulminant hepatic failure will need Liver transplantation. Chronic BCS with fibrosis and synthetic dysfunction will also benefit fromLiver transplantation

Viral Hepatitis (chronic & acute)

Chronic viral hepatitis is the principal cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in the world. Viral Hepatitis A

Hepatitis A virus infection may not cause any signs or symptoms and the elderly are more likely to have symptoms than children. Symptoms can occur abruptly and may include fever, tiredness, loss of appetite, nausea, abdominal discomfort, dark urine, and jaundice (yellowing of the skin and eyes). This lasts less than 2 months and only in less than 2%, severe liver failure may lead to death unless an emergency liver transplant is done.

A blood test (IgM anti-HAV) is needed to diagnose hepatitis A.

Hepatitis A virus is spread from person to person by putting something in the mouth that has been contaminated with the stool of a person with hepatitis A. Most infections result from contact with a household member or sex partner who has hepatitis A. Eating food that has been prepared by someone with hepatitis A can spread the disease.Hepatitis is a self-limiting disease with majority developing immunity to the virus in three weeks. Viral Hepatitis B

Hepatitis B virus (HBV)alone is estimated to have infected 400 million people throughout the globe, making HBV one of the most common human pathogens. Hepatocellular carcinomas (HCC), one of the most common cancers afflicting humans, is primarily caused by chronic HBV infection.

Symptoms during the onset of acute hepatitis B viral infection vary, depending on the individual. Many children and some adults infected with the virus never show any discernible symptoms. However, most infected individuals have some jaundice which tends to develop soon after the virus can be detected in the blood. Often, jaundice is preceded by mild fevers, fatigue, malaise, loss of appetite, and sometimes nausea and vomiting.

Clinical Phases during Acute Infection

Hepatitis infection can be broken into four stages: i) incubation period - time between initial viral entry into the cell to first day of symptoms; ii) prodromal or pre-icteric period; iii) the icteric phase; and iv) recovery.Serological assays are used to differentiate the type of viral infection as well as discriminate between chronic and acute hepatitis B virus (HBV) infection. PCR has also been used in detecting low levels of HBV DNA present in both blood and liver tissue samples.Patients may not have jaundice, but may suffer from gastrointestinal and influenza-like symptoms and are likely to remain undiagnosed unless a clear history of exposure is available. The severity of infection may vary from the asymptomatic and jaundiced (from which recovery is typical) through to fulminant, fatal viral hepatitis.

Cirrhosis

Cirrhosis can be characterized anatomically by widespread nodules in the liver combined with fibrosis. This is a sequelae of chronic hepatitis B hepatitis.

Fulminant hepatitis

This is a rare form of the disease which usually overwhelms the patient within ten days. The patient may become deeply jaundiced. Foreboding signs may be repeated vomiting, fetor hepaticus, confusion, and drowsiness. The 'flapping' tremor may only be transient, but rigidity is usual. These are then supervened by coma, indicating likely acute liver failure.

Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma is the technical term for liver cancer. This form of the disease develops after a long time in individuals suffering from chronic hepatitis B infection.

Hepatitis C is the most common cause of chronic viral hepatitis in the Western world. Ranks second, slightly below chronic alcoholism as a cause of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Half the patients with chronic HCV infection have normal or only minimally elevated serum aminotransferase concentrations, but can have a marked degree of hepatitis as indicated by histologic evidence. (Hepatitis C treatment) Acute Hepatitis A & E

Commonest water borne type of Hepatitis in the developing world andis transmitted primarily by the fecal-oral route and fecal contaminated drinking water is the most commonly documented vehicle of transmission.The incubation period following exposure to HEV ranges from 15 to 60 days (mean, 40 days). Typical clinical signs and symptoms of acute hepatitis E are similar to those of other types of viral hepatitis and include abdominal pain anorexia, dark urine, fever, hepatomegaly, jaundice, malaise, nausea, and vomiting. Other less common symptoms include arthralgia, diarrhea, pruritus, and urticarial rash. The period of infectivity following acute infection has not been determined but virus excretion in stools has been demonstrated up to 14 days after illness onset.Diagnosis is made by a blood test showing detectable IgM antibody to the virus. Majority would recover spontaneously without sequelae. 2% of hepatitis A and < 5% of those with hepatitis E can have a fulminant course of liver failure, needing liver transplantation.

Hepatocellular cancer

Primary cancer of the liver usually occurs in liver cirrhosis and rarely within the non-cirrhotic liver. The tumour is always silent and gets detected on routine scanning of the abdomen. The tumour usually presents when it has grown to a large size. Serum AFP may be elevated in patients with HCC. Need for liver biopsy is rare in diagnosis of HCC. Surgical removal is the best option to treat HCC though only 10% of the tumours are removable due to late presentation. Liver transplantation is the treatment of choice in selected group of patients with HCC and cirrhosis.

Metastatic cancer

Majority of cancers from the GI tract tend to spread to the liver by blood stream, commonest being colonic cancers. Cancers from breast, thyroid, kidneys, pancreas, lungs, etc can also spread to the liver. They are usually multiple and have a typical appearance on CT scan. Diagnosis should be confirmed by tru-cut biopsy of the lesions. The treatment options are limited to chemotherapy, cryotherapy and rarely surgical excision. Surgery is indicated in colonic metastasis and other static residual tumours. There is no role for liver transplantation except in select and unusual tumours like the Neuro-endocrine tumours.

Nonalcoholic steatohepatitis (NASH)

This condition where there are abnormal levels of fat infiltration in the liver has become one of the leading causes (>25%) of liver failure today. It is closely related to modern lifestyle change, diet and sedentary habits. It is often silent, blood tests will show raised liver enzymes and scan of the liver may show fatty change. Diagnosis is confirmed by liver biopsy. It may slowly progress to liver cirrhosis and is replacing viral hepatitis as a major indication for liver transplantation. Treatment is aimed at controlling fat levels, dietary changes, exercise and anti-oxidants.

Wilson’s disease

This is an autosomal recessive disease of copper metabolism due to an abnormal gene localized to chromosome 13. The overall disease incidence is 1:200000. Copper excretion in the bile is reduced resulting in accumulation of copper in the liver causing liver injury and is usually detected after 5 years. Clinical presentation: Stage 1 - asymptomatic copper accumulation, stage 2 - enlargement of liver and spleen, abnormal liver enzymes, acute liver failure or liver cirrhosis with portal hypertension, stage 3 - asymptomatic copper in central nervous system, stage 4 - frank neurological symptoms.

Diagnosis

Low Ceruloplasmin(<20mg/d1), low serum copper(<80mg/L), and high 24 hour urine copper (>100mg/24 hours). False positive reports are common. The copper content of liver is the most reliable test and is >250 mcg/Gm of tissue. Radioactive copper incorporation in Ceruloplasminis decreased in Wilson's.

Treatment

Medical management is first line in treatment with chelating agents. Oral Zinc has also been proven to have a useful role and foods rich in copper such as seafood, chocolates or nuts must be avoided. Indications for liver transplant include failure to improve either liver or neurological function, acute liver failure or cirrhosis with decompensation of function. Rising enzymes, bilirubin and prothrombin time are poor prognostic signs. Jaundice and ascites also correlated with poor prognosis. Results of Liver Transplantation are impressive and indicated for those with synthetic failure or decompensation and in those with fulminant liver failure.

Drug induced hepatitis

Drug-induced hepatitis is rare and is caused by toxic exposure over several months to certain medications, vitamins, herbal remedies, or food supplements. Many drugs like analgesics and antipyretics that contain acetaminophen, the general anesthetic halothane, methyldopa, isoniazid (used for the treatment of tuberculosis), methotrexate, amiodarone, and HMG CoA reductase inhibitors (statins) can cause liver injury, and some drugs like erythromycin, oral contraceptives, chlorpromazine, and anabolic steroids interfere with the flow of bile. Usually liver inflammation subsides within days or weeks, or after the drug is stopped. The incidence is 8 out of 10,000 people.

Most common symptoms are fever, rash or itchy red hives on skin, joint pains, sore muscles, flu-like symptoms, nausea, vomiting, decreased appetite, sore muscles and jaundice.Diagnosis is through history, symptoms, abnormal liver tests, abnormal appearance of liver on ultrasound and rarely a liver biopsy to clinch the diagnosis.

The goal of treatment for drug-induced hepatitis is to discontinue taking the causative agent and monitor the liver closely while it recovers along with supportive therapy.

Primary biliary cirrhosis

The worldwide incidence is 4-5 / million (middle age women).Other autoimmune diseases such as Arthritis, Thyroiditis, Keratoconjunctivitis, Kidney and skin diseases occur with PBC. Patients present with fatigue and itching that progresses over 10-15 years, presenting with progressive jaundice.

Investigations show raised Serum Alkaline Phosphatase, Serum IgM titers and Cholesterol.95% have raised Anti Mitochondrial Antibody titer.Liver biopsy and histopathology study will show chronic inflammation of bile ductules around portal tract, granulomatous destruction of bile ducts, liver cell death in early stages and later fibrosis and disappearing bile ducts lead to frank cirrhosis.

Treatment

Drugs such as Azathioprine, Steroids, Chlorambucil and Cyclosporin can produce biochemical improvement at the cost of bad side effects.Drugs such as UDCA (Ursodeoxycholic acid) and Methotrexate are more promising as they produce biochemical and clinical improvement of symptoms.No known medical therapy can increase patient survival.Liver transplantation has the best chance at cure (80% survival at 1 year). All PBC patients with bilirubin> 5 mg/dl should enroll for liver transplantation.

Prognosis

In older age group, enlarged liver and high level of bilurubin correlates with shorter life span. Serum bilurubin level > 2mg/d1 indicates a mean survival of 4 years.Small percentage can develop recurrent PBC after liver transplantation.

Primary Sclerosing Cholangitis (PSC)

PSC mainly affects males and is characterized by chronic inflammation of the bile ducts resulting in stricture formation and obliteration of the duct lumen. In 70% of the patients it is associated with inflammatory bowel disease (IBD).

Diagnosis and treatment

Presents commonly with Jaundice and bacterial cholangitis. Recurrent episodes of cholangitis indicates need for liver transplantation even if the synthetic function of the liver is normal. Itching is a common presentation and can be present with normal bilirubin level, and in the absence of dominant stricture. 70% patients have Inflammatory Bowel Disease and colonoscopy is indicated to rule out colonic dysplasia or cancer. Cholangiocarcinoma may complicate PSC and usually results in sudden increase in jaundice, weight loss and serum alkaline phosphatase level. The diagnosis of PSC is primarily by liver biopsy.

Identification of dominant strictures in the biliary tree needs dilatation and stent placement. Episodes of recurrent cholangitis (biliary tree infection) require suppressive dose of antibiotics. Drugs may relieve itching.Unlike other chronic liver diseases the indication for listing for Liver Transplantation is for recurrent cholangitis, progressive jaundice and nutritional debility, rather than poor synthetic function of the liver.

Cancers of the gall bladder and bile duct

Cancer of the gallbladder is a malignant tumor arising from the gallbladder. Carcinoma of the bile duct is a malignant tumor of the bile ducts that may occur within or outside the liver. Carcinoma of the gallbladder occurs more frequently compared to the bile duct cancer. Survival rate is poor since most patients are diagnosed at a late stage in the disease. Both these tumours are generally locally aggressive and spread to distant sites only in late stages.

Presentation

Since there are no specific symptoms of carcinoma of the gallbladder, the cancer is usually diagnosed when it has already progressed to an advanced state. Patients may complain of abdominal pain or distention, weight loss, nausea, or anorexia. Jaundice is the first symptom in some patients and is a bad prognostic sign.

Jaundice is the most common symptom of carcinoma of the bile duct, resulting from blockage of the bile duct with tumor. The excess bile components in the bloodstream can cause itching and dark coloration of the urine.

Diagnosis

Carcinoma of the bile duct produces tumor markers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), which are useful in diagnosing carcinoma of the bile duct associated with primary sclerosing cholangitis. Both ultrasound and computed tomography (CT) can detect the actual tumor and the extent to which it has spread.

Treatment

For both carcinoma of the gallbladder and bile duct, the only hope for cure lies with aggressive surgical resection of the tumor and all involved structures. 75% of patients with carcinoma of the gallbladder and 90% of those with carcinoma of the bile duct are diagnosed too late for surgical cure.

For tumors within the liver or high up in the biliary tract, resection of part of the liver may be required. Tumors in the middle portion of the biliary tract can be removed alone. Tumors of the lower end of the biliary tract may require extensive resection of part of the pancreas, small intestine, and stomach to ensure complete resection.

Prognosis

The prognosis of a patient with either of these tumors depends on the stage and resectability of the tumor.Stage I carcinoma of the gallbladder is associated with an excellent prognosis. Survival rate declines with advancing stage - 25% for stage II, 12% for stage III, and 1-2% for stage IV tumors. Since most patients are diagnosed with late-stage disease, less than 5% of all patients live longer than 5 years after diagnosis.Stage I and stage II hilar bile duct cancers (Khlatskintumour) can benefit from liver transplant in super selected cases who also receive adjuvant chemo-radiation.

Primary biliary atresia

Extra Hepatic Biliary Atresia (EHBA) is a defect in the development of the bile ducts that drain from the liver into the intestines that is characterized by obliteration of the biliary system, resulting in obstruction to bile flow. It is the most successfully surgically treatable cause of jaundice encountered during the newborn period. However due to lack of timely diagnosis, secondary biliary cirrhosis or scarring of the liver invariably results.

Presentation

• Type 1 involves obliteration of the common duct, while the proximal ducts are patent.
• Type II is characterized by Atresia of the hepatic duct, with cystic structures found in the porta-hepatitis.
• Type III (> 90% of patients) involves Atresia of the right and left hepatic ducts at the level of the portal hepatitis.

Treatment

Steroid therapy appears to improve survival but does not prevent progression to liver cirrhosis. Surgery is the mainstay of treatment for extra hepatic biliary atresia. Kasai porto-enterostomy done in the first 10 weeks of life, gives 60% long term survival with the native liver, though there may be recurrent liver related illness. Moderate dose of steroids combined with Kasai procedure seems to improve outcome. Diagnosis made after ten weeks and in those with signs of liver failure and failure to thrive, liver transplantation is the only treatment that can ensure long term survival. Dr. M.R Rajasekar’s pioneering liver transplant in India was on an 18 month old child with failed Kasai operation. He is now the longest liver transplant survivor in India (>18 years).

Choledochal cyst

These are congenital anomalies of the bile duct that are seen on a CT scan as cystic dilatations of the biliary tree. In infants, the disease presents with jaundice, acholic stools and an abdominal mass (liver enlargement). In older children present with intermittent biliary obstruction, pancreatitis with abdominal colic and jaundice. About 20% adults present with the classic triad of abdominal pain, jaundice and palpable abdominal mass in the right upper quadrant. Amongst the four variants, Caroli’s disease manifests as dilatation of ductules within the liver and if these cysts are left untreated, can develop cancer.

Diagnosis

Though there are no specific tests, some helpful indicators are a raised white cell count, raised serum Alkaline phosphatase, serum amylase and lipase, and hypochloremic hypokalemic alkalosis in blood chemistry. Abdominal Ultrasound is the test of choice, and a CT scan and MRI are helpful in specific anatomical definitions. A Percutaneous Trans-hepatic Cholangiography (PTC) and Endoscopic Retrograde CholangioPancreatography (ERCP) can be performed to corroborate the non-invasive tests.

Treatment

Surgery is the treatment of choice and the procedures vary based on how anatomically complicated the cysts are and the involvement of the surrounding structures. Usually, the cystic dilations of the ducts outside the liver are removed and the bile drainage is reconstructed.Caroli’s disease may require Liver Transplantation.

Bile duct stones

Bile duct stones are formed from Cholesterol, calcium or bile salts. Cause is multifactorial. Most originate from the Gall bladder while some arise primarily within the duct. They may present as abdominal pain, fever with chills, jaundiceand itching. Diagnosis is made with ultrasound done on empty stomach. Treatment is aimed at control of infection and draining the bile. Most stones are treated by EndoscopicSphincterotomy and drainage with basket removal of stones. Removal of the Gall bladder at a later date is advisable. Alternatively, open surgery (if endoscopy fails)can be performed with removal of stones, and bypass of bile drainage created through the intestines.

Biliary strictures

Strictures or narrowing of the bile duct is uncommon and can be benign or cancerous. Benign strictures are usually a manifestation of PSC. Rarely,theymay be caused by open or laparoscopic gall bladder surgery, and sometimes by stones in the bile duct. Cancerous strictures are caused by primary bile duct cancers or by infiltration of cancer of the pancreas, duodenum, lymph nodes or the Gall bladder. Symptoms include jaundice, itching, fever with chills, fullness in the abdomen or weight loss. Treatment includes rehydration, IV antibiotics for infection, correction of clotting factors, endoscopic bile duct drainage and surgical excision of the tumour or bypass of the blockage, depending on the condition.

Bile duct injuries

Isolated bile duct injuries are uncommon and usually due to major blunt abdominal trauma. This often results in avulsion of right or left hepatic duct with or without liver lacerations. Major duct injuries are best dealt with by combining resection of part of the liver. Primary reconstruction is not advisable. Another common cause of bile duct injury is following laparoscopic gall bladder surgery when the main duct is cut or clipped inadvertently. Presentation is with pain, fever, bile leak with jaundice following Lap Cholecystectomy. The treatment involves complex bile duct reconstruction after correcting sepsis.